Chapter  163:  Carbohydrate and Lipid Disorders and Relevant Considerations in Persons with Spinal Cord Injury

Introduction

Spinal cord injuries (SCI) result in 11,000 hospitalizations of new cases annually in the United States.^{5, 6} More than 240,000 Americans live with a disability related to SCI and the estimated annual cost averages $9.7 billion.^{5, 7, 8} Improved quality of care over the last several decades has resulted in a 40 percent decline in mortality during the two years following the injury.⁹ However, improvement in long-term survival has been smaller. Cardiovascular diseases (CVD) have been reported as the most common cause of death in adults with chronic SCI.^{2, 10}–¹² CVD risk factors associated with SCI include behavior (smoking, limited exercise) and metabolic abnormalities (obesity, metabolic syndrome,¹³–¹⁵ and diabetes¹¹). The prevalence of dyslipidemia^{16, 17} and coronary heart disease has been reported to be higher in adults with SCI compared to the general population.^{10, 18} The Institute of Medicine recently released two reports that emphasized the role of cardiovascular risk assessment and management in adults with chronic SCI.^{6, 11} Some evidence suggests that exercise,¹⁹ diet,^{20, 21} and pharmacological therapy²² may reduce diabetes and CVD risk in these individuals. Furthermore, markers or thresholds of carbohydrate and lipid disorders commonly used in adults without SCI may not apply to the population that has sustained SCI. In particular, because adults with SCI lose muscle mass that is replaced with fat mass, traditional measures of obesity (weight or body mass index [BMI]) may not be appropriate.

Accurate estimates of diabetes prevalence and severity in adults with SCI may: 1) be underestimated relative to able-bodied controls because individuals with SCI may not undergo regular testing, 2) have lower levels of high-density lipoprotein (HDL) cholesterol that go unrecognized if providers only assess total cholesterol (TC) levels or base treatment solely on low-density lipoprotein (LDL) cholesterol, or 3) they have earlier evidence of impaired glucose tolerance or altered insulin sensitivity. Existing guidelines do not include routine evaluation of glucose and lipid abnormalities nor do they provide recommendations for threshold definitions of abnormality or target levels for interventions to achieve it.²³–²⁵ Furthermore, the prevalence, morbidity, and mortality associated with carbohydrate and lipid disorders may differ in adults with SCI compared to able-bodied individuals.

Effective interventions to treat carbohydrate and lipid disorders and reduce cardiovascular complications in able-bodied individuals include dietary, pharmacologic, and exercise therapies. However, adults with SCI have unique physiologic characteristics that may preclude generalization of evidence from able-bodied individuals to those with SCI. Total daily energy expenditure for adults with SCI is difficult to calculate but likely much lower than for able-bodied individuals, especially among individuals requiring motorized wheelchairs for mobility. Treatment of obesity in SCI remains largely empiric, including guidelines developed for dietary intervention in SCI. Pharmacologic therapies to alter carbohydrate and lipid disorders may have different effectiveness and adverse effects in individuals with SCI compared to able-bodied patients. For example, assessment of hepatic or muscle toxicity in SCI individuals may be difficult using traditional serologic measures developed in able-bodied adults because SCI individuals have reduced muscle mass and potentially altered hepatic metabolism.

Despite the expected benefits of exercise for individuals with SCI, this group also faces unique challenges and risks from exercise that are not experienced by the able-bodied population.^{8, 26} For one, lack of access to and choices in exercise modes, depending on the neurological impact and level of the injury, form physical barriers to obtaining exercise. Physiological risks of exercise are also a barrier to improved fitness among those with SCI. Depending on the level and completeness of the spinal injury, motor, sensory, and autonomic reflexes may still be intact but no longer under control of the brain. Individuals with SCI also experience various types of autonomic and circulatory dysregulation.²⁶ Risk of stress-related musculoskeletal injury is of concern, given the reliance on a small group of muscles for activities of daily living as well as for any physical conditioning. Fractures, joint dislocation, and overuse injuries are common for individuals with SCI.²⁷

We conducted a systematic review of published evidence to address the following questions:

Question 1a: What proportion of adult patients with chronic posttraumatic spinal cord injuries have been diagnosed with:

• a

  Insulin resistance syndrome, metabolic syndrome

• b

  Diabetes mellitus Type 2, impaired glucose tolerance

• c

  Dyslipidemia

• d

  Obesity

Question 1b: Is the prevalence of carbohydrate and lipid disorders higher in the subgroups of patients by age, race, and gender compared to the general population? Does the prevalence of carbohydrate and lipid disorders differ by the time after trauma, the level of trauma, and functional impairment?

Question 2: For people with SCI, what is the evidence on contribution to risk of cardiovascular disease of:

• a

  Hyperinsulinemia

• b

  Abnormalities in carbohydrate metabolism

• c

  Abnormalities in lipid metabolism?

• d

  Obesity

This question was refined as:

Question 2: Regarding risk of cardiovascular disease for people with SCI:

• a

  What is cardiovascular prevalence and mortality in adults with chronic posttraumatic spinal cord injuries?

• b

  Does cardiovascular incidence and mortality in adults with chronic posttraumatic spinal cord injuries differ compared to the general population based on age, race, and gender categories?

• c

  What is the strength of the association between cardiovascular incidence and mortality and abnormalities in lipid and glucose metabolism including Type 2 diabetes mellitus after adjustment for possible confounding factors?

• d

  Does association vary depending on age, gender, race, the duration after SCI, the level of SCI, and functional impairment?

Question 3: What are the effects on carbohydrate or lipid-related outcomes in adults with SCI of:

• a

  Exercise

• b

  Dietary and pharmacologic interventions

Methods

Studies addressing prevalence of obesity, diabetes, impaired glucose tolerance, insulin resistance, and lipid disorders through August 2007 were included if:

• 1

  adults had chronic SCI;

• 2

  the total number of spinal cord subjects was at least 100, or totaling at least 100 subjects if a control group was included (SCI + controls ≥100);

• 3

  reported prevalence of obesity, diabetes, impaired glucose tolerance, metabolic syndrome or insulin resistance, or lipid disorders or reported mean BMI or lipid levels,

• 4

  were published in the English language. Abstracts of articles excluded due to small sample size were reviewed to assess for study quality and potential impact.

For Question 2, original epidemiologic investigations of more than 50 adults with chronic SCI and published in English after 1990 were identified in MEDLINE^® via PubMed® and the Cochrane library. Websites of the American Spinal Injury Association, American Paraplegia Society, Paralyzed Veterans of America, Consortium of Spinal Cord Medicine, and the catalog WorldCat identified reviews.

For exercise interventions, the Endnote library containing original and review articles (n=2,212) was searched for abstracts that included the words fitness, physical activity, or exercise, resulting in a subset of 303 citations. A MEDLINE^® search was conducted of articles written in English and published between 1996 and August 2007. Any identified study was included regardless of design, sample size, or duration if it reported carbohydrate, lipid, or cardiovascular results in adults with chronic SCI.

To assess dietary or pharmacologic interventions for treatment of carbohydrate and lipid metabolism disorders in the SCI population, studies were identified by searching in MEDLINE^® through October 2007. Reference lists of included studies or reviews were also searched. Since no randomized trials were identified, nonrandomized studies were eligible. To be included, studies had to:

• 1

  evaluate adults who had chronic SCI, defined as one year or more since sustaining the injury;

• 2

  evaluate pharmacologic or dietary interventions;

• 3

  report carbohydrate and/or lipid-related outcome measures; and

• 4)

  be published in the English language.

Reviewers extracted study and patient characteristics and outcomes onto standardized forms. A second reviewer assessed the findings and disagreements, while rare, were resolved by discussion. Prevalence estimates of obesity, diabetes, lipid disorders, and cardiovascular morbidity and mortality among adults with SCI and, where possible, able-bodied controls, are presented. Findings are reported separately where possible according to age, gender, race, and level/severity of SCI. For Question 3, carbohydrate and lipid outcomes are described according to the exercise, diet, or pharmacologic intervention studied. Due to heterogeneity in populations, interventions, comparator groups, and/or reported outcomes, pooled analyses was generally not conducted.

Results

For Question 1, 23 studies met the inclusion criteria, two studies for insulin resistance/ metabolic syndrome,^{15, 28} 12 studies for diabetes mellitus,^{3, 15, 28}–³⁷ three studies for impaired glucose tolerance,^{28, 29, 31} seven studies for lipid disorders,^{16, 17, 21, 31, 38}–⁴⁰ and ten studies for obesity and body composition.^{28, 31, 36, 38, 40}–⁴⁵ Potentially eligible studies excluded due to small sample size that limited generalizability (n=45, number of SCI individuals in each study ranged from 1–77) were also of low quality and relevance because they were from a single center, not from the United States, lacked controls, and/or did not assess clinically relevant carbohydrate and lipid disorders.

For Question 2, 20 articles of 19 studies met inclusion criteria; most were conducted in the United States.¹–^{3, 30, 32, 34, 36, 37, 39, 46}–⁵⁶ Studies included more than 50,000 patients with SCI. Males (pooled prevalence 86 percent) and Caucasians comprised the majority of individuals. Most used general population controls, were uncontrolled, or did not adjust for known confounding variables including: age, race, gender, smoking status, exercise, or duration of followup. Wide variation existed in the definitions of reported CVD outcomes.

For Question 3a, studies evaluating the following types of exercise were identified: Active Exercise (AE) (seven studies),⁵⁷–⁶³ Functional Electrical Stimulation exercise (FES) (five studies),⁶⁴–⁶⁸ Passive Exercise (PE) (no studies, Self-Reported Physical Activity (six studies),^{13, 14, 54, 69}–⁷¹ and Other (one study).⁷²

For Question 3b, only two prospective studies (neither randomized) evaluating dietary and/or lifestyle interventions to reduce lipid levels met inclusion criteria.^{20, 72}

Discussion

The present report systematically evaluated published evidence regarding the prevalence of lipid and carbohydrate disorders, CVD, and mortality in adults with chronic posttraumatic SCI. The overall quality of evidence is low. Most studies were retrospective, small, lacked adequate controls, and did not assess or adjust for confounding factors. Outcome measure definitions varied widely. However, limited low quality data suggest that adults with SCI are not at markedly higher risk of carbohydrate and lipid disorders or CVD than age and gender matched able-bodied individuals. Assessment of obesity using BMI is likely to be inaccurate and underestimates body fat in adults with SCI.

The prevalence of insulin resistance, metabolic syndrome, diabetes mellitus, impaired glucose tolerance, dyslipidemia, obesity, and CVD in a population are all highly dependent upon the demographics of the population, including, most importantly, the age distribution, but also socioeconomic status and race/ethnicity. The dependence of these conditions on population characteristics makes it difficult to make between-study comparisons, since the population characteristics range greatly both between and within studies. These factors may explain the wide variation in study prevalence estimates as well as the relative risk compared to different able-bodied control populations.

Some potentially eligible studies (n=45) were excluded due to small sample size (i.e., less than 100 SCI subjects if lacking controls or less than 100 total subjects if including controls). Based on review of published abstracts, the impact of these studies on our overall findings regarding carbohydrate, lipid and body composition disorder prevalence, and subsequent clinical decisionmaking is likely to be small. The number of SCI individuals in the excluded studies ranged from one to 77. Only 17 had control groups. The largest excluded study reporting impaired glucose tolerance and insulin resistance in the United States lacked controls, was comprised of 57 adults from a single center, and was published in 1983. The largest excluded controlled study of lipid disorders was a single center report comprised of 60 young SCI adults (mean age = 28 years) and 28 healthy able-bodied controls matched by age and gender. Serum LDL cholesterol was higher (109 mg/dL vs. 91 mg/dL; p = 0.04) and HDL cholesterol lower (33 mg/dL vs. 44 mg/dL; p =0.004) in SCI adults versus controls. The authors concluded that “serum lipoprotein levels should not be ignored for the followup of patients with spinal cord injury.”⁷⁵ We agree with their conclusion. Other excluded studies were of even lower quality and relevance to health care in the United States because they were smaller, from a single center, not from the United States, lacked controls, and/or did not assess clinically relevant carbohydrate and lipid disorders.

A previous review⁷⁶ suggested a high prevalence of CVD in individuals with SCI. However, this report included, but did not differentiate between, highly prevalent self-reported signs and symptoms, such as leg swelling or palpitations⁵⁶ and less common but more serious conditions or those documented in medical records, such as myocardial infarction (0.28 to 3 percent of SCI patients).^{3, 53} Several factors may contribute to the prevalence of undiagnosed CVD in SCI individuals, including access and quality of care, asymptomatic angina in patients with diabetes or upper level injury,^{77, 78} and metabolic syndrome, unstable blood pressure, and cardiac rhythm.^{79, 80} If screening intensity or criteria to detect/define asymptomatic heart diseases, including coronary heart disease, arrhythmias, and autonomic dysreflexia, differs in SCI compared to able-bodied adults this could bias comparative CVD prevalence estimates.

Prevalence of CVD in aging SCI individuals can be attributable to age rather than injury. Patients differed by the prevalence of risk factors prior to injury and by age at the time of injury. Both could modify the association between SCI and CVD. Indeed, a recently published retrospective analysis found that the presence of cardiovascular disease prior to injury was associated with a 280 percent increase in risk of death.⁸¹ For each additional year of age at injury, the relative risk of dying was increased by 8 percent (RR 1.08, 1.06; 1.09).⁸¹ Whether the reported increased risk of all CVD in tetraplegic compared to paraplegic individuals can be interpreted as an evidence of higher morbidity^{53, 76} requires additional studies. Limited evidence suggests that cardiovascular mortality may contribute to approximately 20 percent of all deaths in SCI patients^{1, 36, 49, 52} and coronary heart disease to 9 percent of all deaths.¹–³ There is insufficient evidence to determine whether percentage of deaths due to CVD differs in SCI adults compared to appropriately matched able-bodied individuals. One study suggested that presence of heart diseases was associated with a 3.7 fold increased risk of death in SCI patients compared to SCI patients without CVD, independent of age and other risk factors.⁵² Limited evidence suggests that the contribution of different forms of heart disease (e.g., ischemic vs. nonischemic coronary heart disease) to overall CVD mortality in SCI patients may differ from the general population. However, proportionate mortality in SCI patients cannot give a valid estimation of mortality rates in this population. Standardized mortality ratios from nonischemic heart diseases, artery diseases, and lung emboli were higher in all injured adults compared to the general population.² Mortality from lung emboli contributed the most to the overall differences within the total population. However, the inconsistency of results and the multiplicity of outcomes assessed makes it very plausible that these are chance findings.

Whether the independent contribution of diabetes and impaired glucose tolerance on CVD prevalence differs in adults with versus without SCI has not been reported. The association between metabolic control and CVD in adults with SCI remains unclear. Prevalence of retinopathy was not different in SCI users of the VA health care system who were diabetic compared to diabetic able-bodied veterans.³⁷ The impact of lipid disorders on CVD in SCI individuals is not well documented and needs future investigation.

There is no evidence that diagnostic and treatment threshold for carbohydrate and lipid disorders should differ in SCI vs. able-bodied individuals. Assessment of insulin resistance and impaired glucose tolerance are not routinely performed in able-bodied individuals. The effectiveness of screening to improve clinical outcomes by detection of pre-diabetes (impaired fasting glucose or impaired glucose tolerance), insulin resistance, and diabetes in asymptomatic adults has not been demonstrated.⁷³ Use of these tests is limited due to their inconvenience, complexity of testing requirements, costs, and current lack of accuracy. The OGTT is inconvenient and not ordered by most physicians to diagnose diabetes, even among those at risk. Additionally, about one-half with IGT or OGTT would have normal tests if repeated. Similar concerns exist with the criteria used to define impaired fasting glucose. Because the glucose concentration distribution is unimodal, the choice of cutpoints used to designate abnormalities of carbohydrate metabolism is arbitrary. A recent systematic review assessed the comparative effectiveness and safety of oral medications for Type 2 diabetes mellitus. The authors reported that there was no definitive evidence about the comparative effectiveness of oral diabetes agents on all-cause mortality, cardiovascular mortality, or morbidity, peripheral arterial disease, neuropathy, retinopathy, or nephropathy.⁸² Two more recent meta-analyses of thiazolidinediones have been conducted. Among able-bodied patients with impaired glucose tolerance or Type 2 diabetes (n=14,291), rosiglitazone use for at least 12 months was associated with an increased risk of myocardial infarction and heart failure. There was no difference in increased risk in cardiovascular mortality.⁸³ A review of pioglitazone (n=16,390) showed a significantly lower risk of death, myocardial infarction, or stroke among patients with Type 2 diabetes and inadequate glycemic control. Serious heart failure was increased.⁸⁴ Existing recommendations to assess cardiovascular risk for able-bodied individuals suggest that all adults should have a complete lipid profile, including HDL and LDL cholesterol levels, as well as family history, smoking status, and gender. The treatment recommendations should be based on that comprehensive risk assessment. Future studies are needed to determine if SCI should be included as an independent risk factor.

The evidence that exercise programs alter carbohydrate and lipid outcomes is of poor quality and inconclusive. Only one study examined the effects of exercise on coronary heart disease outcomes or survival, with no identified associations. There were relatively few consistent findings pertaining to plasma glucose, two-hour post-load glucose, fasting insulin, or two-hour post-load insulin. Similarly, little consistency was reported between studies for HDL cholesterol, TC/HDL, and TG. Results may have indicated some overall post-training benefits for outcomes of TC and LDL cholesterol. While many reported findings are suggested as beneficial in the primary papers as well as past reviews,⁸⁵ caution in warranted. There was a general lack of quantity, quality, and consistency in methods and outcomes across studies. Reports were based on short-term exercise protocols, often involved carefully recruited hospital- and/or clinic-based patients, and failed to consider implementation or sustainability of exercise interventions in community-based populations. The exercise described in these papers varied considerably from one study to the next. In the cross-sectional surveys, parameters of physical activity were rarely reported.

Exercise and dietary programs among able-bodied individuals have demonstrated a modest improvement in carbohydrate and lipid parameters among selected highly motivated individuals. Translation of these findings to community settings of SCI adults has not been demonstrated and even the effectiveness in the general able-bodied population is unclear. For example, a recent randomized trial evaluated the effects of 22 weeks of aerobic training, resistance training, or both (three times per week) on glycemic control in 251 able-bodied adults with Type 2 diabetes.⁸⁶ Combined training resulted in a 1 percent absolute reduction in glycated hemoglobin values versus sedentary controls. Reductions due to either resistance or aerobic training alone were about one-half that seen with combination therapy. There was no difference in lipid values, blood pressure, lean body mass, fat mass, or percent body fat of any of the exercise programs versus controls. Adverse events were more common in the exercise group, and 14 percent of those randomized to exercise dropped out.

Conclusions

The available evidence regarding the prevalence, impact, and outcomes of carbohydrate and lipid disorders in adults with chronic SCI is weak. Evidence is limited by relatively small sample size, lack of appropriate control groups, failure to adjust for known confounding variables, and variation in reported outcomes. However, the existing evidence does not indicate that adults with SCI are at markedly greater risk for carbohydrate and lipid disorders or subsequent cardiovascular sequelae than able-bodied adults. The available evidence does not support incorporating SCI status as an independent variable to assess risk of cardiovascular morbidity and mortality or to alter diagnostic/treatment thresholds compared to able-bodied adults. Individuals with SCI may have unique physiologic differences compared to able-bodied individuals. Therefore, caution is advised in attempting to extrapolate findings from studies conducted in able-bodied adults evaluating efficacy and harms of interventions to improve carbohydrate, lipid disorders, and subsequent CVD. Assessment of obesity and body composition by BMI is likely inaccurate and underestimate risks. Alternative methods for assessment in SCI populations are needed. However, unless future high-quality studies suggest otherwise, current evidence supports the conclusion that detection and treatment of carbohydrate and lipid disorders in adults with SCI should be similar to able-bodied individuals.

Future Research

A major gap in the evidence is the lack of high-quality prospective epidemiologic studies assessing the prevalence and impact of lipid and carbohydrate abnormalities and corresponding CVD complications in SCI individuals, especially compared to appropriately matched able-bodied controls. Future research could include a large prospective multicenter cohort study of adults with SCI. Risk assessment should be started at the time of injury and continued during long-term followup. Prevalence and incidence assessment needs to be objective rather than self reported. Inclusion of baseline and followup physiologic and serologic values (e.g. body composition measures, actual lipid and carbohydrate laboratory values) and standardized outcomes should be made according to well-recognized diagnostic criteria of heart diseases. Expansion of existing cohort studies in the VA, a large non-VA cohort study, and future RCTs that aim to test whether more aggressive screening or treatment within SCI populations actually reduces disease prevalence, morbidity, and mortality could be initiated. Additional information on women is needed.

If prospective cohort studies identify an increased risk in adults with SCI, RCTs will be needed to further extend the information. Techniques for identifying and treating these carbohydrate and lipid disorders and CVDs may need to be modified to meet the specific needs of those with SCI.

The level of injury, neurological impairment, and other known or potential confounders including smoking status, hypertension, family history, race, age, diabetes, infections, socioeconomic status, and quality of health care should be analyzed as possible effect modifiers of the association between well known risk factors and cardiovascular morbidity and mortality.

Consistent, higher quality research on exercise and metabolic and cardiovascular health in SCI patients is needed. Studies examining effectiveness as well as efficacy of exercise interventions are needed. Continued research should be conducted to gain a better idea of the important barriers to exercise experienced by individuals with SCI and to develop novel methods to overcome these barriers. Preliminary studies may also assess which patients are most in need of intervention, the best types of exercise programs and equipment, and how to modify them based on characteristics of the injury. Whether qualitative or quantitative, this preliminary work would not only inform the development of exercise programs but also the research used to evaluate efficacy and effectiveness.

Short-term, intermediate outcomes of exercise, as were typically reported in the current studies, may not be ideal or definitive measurements for this type of research. Studies ideally would focus on long-term clinically relevant outcomes such as prevention of or improvement in diabetes mellitus, coronary heart disease, and mortality. Long-term harms and adherence also need to be assessed. Key variables to be included in future studies are age, race, and gender; comorbid conditions; baseline lipid and carbohydrate related measures; duration, level, and completeness of SCI; functional status; baseline physical activity; exercise program type, frequency, intensity, and duration; and life satisfaction and other important psychosocial variables.

An RCT would provide the best evidence for or against the use of exercise to prevent or control carbohydrate and lipid disorders among those with SCI, though conducting adequately sized studies would be difficult and require cooperative group participation. Further research will be needed to translate any findings of exercise efficacy into effective community-based interventions. Even if efficacy is promising, it will remain to be seen if these interventions are feasible in a community setting and if the interventions, as well as health outcomes, are sustainable over time. Further evidence on how best to motivate individuals to sustain exercise, while preventing and identifying potential harms, will be needed.

RCTs evaluating the potential effectiveness and harms of pharmacologic and dietary interventions to alter CVD risk factors (diabetes, lipid abnormalities and/or obesity) and reduce CVD incidence, morbidity, and mortality may be needed if there is continued concern that results may differ in SCI populations compared to able-bodied adults.

Overview

Spinal cord injuries (SCI) result in 11,000 hospitalizations of new cases annually in the United States.^{5, 6} More than 240,000 Americans live with a disability related to SCI and the estimated annual cost averages $9.7 billion.^{5, 7, 8} Improved quality of care over the last several decades has resulted in a 40 percent decline in mortality during the two years following the injury.⁹ However, improvement in long-term survival has been smaller. Cardiovascular diseases (CVD) have been reported as the most common cause of death in adults with chronic SCI.^{2, 10}–¹² CVD risk factors associated with SCI include behavior (smoking, limited exercise) and metabolic abnormalities (obesity, metabolic syndrome,¹³–¹⁵ and diabetes¹¹). The prevalence of dyslipidemia^{16, 17} and coronary heart disease has been reported to be higher in adults with SCI compared to the general population.^{10, 18} The Institute of Medicine recently released two reports that emphasized the role of cardiovascular risk assessment and management in adults with chronic SCI.^{6, 11} Some evidence suggests that exercise,¹⁹ diet,^{20, 21} and pharmacological therapy²² may reduce diabetes and cardiovascular disease risk in these individuals. Furthermore, markers or thresholds of carbohydrate and lipid disorders commonly used in adults without SCI may not apply to the population that has sustained SCI. In particular, because adults with SCI lose muscle mass that is replaced with fat mass, traditional measure of obesity (weight or body mass index [BMI]) may not be appropriate.

Accurate estimates of diabetes prevalence and severity in adults with SCI may:

• 1

  be underestimated relative to able-bodied controls because individuals with SCI may not undergo regular testing,

• 2

  have lower levels of high-density lipoprotein (HDL) cholesterol that go unrecognized if providers only assess total cholesterol (TC) levels or base treatment solely on low-density lipoprotein (LDL) cholesterol, or

• 3

  they have earlier evidence of impaired glucose tolerance or altered insulin sensitivity. Existing guidelines do not include routine evaluation of glucose and lipid abnormalities nor do they provide recommendations for threshold definitions of abnormality or target levels for interventions to achieve.²³–²⁵ Furthermore, the prevalence, morbidity, and mortality associated with carbohydrate and lipid disorders may differ in adults with SCI compared to able-bodied individuals.

Effective interventions to treat carbohydrate and lipid disorders and reduce cardiovascular complications in able-bodied individuals include dietary, pharmacologic, and exercise therapies. However, adults with SCI have unique physiologic characteristics that may preclude generalization of evidence from able-bodied individuals to those with SCI. Total daily energy expenditure for adults with SCI is difficult to calculate but likely much lower than for able-bodied individuals, especially among individuals requiring motorized wheelchairs for mobility. Treatment of obesity in SCI remains largely empiric, including guidelines developed for dietary intervention in SCI. Pharmacologic therapies to alter carbohydrate and lipid disorders may have different effectiveness and adverse effects in individuals with SCI compared to able-bodied patients. For example, assessment of hepatic or muscle toxicity in SCI individuals may be difficult using traditional serologic measures developed in able-bodied adults because SCI individuals have reduced muscle mass and potentially altered hepatic metabolism.

Despite the expected benefits of exercise for individuals with SCI, this group also faces unique challenges and risks from exercise that are not experienced by the able-bodied population.^{8, 26} For one, lack of access to and choices in exercise modes, depending on the neurological impact and level of the injury, form physical barriers to obtaining exercise. Physiological risks of exercise are also a barrier to improved fitness among those with SCI. Depending on the level and completeness of the spinal injury, motor, sensory, and autonomic reflexes may still be intact but no longer under control of the brain. Individuals with SCI also experience various types of autonomic and circulatory dysregulation.²⁶ Risk of stress-related musculoskeletal injury is of concern, given the reliance on a small group of muscles for activities of daily living as well as for any physical conditioning. Fractures, joint dislocation, and overuse injuries are common for individuals with SCI.²⁷

In selected highly motivated able-bodied population, exercise, and its resulting improvements in aerobic capacity, appear to modestly improve carbohydrate metabolism, lipid profiles, and general cardiovascular health.^{7, 87}–⁹⁰ For example, even moderate levels of physical activity, defined as three to six metabolic equivalents (METs) sustained for 30 minutes five to six times per week, may reduce the risk of cardiovascular disease and all-cause mortality.⁹¹ Current Centers for Disease Control and Prevention (CDC) and American College of Sports Medicine recommendations for exercise in the able-bodied population include 30 minutes of moderate physical activity, five to six times per week, or 20 minutes of vigorous (greater than six METs) physical activity, three or more times per week.⁹²

However, translation of these findings to community settings of SCI adults has not been demonstrated, and even the effectiveness in the general able-bodied population is unclear. For example, a recent randomized trial evaluated the effects of 22 weeks of aerobic training, resistance training, or both (three times per week) on glycemic control in 251 able-bodied adults with Type 2 diabetes.⁸⁶ Combined training resulted in a 1 percent absolute reduction in glycated hemoglobin values vs. sedentary controls. Reductions due to either resistance or aerobic training alone were about one-half that seen with combination therapy. There was no difference in lipid values, blood pressure, lean body mass, fat mass, or percent body fat of any of the exercise programs vs. controls. Adverse events were more common in the exercise group and 14 percent of those randomized to exercise dropped out.

Whether this amount of physical activity would produce the same benefits in patients with SCI is unknown. However, it is reasonable to assume that similar metabolic responses to exercise would occur for these individuals. No evidence-based guidelines for exercise in this population currently exist.⁹³ At present, the American College of Sports Medicine's endurance training recommendations for those with SCI are relatively similar to advice directed toward the general population. Generally, the recommended exercise prescription, at least for those with paraplegia, is three to five weekly sessions of 20 to 60 minutes in duration and at an intensity of 50 to 80 percent of the individual's peak heart rate.⁹⁴ Suggested modes of exercise include arm cranking, wheelchair propulsion, swimming, wheelchair sports, circuit resistance training, electrically-stimulated cycling, and electrically-stimulated walking.

Based on a topic and key questions nominated by the Consortium for Spinal Cord Medicine, we conducted a systematic review of published evidence to address the following questions:

Question 1a: What proportion of adult patients with chronic posttraumatic spinal cord injuries have been diagnosed with:

• a

  Insulin resistance syndrome, metabolic syndrome

• b

  Diabetes mellitus Type 2, impaired glucose tolerance

• c

  Dyslipidemia

• d

  Obesity

Question 1b: Is the prevalence of carbohydrate and lipid disorders higher in the subgroups of patients by age, race, and gender compared to the general population? Does the prevalence of carbohydrate and lipid disorders differ by the time after trauma, the level of trauma, and functional impairment?

Question 2: For people with SCI, what is the evidence on contribution to risk of cardiovascular disease of:

• a

  Hyperinsulinemia

• b

  Abnormalities in carbohydrate metabolism

• c

  Abnormalities in lipid metabolism?

• d

  Obesity

This question was refined as:

Question 2: Regarding risk of cardiovascular disease for people with SCI:

• a

  What is cardiovascular prevalence and mortality in adults with chronic posttraumatic spinal cord injuries?

• b

  Does cardiovascular incidence and mortality in adults with chronic posttraumatic spinal cord injuries differ compared to the general population based on age, race, and gender categories?

• c

  What is the strength of the association between cardiovascular incidence and mortality and abnormalities in lipid and glucose metabolism including Type 2 diabetes mellitus after adjustment for possible confounding factors?

• d

  Does association vary depending on age, gender, race, the duration after SCI, the level of SCI, and functional impairment?

Question 3: What are the effects on carbohydrate or lipid-related outcomes in adults with SCI of:

• a

  Exercise

• b

  Dietary and pharmacologic interventions

Topic Assessment and Refinement and Literature Review

A Technical Expert Panel (TEP) was convened, comprised of individuals with expertise in rehabilitation/physical therapy/neuromuscular aspects of chronic SCI, primary care relevant to patients with chronic SCI, lipid and carbohydrate disorders, dietary intervention, exercise, and pharmacotherapy in patients with chronic SCI. Names of individuals who agreed to participate, their CVs, and disclosure statements were sent to the Agency for Healthcare Research and Quality (AHRQ) for review and approval by the end of January 2007. Those members are identified in Appendix A.

Based on discussions with our partner and TEP members, we developed inclusion and exclusion criteria for study design and size, population, intervention, comparator groups, and outcomes. Question 2 was refined to read:

• What is cardiovascular prevalence and mortality in adults with chronic posttraumatic spinal cord injuries?

• Does cardiovascular prevalence and mortality in adults with chronic posttraumatic spinal cord injuries differ compared to the general population based on age, race, and gender categories?

• What is the strength of the association between cardiovascular prevalence and mortality and abnormalities in lipid and glucose metabolism including Type 2 diabetes mellitus, after adjustment for possible confounding factors?

• Does association vary depending on age, gender, race, the duration after SCI, the level of SCI, and functional impairment?

We evaluated, but ultimately did not include, findings from systematic reviews of randomized controlled trials (RCTs) related to behavioral, dietary or pharmacologic interventions as primary prevention of CVD and carbohydrate and lipid disorders in able-bodied adults. The rationale was that little RCT evidence regarding the efficacy and harms of these interventions in SCI individuals existed. It was unlikely that outcomes from these interventions would markedly differ between SCI and able-bodied individuals. Therefore, findings from these intervention studies in able-bodied controls were used to assess baseline lipid and carbohydrate characteristics as well as effectiveness and harms in able-bodied individuals. We also sought to determine whether evidence from these RCTs or current practice guidelines suggested that thresholds for diagnosis or intervention in SCI individuals currently recommended for able-bodied adults should be altered for SCI individuals.

Following the initial conference calls, the Minnesota Evidence-based Practice Center (EPC) conducted a systematic review and meta-analysis (where feasible) of published evidence of the association between lipid and carbohydrate disorders and risk of cardiovascular diseases in adults with chronic SCI. The prevalence of insulin resistance, metabolic syndrome, diabetes mellitus, impaired glucose tolerance, obesity, and abnormalities in lipid metabolism in patients with chronic SCI was estimated from cross-sectional studies that attempted to capture a nationally representative sample of adults with SCI. Observational cohort and case-control studies that tested the hypothesis of the association between carbohydrate and lipid disorders and risk of CVDs in adults with chronic SCI were reviewed. The risk of CVDs among patients with chronic SCI was analyzed. We examined case control and cohort studies to determine if risks of carbohydrate and lipid disorders and CVDs are greater in adults with SCI than in age/gender matched controls without SCI.

The role of different forms of exercise (passive and active, person initiated, and due to electrical stimulation) and diet in the prevention and treatment of carbohydrate and lipid disorders and corresponding sequelae in adults with chronic SCI was evaluated from observational studies and clinical trials. Controlled and randomized trials that examined the effects of exercise, diet, and pharmacological intervention on cardiovascular risk and outcomes in adults with chronic SCI were analyzed. Our preliminary search found few controlled trials of these interventions and only one survey report that assessed their impact on major cardiovascular endpoints, such as morbidity and mortality. Therefore, we estimated the potential impact of early detection and treatment of adults with SCI by evaluating large RCT and systematic reviews of treatments for lipid and carbohydrate disorders in adults without SCI. Our comprehensive work plan covered the assessment and refinement of study questions, proposed literature search and review, inclusion/exclusion criteria, and methods for evaluating the quality of studies and rating the strength of evidence.

Figure 1. Conceptual model. Contribution of carbohydrate (more...)

   Figure 1. Conceptual model. Contribution of carbohydrate and lipid disorders to risk of cardiovascular disease in adults with chronic posttraumatic SCI

Adapted from American College of Endocrinology statement on insulin resistance⁴

Bold - eligible outcomes

Figure 1

Study Identification

Figure 2. Flow chart for Question 1 references

   Figure 2. Flow chart for Question 1 references

Figure 3. Flow chart for Question 2 references

   Figure 3. Flow chart for Question 2 references

Figure 4. Flow chart for Question 3a references (exercise/physical (more...)

   Figure 4. Flow chart for Question 3a references (exercise/physical activity interventions)

Figures 2

4

For Question 3, based on the criteria identified above, 304 citations identified through the keyword search were reduced to 19 for use as evidence. Exclusions were based on the following: 38 due to lack of adult, chronic SCI patient population; 18 due to lack of exercise program or measure of self-reported physical activity; 231 due to lack of relevant carbohydrate or lipid related outcome measures. Upon review of citations from the 18 eligible references and one previous review paper, one additional reference was identified and added to the evidence base.⁶⁹ Thus, results of 19 original studies were synthesized to address this question.

For Question 3b, only two prospective studies in adults with SCI evaluated dietary and/or lifestyle interventions to reduce lipid levels and met inclusion criteria.^{20, 72}

Outcomes

Question 1

Overall Description

The prevalence of insulin resistance syndrome, metabolic syndrome, diabetes mellitus Type 2, impaired glucose tolerance, dyslipidemia, and obesity in a population are all highly dependent upon demographics of the population, including most importantly the age distribution, but also factors such as socioeconomic status and race/ethnicity. The dependence of these conditions on population characteristics makes it difficult to conduct between-study comparisons, since the population characteristics range greatly both between and within studies. For example, one study might include men and women between the ages of 18 and 70, and within such a study one would expect age and gender stratified proportions of Type 2 diabetes to vary several fold; however, studies of this sort might only present an overall percent that are diabetic. Such an overall value is difficult to interpret and nearly meaningless unless the study has an appropriate control group. In the included evidence tables and figures, results have been presented stratified by age and other key factors (including severity or duration of injury) when such information was reported, but the paucity of consistently stratified results makes pooled estimates nearly impossible. Therefore, we have chosen to focus primarily on the higher quality studies (largest observational reports with control groups).

Hyperinsulinemia (insulin resistance/metabolic syndrome)

Little is known regarding the extent to which hyperinsulinemia is related to SCI. Only one relatively small observational study reported results for metabolic syndrome and insulin resistance syndrome (Appendix E Table 1).¹⁵ This study included a convenience sample of 93 SCI subjects (mean age = 50 years) recruited from a single VA and local community clinics (86 percent male). Of these 93 subjects, 11 percent were insulin resistant when relying entirely on mean fasting glucose and insulin values; however, when glucose-regulating medications were taken into account, 22 percent of the subjects were insulin resistant.¹⁵ Metabolic syndrome was defined as the presence of three or more metabolic disorders, including hypertension (systolic blood pressure ≥130 mmg/Hg, diastolic pressure ≥85 mmg/Hg, or the use of antihypertensive medications), obesity (defined by waist circumference), hyperglycemia (fasting glucose ≥110 mg/Dl or presence of glucose-lowering medications), hypertriglyceridemia (fasting serum triglycerides ≥150 mg/dL or taking cholesterol-lowering medications), and low HDL cholesterol (<40 mg/dL). Using this definition, metabolic syndrome was noted in 22 percent. This study did not include a control group or attempt to present results stratified by age and gender or level and duration of injury. The authors definitions for specific metabolic disorders are not widely accepted and are likely to increase the estimated prevalence of a given disorder.⁷³ A second study of 201 SCI patients included results from an oral glucose challenge and reported rates of hyperinsulinemia by type of SCI injury.²⁸ This study found hyperinsulinemia in 53 percent of people with tetraplegia and 37 percent of paraplegics.

Summary

Currently, there are no high quality studies adequately assessing the prevalence of metabolic syndrome and insulin resistance syndrome in a large population of adults with SCI. There are also no data to assess if the prevalence of either metabolic syndrome or insulin resistance are elevated in adults with SCI compared to similar individuals without SCI. Since metabolic and insulin resistance rates are dependent on age, gender, and race/ethnicity, future studies are needed that are large enough to report rates stratified by these key factors.

Abnormalities in carbohydrate metabolism (diabetes mellitus and impaired glucose tolerance)

Figure 5. Diabetes prevalence, SCI vs. Control

   Figure 5. Diabetes prevalence, SCI vs. Control

The prevalence of diabetes in SCI subjects has been reported in multiple studies (Appendix E Table 1).^{3, 15, 28}–³⁷ Several of these studies have also reported a comparison between SCI individuals and non-SCI subjects (Figure 5).^{29, 32, 34, 37}

Figure 6. Prevalence of diagnosed diabetes, undiagnosed (more...)

   Figure 6. Prevalence of diagnosed diabetes, undiagnosed diabetes, and impaired fasting glucose in men (NHANES 1999-2002)¹⁰²

A total of 6,832 persons with SCI and 254,847 controls were included in the reviewed studies, of which the vast majority of all of SCI individuals came from two large Veterans Health Administration (VHA) studies.^{34, 37} The largest of these studies included a national cross-sectional survey of 3,737 SCI adults who were users of the VA health care system, along with a control group of 6,413 non-SCI VA health-care user control subjects and data from the CDC Behavioral Risk Factor Surveillance System 2003 survey of 221,650 community-dwelling adults.³⁷ This large study found a substantially greater portion of VA SCI individuals self reported that they had diabetes compared to the general population surveyed by the CDC (20 percent versus 7.6 percent, p<0.001). However, overall self-reported prevalence of diabetes in VA users with SCI was similar to the prevalence of diabetes in the non-SCI VA user population (20 percent vs. 21 percent). Another large study also from a VA population found similar rates of diabetes in SCI and non-SCI subjects (11 percent vs. 10 percent, respectively).³⁴ Differences in the overall prevalence of diabetes between these two studies are likely due in part to differences in ascertainment of diabetes status (self-report versus diagnosis in administrative dataset) and differences in the ages of the subjects, with the study reporting higher veteran prevalence of diabetes including older subjects and self-reported surveys. Results from national representative able-bodied populations clearly show that the prevalence of diabetes is highly dependent on method of ascertainment or definition (diagnosed vs. undiagnosed diabetes vs. impaired fasting glucose (Figure 6). The two other studies that included non-SCI control groups reported increased diabetes prevalence among SCI individuals.^{29, 32} Both of these studies found several-fold higher rates of diabetes among the SCI subjects but were published more than a decade earlier and had smaller sample sizes. The first of these studies also involved veterans with and without SCI from a single institution. This study had a small number of controls (n=50) and only three controls had diabetes.²⁹ For this study diabetes was diagnosed using a one-time oral glucose tolerance test. There was some evidence that persons with SCI had higher scores on their oral glucose tolerance tests than would be expected based on their fasting plasma glucose levels compared to non-SCI controls. In the non-SCI control group, people who were categorized as diabetics had an average mean fast plasma glucose level of 115 mg/dl while mean levels for paraplegic and tetraplegic diabetics were 99 mg/dl and 102 mg/dl, respectively. The other study presented results from a survey of Japanese subjects with overall diabetes rates much lower than those observed in the U.S. population (the control group had a 1.2 percent prevalence of diabetes).³²

The relationship between increased age and increased diabetes prevalence in both able-bodied individuals and those with SCI is strong and clearly demonstrated in the large survey of SCI individuals by Lavela and colleagues³⁷ and results from the nationally representative NHANES III study (Figure 6).¹⁰² However, we found no evidence to suggest that the association between age and diabetes was substantially different in SCI compared to non-SCI groups.

The prevalence of impaired glucose intolerance (IGT) has been studied less frequently. In the three studies that met our inclusion criteria,^{28, 29, 31} only one study included a non-SCI control group (n=50) (Appendix E Table 1).²⁹ All three studies were of veterans receiving care at a VA hospital, and all reported approximately 30 percent SCI patients with IGT, while only 12 percent of controls had IGT. The fact that only six control individuals with IGT were included in the one study with a non-SCI control group makes it impossible to determine from these data whether IGT is increased or not.

Summary

The prevalence of diabetes appeared higher on average in SCI populations studied as compared to the general population. However, there is considerable reason to believe that the general population groups used were not appropriate controls for SCI patients. For example, lifestyle and comorbidities, irrespective of SCI, could be quite different. Therefore, the extent to which this increased the prevalence of diabetes is due to a causal relationship between the SCI and the development of subsequent diabetes is not well known. Overall, the VA patient control groups tended to be similar to the VA SCI patient populations in their rate of diabetes, and it was only when the rate of diabetes in the VA SCI patients was compared to the general public that the SCI individuals appeared to be at higher risk. Users of the VA health care system have greater comorbidities than either veterans not actively using the VA health care system or non-VA populations. Therefore, current evidence is insufficient to determine to what extent the higher rate of diabetes is independently attributable to SCI or to other factors that might be higher in adults who subsequently have a SCI than in the general public. While there was not consistent evidence that fasting plasma glucose was substantially different in SCI patients, some evidence suggests that these individuals may be more likely to meet IGT or diabetes mellitus diagnostic criteria following oral glucose tolerance tests. More research is needed to determine whether using the oral glucose tolerance test (OGTT) is more likely to diagnose diabetes in SCI compared to non-SCI patients, and whether individuals diagnosed with diabetes by OGTT benefit from treatment.

Abnormalities in lipid metabolism (hyperlipidemia and/or low HDL cholesterol)

Figure 7. Weighted mean differences in lipid levels (more...)

   Figure 7. Weighted mean differences in lipid levels (mg/dL): Spinal cord injured subjects vs. controls

Figure 8. Mean levels of total cholesterol, SCI studies (more...)

   Figure 8. Mean levels of total cholesterol, SCI studies

Figure 9. Mean levels of LDL cholesterol, SCI studies (more...)

   Figure 9. Mean levels of LDL cholesterol, SCI studies

Figure 10. Mean levels of HDL cholesterol, SCI studies (more...)

   Figure 10. Mean levels of HDL cholesterol, SCI studies

Figure 11. Mean levels of triglycerides, SCI studies (more...)

   Figure 11. Mean levels of triglycerides, SCI studies

Figure 12. Total cholesterol, LDL-C and triglyceride (more...)

   Figure 12. Total cholesterol, LDL-C and triglyceride levels of able-bodied males by age (NHANES)

Figure 13. HDL cholesterol levels of able-bodied males (more...)

   Figure 13. HDL cholesterol levels of able-bodied males by age (NHANES)

Lipid disorders among SCI populations have been reported in seven included articles,^{16, 17, 21, 31, 38, 39, 103} of which three appear to have included SCI individuals from the same study.^{16, 17, 40} There appear to be a total of 1,413 SCI individuals in all of these studies. Three studies (n=747 SCI adults) included some form of a non-SCI control group (n=680 for controls assuming the Krum et al. 1992 study included a 1:1 match, even though the number of controls was not reported) (Appendix E Table 1 and Figure 7).^{38, 39, 103} The pooled results of the three studies with control groups (one study only reported total cholesterol) showed that on average individuals with SCI had lower TC, LDL cholesterol, HDL cholesterol, and TG. While these differences were statistically significant, none were likely to result in differences in clinical decisionmaking. All mean values were within less than a half a standard deviation. Furthermore, the mean 7.5 mg/dL lower (worse) value of HDL cholesterol among SCI individuals was counterbalanced by 11 mg/dL lower (better) LDL cholesterol and 10 mg/dL lower TG levels. When the mean lipid values from SCI individuals were compared to those of the able-bodied national male age norms for the NHANES study, the similarities between SCI and able-bodied lipid values were also observed (Figures 8–13). None of the mean lipid values were outside of the threshold established for primary prevention among able-bodied adults. Mean lipid values for SCI individuals were: total cholesterol (six studies) 194 mg/dL (range 188–205); LDL cholesterol (five studies) 125 mg/dL (range 120–126); HDL cholesterol (five studies) 42 mg/dL (range 39–46), and triglycerides (five studies) 122 mg/dL (range 108–148). Therefore in the absence of evidence that SCI status conveys an independent risk for coronary vascular events, detection and treatment strategies would be similar compared to able-bodied individuals.

The small number of SCI adults with reported lipid values makes it difficult to draw conclusions regarding subcategories of SCI adults with respect to age, sex, race/ethnicity, severity of SCI injury, and duration of SCI injury. The largest study of ethnicity and lipid levels in an SCI population included a total of 600 adults (percentage of whom were male was not reported) of whom 27 percent were White, 47 percent were Hispanic, and 27 percent were African American.¹⁷ While this study reported some racial/ethnic differences in lipid levels, there exists almost no evidence regarding whether these possible ethnic differences are unique to SCI individuals. Additionally, this study did not report whether the percentage of individuals who were male differed by ethnicity. The majority of SCI individuals in the studies were men, and even in studies that appeared to contain both men and women, the lipid values were not always reported by sex. In the few studies that did report female-specific lipid values,^{21, 39, 40} only two reported control groups (n=139 SCI women in controlled studies). Therefore, little evidence exists for whether women with SCI have different lipid levels than able-bodied women. With respect to the type of SCI injury (tetraplegia versus paraplegia, complete versus incomplete), the studies did not report a substantial difference in lipid levels.^{16, 31, 38, 40}

Summary

There is some evidence that on average SCI individuals may possess slightly, but likely not clinically meaningfully, reduced total cholesterol, LDL cholesterol, triglycerides (beneficial) and HDL cholesterol (detrimental). The evidence does not support a policy that lipid screening should differ in SCI adults compared to able-bodied adults.

Obesity

Reports in the general population have consistently shown that the level of obesity is increasing in the United States¹⁰⁴ and that this increase in obesity is contributing to an excess in mortality.¹⁰⁵ BMI is the primary method used for assessing obesity in population-based studies. However, several alternative methods for assessing obesity exist, including waist circumference, waist-to-hip ratio, percent body fat measured through multiple different techniques, percentage of ideal weight, and others. The use of general population cutpoints for obesity from BMI (>30 kg/m²) have been called into question by the finding that SCI individuals tend to have lower body fat at a given BMI as compared to non-SCI individuals.⁴² BMI has been and remains the predominant measure of obesity reported in SCI studies.

The prevalence of obesity among SCI populations has been reported in multiple studies,^{28, 31, 36, 38, 40}–⁴⁵ most of which have included some form of a non-SCI control group.^{38, 40, 42, 43, 45}

Figure 14. Mean BMI, SCI, and Control

   Figure 14. Mean BMI, SCI, and Control

Figure 15. Prevalence of BMI levels by age group (NHANES (more...)

   Figure 15. Prevalence of BMI levels by age group (NHANES 1999-2002)¹⁰⁵

A total of 10,226 persons with SCI (7,959 from one large VA clinical and administrative database study)⁴⁵ and 246,478 control subjects (246,025 from one national population-based survey)⁴³ contributed data to this section. Across these studies, mean BMI between SCI and non-SCI populations were relatively similar with non-SCI populations consistently having slightly elevated mean BMI (Figures 14 and 15). However, differences in mean BMI are difficult to interpret, not only because BMI might underestimate obesity in SCI individuals, but also because the relationship between BMI and disease is typically U- or J-shaped with those in the middle categories of BMI having the lowest risk compared to the lowest extreme and upper levels of BMI. Separating out the studies by category of BMI is therefore important. However, whether the category cutpoints for underweight, normal, overweight, and obese used in able-bodied populations can be applied to adults with SCI, is worthy of greater discussion and cannot be addressed based upon the available research. To date, many of the studies have either only reported mean BMI or merged underweight and normal weight categories together. Also, the extent to which the lower mean BMI findings in SCI populations compared to controls are due to an underestimate of obesity by BMI in individuals with SCI is difficult to address.

Only one of the included studies directly assessed obesity by means other than algorithms based on weight and/or height, primarily recorded as BMI.⁴² This study of 133 SCI individuals and 100 age-, height-, and ethnicity-matched able-bodied male controls measured percent fat mass using dual energy x-ray absorptiometry (DXA). This study found that total percent lean mass was lower and total percent fat mass higher in SCI individuals for a given level of BMI. The findings from this study combined with the prior studies showing no striking difference in BMI between SCI and able-bodied populations would suggest that future studies should focus less on comparing BMI and should investigate whether other indicators of obesity are more relevant for this population and correspondingly more predictive of future adverse health events. However, it should be noted that while DXA is a reliable measure of body composition, it is also much more difficult and expensive to obtain than BMI.

Several studies have attempted to explore whether differences in injury type (paraplegia versus tetraplegia or complete versus incomplete) or injury duration are correlated with obesity, but as with the overall studies of obesity and SCI, these studies are mostly conducted only with BMI measurements of obesity. Studies that have looked at injury type have tended to find a slightly higher average BMI in adults with paraplegia versus tetraplegia.^{28, 38, 42}–⁴⁵ However, it is not clear from these studies the extent to which mean BMI is driven by more underweight individuals with tetraplegia or possibly a greater tendency for BMI to underreport obesity in people with tetraplegia compared to people with paraplegia.

Several clinical and research questions remain to be answered, including what is an appropriate definition for obesity in an SCI population? For example, can BMI be used to define obesity? If not, what should be used in its place? If so, can current general population cutpoints for BMI be used or does the cutpoint need to be different (i.e., either specific for SCI in general or even more specific for type of SCI injury)?

Summary

There is no high-quality evidence that obesity defined by BMI is elevated in SCI individuals compared to appropriately matched controls. While several authors have reported that BMI might not be an accurate measure of obesity in the SCI population, it is by far the predominant measure used in research studies of the prevalence of obesity. There is some evidence that when obesity is measured as percent body fat, SCI individuals may be at elevated risk; however, the absence of large studies that include accurate measurements of body fat preclude stronger conclusions from being made about the burden of obesity on individuals with SCI and the impact of injury type and duration on the extent of obesity.

Question 2

Subject characteristics

Table 1

Patient characteristics in studies that reported cardiovascular (more...)

Table 1

Patient characteristics in studies that reported cardiovascular events in adults with SCI

Author	Sample	Patients
	Country
Cardus, 199246	96	Patients after traumatic SCI who resided in the county area and had to use assistive device for walking. Age: >18 years; Time after injury: >9 months. Controls: 96 nontrained able-bodied men matched by age.
	USA
Krum, 199239	327	Patients with SCI and age and sex matched controls from the 1983 Australian Risk Factor Prevalence Study. Gender: 19% female; 25–64 years old; Time after injury: 34% more than 10 years after injury; Injury: 40% with cervical, 35% with lower thoracic, 13% with upper thoracic, and 12% with lumbar levels of injury; ~41% with Frankel Grade A of completeness - complete motor and sensory deficit.
	Australia
Whiteneck, 199252	834	Patients with SCI, treated at the British spinal injury centers; Gender: 13% female; Age at time of injury was between 15 and 55 years—15–24 years 42%, 25–34 years 27%, 35–44 years 18%, 45–55 years; median survival time 32 years; Time after injury: >20 years; 412 survivors, Median survival time 32 years; 85% survived at 10 years, 71% at 20 years, 53% at 30 years, and 35% at 40 years after injury.
	UK
DeVivo, 19932	9,135	Patients injured between 1973 and 1984 and treated at any of 13 regional SCI care systems.
	USA
Imai, 199430	244	Males with SCI identified during the National Livelihood Basic Survey in Japan engaged in light work at special centers, who had medical examination for blood pressure and medical history. Mean age: 49.5 years; Time after injury: average 17.9 years; Injury: 19 patients injured at level C-T5, 24 at T6–T10, 139 at T11-L1, and 13 at L2 or lower.
	Japan
Nam, 199447	1,027+2,007	Patients admitted to medical centers with stroke and patients with traumatic SCI (paraplegia or quadriplegia). Population: average age 37.2±16.1 years.
	USA
Levi, 199555	326	Patients with traumatic SCI from the Stockholm Spinal Cord Injury Study, residents of the Greater Stockholm area. Control: participants in the Swedish Annual Level-of Living Survey (1,978 interviews).
	Sweden
Levi, 199556	353	Patients with traumatic SCI, participants in The Stockholm Spinal Cord Injury Study. Time after injury: 0–4 years after injury 23.97%; 5–17 years after injury 48.76%; 18–44 years after injury 24.52%.
	Sweden
McGlinchey-Berroth, 199548	534	Patients with traumatic SCI admitted to the high quality Spinal Cord Injury Service of the VA Medical Center; mean age of 50 years (16–84 years), 23% were at least 65 years of age; Gender: 99% males; Time after injury: 16±13.1 years, 12 hospital admissions since injury.
	USA
	VA settings
	Time: 1989-1992
Imai, 199632(the same population as Imai, 1994)30	244, Japan	Males with traumatic SCI at several rehabilitation centers; ages 22 to 69 years (mean 47.6); Time after injury: 17.3 years; Injury: C-T5 level 1%; T6–T10 12%; T11-Ll 69%; L2 8%. Control group (general population) National Livelihood Basic Survey conducted by the Ministry of Health and Welfare in 1989, on 800,000 people in 240,000 households.
Hartkopp, 19971	888	Patients (713 men and 175 women) who survived traumatic SCI and were rehabilitated at the Centre for Spinal Cord Injured in Hornbnk, Denmark. Population: median age at the time of injury 27.5 in 1953-1971 and 28.5 in 1972-1990.
	Denmark
Rish, 19973	230	Patients with traumatic SCI identified in the Vietnam Head and Spinal Cord Injury Study Registry who survived more then 72 hours, with significant myelopathy; mean age at injury 21.4 years, with previous excellent health (active duty military personnel) mean age at injury 21.4 years; median time after injury 25 years.
	USA
	VA settings
	Time: 1967-1970 to 1995
DeVivo, 199949	28,239	Patients admitted to the model system or to a Shriner's Hospital within 1 year of traumatic SCI who survived at least 24 hours after injury; Gender: 19% female; Race: 67.6% Caucasian, 20.7% African American, 8.1% Hispanic, 3.6% Asian, Native American, or other; Time at injury: 54% of injuries occurred between the ages of 16 and 30 years, and 23% between 31 and 45 years; Injury: 53% cervical, C5–C8 34.5% and C1–C4 18.5% of the population; 53.8% neurologically complete, 27.2% motor functional, 19% sensory sparing or motor nonfunctional; 2.9% were ventilator-dependent.
	USA
Groah, 200153	834	Patients alive >20 years after SCI identified in 2 British spinal Injury centers; Mean age 57±10 years; Gender: 14% females; Time after injury: 29±6 years.
	UK
Davies, 200254	97	Patients with segmental, nonprogressive traumatic SCI; mean age 47.5±4.5; Gender: 10% females; Age at injury: 31.67±16.4; Time after injury: 15.9±10.1 years; Injury: Quadriplegic 42%; Paraplegic 57%; Undetermined 1%; Complete 33%; Incomplete 64%; Undetermined 3%; Traumatic 87%.
	Canada
Prakash, 200234	654	47,070 patients with at least one ECG obtained in the Palo Alto Veterans Affairs Health Care System; 26,734 able-bodied male veterans and 654 patients with SCI. Mean age: 50±14 years.
	USA
	VA settings
	Time: 1987-1999
Cardenas, 200450	8,668	Patients with traumatic SCI identified in the Model System (hospitalized between acute hospitalization and comprehensive inpatient rehabilitation, admitted to a Model System within 365 days of injury) who reside in the geographic region in which the Model System facility is located; 3,904 patients with 11,047 followup interviews, Gender: 21.4% female; Race: 61.4% White
	USA	Injury: C1–4 ASIA grades A, B, C: 4.6%
		C1–4 ASIA grade D: 6.1%
		C5–8 ASIA grades A, B, C: 19.1%
		C5–8 ASIA grade D: 8.5%
		T1-S5 ASIA grades A, B, C: 33.1%
		T1-S5 ASIA grade D: 4.2%
Lavela, 200637	5,690	Veterans with SCI and disorders who use VA health services; Mean age 60 years; Gender: 97% males; Race: White 81%; Time after injury: 24 years; Injury: 52% with paraplegic level injury. Control: 2003 Behavioral Risk Factor Surveillance System survey data for veteran and general population from the Centers for Disease Control and prevention. 6,433 general veteran group and 221,650 general population group.
	USA
	VA settings
	Time: 2003
Lee, 200651	168	Patients with SCI identified in the Spinal Cord Injury Service of the Veterans Affairs Palo Alto Medical Center; Mean age 50.27±12.8 years; Gender: 11% female; Race: 62% White; Time after injury: 19.17±13 years; Injury: 73 (43%) had paraplegia and 95 (56%) tetraplegia.
	USA
	VA settings
Garshick, 200536	361	Males with chronic SCI, >20 years of age previously treated by the SCI Service at Veterans Affairs Boston Healthcare System, registered in the National Spinal Cord Injury Association database in Massachusetts, New Hampshire, Vermont, Maine, and Rhode Island (289 veterans and 72 nonveterans); Mean age: 50.6±15.0 years (range 23–87), Race: 93% Caucasian, 5% African American, and 2% other races; Time after injury: 17.5±12.8 years (range 1.0–56.5); Injury: 92% SCI was due to traumatic injury; 37 deaths.
	USA
	VA settings
	Time: 1994-2000

The studies included more than 50,000 patients with SCI. Sample size ranged from 96⁴⁶ to 28,239.⁴⁹ Males (pooled prevalence 86 percent, 95 percent CI 80.4; 90.9) and Caucasians comprised the majority of individuals; all studies identified patients at clinics or administrative health care databases (Table 1 and Appendix E Table 2). Among American studies, large cohorts^{2, 49, 50} (studies that analyzed nationally representative databases, including the Centers for Disease Control and Prevention and the national Behavioral Risk Factor Surveillance System Survey),³⁷ were considered to have higher generalizability. Applicability of several large studies from the VA Spinal Cord Injury Services can be generalized to veterans seeking care in the VA clinics and, to a lesser extent, general veterans with SCI or the overall adult SCI population.^{3, 34, 37, 48, 51} Individuals differed by the level of injury, the time after injury, and functional status, but few studies included these factors in the analysis. Several studies reported prevalence of hypertension,^{3, 30, 32, 34, 37, 39, 48, 51, 53, 55} but only a few examined other risk factors of cardiovascular diseases, including smoking and lipid levels.^{37, 39, 54} Furthermore, definitions of these comorbidities and methods to measure (and therefore, likely prevalence) varied across studies. The majority of the studies obtained events with ICD codes (the conceptual definition of outcomes is shown in Appendix F). However, the studies reported the prevalence of the outcomes obtained with different ICD codes. For example, one study⁵³ defined CVDs with ICD codes 390–448 and 745–747 that included rheumatic and hypertensive diseases as well as congenital anomalies of the heart while another⁵⁰ defined outcome as rehospitalization for diseases of the circulatory system, including heart disease, hypertension, pulmonary embolus, cerebrovascular diseases, and disease of the arteries and veins. Therefore, definitive comparisons of outcomes were not possible. The accuracy and reliability of the coding in different settings could not be estimated from the published articles.

Cardiovascular prevalence in adults with chronic SCI

Table 2

Prevalence of CVD in adults with SCI

Table 2

Prevalence of CVD in adults with SCI

Author	Age, Years	Outcomes	Sample (n)	Prevalence, %
Garshick, 200536	Mean 50.6±15.0	Hypertension	361	24.4
Groah,* 200153	Mean 57±10	Hypertension	834	0.58
Krum, 199239		Hypertension	102	9
Lavela, 200637	Mean 60	Hypertension	18,372	49
Lee,* 200651	Mean 50.27±12.8	Hypertension	168	45.14
Levi, 199555		Hypertension	326	0
Prakash,* 200234	Mean 50±14	Hypertension	654	7
Rish,* 19973	Mean at injury 21.4, median time after injury 25	Hypertension	230	21
Imai, 199632	Mean 47.6	Hypertension	244	16.39
Imai, 199632	Mean 47.6	Hypotension	244	1.64
Lee,* 200651	Mean 50.27±12.8	Prehypertension	168	32.74
		Stage 1 hypertension	168	16.07
		Stage 2 hypertension	168	8.33
Krum, 199239	Range 25–64	Cerebrovascular accident	102	1
Rish,* 19973	Mean at injury 21.4, median time after injury 25	Cerebrovascular accident	230	2
Groah,* 200153	Mean 57±10	Cerebrovascular diseases	834	0.05
		Angina	834	0.07
Krum, 199239	Range 25–64	Angina	102	2
Prakash,* 200234	Mean 50±14	Coronary artery disease	654	1.7
Rish,* 19973	Mean at injury 21.4, median time after injury 25	Coronary artery disease	230	6
Groah,* 200153	Mean 57±10	Coronary atherosclerosis	834	0.27
Lavela, 200637	Mean 60	Coronary heart disease	18,372	12
Groah,* 200153	Mean 57±10	Ischemic heart diseases	834	0.65
Imai, 199632	Mean 47.6	Ischemic heart diseases	244	1.64
Groah,* 200153	Mean 57±10	Myocardial infarction	834	0.28
Krum, 199239	Range 25–64	Myocardial infarction	102	1.9
Lavela, 200637	Mean 60	Myocardial infarction	18,372	14
Rish,* 19973	Mean at injury 21.4, median time after injury 25	Myocardial infarction	230	3
Levi, 199555		Cardiac diseases	326	2
Davies, 200254	Mean 47.5±4.5	Cardiovascular morbidity	140	13.4
Groah,* 200153	Mean 57±10	Cardiovascular morbidity	834	2.72
Imai, 199632	Mean 47.6	Circulatory diseases	244	0.82
Levi, 199555		Circulatory diseases	326	2
Prakash,* 200234	Mean 50 ± 14	Congestive heart failure	654	1.7
Groah,* 200153	Mean 57±10	Dysrhythmia	834	0.43
		Left bundle branch block	834	0.02
		Other CVD	834	0.81
		Valvular disease	834	0.2
Levi, 199556		Cardiovascular symptoms: ankle-leg edema, chest pain, palpitations	353	58

*

Outcomes events obtained with ICD codes

†

Hospitalizations with CVD diagnosis

Table 3

Prevalence of CVD in adults with SCI by age and years (more...)

Table 3

Prevalence of CVD in adults with SCI by age and years after injury

Author	Sample (n)	Age at Injury	Prevalence, %
All CVD
Whiteneck, 1992*52	834	<30 years	2
		30–39 years	2.9
		40–49 years	5.2
		50–59 years	8.1
		60+ years	19.3
CVD symptoms
Levi, 199556	162	21–40 years	57
		41–77 years	61
Hypertension
McGlinchey-Berroth, 1995*†48	255	<50 years and <50 years at index submission	5.09
	162	<50 years and >50 years at the time of index admission	25.3
	93	Age at injury and index hospital admission >50 years	33.33
Myocardial infarction
McGlinchey-Berroth, 1995†*48	255	<50 years and <5 years at index submission	5.09
	162	<50 years of age and >50 years at the time of index admission	25.3
	93	>50 years of age	33.33
		Years after Injury
All CVD
Whiteneck, 1992*52	834	<10 years	2.9
		10–19 years	5.4
		20–29 years	10
		30+ years	14.2
Cardenas, 2004*†50	3,978	1 year	0.73
	1,714	10 years	0.41
	1,653	15 years	0.79
	1,251	20 years	0.4
	2,451	5 years	0.53
CVD symptoms
Levi, 199556	87	0–4 years	48
	89	18–44 years	72
	177	5–17 years	55

*

Outcomes events obtained with ICD codes

†

Hospitalizations with CVD diagnosis

Crude prevalence estimates were reported in the majority of the studies and ranged from 0.05 percent for cerebrovascular disease⁵³ to 58 percent for self reported cardiovascular symptoms⁵⁶ and differed, depending on how events were defined and measured (self reported or identified with ICD codes) and on age and time after SCI. Therefore, an overall summary estimate was not provided. The prevalence of cardiovascular diseases was <1 percent in two studies^{32, 50} and 2 to 3 percent in three studies^{52, 53, 55} (Table 2). One smaller study of 140 patients used the London School of Hygiene Questionnaire on Chest Pain and Intermittent Claudication and reported a higher prevalence of CVDs (13.4 percent).⁵⁴ One study found an increase in prevalence in older patients to 19.3 percent after 60 years of age at time of injury and to 14.2 percent 30 or more years after injury (Table 3).⁵² The prevalence of congestive heart failure was 2.7 percent in one study,³⁴ and the prevalence of other cardiac diseases 2 percent⁵⁵ or <2 percent.⁵³ The prevalence of cerebrovascular diseases varied from <1 percent,⁵³ to 1 percent³⁹ or 2 percent.³ The prevalence of coronary heart disease was 2 percent or less in three studies,^{32, 39, 53} 6 percent among patients from the Vietnam Head and Spinal Cord Injury Study Registry,³ and the highest was 12 percent among members of Paralyzed Veterans of America.³⁷ The Stockholm Spinal Cord Injury Study⁵⁶ examined self reported prevalence of “cardiovascular symptoms” and included ankle-leg edema, chest pain, and palpitations. More than half of the patients with SCI reported symptoms (55 percent of males and 69 percent of injured females). However, prevalence of diagnosed cardiac diseases was only 2 percent. Whether this represents under diagnosis of cardiovascular diseases or classification of nonspecific symptoms which did not reflect CVD is not known. Seventy-two percent of patients with complete cervical and thoracic injury reported having cardiovascular symptoms. The prevalence of arterial hypertension was <3 percent in three studies,^{30, 32, 53, 55} 5–10 percent in four studies,^{30, 34, 39, 48} and more than 20 percent in four studies.^{3, 37, 48, 51} The Vietnam Head and Spinal Cord Injury Study reported that 21 percent of the injured adults had hypertension³ and 25–49 percent of the patients of the Spinal Cord Injury Service of VA medical centers were diagnosed with arterial hypertension.^{37, 48, 51} In addition, borderline hypertension was found in 33 percent of the injured veterans.⁵¹ The prevalence of myocardial infarction was <5 percent in three studies.^{3, 39, 53}

Table 4

Prevalence of CVD* according to SCI neurological category (more...)

Table 4

Prevalence of CVD* according to SCI neurological category53

Neurological Category	All SCI (N=834)		Tetra ABC (N=99)		Para ABC (N=285)		All D (N=161)
	Number	Rate	Number	Rate	Number	Rate	Number	Rate
All CVD	458	27.2	64	35.2	279	29.9	115	21.2
Coronary heart disease	109	6.5	5	2.1	63	6.6	41	7.4
Myocardial infarction	47	2.8	1	0.3	31	3.2	15	2.6
Angina	12	0.7	0		4	0.4	8	1.7
Coronary atherosclerosis	46	2.7	3	1	25	2.7	18	3.1
LBBB	4	0.2	1	0.3	3	0.3	0
Hypertension	98	5.8	5	1.7	71	7.6	22	4.5
Cerebrovascular disease	8	0.5	4	1.5	3	0.3	1	0.2
Dysrhythmia	73	4.3	20	13.1	42	3.3	11	1.3
Valvular disease	34	2	10	5	14	1.5	10	1.7
Other CVD	136	8.1	20	9.2	86	1.4	30	1.5

*

Age adjusted rates per 1,000 SCI person years by neurological category

SCI veterans had higher prevalence of myocardial infarction, 14 percent³⁷ to 25 percent among those who were younger than 50 years at the time of injury and older than 50 years at the time of index admission to the Veterans hospital⁴⁸ (Table 3). The highest prevalence of 33 percent was reported among veterans who were older than 50 years at the time of injury representing the effect of age rather than injury ⁴⁸ Patients with tetraplegia and ABC functional status had lower age adjusted rates of coronary heart diseases, including myocardial infarction, and higher rates of cerebrovascular diseases, dysrhythmia, and valvular disease (Table 4) by neurologic category among 834 patients.⁵³ Prevalence of cardiovascular symptoms and arterial hypertension appeared to vary by the level of injury, though statistical differences in rates were not provided (Appendix E Table 3).

Asymptomatic heart conditions in patients with SCI

Three studies reported cases of silent ischemia in asymptomatic adults with SCI.^{10, 106, 107} Tomographic thallium-201 myocardial perfusion imaging detected scintigraphic evidence of ischemia in 3 of 6 patients (50 percent) with tetraplegia and signs of infarction in one patient.¹⁰⁶ A simple arm ergometry and radionuclide tomographic image test detected silent scintigraphic evidence of ischemia in 13 SCI patients with paraplegia from 20 tested having normal resting electrocardiograms (65 percent). Since five subjects had ECG evidence of ischemia on exercise testing, eight patients (62 percent) experienced undiagnosed coronary heart disease.¹⁰⁷ Latent coronary artery was diagnosed in 12 of 19 subjects with paraplegia (63 percent) using radionuclide myocardial perfusion imaging after upper body ergometry exercise.¹⁰ A recently published case control study¹⁰⁸ of coronary scanning showed that 91 patients with chronic SCI had the higher mean calcium scores (75±218 versus 28±104, p <0.001) compared to 273 age matched non-SCI controls. The prevalence of coronary artery calcification was greater in the SCI population than the control population (16 percent versus 7 percent, p <0.01).

Pooled analysis detected a significant heterogeneity between studies in estimated prevalence of cardiovascular diseases (data not shown). Therefore, methodological heterogeneity made the pooled estimations not valid. Almost all variations in pooled prevalence of hypertension (14 percent) and myocardial infarction (8 percent) were attributable to heterogeneity between studies. The fact that the summarized prevalence of all CVD events, including coronary heart and non ischemic heart diseases, was less than different forms of CVDs reported in the studies. Such discrepancy can reflect overlap and different definitions and methods to measure outcomes, and, probably, some proportion of undiagnosed cardiac pathology in SCI populations. Three studies reported prevalence in subgroups^{48, 50, 52} but not in the total sample. Conclusions and decisions based on pooled prevalence cannot be made.

Cardiovascular mortality

Table 5

Mortality from CVD in adults with SCI

Table 5

Mortality from CVD in adults with SCI

Author	Sample	Patient Characteristics	Mortality, % Among all SCI Patients
Arterial diseases
DeVivo, 199949	28,239	All SCI	0.08
Time: 1973-1998
DeVivo, 19932	9,135	All SCI	0.15
Time: 1973-1985		Ages 25–54 years	0.04
		Age >54 years	0.10
		Incomplete paraplegia	0.03
		Complete paraplegia	0.03
		Incomplete quadriplegia	0.04
		Complete quadriplegia	0.04
		Survival 1–5 years	0.09
		Survival >5 years	0.01
Cardiovascular diseases
Garshick, 200536	361	All SCI	2.2
Time: 1994-2000
Mean age: 50.6±15
DeVivo, 199949	28,239	All SCI	1.03
Time: 1973-1998
Hartkopp, 19971	888	All SCI	6.31
Time: 1954-1992		Thoracic-lumbar injury/Frankel A-C	1.58
Median age at time of injury: 27.5 from 1953-1971 and 28.5 from 1972-1990		Frankel D	3.04
		Frankel E	0.68
		Cervical lesion	0.00
		Thoracic/lumbar lesion	0.00
		Men	5.29
		Women	1.01
Whiteneck, 199252	834	All patients	10.07
Time: 1943-1970		Paraplegia, ABC	5.76
Age at time of injury 15–55, 42% 15–24 years, 27% 25–34 years, 18% 35–44 years, 13% 45–55 years; Median survival time 32 years		Quadriplegia, ABC	0.96
		All D and E	3.36
		15–24	0.08
		25–34	0.07
		35–44	0.24
		45–54	0.44
		55–64	1.33
		65–74	2.12
		75–84	10.20
Cerebrovascular diseases
Hartkopp, 19971	888	All patients	0.90
Time: 1954-1992		Thoracic-lumbar injury/Frankel A-C	0.23
Median age at the time of injury 27.5 in 1953-1971 and 28.5 in 1972-1990		Frankel D	0.45
		Frankel E	0.00
		Men	0.68
		Women	0.23
DeVivo, 19932	9,135	All patients	0.24
Time:1973-1985		Ages 25–54 years	0.15
		Age >54 years	0.04
		Incomplete paraplegia	0.03
		Complete paraplegia	0.02
		Incomplete quadriplegia	0.09
		Complete quadriplegia	0.10
		Survival 1–5 years	0.12
		Survival >5 years	0.07
Ischemic heart disease
Hartkopp, 19971	888	All patients	2.48
Time: 1954-1992		Thoracic-lumbar injury/Frankel A-C	0.56
Median age at time of injury: 27.5 from 1953-1971 and 28.5 from 1972-1990		Frankel D	1.13
		Frankel E	0.56
		Men	2.14
		Women	0.34
DeVivo, 19932	9,135	All patients	0.67
Time: 1973-1985		Ages 25–54 years	0.19
		Age >54 years	0.44
		Incomplete paraplegia	0.14
		Complete paraplegia	0.12
		Incomplete quadriplegia	0.23
		Complete quadriplegia	0.18
		Survival 1–5 years	0.27
		Survival >5 years	0.12
Rish, 19973	230	All patients	0.02
Time: 1954-1992		Survival 5 years	0.43
Mean age at injury 21.4 years, Median time after injury 25 years		Survival 20 years	0.87
		Survival >20 years	0.87
Lung embolus
Hartkopp, 19971	888	All patients	0.68
Time: 1954-1992		Thoracic-lumbar injury/Frankel A-C	0.11
Median age at time of injury 27.5 from 1953-1971 and 28.5 from 1972-1990		Frankel D	0.34
		Frankel E	0.11
		Men	0.68
		Women	0.00
Non ischemic heart disease
DeVivo, 19932	9,135	All patients	0.92
Time: 1973-1985		Ages 25–54 years	0.31
		Age >54 years	0.47
		Incomplete paraplegia	0.04
		Complete paraplegia	0.11
		Incomplete quadriplegia	0.28
		Complete quadriplegia	0.48
		Survival 1–5 years	0.32
		Survival >5 years	0.18
Stroke
DeVivo, 199949	28,239	All patients	0.19
Time: 1973-1998

Figure 16. Percent of all deaths due to coronary heart (more...)

   Figure 16. Percent of all deaths due to coronary heart disease among adults with SCI

Table 6

Percent of all deaths from CVD among adults with SCI (more...)

Table 6

Percent of all deaths from CVD among adults with SCI

Author	Disease (ICD Codes)	% of all SCI Deaths
Hartkopp, 19971	CVD (390–458)	24.0
	Ischemic heart disease (410–414)	9.0
DeVivo, 199949	Heart	18.8
DeVivo, 19932	Ischemic heart disease (410–414)	7.1
Garshick, 200536	Circulatory system disorder (390–459)	21.6
	Circulatory system disorder (390–459) as contributing cause of death	18.9
Rish, 19973	Myocardial infarction	8.8
Whiteneck, 199252	CVD	23.2

Mortality from CVDs was more consistent than prevalence across five studies that reported this outcome (Table 5).¹–^{3, 49, 52} Patients with SCI died from diseases of the arteries (ICD codes 440–448) in 0.8⁴⁹ to 1.5² per 1,000 injured according to two large studies of more than 29,000 patients.^{2, 49} CVD (ICD codes 390–458) caused death in 1 percent⁴⁹ to 6.3 percent¹ to 10 percent⁵² of those injured. Men with SCI had higher CVD mortality (5.3 percent) compared to women (1 percent), with no formal statistical test of the effect modification reported.¹ Results were not controlled for potential differences in other CVD risk factors such as smoking status, diabetes, hypertension, and family history. Mortality increased with the age of the patients, being the highest after 75 years (10 percent).⁵² Less than 1 percent of SCI patients died from cerebrovascular diseases^{1, 2} and stroke.⁴⁹ Cerebrovascular deaths were more common in men (0.7 percent) than women (0.2 percent) with unknown statistical significance of the differences.¹ Mortality from cerebrovascular diseases was 0.1 percent² among patients with complete tetraplegia and 0.2 percent after cervical or thoracic injury with no functional motor preservation.¹ Mortality from ischemic heart disease was <1 percent in two studies.^{2, 3} One European study that obtained post mortem records found that 2.5 percent, including 2 percent men, died from ischemic heart disease.¹ One long-term followup study in U.S. veterans reported a two-fold increase in mortality from 5 years (0.4 percent) to 20 years (0.9 percent) after injury, representing the association between age and mortality rather than SCI.³ Lung embolus caused death in 0.7 percent of patients with chronic SCI.¹ Three studies reported that coronary heart disease was the primary cause of death in approximately 9 percent of patients with SCI (Figure 16). The proportion of deaths attributable to CVDs varied from 7.1 percent for ischemic heart disease⁴⁹ to 24 percent for any CVD¹ (Table 6). CVDs are among the leading causes of death in patients with chronic SCI;^{1, 49, 52} however, the contribution of age cannot be estimated by analyzing the crude proportion of aging SCI patients who died from heart diseases. One study of 402 veterans with chronic SCI followed for 55.6 months³⁶ showed that diabetes (relative risk 2.62, 95 percent CI 1.19; 5.77) and heart diseases (relative risk 3.66, 95 percent CI 1.77; 7.78) were significant risk factors for death after adjustment for age.

Cardiovascular prevalence and mortality in adults with chronic SCI compared to the general population according to age, race, and gender

Table 7

Odds ratios of diabetes or CVD in adults with SCI compared (more...)

Table 7

Odds ratios of diabetes or CVD in adults with SCI compared to able bodied

Conditions	Odds Ratio (95% CI)
	Lavela, 200637VA Settings %; Mean Age 60 Years	Prakash, 200234VA Settings Age 50±14	Krum, 199239Ages 25–64
Coronary heart disease		0.24 (0.13; 0.43)
Myocardial infarction			1.00 (0.14; 7.24)†
Arterial hypertension		0.16 (0.12; 0.21)	0.40 (0.17; 0.92) †
High cholesterol
Stroke
Diabetes	3.3 (1.3; 8.3)*	1.1 (0.88; 1.37)	3.13 (0.62; 15.89) †
Congestive heart failure		0.24 (0.13; 0.43)
Angina			0.67 (0.11; 4.1) †
Cerebrovascular diseases			1.00 (0.06; 16.21) †

*

Adjusted for age, race, marital status, duration of injury, employments status, and educational level

†

Adjustment for age, matching by gender

Bold - significant association at 95% confidence level

Figure 17. Odds ratios* of cardiovascular outcomes (more...)

   Figure 17. Odds ratios* of cardiovascular outcomes in VA users with SCI and diabetes vs. SCI but no diabetes³⁷

Published evidence did not suggest that adults with chronic SCI experience CVDs more frequently than the general population. The Australian Risk Factor Prevalence Study of 327 patients with SCI and age and sex matched controls found that adults with SCI had a 50 percent reduction in arterial hypertension and no differences in odds of diabetes, myocardial infraction, angina pectoris, and cerebrovascular diseases (Table 7).³⁹ Crude odds of arterial hypertension were lower by 84 percent³⁴ in another study of 654 male veterans with SCI.³⁴ The same study reported lower odds of congestive heart failure in injured compared to able-bodied veterans.³⁴ The Stockholm Spinal Cord Injury Study showed that prevalence of circulatory diseases was lower by 75 percent in injured patients compared to healthy controls after adjustment for age, sex, socioeconomic status (odds ratio 0.25 p value = 0.014),⁵⁵ with no differences in rates of cardiac diseases, and use of cardiac medications. One larger study of 18,372 veterans with SCI, 6,433 able-bodied veterans, and 221,650 in the general population, using 2003 Behavioral Risk Factor Surveillance System survey data,³⁷ reported a three times higher rate of diabetes in injured veterans compared to the general population (20 percent versus 6.7 percent, odds ratio 3.32, 95 percent CI 1.34; 8.26),³⁷ but similar odds compared to other veterans (21 percent, odds ratio 0.94, 95 percent CI 0.47; 1.87). SCI adults with diabetes had higher adjusted rates of coronary heart disease by 280 percent, myocardial infarction by 270 percent, arterial hypertension by 250 percent, and stroke by 230 percent compared to SCI patients without diabetes (Figure 17).³⁷ Diabetes is associated with an increased risk of heart disease, independent of SCI. The authors did not compare relative risk of heart diseases in diabetics with and without injury to estimate the effect of injury.

Table 8

Diabetes management and diabetes complications in VA (more...)

Table 8

Diabetes management and diabetes complications in VA users with SCI, in VA users without SCI, and non-VA user general population without SCI37

Diabetes Management or Complications	Prevalence in VA SCI(%)	Prevalence in VA Non SCI(%)	Odds Ratio in VA SCI Compared to the VA Non SCI Population (95% CI)	Prevalence in Non VA General Population (%)	Odds Ratio in VA SCI Compared to Non VA General Population (95% CI)
Duration of diabetes (>25 years)	13.55	10.94	1.27 (0.97; 1.66)	9.75	1.44 (1.16; 1.79)
Insulin therapy	26.03	28.51	0.88 (0.72; 1.08)	25.9	1.01 (0.85; 1.19)
Oral agent	62.97	69.54	0.75 (0.62; 0.90)	66.35	0.86 (0.74; 1.01)
Insulin + oral agent	11.25	12.82	0.86 (0.65; 1.13)	11.17	1.00 (0.79; 1.27)
Foot sores with >4 weeks to heal	41.37	17.85	3.25 (2.65; 3.98)	13.12	4.68 (4.02; 5.46)
Retinopathy	25.31	24.24	1.06 (0.86; 1.31)	22.27	1.19 (1.00; 1.41)
Diabetes education	63.04	60.16	1.13 (0.94; 1.36)	49.84	1.72 (1.47; 2.00)

Bold - significant association at 95% confidence level

Odds ratios of cardiovascular outcomes were reported after adjustment for age. However, age may modify the association with injury and diabetes. For example, odds of diabetes were higher in injured veterans compared to the general population in all age groups but higher compared to able bodied veterans in those of 45–59, 55–59, and older than 70 years of age (Appendix E Table 4). Despite no difference in management of diabetes, adults with SCI and diabetes had three to five times higher rates of foot sores compared with diabetics in the general population and able-bodied veterans with diabetes. Risk of diabetic retinopathy was 19 percent higher compared to diabetics in the general population (Table 8).

Figure 18. Adjusted odds ratio of CVD in patients with (more...)

   Figure 18. Adjusted odds ratio of CVD in patients with SCI: Tetraplegia with no functional motor preservation compared to paraplegia and no functional motor preservation ⁵³

Evidence from one study suggested that neurological functional status may be associated with cardiovascular morbidity (Table 4). Patients with tetraplegia and no functional motor preservation had higher age adjusted odds ratio of cerebrovascular diseases, dysrhythmia, and valvular diseases and lower odds ratio of coronary heart disease compared to paraplegic patients (Figure 18). Adults with SCI and functional motor preservation had higher age adjusted odds of all CVDs, coronary atherosclerosis, dysrhythmia, and valvular disease compared to paraplegic and no functional motor preservation.⁵³

Table 9

Hazard ratio of dying having ECG abnormality vs. normal (more...)

Table 9

Hazard ratio of dying having ECG abnormality vs. normal ECG among patients with SCI and able-bodied veterans 34

ECG Abnormalities	Spinal Cord Injury Hazard Ratio 95% CI	Able-bodied Hazard Ratio 95% CI
Right bundle branch block	1.23 (0.4; 4)	2.21 (1.97; 2.47)
Left bundle branch block	4.24 (1.5; 12)	1.98 (1.62; 2.42)
Intraventricular conduction delay	1.15 (0.3; 5)	1.13 (0.99; 1.3)
LVH with strain	3.28 (1.2; 9)	1.31 (1.14; 1.52)
Left atrial abnormality	0.59 (0.2; 1.9)	1.55 (1.39; 1.74)
Anterior Q wave	1.44 (0.5; 4.6)	2 (1.76; 2.28)
Inferior Q wave	0.78 (0.3; 1.8)	1.32 (1.21; 1.43)
Atrial fibrillation	3.54 (1.2; 11)	2.02 (1.79; 2.27)
Premature ventricular contraction	0.33 (0.05; 2.5)	1.51 (1.36; 1.67)
Abnormal ST depression	1 (0.5; 1.9)	1.9 (1.77; 2.04)
Abnormal QT interval	0.27 (0.1; 18)	1.91 (1.77; 2.06)

Bold - significant association at 95% confidence level

Figure 19. Hazard ratio of dying based on ECG abnormality (more...)

   Figure 19. Hazard ratio of dying based on ECG abnormality vs. normal ECG among VA users with SCI and able-bodied VA users³⁴

Morbidity can be estimated using surrogate outcomes. ECG is the most important single diagnostic indicator of cardiac arrhythmias and myocardial infarction.³⁴ One large study of 26,734 able-bodied male veterans and 654 patients with SCI found a decreased relative risk of ECG abnormalities in injured patients, only ST segment elevation in younger injured was observed more often in younger patients (Appendix E Table 5). Injured veterans with intact sympathetic innervation to the heart (injury level T6 and below) had lower risk of any ECG abnormalities compared to impaired sympathetic activity (injury level T5 and above) (Appendix E Table 6). Younger patients had lower risk of ECG abnormalities (Appendix E Table 7). Nearly all examined ECG abnormalities were associated with increased risk of death in able-bodied veterans, but only left bundle branch block (LBBB), left ventricular hypertrophy with strain, and atrial fibrillation accompanied the higher hazard ratio of death in patients with SCI (Table 9). Furthermore, these abnormalities were associated with a greater risk of dying in SCI compared to able-bodied adults. The rates of diagnosed hypertension (44 percent vs. 7 percent), congestive heart failure (7 percent versus 1.7 percent), and coronary heart diseases (7 percent versus 1.7 percent) were lower among SCI veterans compared to able-bodied (Figure 19).³⁴ The contribution of undiagnosed heart disease on death in SCI patients is not known and requires future research.

Table 10

Age standardized mortality ratios in adults with chronic (more...)

Table 10

Age standardized mortality ratios in adults with chronic SCI compared to the general population (no adjustment for other confounding factors)2

Risk Factors	Death (N)	Standardized Mortality Ratio(95% CI)
Ischemic heart disease (ICD codes 410–414)
Age 25–54 years	17	1.4 (0.8; 2.0)
Age >54 years	40	1.1 (0.8; 1.4)
Incomplete paraplegia	13	1.4 (0.7; 2.1)
Complete paraplegia	11	1 (0.4; 1.6)
Incomplete quadriplegia	21	1 (0.6; 1.4)
Complete quadriplegia	16	2.6 (1.3; 3.9)
Survival 1–5 years	25	1.1 (0.7; 1.5)
Survival >5 years	11	0.6 (0.2; 1.0)
Non ischemic heart disease (ICD codes 420–429)
Age 25–54 years	28	6.5 (4.1; 10.8)
Age >54 years	43	4.2 (3; 5.4)
Incomplete paraplegia	4	1.4 (0.4; 2.4)
Complete paraplegia	10	2.8 (1.1; 4.5)
Incomplete quadriplegia	26	4 (2.5; 5.5)
Complete quadriplegia	44	23.4 (16.5; 30.3)
Survival 1–5 years	29	4.1 (2.6; 5.6)
Survival >5 years	16	3 (1.5; 4.5)
Cerebrovascular diseases (ICD codes 430–438)
Age 25–54 years	14	4.6 (2.2; 7.0)
Age >54 years	4	0.4 (0; 0.8)
Incomplete paraplegia	3	1.3 (0; 2.8)
Complete paraplegia	2	0.8 (0; 1.9)
Incomplete quadriplegia	8	1.4 (0.4; 2.4)
Complete quadriplegia	9	5.4 (1.8; 9.0)
Survival 1–5 years	11	2 (0.8; 3.2)
Survival >5years	6	1.3 (0.2; 2.4)
Diseases of arteries (ICD codes 440–448)
Age 25–54 years	4	8.2 (0.2; 16.2)
Age >54 years	9	1.2 (0; 3.5)
Incomplete paraplegia	3	5.4 (0; 11.5)
Complete paraplegia	3	5 (0; 10.6)
Incomplete quadriplegia	4	2.7 (0.1; 5.3)
Complete quadriplegia	4	9.4 (0.2; 18.6)
Survival 1–5 years	8	5.8 (1.8; 9.8)
Survival >5 years	1	0.9 (0; 2.7)

Bold - significant association at 95% confidence level

Table 11

Age standardized mortality ratios for cardiovascular (more...)

Table 11

Age standardized mortality ratios for cardiovascular death by gender compared to able bodied1

Cause of Death	Standardized Mortality Ratio (95% CI)
	Men	Women	Both Genders
Period of injury 1953-1990 (end of followup: December 31, 1992)
CVD	1.2 (0.85; 1.53)	1 (0.52; 2.14)	1.2 (0.87; 1.49)
Ischemic heart disease	0.7 (0.41; 1.06)	1 (0.14; 1.96)	0.7 (0.42; 1.02)
Cerebrovascular disease	1 (0.35; 2.07)	1 (0.13; 3.98)	1 (0.43; 1.94)
Lung embolus	14 (5.25; 31.1)		11 (4.19; 24.8)
Total	2.1 (1.79; 2.38)	2 (1.53; 2.94)	2.1 (1.83; 2.37)
Period of injury 1953-1971 (end of followup: December 31, 1973)
CVD	3.2 (1.38; 6.29)	4 (0.09; 19.5)	3.2 (1.47; 6.12)
Ischemic heart disease			1.1 (0.13; 3.91)
Cerebrovascular disease
Lung embolus	131 (27.1; 384)		107 (22.1; 313)
Total	6.5 (4.66; 8.74)	12 (5.81; 22.3)	7.1 (5.31; 9.32)
Period of injury 1972-1990 (end of followup: December 31, 1992)
CVD	1.3 (0.71; 2.09)	3 (0.86; 6.16)	1.5 (0.89; 2.25)
Ischemic heart disease	1.2 (0.58; 2.24)		1.2 (0.59; 2.13)
Cerebrovascular disease		4 (0.53; 15.9)	1.4 (0.28; 3.96)
Total	2.3 (1.79; 2.90)	3 (1.91; 5.09)	2.4 (1.95; 3.01)

Bold - significant association at 95% confidence level

Table 12

Age standardized mortality ratios from CVD in adults (more...)

Table 12

Age standardized mortality ratios from CVD in adults with SCI compared to the general population

Author Sample	Patient Characteristics	Mortality/1,000 SCI	Standardized Mortality Ratios (95% CI)
Artery diseases
DeVivo, 19932	Survival >5 years	0.11	0.9 (0; 2.7)
N = 9,135	Age >54 years	0.99	1.2 (0; 3.5)
(standardization by age, sex, and race)	Incomplete quadriplegia	0.44	2.7 (0.1; 5.3)
	All patients	1.53	4.5 (2.1; 6.9)
	Complete paraplegia	0.33	5 (0; 10.6)
	Incomplete paraplegia	0.33	5.4 (0; 11.5)
	Survival 1–5 years	0.88	5.8 (1.8; 9.8)
	Age 25–54 years	0.44	8.2 (0.2; 16.2)
	Complete quadriplegia	0.44	9.4 (0.2; 18.6)
Garshick, 200536	All patients		1.15 (0.13–4.15)
N = 361
Cerebrovascular diseases
DeVivo, 19932	Age >54 years	0.44	0.4 (0; 0.8)
N = 9,135	Complete paraplegia	0.22	0.8 (0; 1.9)
(standardization by age, sex, and race)	Incomplete paraplegia	0.33	1.3 (0; 2.8)
	Survival >5 years	0.66	1.3 (0.2; 2.4)
	Incomplete quadriplegia	0.88	1.4 (0.4; 2.4)
	All patients	2.41	1.8 (1; 2.6)
	Survival 1–5 years	1.20	2 (0.8; 3.2)
	Age 25–54 years	1.53	4.6 (2.2; 7)
	Complete quadriplegia	0.99	5.4 (1.8; 9)
Hartkopp, 19971	Men	6.76	0.95 (0.35; 2.07)
N = 888	All patients	9.01	0.99 (0.43; 1.94)
	Women	2.25	1.1 (0.13; 3.98)
Cardiovascular diseases
Hartkopp, 19971	Cervical lesion		1.07 (0.72; 1.53)
N = 888	Women	10.14	1.13 (0.52; 2.14)
	Men	52.93	1.15 (0.85; 1.53)
	All patients	63.06	1.15 (0.87; 1.49)
	Thoracic/lumbar lesion		1.26 (0.82; 1.84)
Ischemic heart disease
DeVivo, 19932	Survival >5 years	1.20	0.6 (0.2; 1)
N = 9,135
(standardization by age, sex, and race)
Hartkopp, 19971	Women	3.38	0.67 (0.14; 1.96)
N = 888	Men	21.40	0.68 (0.41; 1.06)
	All patients	24.77	0.68 (0.42; 1.02)
DeVivo, 19932	Complete paraplegia	1.20	1 (0.4; 1.6)
N = 9,135	Incomplete quadriplegia	2.30	1 (0.6; 1.4)
(standardization by age, sex, and race)	Age >54 years	4.38	1.1 (0.8; 1.4)
	Survival 1–5 years	2.74	1.1 (0.7; 1.5)
	All patients	6.68	1.3 (1; 1.6)
	Age 25–54 years	1.86	1.4 (0.8; 2)
	Incomplete paraplegia	1.42	1.4 (0.7; 2.1)
	Complete quadriplegia	1.75	2.6 (1.3; 3.9)
Lung embolus
Hartkopp, 19971	All patients	6.76	11.4 (4.19; 24.8)
N = 888	Men	6.76	14.3 (5.25; 31.1)
Nonischemic heart disease
DeVivo, 19932	Incomplete paraplegia	0.44	1.4 (0.4; 2.4)
N = 9,135	Complete paraplegia	1.09	2.8 (1.1; 4.5)
	Survival >5 years	1.75	3 (1.5; 4.5)
	Incomplete quadriplegia	2.85	4 (2.5; 5.5)
	Survival 1–5 years	3.17	4.1 (2.6; 5.6)
	Age >54 years	4.71	4.2 (3; 5.4)
	All SCI	9.20	5.6 (4.4; 6.8)
	Age 25–54 years	3.07	6.5 (4.1; 10.8)
	Complete quadriplegia	4.82	23.4 (16.5; 30.3)
Diseases of the heart
Garshick, 200536	All patients		0.59 (0.19;1.38)
N = 361
Other diseases of the circulatory system
Garshick, 200536	All patients		1.49 (0.31;4.36)
N = 361

Bold - significant association at 95% confidence level

In addition to reported relative risk, three studies^{1, 2, 36} estimated age standardized mortality ratios from CVDs in SCI patients compared to the general population (Tables 10 and 11). Injured patients died from all cardiovascular diseases more often than age matched able-bodied adults (standardized mortality ratio 2.1, 95 percent CI 1.83; 2.37.¹ However, the ratio was significant only for lung embolus (standardized mortality ratio 11, 95 percent CI 4.19; 24.8) but not for other forms of CVD. SCI was associated with comparable increase in rates of cardiovascular death in men and women (Table 11). Cardiovascular mortality was lower in those injured after 1972 (standardized mortality ratio 2.4, 95 percent CI 1.95; 3.01) compared to those injured from 1953-1971 (standardized mortality ratio 7.1, 95 percent CI 2.31; 9.32) (Table 12).¹ Standardized mortality ratios in patients with cervical (standardized mortality ratio 1.1, 95 percent CI 0.72; 1.53) or thoracic injuries (standardized mortality ratio 1, 95 percent CI 0.82; 1.84) did not differ from the general population in the European study of 888 injured adults followed up from 1953 to 1992.¹

The role of functional status was reported in one study. Patients with complete tetraplegia died from ischemic heart disease (ICD codes 410–414) (standardized mortality ratio 2.6, 95 percent CI 1.3; 3.9), non ischemic heart diseases (standardized mortality ratio 23.4, 95 percent CI 16.5; 30.3), and cerebrovascular diseases (standardized mortality ratio 5.4, 95 percent CI 1.8; 9) more often than would be expected from the same age able-bodied adults.²

Mortality from nonischemic heart diseases (standardized mortality ratio 5.6, 95 percent CI 4.4; 6.8), artery diseases (standardized mortality ratio 4.5, 95 percent CI 2.1; 6.9), and lung emboli (standardized mortality ratio 11.4, 95 percent CI 4.2; 24.8) was higher in all injured adults compared to the general population.² Mortality from lung emboli contributed the most to the overall differences within the total population. The role of carbohydrate and lipid disorders (the focus of this review) in nonischemic heart disease and biologic plausibility for this finding is not well known. Therefore, it is possible that these are spurious findings based on multiple comparisons.

Three studies reported that coronary heart disease constitutes approximately 9 percent among primary causes of death in SCI patients.¹–³ The proportion of deaths attributable to all CVDs varied from 18.8 percent for diseases of the heart⁴⁹ to 24 percent for circulatory system disorders.¹ Cardiovascular diseases are among the leading causes of death in patients with chronic SCI.^{1, 49, 52} However, the contribution of age cannot be estimated analyzing crude proportion of aging SCI patients who died from heart diseases. One study of 402 veterans with chronic SCI followed by 55.6 months³⁶ showed that diabetes (relative risk 2.62, 95 percent CI 1.19; 5.77) and heart diseases (relative risk 3.66, 95 percent CI 1.77; 7.78) were significant risk factors for death after adjustment for age.

The role of lipid disorders to increase the risk of cardiovascular morbidity and mortality has not been evaluated in the published articles. The Australian Risk Factor Prevalence Study examined the overall cardiovascular risk in 102 injured patients and age matched control with scores from the MRFIT study (age, diastolic blood pressure, total cholesterol level, cigarettes per day, and sex).³⁹ The injured patients had overall percentile position of risk <50 percent independent of age and years after injury. The authors concluded that increased blood pressure, elevated blood cholesterol, or smoking could not explain cardiovascular prevalence in SCI patients.³⁹ Physical activity, BMI, cigarette use, and alcohol consumption were not associated with increased risk of cardiovascular diseases in the study of 97 injured adults.⁵⁴ However, the size of this study was too small to rule out clinically meaningful associations. One study showed that diabetes in SCI patients was associated with an increased risk of coronary heart disease, myocardial infarction, arterial hypertension, high cholesterol, and stroke, the well known association in able-bodied adults.³⁷

Interpretation of findings

Published evidence suggested that for people with SCI, diabetes mellitus contributed to an increased risk of CVDs.³⁷ The role of metabolic syndrome and lipid disorders had not yet been investigated. Increased rates of diabetes in SCI compared to able-bodied adults were reported in three articles^{30, 32, 37} with no differences in the other three.^{34, 39, 55} The degree of neurological impairment may be associated with cardiovascular mortality in SCI patients with no documented evidence of independent contribution of glucose and lipid disorders. Cardiovascular morbidity varied substantially among studies, being highest in injured veterans. Many important confounders might explain such differences beyond the veteran status, since many veterans do not seek care from the VA.⁷⁴ The studied veterans are more likely to be poor, without private insurance, have minority status, and/or have a service connected injury.⁷⁴ Indirect comparisons of cardiovascular morbidity in injured patients with known incidence of CVD in the general population does not permit and accurately estimate the contribution of metabolic disorders in patients with SCI.

Summary

Cardiovascular diseases are among the leading causes of death in patients with chronic SCI. However, when compared to able-bodied adults, cardiovascular prevalence in SCI patients did not show significant differences.

• a

  Cardiovascular mortality in injured patients was compared to standardized by age mortality in the general population in three studies. Age adjusted mortality from nonischemic heart diseases (standardized mortality ratio 5.6, 95 percent CI 4.4; 6.8), artery diseases (standardized mortality ratio 4.5, 95 percent CI 2.1; 6.9), and lung emboli (standardized mortality ratio 11.4, 95 percent CI 4.2; 24.8) was higher in all injured adults compared to the general population. Cardiovascular mortality was lower in those injured after 1972 (standardized mortality ratio 2.4, 95 percent CI 1.95; 3.01) compared to those injured from 1953-1971 (standardized mortality ratio 7.1, 95 percent CI 2.31; 9.32).

  Limited inconsistent evidence suggested higher risk of morbidity and mortality in adults who were older at time of injury. The role of functional status was examined in two studies reporting that patients with tetraplegia had higher odds of having and dying from cerebrovascular diseases. Inconsistent evidence suggested that patients with complete tetraplegia died from ischemic heart disease (standardized mortality ratio 2.6, 95 percent CI 1.3; 3.9) and nonischemic heart diseases (standardized mortality ratio 23.4, 95 percent CI 16.5; 30.3) more often than would be expected from the same age able-bodied adults. However, these findings may be based on chance due to the multiple comparisons and lack of significant associations with other cardiovascular outcomes.

• b

  Diabetes contributed to higher risk of CVD in veterans with SCI compared to nondiabetic SCI veterans in one large study. No studies compared risk of CVD among diabetics with SCI to able-bodied diabetics. The role of lipid disorders to increase the risk of cardiovascular morbidity and mortality has not been evaluated in the published articles. One study concluded that increased blood pressure, elevated blood cholesterol, or smoking could not explain increased cardiovascular prevalence in SCI patients.

Question 3

Exercise in adults with SCI

Table 13

Description of exercise intervention studies with carbohydrate (more...)

Table 13

Description of exercise intervention studies with carbohydrate related outcomes in people with SC

Reference	Study Design; Sample Size	Intervention Type	Frequency; Intensity; Duration	Subject Characteristics	Outcomes of Interest	Findings
A. Active exercise
de Groot, 200358	Case series	Arm crank exercise	3 sessions/week;	4 males, 2 females; Age range 19–54 years;	Insulin sensitivity (post-test/pre-test)	Nonsignificant decline in HI group (67%±9%) and nonsignificant improvement in LI group (156%±55%) from baseline
	n=6		60 minutes/session; High-intensity (HI; 70–80% heart rate reserve (HRR)) vs. low-intensity (LI; 40–50% HRR)	Mean duration since injury 116±77 days;
	Random assignment to high vs. low intensity		8 weeks of training	6 paraplegic (C5-L1)
Midha, 199960	Case series	Wheelchair aerobic fitness trainer (WAFT) training program	2–3 sessions/week;	11 males, 1 female;	Fasting serum glucose (mg/dL)	No change from pre-training to post-training (86±35 to 85±32)
	n=12 (Includes 2 nonSCI subjects)		20–30 minutes, until target heart rate of 90% age-predicted maximum reached; mean intensity 177 watts	Age range 22–58;
			10 weeks of training	Duration since injury range 4–29 years;
				3 quadriplegic;
				7 paraplegic;
				1 stroke;
				1 amputee
Phillips, 200462	Case series	Body-weight supported treadmill training program	68 sessions (2.8±0.2 sessions/week);	8 males, 1 female;	A Glucose tolerance (area under glucose × time curve) B Blood insulin concentration (area under insulin × time curve)	A 15%±4% (range 6–26%) reduction from baseline (p <.05) B 33%±8% (range 17–47%) reduction from baseline (p <.01)
	n=9		Velocity and % weight supported varied for each participant;	Mean age 31±3 years;
			6.0±0.3 months of training	Mean duration since injury 8.1 years;
				9 incomplete (C4-T12)
B. Functional electrical stimulation exercise
Chilibeck, 199964	Case series	Electrically stimulated leg cycling program	3 sessions/week;	4 males, 1 female;	A Glucose tolerance (area under glucose × time curve) B Fasting serum insulin (area under insulin × time curve) C Insulin sensitivity index	A Nonsignificant decreases from pre-training to post-training B Nonsignificant decreases from pre-training to post-training C Increase from pre-training (~0.9) to post-training (~1.3) (p <.05)
	n=5		30 minutes/session;	Age range 31–50 years;
			Power 6.0 watts, increased as possible each session;	Duration since injury range 3–25 years;
			50 revolutions/minute;	5 complete (C5-T8)
			8 weeks of training
Hjeltnes, 199865	Case series	Electrically stimulated leg cycling program	7 sessions/week;	5 males, 0 females;	A Insulin-mediated glucose disposal (uM/kg/minute) B Mean steady-state insulin (uU/mL) C Mean steady-state glucose (mM)	A 33%±13% increased whole body insulin-stimulated glucose uptake from baseline (p <.05) B No change from pre-training to post-training (97±1 to 94 ±1) C No change from pre-training to post-training (5.8±0.4 to 5.9±0.4)
	n=5		30 minutes/session or until fatigued;	Mean age 35±3 years;
			Power 6.0 watts, increased by 6.1 watts each session;	Mean duration since injury 10.2±3.4 years;
			50 revolutions/minute;	5 tetraplegic;
			8 weeks of training	5 complete (C5–C7)
Jeon, 200266	Case series	Electrically stimulated leg cycling program	3 sessions/week;	5 males, 2 females;	A 2-hour postload glucose (mg/dL); B 2-hour postload insulin (uU/mL)	A Reduction from pre-training to post-training (139.9±16 to 122.4±10; p = .014); B Nonsignificant reduction from pre-training to post-training (118.4±42.6 to 87.5±10)
	n=7		30 minutes/session;	Age range 30–53 years;
			50–60% VO2 maximum;	Duration since injury range 3–40 years;
			8 weeks of training	3 tetraplegic
				4 paraplegic
				7 complete (C5-T10)
Mahoney, 200567	Case series	Resistance exercise training program	2 sessions/week;	5 males, 0 females;	A Plasma glucose levels (mg/dL) B Insulin concentration	A Nonsignificant trend for reduction from pre-training to post-training (p = .074) B No change from pre-training to post-training
	n=5		4 sets of 10 unilateral, dynamic knee extensions;	Mean age 35.6±4.9 years;
			12 weeks of training	Mean duration since injury 13.4±6.5 years;
				5 complete (C5-T9)
Mohr, 200168	Case series	Exercise program with functional electrical stimulation cycling ergometer	3 sessions/week;	8 males, 2 females;	A 2-hour postload insulin (uU/mL) B 2-hour postload glucose (mM/L) C Insulin-stimulated glucose uptake rates (mg/min/kg)	A No change from pre-training to post-training (93±7 to 88±8) B No change from pre-training to post-training C Increased from pre-training to post-training (4.9±0.5 to 6.2±0.6; p <0.05)
	n=10		30 minutes/session;	Mean age 35±2 years;
			50 revolutions/minute;	Mean duration since injury 12±2;
			1 year of training	6 tetraplegic (C6);
				4 paraplegic (T4)
C. Passive exercise
No eligible studies
D. Self-reported physical activity
Jones, 200414	Cross-sectional case-control survey	NA	NA	20 males, 0 females;	A Fasting plasma glucose (mM/L) B Log 2-hour postload glucose (mM/L) C Log fasting plasma insulin (uU/mL) D Log 2-hour postload insulin (uU/mL)	A Nonsignificant inverse association with physical activity (r = -0.40) B Inverse association with physical activity (r = -0.59; p <.01) C No association with physical activity (r = -0.07) D Inverse association with physical activity (r = -0.79; p <.01)
	n=20	Assessed physical activity levels (minutes/week) and metabolic variables		Age range 16–52 years;
				Mean duration since injury 10.3±1.8 years;
				11 tetraplegic (C4–C7);
				9 paraplegic (T5-L5)
Manns, 200513	Cross-sectional survey	NA	NA	22 males, 0 females;	A Fasting plasma glucose (mM/L) B 2-hour postload glucose (mM/L) C Fasting plasma insulin (uM/ml) D 2-hour postlload insulin (uM/ml)	A Inverse association with physical activity (r = -0.525; p <.05) B Nonsignificant inverse association with physical activity ( r= -0.34) C Nonsignificant inverse association with physical activity (r = -0.40) D No association with physical activity (r = -0.16)
	n=22	Assessed physical activity levels and metabolic variables		Mean age 39±-9 years;
				Mean duration since injury 17±9 years;
				22 paraplegic (T2-L2);
				22 complete
E. Other
No eligible studies

Table 14

Description of exercise intervention studies with lipid (more...)

Table 14

Description of exercise intervention studies with lipid or cardiovascular related outcomes in people with SCI

Reference	Study Design; Sample Size	Intervention Type	Frequency; Intensity; Duration	Subject Characteristics	Outcomes of Interest	Findings
A. Active exercise
Durán, 200157	Case series	Training program including mobility, strength, coordination, aerobic resistance, and relaxation activities	3 sessions/week;	12 males, 1 female;	A HDL (mg/dL) B LDL (mg/dL) C TC/HDL	A No change from pre-training (38±11.6) to post-training (p <008) B No change from pre-training (94±39.8) to post-training (p <0.25) C No change from pre-training (4.75+/-2.15) to post-training (p <0.076)
	n=13		120 minutes/session;	Mean age 26.3±8.3 years;
			Target HR 40%–80% of maximal HR;	Duration since injury range 2–120 months;
			16 weeks of training	13 paraplegic
				4 T6 or higher;
				9 T6 or lower
de Groot, 200358	Case series	Arm crank exercise program	3 sessions/week;	4 males, 2 females;	A TC (post-test/pre-test) B HDL (post-test/ pre-test) C LDL (post-test/pre-test) D TC/HDL-C (post-test/pre-test) F TG (post-test/pre-test)	A No significant differences for HI or LI groups (-11% and -6%) B No significant differences for HI or LI groups (+13% and -5%) C No significant differences for HI or LI groups (-14% and -5%) D Reduction in HI group (-23%) but not LI group (0%) F Reduction in HI group (31%) but not LI group (-5%)
	n=6		60 minutes/session;	Age range 19–54 years;
	Random assignment to high vs. low intensity		High intensity (HI; 70–80% heart rate reserve) vs. low intensity (LI; 40–50% HRR);	Mean duration since injury 116±77 days;
			8 weeks of training	6 paraplegic (C5-L1)
El-Sayed, 200559	Controlled case series	Arm crank exercise program	3 sessions/week;	5 paraplegic (SCI);	A TC (mM/L) B HDL-C (mM/L) C TG (mM/L)	A No change from pre-training to post-training in AB or SCI B Increase (p <0.05) from pre-training to post-training in SCI C No change from pre-training to post-training in AB or SCI
	n=12		30 minutes/session;	7 able-bodied (AB);
			60–65% VO2 peak;	Mean age 32±1.6 years for AB;
			12 weeks of training	Mean age 31±2.9 years for SCI
Midha, 199960	Case series	WAFT training program	2–3 sessions/week;	11 males, 1 female;	A TC (mg/dL) B TG (mg/dL) C HDL-C (mg/dL) D TC/HDL-C	A Reduction from pre-training to post-training (185±42 to 170±32, p = 0.04) B No change from pre-training to post-training (117±52 to 110±60) C No change from pre-training to post-training (48±10 to 48±10) D No change from pre-training to post-training (4±1 to 3.8±1)
	n=12 (includes 2 non-SCI subjects)		20–30 minutes, until target heart rate of 90% age-predicted maximum reached;	Age range 22–58;
			Mean intensity 177 watts;	Duration since injury range 4–29 years;
			10 weeks of training	3 tetraplegic;
				7 paraplegic;
				1 stroke;
				1 amputee
Nash, 200161	Case series	Arm crank exercise program, with focus on resistance and endurance	3 sessions/week;	5 males, 0 females;	A TC (mg/dL) B HDL (mg/dL) C LDL (mg/dL) D TC/HDL-C E TG (mg/dL)	A Nonsignificant decrease pre-training to post-training (183±26 to 167±33) B Nonsignificant increase pre-training to post-training (41±5 to 45±12) C Decrease pre-training to post-training (118±22 to 88±30, p = 0.05) D Decrease pre-training to post-training (5.0±1.1 to 3.9±0.7, p = 0.05) E Nonsignificant decrease pre-training to post-training (202±120 to 190±91)
	n=5		45 minutes/session;	Age range 34–43 years;
			Power output 400 kpm + 100 kpm every 3 minutes until peak VO2 maximum;	Mean duration since injury 4.8±1.4 years;
			3 months of training	6 paraplegic;
				5 complete (T6-L1)
Stewart, 200463	Case series	Body-weight supported treadmill training program	68 sessions (2.8±0.2 sessions/week);	8 males, 1 female;	A TC (mM) B HDL-C (mM) C LDL-C (mM) D TC/HDL-C (mM) E TG (mM)	A Decrease from pre-training to post-training (4.9±0.2 to 4.4±0.1, p = 0.021) B Nonsignificant increase pre-training to post-training (1.3±0.2 to 1.4±0.3, p = .19) C Decrease from pre-training to post-training (3.3±0.2 to 2.8±0.3, p = 0.046) D Decrease from pre-training to post-training (3.8±0.3 to 3.1±0.3, p = .041) E Nonsignificant decrease pre-training to post-training (1.5±0.2 to 1.3±0.2, p = .17)
	n=9		Velocity and % weight support varied for each participant;	Mean age 31±3 years;
			6.0±0.3 months of training	Mean duration since injury 8.1 years;
				9 incomplete (C4-T12)
B. Functional electrical stimulation exercise
No eligible studies
C. Passive exercise
No eligible studies
D. Self-reported physical activity
Dallmeijer, 199970	Case-series survey	NA	NA	15 males, 4 females;	A Difference TC (mM/L) B Difference LDL-C (mM/L) C Difference TC/HDL-C (mML) D TG (mM/L)	A Inverse association with sport activity (r = -0.35; p = 0.008) B Inverse association with sport activity (r = -0.28; p = 0.003) C Inverse association with sport activity (r = -0.49; p = 0.035) D No change in values from t1 to t2
	n=19	Assessed risk profiles and sport activity (hours/week) at t1 (during rehab) and t2 (1 year post-discharge)		Mean age 40.7±14.7 years;
				Mean duration since injury 760±169 days;
				9 tetraplegic;
				10 paraplegic
Dallmeijer, 199769	Cross-sectional survey	NA	NA	24 males, 0 females	A TC (mM/L) B HDL (mM/L) C LDL-C (mM/L) D TC/HDL-C E TG	A No difference between groups B Higher for physically active (1.1±0.21) than sedentary (0.95±0.20) (p <0.05) C No difference between groups D Lower for physically active (1.34±0.67) than sedentary (1.96±1.01) (p <0.05) E Nonsignificantly lower for physically active (1.34±0.67) than sedentary (1.96±1.01)
	n=24	Compared lipid levels between physically active (1.5–6.0 hours/week) and sedentary SCI patients		11 physically active
				13 sedentary
				24 tetraplegic
				4 incomplete
				20 complete
Davies, 200254	Cross-sectional survey	NA	NA	87 males, 10 females;	Cardiovascular morbidity	No association with physical activity
	n=97	Assessed physical activity as determinant of cardiovascular morbidity (both measurements made with valid and reliable scale)		Mean age 47.5±4.5 years;
				Mean duration since injury 15.9±10.1 years;
				41 tetraplegic
				55 paraplegic
				1 undetermined
				32 complete
				62 incomplete
				3 undetermined
Janssen, 199771	Cross-sectional survey	NA	NA	37 males, 0 females;	A TC (mM/L) B HDL (mM/L) C LDL-C (mM/L) E TC/HDL-C F TG	A Inverse association with physical activity (r = -0.33; p <0.05) B No association with physical activity (r = -0.14) C Inverse association with physical activity (r = -0.40; p <0.01) E No association with physical activity (r = -0.17) F No association with physical activity (r = 0.06)
	n=37	Assessed sport activity (hours/week) as determinant of lipid profiles		Age range 19–71 years;
				Duration since injury range 4–33 years;
				8 tetraplegic
				29 paraplegic
				23 complete
Jones, 200414	Cross-sectional case-control survey	NA	NA	20 males, 0 females;	A TC/HDL (mM/L) B Log HDL (mM/L)	A Inverse association with physical activity (r = -0.49; p <0.05) B Direct association with physical activity (r = 0.46; p <0.05)
	n=20	Assessed physical activity levels (minutes/week) and metabolic variables		Age range 16–52 years;
				Mean duration since injury 10.3±1.8 years;
				11 tetraplegic (C4–C7)
				9 paraplegic (T5-L5)
Manns, 200513	Cross-sectional survey	NA	NA	22 males, 0 females;	A HDL-C (mM/L) B TG (mM/L)	A Direct association with physical activity (r = 0.625; p <0.05) B No association with physical activity (r = -0.256)
	n=22	Assessed physical activity levels and metabolic variables		Age range 39±9 years;
				Mean duration since injury 17±9 years;
				22 paraplegic (T2-L2);
				22 complete
E. Other
Chen, 200672	Case series	NA	Followup testing at 12 weeks and 24 weeks	9 males, 7 females;	A TC (mg/dL) B HDL-C (mg/dL) C LDL-C (mg/dL)	A Nonsignificant decrease pre-program to post-program (-5.8±20.9, p = 0.28) B Decrease from pre-program to post-program (-3.2±5.4, p = .03) C Nonsignificant decrease pre-program to post-program
	n=16	Participation in weight management program where exercise behavior was taught		Age range 21–66 years;		(-1.8±22.1, p = .76)
				Mean duration since injury 17.5 years
				15 SCI
				1 spinal cord illness

Of the 19 peer reviewed original articles, there were none reporting results of RCTs. The majority consisted of small, uncontrolled intervention trials (case series) or cross-sectional surveys using measures of self-reported physical activity. Variation in study design, intervention, and reported outcomes precluded quantitative pooling of results. A summary of findings from individual studies according to intervention type and outcomes was conducted. To facilitate review, these studies were separated by outcomes of interest: Carbohydrate-related outcomes (n=10) (Table 13) and lipid-related outcomes (n=13) (Table 14). These were then further organized by type of reported exercise, as follows:

• A

  Active Exercise (AE): n=six studies of 57 individuals (40 males, five females, 12 unreported; 36 paraplegic, three tetraplegic, nine unclassified and nine other) (8–24 weeks exercise duration).⁵⁷–⁶³

• B

  Functional Electrical Stimulation Exercise (FES): n=five studies of 32 individuals (27 males, five females; eight paraplegic, 14 tetraplegic and ten unclassified) (8–52 weeks exercise duration)⁶⁴–⁶⁸

• C

  Passive Exercise (PE): n=0 studies

• D

  Self-Reported Physical Activity: n=six studies of 215 individuals (205 males, 14 females; 125 paraplegic, 93 tetraplegic, one unclassified) (no report of duration)^{13, 14, 54, 69}–⁷¹

• E

  Other: n=one study (nine males, seven females) (no report of duration)⁷²

Description of exercise intervention studies with carbohydrate related outcomes (Table 13) (n=10 studies of 101 individuals).^{13, 14, 58, 60, 62, 64}–⁶⁸

The overall quality, quantity, and consistency of evidence for exercise as an intervention for carbohydrate disorders is poor. Study characteristics ranged from a case series using pre-post assessment of outcomes for six individuals randomly assigned to eight weeks of high- versus low-intensity arm crank exercise⁵⁸ to a cross-sectional survey of 22 individuals who provided self-assessed physical activity levels and metabolic variables.¹³ The intervention type, frequency, intensity, and duration varied considerably across studies. Most involved several sessions of supervised exercise per week with a study duration ranging from eight weeks to one year. SCI level and severity, and duration since injury, varied across studies. More than 90 percent of subjects were men. One study was a survey of self-reported exercise or physical activity and assessed the impact of the respondent's activity on major cardiovascular endpoints.⁵⁴ Three studies examined the effects of active exercise (AE),^{58, 60, 62} while five examined the effects of FES exercise,⁶⁴–⁶⁸ on carbohydrate related measures. Two survey studies assessed the association between self-reported physical activity and these measures.^{13, 14} The most commonly assessed measures were fasting plasma glucose and oral glucose tolerance tests, measuring post-oral load levels of glucose and insulin. None assessed glycosylated hemoglobin.

Impact of exercise programs on carbohydrate related measures

There is mixed, low-quality evidence that a program of exercise improves carbohydrate-related measures. Of the five studies that measured fasting plasma glucose only one showed a statistically significant difference. Two (one AE; one FES) found no differences before and after intervention,^{60, 65} while one FES study found a nonstatistically significant trend for reduction.⁶⁷ Two surveys identified inverse correlations (r = -.53 and -.40 respectively) between self-reported physical activity and plasma glucose; one was statistically significant¹³ while the other was not.¹⁴ Measures of two-hour post-load glucose were mixed. One FES study found a significant (p = .014), 13 percent post-training reduction in glucose levels, averaged across participants,⁶⁶ while another FES study showed no change.⁶⁸ Both survey studies of self-reported physical activity identified inverse correlations (r = -.59 and -.34 respectively) with two-hour post-load glucose; the prior was statistically significant (p <0.01)¹⁴ while the latter was not.¹³ Impaired glucose tolerance and clearing were also reported. One AE study showed a statistically significant post-training 15 percent average reduction in area under the curve after glucose load,⁶² and one FES study found a significant 33 percent average increase in glucose disposal.⁶⁵

Measures of insulin levels were no more uniform than for glucose. Some studies assessed fasting insulin levels, while others assessed insulin levels after a standard glucose load or insulin area under the curve. One possible consistency in these studies is the lack of change in fasting plasma insulin levels after training. Two FES studies found no difference in fasting plasma insulin,^{65, 67} while one identified decreased levels that were not significant.⁶⁴ One survey study showed no correlation between self-reported physical activity and insulin;¹⁴ the other survey study did identify an inverse correlation (r = -.40), but it was not statistically significant (p >0.05).¹³ Plasma insulin concentrations after oral glucose load were also inconsistent. One FES study identified a nonsignificant 26 percent average reduction in two-hour post-load levels,⁶⁶ while another FES study found no change.⁶⁸ Similarly, one survey study identified a statistically significant inverse correlation (r = -.79. p <0.01) between self-reported physical activity and post-load insulin,¹⁴ while the other found no correlation.¹³ One AE study identified a significant 33 percent average reduction in area under the curve for plasma insulin concentrations after glucose load.⁶² To further complicate any possible conclusions, the AE study comparing two programs of exercise (low intensity vs. high intensity)⁵⁸ found insulin sensitivity to be decreased by an average of 33 percent for those assigned the low intensity intervention, but increased an average of 56 percent for those in the high intensity intervention.

Description of exercise intervention studies with lipid or cardiovascular related outcomes (Table 14) (n=13 studies of 292 individuals).^{13, 14, 54, 57}–^{61, 63, 69}–⁷²

The quality, quantity, and consistency of evidence for studies reporting lipid related measures is also poor. Study designs were primarily reports of case series and cross-sectional surveys, with intervention type, frequency, intensity, and duration varied across studies. Nearly 90 percent of subjects were men, thus limiting extrapolation of findings in women. Six studies examined the effects of AE on lipid related measures.⁵⁷–^{61, 63} No eligible studies examined FES exercise. There were six survey studies that assessed the association between self-reported physical activity and lipid measures.^{13, 14, 54, 69}–⁷¹ One of these examined the association between physical activity and cardiovascular morbidity.⁵⁴ One study, categorized as “other,” examined the effects of a weight management training program, including curriculum on exercise, on lipid outcomes.⁷² The most common lipid related measures were TC, HDL-C, LDL-C, the ratio of TC to HDL-C (TC/HDL-C), and TG.

Impact of exercise programs on lipid or cardiovascular related measures

Evidence may point to improved levels of TC after a training intervention, or with self-reported physical activity. Among the studies examining effects of AE interventions, two identified statistically significant reductions in TC levels (on average, 8 percent and 10 percent less than pre-training);^{60, 63} these involved training programs with a body-weight supported treadmill⁶³ or a wheelchair aerobic fitness trainer.⁶⁰ One study found a nonsignificant 9 percent average decrease,⁶¹ while two showed no changes;^{58, 59} all three of these studies involved arm crank exercise. Three survey studies examined self-reported exercise and TC levels.⁶⁹–⁷¹ While one found no difference in TC levels between those who were physically active and those who were sedentary,⁶⁹ two others identified significant inverse correlations (r = -.35 and -.33, p = 0.008 and p <0.05, respectively). The study examining the weight management training program also identified a nonsignificant decrease in TC.⁷²

Six AE studies reported outcomes for HDL-C.⁵⁷–^{61, 63} While three reported no changes,^{57, 58, 60} one reported a statistically significant increase⁵⁹ and two reported very small, nonsignificant increases (10 percent and 8 percent).^{61, 63} Four survey studies reported on HDL-C, with one identifying a significantly significant 14 percent decrease (p <0.05) for individuals who were physically active compared to those who were sedentary.⁶⁹ Two others identified significant positive correlations (r = .46 and .63, p <0.05),^{13, 14} while another reported no correlation.⁷¹ Oddly, the weight management study reported a significant decrease in HDL-C.⁷² Measures for TC/HDL-C were similarly inconclusive. Of five AE studies, two reported no changes,^{57, 60} while three reported statistically significant reductions in values ranging from 18 percent to 23 percent.^{58, 61, 63} Two survey studies identified significant inverse correlations between physical activity and TC/HDL-C (r = -.49, p <0.05 for both),^{14, 70} one identified a significant reduction (p <0.05) among those who were physically active compared to sedentary,⁶⁹ and one showed no correlation.⁷¹

In two of four AE studies reporting LDL-C measures, levels were significantly decreased by 15 percent and 25 percent (p = .05 for both);^{61, 63} no changes were observed in the others.^{57, 58} However, two of three survey studies identified significant inverse correlations between self-reported physical activity and LDL-C levels (r = -.28 and -.40, p = 0.003 and p <0.01 respectively).^{70, 71} The third survey study found no difference between groups.⁶⁹ The weight management program was associated with a nonsignificant decrease.⁷²

While one study identified a statistically significant 31 percent average decrease in TG among those assigned a high intensity AE training protocol,⁵⁸ two others showed decreases that were nonsignificant,^{61, 63} and still two others found no change.^{59, 60} Among the four self-report surveys, one identified a nonsignificant 32 percent decrease among those who were physically active compared to sedentary.⁶⁹ Three others identified no correlation between physical activity and TG levels.^{13, 70, 71}

The study by Davies and McColl⁵⁴ identified no association between physical activity levels and overall cardiovascular morbidity.

Summary

Evidence on effects of exercise on lipid and carbohydrate metabolism disorders is inconclusive. Studies to date have been short in duration, involved few subjects, and relied on study designs highly susceptible to error. Future collaborative research is needed to study both efficacy and effectiveness of such interventions in the population of individuals with SCI.

Dietary and pharmacologic intervention studies with carbohydrate or lipid related outcomes in adults with SCI

Carbohydrate outcomes

There were no prospective studies that evaluated dietary and/or lifestyle interventions on carbohydrate related outcomes.

Lipid related outcomes (Table 15.)

Only two prospective studies that evaluated dietary and/or lifestyle interventions to reduce lipid levels were identified and met inclusion criteria.^{20, 72} No studies assessing pharmacologic interventions were identified. The two dietary/lifestyle case series studies included 238 subjects, overwhelmingly male (87 percent). Quality of the two studies was poor.

One controlled clinical trial compared the effect of a dietary intervention referral compared to no dietary referral over a mean of 16 months.²⁰ Overall, mean age was 38.5 years and 89 percent were male. All subjects must have had an SCI of at least two years in duration. Group 1 (n=86) received a dietary intervention referral based on the recommendations of the American Heart Association and American Dietetic Association Guidelines. These subjects had a total cholesterol level greater than 200 mg/dL. Group 2 (n=136) received no dietary intervention referral. All subjects had a total cholesterol level ≤200 mg/dL. Group 1 subjects were significantly older (mean 42.8 versus 35.7, p <0.0001) and had a longer post-injury duration (15.6 versus 11.1 years, p <0.0001) compared to Group 2 subjects. Dietary intervention was effective in reducing some lipid parameters. There were significant reductions in total and low density lipoprotein cholesterol levels from baseline in Group 1, 234 to 224 (p <0.001) and 159 to 151 (p = 0.004), respectively. Levels increased slightly but not significantly in Group 2. In Group 1, 67 percent had decreases in LDL-C compared to 47 percent in Group 2 (p = 0.007). Secondary analysis found 15 percent had reductions ranging from 30 to 69 mg/dL and the LDL-C values declined from greater than 135 mg/dL to <135 mg/dL in 21 percent. There were no significant effects on high density lipoprotein cholesterol or triglyceride levels in either group.

The second uncontrolled pilot study evaluated a weight management program consisting of 12 classes for 12 weeks, primarily led by a registered dietician.⁷² Classes covered nutrition, exercise, and behavior modification. The dietary approach utilized a time-calorie displacement diet. The study followed 16 overweight subjects (BMI ≥25), up to 24 weeks. Subjects were on average 44 years of age, nine were men, 13 were White, and three were African American. There were no significant changes in total and LDL cholesterol levels from baseline at weeks 12 and 24. At week 12, TCl was reduced by 5.8 mg/dL (p = 0.28) and LDL cholesterol by 1.8 mg/dL (p = 0.76). By week 24, the mean changes were 0.3 mg/dL (p = 0.96) and -4.2 mg/dL (p = 0.42), respectively. HDL cholesterol was reduced significantly by 3.2 mg/dL from a baseline value of 43.1 mg/dL (p = 0.03) at week 12 and -0.9 mg/dL (p = 0.59) by week 24.

Prevalence and Risk Estimates

The present systematic review evaluated published evidence regarding the prevalence of lipid and carbohydrate disorders, CVDs, and mortality in adults with chronic posttraumatic SCI. We attempted to assess the contribution of risk of these disorders to CVD morbidity and mortality and whether they vary according to SCI status or compared to able-bodied individuals. The potential efficacy and harms of interventions to improve carbohydrate and lipid disorders in this population was also examined. This information was synthesized to determine if compared to able-bodied adults individuals with SCI:

• 1

  have a different prevalence of carbohydrate disorders;

• 2

  have increased risk of CVD morbidity and mortality,

• 3

  have CVD and/or carbohydrate/lipid benefits from specific interventions;

• 4

  should have thresholds/methods for detection or treatment modified.

The level of evidence addressing these issues is low. Most studies were retrospective, small, lacked adequate controls, and did not assess or adjust for confounding factors. Outcome measure definitions varied widely. However, limited low quality data suggest that adults with SCI are not at markedly higher risk of carbohydrate and lipid disorders or CVD than appropriately matched able-bodied individuals. Except for assessment of body composition/obesity, evidence does not support that diagnostic and treatment thresholds or methods for carbohydrate and lipid disorders should differ in SCI compared to able-bodied individuals. Assessment of insulin resistance and impaired glucose tolerance are not routinely performed in able-bodied individuals. The effectiveness of screening to improve clinical outcomes by detection of pre-diabetes (impaired fasting glucose or impaired glucose tolerance), insulin resistance, and diabetes in asymptomatic adults has not been demonstrated.⁷³ Use of these tests is limited due to their inconvenience, complexity of testing requirements, costs, and current lack of accuracy. The OGTT is inconvenient and not ordered by most physicians to diagnose diabetes, even among those at risk. Additionally, about one-half with IGT or OGTT would have normal tests if repeated. Similar concerns exist with the criteria used to define impaired fasting glucose. Because the glucose concentration distribution is unimodal, the choice of cutpoints used to designate abnormalities of carbohydrate metabolism is arbitrary. Very little high quality data exist on the independent role of gender, race, disease severity, level, or duration. Any observed differences in prevalence or risk is relatively small in magnitude, inconsistent in direction according to study or risk characteristic, and/or could be confounded by differences in other known risk factors: age, smoking, exercise status, family history, etc.).

Assessment of obesity using BMI, is likely to be inaccurate and underestimate body fat assessment in adults with SCI. For other measures of carbohydrate and lipid abnormalities there is no high quality evidence to indicate that different thresholds (or biomarkers) should exist for SCI individuals compared to able-bodied adults to identify patient risk level, define disease status, or initiate treatment. Little data exist on the effects of interventions to improve carbohydrate and lipid abnormalities, including the effect of exercise.

Several previous reports and reviews have suggested that the prevalence of carbohydrate and lipid disorders, as well as cardiovascular morbidity and mortality, is much higher in adults with SCI compared to able-bodied individuals. However, the prevalence of insulin resistance, metabolic syndrome, diabetes mellitus, impaired glucose tolerance, dyslipidemia, and obesity in a population is highly dependent upon demographics of the population, including most importantly the age distribution, but also socioeconomic status and race/ethnicity. The dependence of these conditions on population characteristics makes it difficult to make between study comparisons, since the population characteristics vary greatly both between and within studies. These factors may explain the wide variation in study prevalence estimates as well as the relative risk compared to different able-bodied control populations. Additionally, definitions of disease or condition may also alter prevalence estimates. In the one included study assessing metabolic syndrome, the definitions used by the authors for hypertension, obesity, diabetes, and lipid disorders are not widely accepted or utilized in studies in able-bodied adults. Their definitions increase the estimated prevalence of disease in their population and relative to studies of able-bodied individuals that use established definitions.

Our findings of cardiovascular disease prevalence and mortality were lower than frequently reported. Previous reviews often incorporated a broad definition of CVD.⁷⁶ Definitions included in these reports were hypertension, as well as self-reported signs and symptoms of leg swelling or palpitations.⁵⁶ The clinical significance and the relation to CVD of leg swelling and palpitations are not clear. Accurate assessment of blood pressure in SCI individuals is problematic. No validated definitions or thresholds for hypertension interventions exist in SCI patients due to blood pressure measurement issues related to autonomic dysreflexia, muscle spasticity or hypotonicity, use of arms for wheelchair transportation, and, most importantly, the lack of long-term data correlating blood pressure and treatment with morbidity and mortality in SCI individuals. These highly prevalent conditions are much more common and inflate prevalence estimates of cardiovascular disease in SCI individuals but result in less morbidity than myocardial infarction or stroke. Use of self-reported disease classification or death certificates for cause of death may also result in biased estimates of disease prevalence or mortality. Several factors may contribute to the increased prevalence of undiagnosed CVD in SCI individuals, including access and quality of care, asymptomatic angina in patients with diabetes or upper level injury,^{77, 78} and metabolic syndrome, unstable blood pressure, and cardiac rhythm.^{79, 80} Screening to detect asymptomatic heart diseases, including coronary heart disease, arrhythmias, and autonomic dysreflexia, may result in higher prevalence of CVD in this population.

Prevalence of CVD in aging SCI individuals can be attributable to age rather than injury. Patients differed by the prevalence of risk factors prior to injury and by age at the time of injury, both could modify the association between SCI and CVD. Indeed, recently published retrospective analysis found that presence of cardiovascular disease prior to injury was associated with a 280 percent increase in risk of death (relative risk 2.8, 95 percent CI 1.22; 6.40).⁸¹ For each additional year of age at injury, the relative risk of dying was increased by 8 percent (RR 1.08, 95 percent CI 1.06; 1.09).⁸¹

Whether the reported increased risk of all CVD in tetraplegic compared to paraplegic individuals can be interpreted as an evidence of higher morbidity^{53, 76} requires additional studies. Limited evidence suggests that CVD may contribute to approximately 20 percent of all deaths in SCI patients^{1, 36, 49, 52} and coronary heart disease in 9¹–³ to 13⁸¹ percent of all deaths.¹–^{3, 81} There is insufficient evidence to determine whether percentage of deaths due to CVD differs in SCI adults compared to appropriately matched able-bodied individuals. One study suggested that presence of heart diseases was associated with an increased risk of death by 3.7 fold in SCI patients independent of age and other risk factors.⁵² Limited evidence suggests that the contribution of different forms of heart disease (e.g., ischemic versus nonischemic coronary heart disease) to overall CVD mortality in SCI patients may differ from the general population.

CVD morbidity and mortality in SCI patients showed inconsistent differences compared to the general population. Survival rates in aging injured patients can depend on severity of CVD and quality of care. Whether the incidence of CVD was not well documented in the studies or the prognosis of CVD is worse in the SCI than in the able-bodied population is unclear. Case fatality from CVD in SCI patients compared to the general populations is not well established. However, some evidence suggested that case fatality rate for pneumonia was higher in injured than in the general population.¹⁰⁹

The independent contribution of diabetes and impaired glucose tolerance on CVD prevalence in adults with versus without SCI has not been reported. The association between metabolic control and CVD in adults with SCI remains unclear. Vascular complications were not different in SCI users of the VA health care system who were diabetic compared to diabetic able-bodied veterans.³⁷ The role of lipid disorders on CVD in SCI individuals is not well documented and needs future investigation.

Some potentially eligible studies that may be cited as evidence of altered risk were excluded due to small sample size that limited generalizability (n=45, number of SCI individuals in each study ranged from 1–77). These studies were also of low quality and relevance because they were from a single center, not from the United States, lacked controls, and/or did not assess clinically relevant carbohydrate and lipid disorders. The impact of these studies on our overall findings regarding carbohydrate, lipid and body composition disorder prevalence, and subsequent clinical decision making is likely to be small. Only 17 excluded studies had control groups. The largest study reporting glucose intolerance and insulin resistance in the United States lacked controls, was comprised of 57 adults from a single center, and was published in 1983. The largest excluded controlled study of lipid disorders was a single center report comprised of 60 young SCI adults (mean age = 28 years) and 28 age and gender matched healthy able-bodied controls. Serum LDL cholesterol was higher (109 mg/dL vs. 91 mg/dL; p = 0.04) and HDL cholesterol lower (33 mg/dL vs. 44 mg/dL; p = 0.004) in SCI adults versus controls. The authors concluded that “serum lipoprotein levels should not be ignored for the followup of the patients with spinal cord injury.”⁷⁵ We agree with their conclusion. Other excluded studies were of even lower quality and relevance to health care in the United States because they were smaller, from a single center, not from the United States, lacked controls, and/or did not assess clinically relevant carbohydrate and lipid disorders.

Role of Exercise, Diet, and Pharmacologic Interventions

The evidence that exercise programs alter carbohydrate and lipid outcomes is of poor quality and inconclusive. There were relatively few consistent findings pertaining to plasma glucose, two-hour post-load glucose, fasting insulin, or two-hour post-load insulin. Similarly, little consistency was reported between studies for HDL-C, TC/HDL, and TG. Results may have indicated some overall post-training benefits for outcomes of TC and LDL-C. While many reported findings appear to be encouraging and are suggested as such in the primary papers as well as past reviews,^{85, 110} caution is warranted when interpreting these studies. There was a general lack of quantity, quality, and consistency in methods and outcomes across studies. Overall, reports were based on short-term exercise protocols, often involved carefully recruited hospital- and/or clinic-based patients, and failed to consider implementation or sustainability of exercise interventions in community-based populations. Only one study examined the effects of exercise on coronary heart disease outcomes.⁵⁴

The exercise described in these papers varied considerably from one study to the next. In the cross-sectional surveys,^{13, 14, 54, 69}–⁷¹ parameters of physical activity were rarely reported. Generally, questions pertaining to amount of physical activity per week were asked.^{14, 69}–⁷¹ In exercise intervention studies, little consistency in duration, mode, frequency, or intensity of the exercise programs existed. The length of the exercise protocols ranged from 8 to 52 weeks; most were only 8 to 16 weeks in duration.⁵⁷–^{61, 64}–⁶⁷ These studies may not have been long enough to impart measurable physiological benefits to study participants. Further, the types of exercise, frequency of sessions, and intensity of exertion were also varied, making results about preferred forms of exercise inconclusive.

Patient populations and outcome measures were also highly inconsistent. Study designs consisted only of case series, involving small numbers of subjects in hospital or clinical settings, or the cross-sectional surveys. The total number of subjects participating was low (n=101 for carbohydrate studies and n=292 for lipid studies) and, for the most part, subjects were not randomly selected from broader patient or community populations. These methods are considered highly susceptible to bias. Subjects that participated in the case series studies were likely a highly-motivated group of individuals, nonrepresentative of the broader population of those with SCI. Little information was presented on those asked to participate but who chose to abstain. Further, the measures of self-reported exercise or physical activity utilized in the cross-sectional surveys likely led to misclassification through recall error and social desirability issues. Even if measurement of physical activity was accurate, the cross-sectional nature of these surveys leaves results highly questionable due to possible confounding. For example, those who did not exercise may have had underlying carbohydrate and/or lipid metabolism disorders. This would make physical activity positively correlated, but not necessarily causally associated, with better carbohydrate and lipid measures.

None of the intervention studies used improvement in glycated hemoglobin (A1C) as an outcome. The effect of exercise on blood glucose often is delayed for several hours. A1C reflects the integrated effect on blood glucose throughout the day and A1C is easy to measure. Therefore, it would likely be preferable for future studies to track A1C changes rather than transient and more difficult to measure insulin or glucose levels or areas under the insulin and glucose curves for a few hours.

Even if consistent, convincing data were generated from these types of studies, there is no evidence for subsequent, successful translation of exercise interventions to a lesser motivated or community-based SCI population. Effectiveness of exercise interventions has yet to be studied in a population of individuals with SCI. Implementation and sustainability of exercise in this population is likely to be more challenging than in an able-bodied population, given the environmental barriers and physical risks, such as exercise-induced autonomic dysfunction and musculoskeletal injury.^{8, 26} The risk of further, unperceived health problems, such as silent ischemia, in denervated subjects should be carefully considered prior to implementing exercise-related recommendations or policies.

Exercise and dietary programs among able-bodied individuals have demonstrated a modest improvement in carbohydrate and lipid parameters among selected highly motivated individuals. Translation of these findings to community settings of SCI adults has not been demonstrated, and even the effectiveness in the general able-bodied population is unclear. For example, a recent randomized trial evaluated the effects of 22 weeks of aerobic training, resistance training, or both (three times per week) on glycemic control in 251 able-bodied adults with Type 2 diabetes.⁸⁶ Combined training resulted in a 1 percent absolute reduction in glycated hemoglobin values versus sedentary controls. Reductions due to either resistance or aerobic training alone were about one-half that seen with combination therapy. Their was no difference in lipid values, blood pressure, lean body mass, fat mass, or percent body fat of any of the exercise programs versus controls. Adverse events were more common in the exercise group, and 14 percent of those randomized to exercise dropped out.

Ultimately, higher-quality studies examining effects of exercise on the health of subjects with SCI need to be conducted. While carbohydrate and lipid metabolism measurements are important, intermediate measures, extending such studies into longer term outcomes such as diabetes mellitus, coronary heart disease, and survival are important. In addition, clinical and research questions pertaining to obesity in individuals with SCI remain to be answered. The most appropriate measurements and definition of obesity for those with SCI have not been identified at this time. To continue the use of BMI as a measurement of obesity, it must be assessed whether current BMI cutpoints for the general population can be extrapolated to those with SCI, or whether cutpoints need to be specific to this population, considering both SCI type and level.

Little information exists regarding the impact of dietary or pharmacologic interventions on adults with SCI. Recommendations currently exist for disease definitions for diabetes and lipid abnormalities in able-bodied adults. Several large RCTs have established the effectiveness of statins used for primary prevention in able-bodied adults with mean baseline LDL cholesterol of approximately 150 mg/dL. Many of these individuals had other competing risks such as hypertension and cigarette use. Use of statins in able-bodied adults with diabetes have been demonstrated to be effective even if baseline LDL-C is less than 130 mg/dL. The mean baseline LDL-C in populations of SCI individuals included in this review was 125 mg/dl. Effectiveness and harms associated with statins may differ in SCI individuals compared to able-bodied adults. However, unless contrary data exist, it seems reasonable to extrapolate these findings and recommendations for similar pharmacologic intervention thresholds for treatment of lipid abnormalities in SCI individuals as used in able-bodied adults. There have been no primary prevention studies among individuals with low HDL-C. Recent studies of treatments to raise HDL-C have been stopped due to harm. Existing recommendations to assess cardiovascular risk for able-bodied individuals suggest that all adults should have a complete lipid profile, including HDL and LDL cholesterol levels, as well as family history, smoking status, and gender. The treatment recommendations should be based on that comprehensive risk assessment. Future studies are needed to determine if SCI should be included as an independent risk factor.

With regard to interventions to prevent and treat diabetes, currently no large scale randomized trials have demonstrated that aggressive control of Type 2 diabetes reduces cardiovascular complications. A recent systematic review assessed the comparative effectiveness and safety of oral medications for Type 2 diabetes mellitus. The authors reported that there was no definitive evidence about the comparative effectiveness of oral diabetes agents on all-cause mortality, cardiovascular mortality or morbidity, peripheral arterial disease, neuropathy, retinopathy, or nephropathy.⁸² Two more recent meta-analyses of thiazolidinediones have been conducted. Among able-bodied patients with impaired glucose tolerance or Type 2 diabetes (n=14,291), rosiglitazone use for at least 12 months was associated with an increased risk of myocardial infarction and heart failure. There was no difference in increase risk in cardiovascular mortality.⁸³ A review of pioglitazone (n=16,390) showed a significantly lower risk of death myocardial infarction or stroke among patients with Type 2 diabetes and inadequately glycemic control. Serious heart failure was increased.⁸⁴ Unless future RCTs demonstrate evidence to the contrary, a reasonable policy would be to implement existing diabetes detection and management guidelines used for able-bodied adults.

Conclusions and Policy Implications

Available evidence regarding the prevalence, impact, and outcomes of carbohydrate and lipid disorders in adults with chronic SCI is weak. Evidence is limited by relatively few studies, small sample size, lack of appropriate control groups, failure to adjust for known confounding variables, and variation in reported outcomes. However, the existing evidence does not indicate that adults with SCI are at markedly greater risk for carbohydrate and lipid disorders or subsequent cardiovascular sequelae than able-bodied adults. Cardiovascular diseases are among the leading causes of death in aging patients with chronic SCI. Therefore, patients with SCI should be assessed and treated according to existing guidelines for able-bodied individuals to reduce cardiac morbidity and mortality in this population associated with carbohydrate and lipid disorders.

BMI to assess obesity and body composition is likely inaccurate and underestimates fat mass in adults with SCI. Available evidence does not support establishing different thresholds to define and treat abnormal traditional lipid and carbohydrate measures or to utilize other markers (e.g., insulin sensitivity or impaired glucose tolerance) for SCI individuals compared to able-bodied adults. Because evidence is weak, it is not possible to conclude that an increased risk of these disorders and their subsequent cardiovascular sequelae do not exist or that use of alternative measures of abnormality may not someday be found beneficial.

Individuals with SCI may have unique physiologic differences compared to able-bodied individuals. Therefore, caution is advised in attempting to extrapolate findings from studies conducted in able-bodied adults evaluating efficacy and harms of interventions to improve carbohydrate, lipid disorders and subsequent coronary vascular disease.

If clinical uncertainty regarding carbohydrate and lipid disorder risks in adults with SCI and determining the most appropriate interventions remain high priority areas, then future high quality research is needed. Until that time, a reasonable policy would be to use similar criteria to identify and treat carbohydrate and lipid disorders (outside of body composition assessment) in adults with SCI as currently recommended for able-bodied adults. The role of exercise in SCI individuals also represents a unique challenge and requires further exploration into the benefits, risks, and potential implications of broader based exercise programs. This systematic review did not assess the diagnosis and treatment of hypertension in SCI individuals or the other potential benefits of diagnosis and management of SCI individuals, such as improved wound healing. Additional clinical and research activities are needed to address these issues.

Future Research

A major gap in the evidence is the lack of high-quality prospective epidemiologic studies assessing the prevalence and impact of lipid and carbohydrate abnormalities and corresponding CVD complications in SCI individuals, especially compared to appropriately matched able-bodied controls. Future research could include a large prospective multicenter cohort study of adults with SCI. Risk assessment should be started at the time of injury and continued during long-term followup. Prevalence and incidence assessment needs to be objective rather than self reported. Inclusion of baseline and followup physiologic and serologic values (e.g., body composition measures, actual lipid and carbohydrate laboratory values) and standardized outcomes are made according to well-recognized diagnostic criteria of heart diseases. Expansion of existing cohort studies in the VA, a large non-VA cohort study, and future RCTs that aim to test whether more aggressive screening or treatment within SCI populations actually reduces disease prevalence, morbidity, and mortality could be initiated. Additional information on women is needed.

To a large extent, research within the VHA patient population has provided an important foundation to the current knowledge, particularly within the United States, regarding the prevalence of carbohydrate and lipid disorders and relevant considerations in persons with SCI. If there is continued concern that adults with chronic SCI have a different prevalence than adults without SCI, then future research would benefit from an expansion of the existing cohort studies in the VA, a large non-VA cohort study, and future RCTs that aim to test whether more aggressive screening or treatment within SCI populations actually reduces disease prevalence, morbidity, and mortality.

The VA administrative and clinical datasets and data from other large health care systems provide researchers with a wealth of information regarding the epidemiology of carbohydrate and lipid disorders with SCI patients. These datasets allow for rapid estimation of the magnitude of disease burden from carbohydrate and lipid disorders and can help to develop hypotheses about the role SCI may play in the development of disease. However, administrative datasets often suffer from selection bias in terms of the persons included and the measurements obtained. Therefore, such datasets need to be enriched with prospective cohort style data collection. This can be accomplished by designing a registry of adults with SCI and collecting a baseline battery of key measurements on all persons. This comprehensive set of baseline measurements can then be combined with standard outcomes data collected in these healthcare settings to provide a detailed description of the natural history and etiology of various diseases.

While in many ways the VHA provides an ideal U.S. setting to obtain important information on persons with SCI, it must be accompanied by complementary research on representative SCI persons from health systems outside of the VA. This is particularly important, since women are currently underrepresented in VHA datasets, and veterans have often been found to have more competing comorbidities than nonveteran populations,³⁷ which can make generalizations difficult without complementary non-VA data. Additionally, current reports indicate that approximately 90 percent of SCI subjects were men. It is not known if this is representative of the U.S. SCI population or only those reporting this information.

RCTs will be needed to further extend the information obtained from future prospective observational studies. Regardless of whether or not future trials indicate that individuals with SCI are at an increased risk of carbohydrate and/or lipid disorders, it is clear that, like the general population, a significant number of SCI individuals do have carbohydrate and lipid disorders and techniques for treating these disorders may need to be modified to meet the specific needs of those with SCI to ensure that they are being most appropriately treated. RCTs will therefore be needed to compare the effectiveness of any such modifications in treatment technique and intensity, including the same pharmacological agents recommended for the general population and specific for SCI patients' treatment options that would target impaired glucose tolerance and insulin sensitivity.

If prospective cohort studies identify an increased risk in adults with SCI, RCTs will be needed to further extend the information. Techniques for identifying and treating these carbohydrate and lipid disorders and CVDs may need to be modified to meet the specific needs of those with SCI. In addition, continued clinical and research questions pertaining to obesity in individuals with SCI remain to be answered. These include identification of the most appropriate measurements and definition of obesity for those with SCI, and whether current BMI cutpoints for the general population can be validly extrapolated to those with SCI.

RCTs evaluating the potential effectiveness and harms of interventions to alter CVD risk factors and reduce CVD incidence, morbidity, and mortality are needed. The level of injury, neurological impairment, and other known or potential confounders including smoking status, hypertension, family history, race, age, diabetes, infections including, socioeconomic status, and quality of health care should be analyzed as possible effect modifiers of the association between well-known risk factors and cardiovascular morbidity and mortality.

Given the variation in design across studies, the lack of consistent findings in this review was not surprising. While improved studies will be challenging due to limited resources, complicated study questions, a relatively small subject population, and invasive intervention, policy recommendations cannot be generated until higher quality evidence is available. Consistent, higher quality research on exercise and metabolic and cardiovascular health in SCI patients is needed. Studies examining efficacy as well as effectiveness of exercise interventions are needed.

Continued research should be conducted to gain a better idea of the important barriers to exercise experienced by individuals with SCI and to develop novel methods to overcome these barriers. Preliminary studies may also assess which patients are most in need of intervention, the best types of exercise programs and equipment, and how to modify them based on characteristics of the injury. For example, telemedicine approaches to home-based exercise programs could potentially help overcome barriers to accessing traditional facilities or equipment. Whether qualitative or quantitative, this preliminary work would not only inform the development of exercise programs but also the research used to evaluate efficacy and effectiveness.

Accomplishing the level of research needed will likely require a collaboration of researchers across sites. Convening a consortium of experts is a practical first step. Cooperative research groups could determine the most appropriate and pragmatic study parameters, including intervention type and outcome measures, and could propose the most feasible quality studies. RCTs and prospective epidemiologic studies for individuals with SCI could both contribute enhanced knowledge to the current evidence base. While such studies are resource intensive, these accomplishments could perhaps be better achieved through the pooling of resources, either by funding agencies, or by researchers through multiple site collaborations. The VA medical system, the SCI model systems sites, or the National SCI Statistical Center at the University of Alabama Birmingham may be poised to lead such multi-site collaboration and studies.

Short-term, intermediate outcomes of exercise, as were typically reported in the current studies, may not be ideal or definitive measurements for this type of research. Studies ideally would focus on long-term clinically relevant outcomes such as prevention of diabetes mellitus, coronary heart disease, and mortality.

An RCT would provide the best evidence for or against the use of exercise to prevent or control carbohydrate and lipid disorders among those with SCI, though conducting adequately sized studies would be difficult and would require cooperative group participation. Studies on exercise and metabolic and cardiovascular outcomes in the SCI population will be more definitive if important demographic and injury parameters are considered. Key variables that should be included in future studies are patient age, race, and gender; comorbid conditions; baseline lipid and carbohydrate related measures; duration, level, and completeness of SCI; functional status; baseline physical activity; exercise program type, frequency, intensity, and duration; and life satisfaction and other important psychosocial variables. RCTs and prospective epidemiologic studies with adequate numbers of participants should provide the least confounded evidence for or against exercise programs if the intervention and control groups are appropriately balanced and/or stratified by these variables.

Further research will be needed to translate any findings of exercise efficacy into effective community-based interventions. Even if efficacy is promising, it will remain to be seen if these interventions are feasible in a community setting, and if the interventions, as well as health outcomes, are sustainable over time. Further evidence on how best to motivate individuals to sustain exercise, while preventing and identifying potential harms, will be needed.

RCTs evaluating the potential effectiveness and harms of pharmacologic and dietary interventions to alter CVD risk factors (diabetes, lipid abnormalities, and/or obesity) and reduce CVD incidence, morbidity, and mortality may be needed if there is continued concern that results may differ in SCI populations compared to able-bodied adults.

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59.

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61.

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65.

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67.

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68.

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69.

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70.

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71.

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72.

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73.

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74.

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75.

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76.

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77.

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78.

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79.

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80.

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81.

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82.

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83.

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84.

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85.

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86.

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87.

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88.

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89.

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90.

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91.

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92.

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93.

Chao CY, Cheing GL. The effects of lower-extremity functional electric stimulation on the orthostatic responses of people with tetraplegia. Arch Phys Med Rehabil. 2005 Jul;86(7): 1427–33. Not eligible target population. [PubMed]

94.

Chen CJ, Fang W, Chen CM, Wan YL. Spontaneous spinal epidural haematomas with repeated remission and relapse. Neuroradiology. 1997 Oct;39(10): 737–40. Case report. [PubMed]

95.

Chen CJ, Hsu WC. Imaging findings of spontaneous spinal epidural hematoma. J Formos Med Assoc. 1997 Apr;96(4): 283–7. Not eligible target population. [PubMed]

96.

Chen JT, Chen CC, Kao KP, Wu ZA, Liao KK. Conditioning effect on the long latency potentials in the lower limb to transcranial magnetic stimulation. Acta Neurol Scand. 1998 Dec;98(6): 412–21. Not eligible outcomes. [PubMed]

97.

Chen SC, Lai CH, Chan WP, Huang MH, Tsai HW, Chen JJ. Increases in bone mineral density after functional electrical stimulation cycling exercises in spinal cord injured patients. Disabil Rehabil. 2005; 27(22): 1337–41. No relevant outcomes. [PubMed]

98.

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99.

Chen Y, Henson S, Jackson AB, Richards JS. Obesity intervention in persons with spinal cord injury. Spinal Cord. 2006; 44(2): 82–91. Less than 100 patients in study. [PubMed]

100.

Chilibeck PD, Jeon J, Weiss C, Bell G, Burnham R. Histochemical changes in muscle of individuals with spinal cord injury following functional electrical stimulated exercise training. Spinal Cord. 1999; 37(4): 264–8. No relevant outcomes. [PubMed]

101.

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102.

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103.

Chuang TY, Robinson LR, Nelson MR, Moss F, Chiou-Tan FY. Effect of isometric contraction on threshold somatosensory evoked potentials. Am J Phys Med Rehabil. 1999; 78(1): 2–6. Not adult chronic SCI patients. [PubMed]

104.

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105.

Claydon VE, Elliott SL, Sheel AW, Krassioukov A. Cardiovascular responses to vibrostimulation for sperm retrieval in men with spinal cord injury. J Spinal Cord Med. 2006; 29(3): 207–16. Case-series. [PubMed] [Free Full text in PMC]

106.

Claydon VE, Hol AT, Eng JJ, Krassioukov AV. Cardiovascular responses and postexercise hypotension after arm cycling exercise in subjects with spinal cord injury. Arch Phys Med Rehabil. 2006; 87(8): 1106–14. No relevant outcomes. [PubMed]

107.

Claydon VE, Krassioukov AV. Orthostatic hypotension and autonomic pathways after spinal cord injury. J Neurotrauma. 2006 Dec;23(12): 1713–25. Not eligible outcomes. [PubMed]

108.

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109.

Cohen AT. Venous thromboembolic disease management of the nonsurgical moderate- and high-risk patient. Seminars in Hematology. 2000; 37(3 Suppl 5): 19–22. Not adult spinal cord injury patients. [PubMed]

110.

Colachis SC 3rd, Clinchot DM. The association between deep venous thrombosis and heterotopic ossification in patients with acute traumatic spinal cord injury. Paraplegia. 1993 Aug;31(8): 507–12. Not eligible target population. [PubMed]

111.

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112.

Collins HL, Rodenbaugh DW, DiCarlo SE. Spinal cord injury alters cardiac electrophysiology and increases the susceptibility to ventricular arrhythmias. Progress in Brain Research. 2006; 152: 275–88. No relevant data. [PubMed]

113.

Conrad MF, Crawford RS, Davison JK, Cambria RP. Thoracoabdominal aneurysm repair: a 20-year perspective. Ann Thorac Surg. 2007 Feb;83(2): S856–61. discussion S90–2. Not eligible target population. [PubMed]

114.

Cooper RA, Baldini FD, Boninger ML, Cooper R. Physiological responses to two wheelchair-racing exercise protocols. Neurorehabil Neural Repair. 2001; 15(3): 191–5. No relevant outcomes. [PubMed]

115.

Corfman TA, Cooper RA, Boninger ML, Koontz AM, Fitzgerald SG. Range of motion and stroke frequency differences between manual wheelchair propulsion and pushrim-activated power-assisted wheelchair propulsion. J Spinal Cord Med. 2003; 26(2): 135–40. No relevant outcomes. [PubMed]

116.

Cosman BC, Eastman DA, Perkash I, Stone JM. Hemorrhoidal bleeding in chronic spinal cord injury: results of multiple banding. Int J Colorectal Dis. 1994; 9(4): 174–6. Not eligible outcomes. [PubMed]

117.

Cosman BC, Vu TT. Lidocaine anal block limits autonomic dysreflexia during anorectal procedures in spinal cord injury: a randomized, double-blind, placebo-controlled trial. Dis Colon Rectum. 2005 Aug;48(8): 1556–61. Not eligible outcomes. [PubMed]

118.

Courtois F, Geoffrion R, Landry E, Belanger M. H-reflex and physiologic measures of ejaculation in men with spinal cord injury. Arch Phys Med Rehabil. 2004 Jun;85(6): 910–8. Case-series. [PubMed]

119.

Croxford JL. Therapeutic potential of cannabinoids in CNS disease. [Review] [219 refs]. CNS Drugs. 2003; 17(3): 179–202. Not adult spinal cord injury patients. [PubMed]

120.

Cruse JM, Lewis RE Jr, Bishop GR, Kliesch WF, Gaitan E, Britt R. Decreased immune reactivity and neuroendocrine alterations related to chronic stress in spinal cord injury and stroke patients. Pathobiology. 1993; 61(34): 183–92. Not eligible target population. [PubMed]

121.

Curtis KA, McClanahan S, Hall KM, Dillon D, Brown KF. Health, vocational, and functional status in spinal cord injured athletes and nonathletes. Archives of Physical Medicine & Rehabilitation. 1986; 67(12): 862–5. Less than 100 patients in study. [PubMed]

122.

Curtis KA, Tyner TM, Zachary L, Lentell G, Brink D, Didyk T. et al. Effect of a standard exercise protocol on shoulder pain in long-term wheelchair users. Spinal Cord. 1999; 37(6): 421–9. No relevant outcomes. [PubMed]

123.

Dallmeijer AJ, Hopman MT, van As HH, van der Woude LH. Physical capacity and physical strain in persons with tetraplegia; the role of sport activity. Spinal Cord. 1996; 34(12): 729–35. No relevant outcomes. [PubMed]

124.

Dallmeijer AJ, van der Woude LH, Hollander AP, van As HH. Physical performance during rehabilitation in persons with spinal cord injuries. Med Sci Sports Exerc. 1999; 31(9): 1330–5. No relevant outcomes. [PubMed]

125.

Dallmeijer AJ, van der Woude LH, Hollander PA, Angenot EL. Physical performance in persons with spinal cord injuries after discharge from rehabilitation. Med Sci Sports Exerc. 1999; 31(8): 1111–7. No relevant outcomes. [PubMed]

126.

Dallmeijer AJ, Zentgraaff ID, Zijp NI, van der Woude LH. Submaximal physical strain and peak performance in handcycling versus handrim wheelchair propulsion. Spinal Cord. 2004; 42(2): 91–8. No relevant outcomes. [PubMed]

127.

Daniel WW, Coogler CE. Statistical applications in physical medicine. part II. American Journal of Physical Medicine. 1975; 54(1): 25–47. No relevant data. [PubMed]

128.

Davis R, Patrick J, Barriskill A. Development of functional electrical stimulators utilizing cochlear implant technology. Med Eng Phys. 2001; 23(1): 61–8. No exercise program or physical activity. [PubMed]

129.

Davoodi R, Andrews BJ, Wheeler GD, Lederer R. Development of an indoor rowing machine with manual FES controller for total body exercise in paraplegia. IEEE Trans Neural Syst Rehabil Eng. 2002; 10(3): 197–203. No relevant outcomes. [PubMed]

130.

de Carvalho DC, Cliquet A Jr. Energy expenditure during rest and treadmill gait training in quadriplegic subjects. Spinal Cord. 2005; 43(11): 658–63. No relevant outcomes. [PubMed]

131.

de Groot PC, Poelkens F, Kooijman M, Hopman MT. Preserved flow-mediated dilation in the inactive legs of spinal cord-injured individuals. Am J Physiol Heart Circ Physiol. 2004 Jul;287(1): H374–80. Not eligible outcomes. [PubMed]

132.

de Groot S, Dallmeijer AJ, Kilkens OJ, van Asbeck FW, Nene AV, Angenot EL. et al. Course of gross mechanical efficiency in handrim wheelchair propulsion during rehabilitation of people with spinal cord injury: a prospective cohort study. Arch Phys Med Rehabil. 2005; 86(7): 1452–60. No relevant outcomes. [PubMed]

133.

De Mello MT, Esteves AM, Tufik S. Comparison between dopaminergic agents and physical exercise as treatment for periodic limb movements in patients with spinal cord injury. Spinal Cord. 2004; 42(4): 218–21. No relevant outcomes. [PubMed]

134.

de Mello MT, Lauro FA, Silva AC, Tufik S. Incidence of periodic leg movements and of the restless legs syndrome during sleep following acute physical activity in spinal cord injury subjects. Spinal Cord. 1996; 34(5): 294–6. No relevant outcomes. [PubMed]

135.

De Mello MT, Silva AC, Esteves AM, Tufik S. Reduction of periodic leg movement in individuals with paraplegia following aerobic physical exercise. Spinal Cord. 2002; 40(12): 646–9. No relevant outcomes. [PubMed]

136.

de Seze J, Delalande S, Fauchais AL, Hachulla E, Stojkovic T, Ferriby D. et al. Myelopathies secondary to Sjogren's syndrome: treatment with monthly intravenous cyclophosphamide associated with corticosteroids. J Rheumatol. 2006; 33(4): 709–11. Not adult chronic SCI patients. [PubMed]

137.

Dela F, Stallknecht B, Biering-Sorensen F. An intact central nervous system is not necessary for insulin-mediated increases in leg blood flow in humans. Pflugers Archiv - European Journal of Physiology. 2000; 441(23): 241–50. Less than 100 patients in study. [PubMed]

138.

Demirel S, Demirel G, Tukek T, Erk O, Yilmaz H. Risk factors for coronary heart disease in patients with spinal cord injury in Turkey. Spinal Cord. 2001 Mar;39(3): 134–8. Not eligible outcomes. [PubMed]

139.

DeVivo MJ, Rutt RD, Black KJ, Go BK, Stover SL. Trends in spinal cord injury demographics and treatment outcomes between 1973 and 1986. Arch Phys Med Rehabil. 1992 May;73(5): 424–30. Nto eligible outcomes. [PubMed]

140.

DeVivo MJ, Shewchuk RM, Stover SL, Black KJ, Go BK. A cross-sectional study of the relationship between age and current health status for persons with spinal cord injuries. Paraplegia. 1992 Dec;30(12): 820–7. Not eligible outcomes. [PubMed]

141.

DeVivo MJ, Stover SL, Black KJ. Prognostic factors for 12-year survival after spinal cord injury. Arch Phys Med Rehabil. 1992 Feb;73(2): 156–62. Not eligible outcomes. [PubMed]

142.

Diego MA, Field T, Hernandez-Reif M, Hart S, Brucker B, Field T. et al. Spinal cord patients benefit from massage therapy. Int J Neurosci. 2002; 112(2): 133–42. No relevant outcomes. [PubMed]

143.

Dietz V, Colombo G, Muller R. Single joint perturbation during gait: neuronal control of movement trajectory. Exp Brain Res. 2004; 158(3): 308–16. Not adult chronic SCI patients. [PubMed]

144.

Dihlmann SW, Mayer HM. Lumbar epidural lipomatosis. Zeitschrift fur Rheumatologie. 1995; 54(6): 417–23. Not english language. [PubMed]

145.

Dimond B. Mental capacity requirements and a patient's right to die. Br J Nurs. 2006 Nov 9–22;15(20): 1130–1. Legal Cases. [PubMed]

146.

Dishman RK, Berthoud HR, Booth FW, Cotman CW, Edgerton VR, Fleshner MR. et al. Neurobiology of exercise. Obesity. 2006; 14(3): 345–56. Not adult spinal cord injury patients. [PubMed]

147.

Ditor DS, Kamath MV, MacDonald MJ, Bugaresti J, McCartney N, Hicks AL. Effects of body weight-supported treadmill training on heart rate variability and blood pressure variability in individuals with spinal cord injury. J Appl Physiol. 2005; 98(4): 1519–25. No relevant outcomes. [PubMed]

148.

Ditor DS, Latimer AE, Ginis KA, Arbour KP, McCartney N, Hicks AL. Maintenance of exercise participation in individuals with spinal cord injury: effects on quality of life, stress and pain. Spinal Cord. 2003; 41(8): 446–50. No relevant outcomes. [PubMed]

149.

Ditor DS, Macdonald MJ, Kamath MV, Bugaresti J, Adams M, McCartney N. et al. The effects of body-weight supported treadmill training on cardiovascular regulation in individuals with motor-complete SCI. Spinal Cord. 2005; 43(11): 664–73. No relevant outcomes. [PubMed]

150.

Do Ouro S, Esteban S, Sibirceva U, Whittenberg B, Portenoy R, Cruciani RA. Safety and tolerability of high doses of intrathecal fentanyl for the treatment of chronic pain. Journal of Opioid Management. 2006; 2(6): 365–8. Less than 100 patients in study. [PubMed]

151.

Dobkin B, Apple D, Barbeau H, Basso M, Behrman A, Deforge D. et al. Weight-supported treadmill vs over-ground training for walking after acute incomplete SCI. Neurology. 2006; 66(4): 484–93. No relevant outcomes. [PubMed]

152.

Doita M, Sakai H, Harada T, Nishida K, Miyamoto H, Kaneko T. et al. Evaluation of impairment of hand function in patients with cervical myelopathy. J Spinal Disord Tech. 2006; 19(4): 276–80. Not adult chronic SCI patients. [PubMed]

153.

Donato V, Bonfili P, Bulzonetti N, Santarelli M, Osti MF, Tombolini V. et al. Radiation therapy for oncological emergencies. Anticancer Res. 2001 May–Jun;21(3C): 2219–24. Not eligible target population. [PubMed]

154.

Douglas H, Swanson C, Gee T, Bellamy N. Outcome measurement in Australian rehabilitation environments. J Rehabil Med. 2005 Sep;37(5): 325–9. Not eligible target population. [PubMed]

155.

Dubras P. Predictors of physical activity among individuals with spinal cord injuries. Ottawa: National Library of Canada = Bibliothèque nationale du Canada; 2002.

156.

Ducker TB. C6 cervical radiculopathy and assymptomatic large C3/4 central disc herniation. Journal of Spinal Disorders. 1994; 7(4): 361–2. discussion 2–4. Not adult spinal cord injury patients. [PubMed]

157.

Duckworth WC, Jallepalli P, Solomon SS. Glucose intolerance in spinal cord injury. Archives of Physical Medicine & Rehabilitation. 1983; 64(3): 107–10. Less than 100 patients in study. [PubMed]

158.

Duckworth WC, Solomon SS, Jallepalli P, Heckemeyer C, Finnern J, Powers A. Glucose intolerance due to insulin resistance in patients with spinal cord injuries. Diabetes. 1980; 29(11): 906–10. Less than 100 patients in study. [PubMed]

159.

Dudgeon BJ, Tyler EJ, Rhodes LA, Jensen MP. Managing usual and unexpected pain with physical disability: a qualitative analysis. Am J Occup Ther. 2006; 60(1): 92–103. No exercise program or physical activity. [PubMed]

160.

Dudra J, Shiiya N, Matsui Y, Sakuma M, Ishii K, Asada M. et al. Operative results of thoracoabdominal repair for chronic type B aortic dissection. J Cardiovasc Surg (Torino). 1997 Apr;38(2): 147–51. Not eligible target population.

161.

Dujardin L, Marcelli C, Herisson C, Simon L. Epidural lipomatosis: complication of long-term corticotherapy. Apropos of 2 cases. Revue de Medecine Interne. 1996; 17(7): 563–7. Not english language. [PubMed]

162.

Edwards CC 2nd, Heller JG, Silcox DH 3rd. T-Saw laminoplasty for the management of cervical spondylotic myelopathy: clinical and radiographic outcome. Spine. 2000; 25(14): 1788–94. Not adult chronic SCI patients. [PubMed]

163.

Effing TW, van Meeteren NL, van Asbeck FW, Prevo AJ. Body weight-supported treadmill training in chronic incomplete spinal cord injury: a pilot study evaluating functional health status and quality of life. Spinal Cord. 2006; 44(5): 287–96. No relevant outcomes. [PubMed]

164.

Elder CP, Apple DF, Bickel CS, Meyer RA, Dudley GA. Intramuscular fat and glucose tolerance after spinal cord injury—a cross-sectional study. Spinal Cord. 2004; 42(12): 711–6. Less than 100 patients in study. [PubMed]

165.

Elokda AS, Nielsen DH, Shields RK. Effect of functional neuromuscular stimulation on postural related orthostatic stress in individuals with acute spinal cord injury. J Rehabil Res Dev. 2000 Sep–Oct;37(5): 535–42. Not eligible target population. [PubMed]

166.

El-Sayed MS, Younesian A. Lipid profiles are influenced by arm cranking exercise and training in individuals with spinal cord injury. Spinal Cord. 2005; 43(5): 299–305. Less than 100 patients in study. [PubMed]

167.

El-Sayed MS, Younesian A, Rahman K, Ismail FM, El-Sayed A. The effects of arm cranking exercise and training on platelet aggregation in male spinal cord individuals. Thromb Res. 2004; 113(2): 129–36. No relevant outcomes. [PubMed]

168.

El-Zaatari MM, Hulten K, Fares Y, Baassiri A, Balkis M, Almashhrawi A. et al. Successful treatment of Candida albicans osteomyelitis of the spine with fluconazole and surgical debridement: case report. Journal of Chemotherapy. 2002; 14(6): 627–30. Not adult spinal cord injury patients. [PubMed]

169.

Epstein N. Thoracic ossification of the posterior longitudinal ligament, ossification of the yellow ligament from T9–T12 with superimposed acute T10/T11 disc herniation: controversies in surgical management. Journal of Spinal Disorders. 1996; 9(5): 446–7. discussion 7–50. Not adult spinal cord injury patients. [PubMed]

170.

Epstein SK, Singh N. Respiratory acidosis. Respiratory Care. 2001; 46(4): 366–83. Not adult spinal cord injury patients. [PubMed]

171.

Eser PC, Donaldson Nde N, Knecht H, Stussi E. Influence of different stimulation frequencies on power output and fatigue during FES-cycling in recently injured SCI people. IEEE Trans Neural Syst Rehabil Eng. 2003; 11(3): 236–40. No relevant outcomes. [PubMed]

172.

Esmail Z, Shalansky KF, Sunderji R, Anton H, Chambers K, Fish W. Evaluation of captopril for the management of hypertension in autonomic dysreflexia: a pilot study. Arch Phys Med Rehabil. 2002 May;83(5): 604–8. Not eligible outcomes. [PubMed]

173.

Excoffon SG, Wallace H. Chiropractic and rehabilitative management of a patient with progressive lumbar disk injury, spondylolisthesis, and spondyloptosis. J Manipulative Physiol Ther. 2006; 29(1): 66–71. Not adult chronic SCI patients. [PubMed]

174.

Faghri PD, Yount J. Electrically induced and voluntary activation of physiologic muscle pump: a comparison between spinal cord-injured and able-bodied individuals. Clin Rehabil. 2002 Dec;16(8): 878–85. Not eligible outcomes. [PubMed]

175.

Faghri PD, Yount JP, Pesce WJ, Seetharama S, Votto JJ. Circulatory hypokinesis and functional electric stimulation during standing in persons with spinal cord injury. Arch Phys Med Rehabil. 2001 Nov;82(11): 1587–95. Not eligible outcomes. [PubMed]

176.

Faist M, Ertel M, Berger W, Dietz V. Impaired modulation of quadriceps tendon jerk reflex during spastic gait: differences between spinal and cerebral lesions. Brain. 1999 Mar;122( Pt 3): 567–79. Not eligible outcomes. [PubMed]

177.

Fedoroff JP, Lipsey JR, Starkstein SE, Forrester A, Price TR, Robinson RG. Phenomenological comparisons of major depression following stroke, myocardial infarction or spinal cord lesions. J Affect Disord. 1991 May–Jun;22(12): 83–9. Not eligible target population. [PubMed]

178.

Felici F, Bernardi M, Radio A, Marchettoni P, Castellano V, Macaluso A. Rehabilitation of walking for paraplegic patients by means of a treadmill. Spinal Cord. 1997; 35(6): 383–5. No relevant outcomes. [PubMed]

179.

Fiedler RC, Granger CV. Uniform data system for medical rehabilitation: report of first admissions for 1996. Am J Phys Med Rehabil. 1998 Jan–Feb;77(1): 69–75. Not eliglble target population. [PubMed]

180.

Field-Fote EC. Combined use of body weight support, functional electric stimulation, and treadmill training to improve walking ability in individuals with chronic incomplete spinal cord injury. Arch Phys Med Rehabil. 2001; 82(6): 818–24. No relevant outcomes. [PubMed]

181.

Field-Fote EC, Tepavac D. Improved intralimb coordination in people with incomplete spinal cord injury following training with body weight support and electrical stimulation. Phys Ther. 2002; 82(7): 707–15. No relevant outcomes. [PubMed]

182.

Fitzgerald SG, Cooper RA, Thorman T, Cooper R, Guo S, Boninger ML. The GAME(Cycle) exercise system: comparison with standard ergometry. J Spinal Cord Med. 2004; 27(5): 453–9. No relevant outcomes. [PubMed]

183.

Fletcher DJ, Taddonio RF, Byrne DW, Wexler LM, Cayten CG, Nealon SM. et al. Incidence of acute care complications in vertebral column fracture patients with and without spinal cord injury. Spine. 1995 May 15;20(10): 1136–46. Not eligible target population. [PubMed]

184.

Flores J, Kunihara T, Shiiya N, Yoshimoto K, Matsuzaki K, Yasuda K. Extensive deployment of the stented elephant trunk is associated with an increased risk of spinal cord injury. J Thorac Cardiovasc Surg. 2006 Feb;131(2): 336–42. Not eligible target population. [PubMed]

185.

Flores J, Shiiya N, Kunihara T, Matsuzaki K, Yasuda K. Risk of spinal cord injury after operations of recurrent aneurysms of the descending aorta. Ann Thorac Surg. 2005 Apr;79(4): 1245–9. discussion 9. Not eligible target population. [PubMed]

186.

Fogel GR, Cunningham PY 3rd, Esses SI. Spinal epidural lipomatosis: case reports, literature review and meta-analysis. Spine Journal: Official Journal of the North American Spine Society. 2005; 5(2): 202–11. Not adult spinal cord injury patients.

187.

Fornusek C, Davis GM. Maximizing muscle force via low-cadence functional electrical stimulation cycling. J Rehabil Med. 2004; 36(5): 232–7. No relevant outcomes. [PubMed]

188.

Franco JC, Perell KL, Gregor RJ, Scremin AM. Knee kinetics during functional electrical stimulation induced cycling in subjects with spinal cord injury: a preliminary study. J Rehabil Res Dev. 1999; 36(3): 207–16. No relevant outcomes. [PubMed]

189.

Franga DL, Hawkins ML, Medeiros RS, Adewumi D. Recurrent asystole resulting from high cervical spinal cord injuries. Am Surg. 2006 Jun;72(6): 525–9. Case-series. [PubMed]

190.

Frank E. Endoscopic suction decompression of idiopathic epidural lipomatosis. Surgical Neurology. 1998; 50(4): 333–5. discussion 5. Not adult spinal cord injury patients. [PubMed]

191.

Freedman G, Entero H, Brem H. Practical treatment of pain in patients with chronic wounds: pathogenesis-guided management. American Journal of Surgery. 2004; 188(1A Suppl): 31–5. Not adult spinal cord injury patients. [PubMed]

192.

Frey GC, McCubbin JA, Dunn JM, Mazzeo RS. Plasma catecholamine and lactate relationship during graded exercise in men with spinal cord injury. Med Sci Sports Exerc. 1997; 29(4): 451–6. No relevant outcomes. [PubMed]

193.

Friedman D, Flanders A, Thomas C, Millar W. Vertebral artery injury after acute cervical spine trauma: rate of occurrence as detected by MR angiography and assessment of clinical consequences. AJR Am J Roentgenol. 1995 Feb;164(2): 443–7. discussion 8–9. Not eligible target population. [PubMed]

194.

Frisbie JH. Microvascular instability in tetraplegic patients: preliminary observations. Spinal Cord. 2004 May;42(5): 290–3. Not eligible outcomes. [PubMed]

195.

Frisbie JH. Fibrinogen metabolism in patients with spinal cord injury. J Spinal Cord Med. 2006; 29(5): 507–10. Not eligible outcomes. [PubMed] [Free Full text in PMC]

196.

Frisbie JH, Sharma GV. Circadian rhythm of pulmonary embolism in patients with acute spinal cord injury. Am J Cardiol. 1992 Sep 15;70(7): 827–8. Not eligible target population. [PubMed]

197.

Frisbie JH, Sharma GV. Pulmonary embolism manifesting as acute disturbances of behavior in patients with spinal cord injury. Paraplegia. 1994 Aug;32(8): 570–2. Not eligible target population. [PubMed]

198.

Fujii Y, Mammen EF, Farag A, Muz J, Salciccioli GG, Weingarden ST. Thrombosis in spinal cord injury. Thromb Res. 1992 Dec;68(45): 357–68. Case-series. [PubMed]

199.

Fukui MB, Swarnkar AS, Williams RL. Acute spontaneous spinal epidural hematomas. AJNR Am J Neuroradiol. 1999 Aug;20(7): 1365–72. Not eligible target population. [PubMed]

200.

Fukuoka Y, Endo M, Kagawa H, Itoh M, Nakanishi R. Kinetics and steady-state of VO2 responses to arm exercise in trained spinal cord injury humans. Spinal Cord. 2002; 40(12): 631–8. No relevant outcomes. [PubMed]

201.

Fuller DA, Mark A, Keenan MA. Excision of heterotopic ossification from the knee: a functional outcome study. Clin Orthop Relat Res. 2005 Sep;438: 197–203. Case report. [PubMed]

202.

Galea M, Tumminia J, Garback LM. Telerehabilitation in spinal cord injury persons: a novel approach. Telemedicine Journal & E-Health. 2006; 12(2): 160–2. No relevant data. [PubMed]

203.

Galla JD, Ergin MA, Lansman SL, McCullough JN, Nguyen KH, Spielvogel D. et al. Use of somatosensory evoked potentials for thoracic and thoracoabdominal aortic resections. Ann Thorac Surg. 1999 Jun;67(6): 1947–52. discussion 53–8. Not eligible target population. [PubMed]

204.

Gandevia SC, Petersen N, Butler JE, Taylor JL. Impaired response of human motoneurones to corticospinal stimulation after voluntary exercise. J Physiol. 1999; 521(Pt 3): 749–59. Not adult chronic SCI patients. [PubMed] [Free Full text in PMC]

205.

Gao CG, Ge JP, Chen LS. The situation of sildenafil in the treatment of men with erectile dysfunction. Zhong Hua Nan Ke Xue. 2002; 8(4): 302–4. Not english language.

206.

Gardner MB, Holden MK, Leikauskas JM, Richard RL. Partial body weight support with treadmill locomotion to improve gait after incomplete spinal cord injury: a single-subject experimental design. Phys Ther. 1998; 78(4): 361–74. No relevant outcomes. [PubMed]

207.

Garland DE, Adkins RH, Stewart CA, Ashford R, Vigil D. Regional osteoporosis in women who have a complete spinal cord injury. J Bone Joint Surg Am. 2001 Aug;83-A(8): 1195–200. Not eligible outcomes. [PubMed]

208.

Gass EM, Gass GC. Thermoregulatory responses to repeated warm water immersion in subjects who are paraplegic. Spinal Cord. 2001; 39(3): 149–55. No relevant outcomes. [PubMed]

209.

Gass EM, Gass GC, Pitetti K. Thermoregulatory responses to exercise and warm water immersion in physically trained men with tetraplegia. Spinal Cord. 2002; 40(9): 474–80. No relevant outcomes. [PubMed]

210.

Gates PE, Campbell IG, George KP. Absence of training-specific cardiac adaptation in paraplegic athletes. Med Sci Sports Exerc. 2002; 34(11): 1699–704. No relevant outcomes. [PubMed]

211.

Gazzani F, Bernardi M, Macaluso A, Coratella D, Ditunno JF Jr, Castellano V. et al. Ambulation training of neurological patients on the treadmill with a new Walking Assistance and Rehabilitation Device (WARD). Spinal Cord. 1999; 37(5): 336–44. No relevant outcomes. [PubMed]

212.

Geist RA. Onset of chronic illness in children and adolescents: psychotherapeutic and consultative intervention. American Journal of Orthopsychiatry. 1979; 49(1): 4–23. Not adult spinal cord injury patients. [PubMed]

213.

Gerrits HL, de Haan A, Sargeant AJ, Dallmeijer A, Hopman MT. Altered contractile properties of the quadriceps muscle in people with spinal cord injury following functional electrical stimulated cycle training. Spinal Cord. 2000; 38(4): 214–23. No relevant outcomes. [PubMed]

214.

Gerrits HL, de Haan A, Sargeant AJ, van Langen H, Hopman MT. Peripheral vascular changes after electrically stimulated cycle training in people with spinal cord injury. Arch Phys Med Rehabil. 2001; 82(6): 832–9. No relevant outcomes. [PubMed]

215.

Gerrits HL, Hopman MT, Offringa C, Engelen BG, Sargeant AJ, Jones DA. et al. Variability in fibre properties in paralysed human quadriceps muscles and effects of training. Pflugers Arch. 2003; 445(6): 734–40. No relevant outcomes. [PubMed]

216.

Gerrits HL, Hopman MT, Sargeant AJ, Jones DA, De Haan A. Effects of training on contractile properties of paralyzed quadriceps muscle. Muscle Nerve. 2002; 25(4): 559–67. No relevant outcomes. [PubMed]

217.

Gfohler M, Lugner P. Dynamic simulation of FES-cycling: influence of individual parameters. IEEE Trans Neural Syst Rehabil Eng. 2004; 12(4): 398–405. No relevant outcomes. [PubMed]

218.

Giangregorio LM, Hicks AL, Webber CE, Phillips SM, Craven BC, Bugaresti JM. et al. Body weight supported treadmill training in acute spinal cord injury: impact on muscle and bone. Spinal Cord. 2005; 43(11): 649–57. No relevant outcomes. [PubMed]

219.

Giangregorio LM, Webber CE, Phillips SM, Hicks AL, Craven BC, Bugaresti JM. et al. Can body weight supported treadmill training increase bone mass and reverse muscle atrophy in individuals with chronic incomplete spinal cord injury? Appl Physiol Nutr Metab. 2006; 31(3): 283–91. No relevant outcomes. [PubMed]

220.

Gibberd FB. The neurogenic bladder. Clinics in Obstetrics & Gynaecology. 1981; 8(1): 149–60. Not adult spinal cord injury patients. [PubMed]

221.

Ginis KA, Latimer AE, Hicks AL, Craven BC. Development and evaluation of an activity measure for people with spinal cord injury. Med Sci Sports Exerc. 2005; 37(7): 1099–111. No relevant outcomes. [PubMed]

222.

Godin LM. Physical self-perceptions and physical activity participation of adult males with acquired spinal cord injuries [Dissertation/Thesis]; 2002.

223.

Golden MA, Donaldson MC, Whittemore AD, Mannick JA. Evolving experience with thoracoabdominal aortic aneurysm repair at a single institution. J Vasc Surg. 1991 Jun;13(6): 792–6. discussion 6–7. Not eligible target population. [PubMed]

224.

Goldstein I, Kim E, Steers WD, Pryor JL, Wilde DW, Natanegara F. et al. Efficacy and safety of tadalafil in men with erectile dysfunction with a high prevalence of comorbid conditions: results from MOMENTUS: multiple observations in men with erectile dysfunction in National Tadalafil Study in the US. Journal of Sexual Medicine. 2007; 4(1): 166–75. No relevant data. [PubMed]

225.

Gonzalez F, Chang JY, Banovac K, Messina D, Martinez-Arizala A, Kelley RE. Autoregulation of cerebral blood flow in patients with orthostatic hypotension after spinal cord injury. Paraplegia. 1991 Jan;29(1): 1–7. Not eligible outcomes. [PubMed]

226.

Gordon IL, Kohl CA, Arefi M, Complin RA, Vulpe M. Spinal cord injury increases the risk of abdominal aortic aneurysm. Am Surg. 1996 Mar;62(3): 249–52. Not eligible outcomes. [PubMed]

227.

Grange CC, Bougenot MP, Groslambert A, Tordi N, Rouillon JD. Perceived exertion and rehabilitation with wheelchair ergometer: comparison between patients with spinal cord injury and healthy subjects. Spinal Cord. 2002; 40(10): 513–8. No relevant outcomes. [PubMed]

228.

Grasso R, Ivanenko YP, Zago M, Molinari M, Scivoletto G, Castellano V. et al. Distributed plasticity of locomotor pattern generators in spinal cord injured patients. Brain. 2004; 127: 1019–34. No relevant outcomes. [PubMed]

229.

Grasso R, Ivanenko YP, Zago M, Molinari M, Scivoletto G, Lacquaniti F. Recovery of forward stepping in spinal cord injured patients does not transfer to untrained backward stepping. Exp Brain Res. 2004; 157(3): 377–82. No relevant outcomes. [PubMed]

230.

Greco S, Auriti A, Fiume D, Gazzeri G, Gentilucci G, Antonini L. et al. Spinal cord stimulation for the treatment of refractory angina pectoris: a two-year follow-up. Pacing Clin Electrophysiol. 1999; 22(1): 26–32. Not adult chronic SCI patients. [PubMed]

231.

Green D, Chen D, Chmiel JS, Olsen NK, Berkowitz M, Novick A. et al. Prevention of thromboembolism in spinal cord injury: role of low molecular weight heparin. Arch Phys Med Rehabil. 1994 Mar;75(3): 290–2. Not eligible target population. [PubMed]

232.

Green D, Lee MY, Lim AC, Chmiel JS, Vetter M, Pang T. et al. Prevention of thromboembolism after spinal cord injury using low-molecular-weight heparin. Ann Intern Med. 1990 Oct 15;113(8): 571–4. Not eligible target population. [PubMed]

233.

Green D, Twardowski P, Wei R, Rademaker AW. Fatal pulmonary embolism in spinal cord injury. Chest. 1994 Mar;105(3): 853–5. Not eligible target population. [PubMed]

234.

Greydanus DE, Demarest DS, Sears JM. Sexual dysfunction in adolescents. Seminars in Adolescent Medicine. 1985; 1(3): 177–87. Not adult spinal cord injury patients. [PubMed]

235.

Griepp RB, Ergin MA, Galla JD, Lansman S, Khan N, Quintana C. et al. Looking for the artery of Adamkiewicz: a quest to minimize paraplegia after operations for aneurysms of the descending thoracic and thoracoabdominal aorta. J Thorac Cardiovasc Surg. 1996 Nov;112(5): 1202–13. discussion 13–5. Not eligible target population. [PubMed]

236.

Grigorenko A, Bjerkefors A, Rosdahl H, Hultling C, Alm M, Thorstensson A. Sitting balance and effects of kayak training in paraplegics. J Rehabil Med. 2004; 36(3): 110–6. No relevant outcomes. [PubMed]

237.

Grimm DR, Almenoff PL, Bauman WA, De Meersman RE. Baroreceptor sensitivity response to phase IV of the Valsalva maneuver in spinal cord injury. Clin Auton Res. 1998 Apr;8(2): 111–8. Not eligible outcomes. [PubMed]

238.

Grossman S. How can nurses use limit setting to facilitate spinal cord patients' independence? SCI Nurs. 1997; 14(3): 105–7. No exercise program or physical activity. [PubMed]

239.

Grote EH. The CNS control of glucose metabolism. Acta Neurochirurgica - Supplementum. 1981; 31: 1–160. Review. [PubMed]

240.

Guihan M, Simmons B, Nelson A, Bosshart HT, Burns SP. Spinal cord injury providers' perceptions of barriers to implementing selected clinical practice guideline recommendations. J Spinal Cord Med. 2003 Spring;26(1): 48–58. Not eligible target population. [PubMed]

241.

Gunduz S, Ogur E, Mohur H, Somuncu I, Acjksoz E, Ustunsoz B. Deep vein thrombosis in spinal cord injured patients. Paraplegia. 1993 Sep;31(9): 606–10. Not eligible target population. [PubMed]

242.

Gurney AB, Robergs RA, Aisenbrey J, Cordova JC, McClanahan L. Detraining from total body exercise ergometry in individuals with spinal cord injury. Spinal Cord. 1998; 36(11): 782–9. No relevant outcomes. [PubMed]

243.

Gutterman P. Acute spinal subdural hematoma following lumbar puncture. Surgical Neurology. 1977; 7(6): 355–6. Not adult spinal cord injury patients. [PubMed]

244.

Hagerman F, Jacobs P, Backus D, Dudley GA. Exercise responses and adaptations in rowers and spinal cord injury individuals. Med Sci Sports Exerc. 2006; 38(5): 958–62. No relevant outcomes. [PubMed]

245.

Hagisawa S, Ferguson-Pell M, Cardi M, Miller SD. Assessment of skin blood content and oxygenation in spinal cord injured subjects during reactive hyperemia. J Rehabil Res Dev. 1994; 31(1): 1–14. Not eligible outcomes. [PubMed]

246.

Hagobian TA, Jacobs KA, Kiratli BJ, Friedlander AL. Foot cooling reduces exercise-induced hyperthermia in men with spinal cord injury. Med Sci Sports Exerc. 2004; 36(3): 411–7. No relevant outcomes. [PubMed]

247.

Haldeman S, Bradley WE, Bhatia N. Evoked responses from the pudendal nerve. Journal of Urology. 1982; 128(5): 974–80. Not adult spinal cord injury patients. [PubMed]

248.

Haldi PA. Double trouble: diabetes and SCI. Sci Nursing. 2003; 20(2): 106–8. Less than 100 patients in study. [PubMed]

249.

Halliday SE, Zavatsky AB, Hase K. Can functional electric stimulation-assisted rowing reproduce a race-winning rowing stroke? Arch Phys Med Rehabil. 2004; 85(8): 1265–72. No relevant outcomes. [PubMed]

250.

Hansen NL, Conway BA, Halliday DM, Hansen S, Pyndt HS, Biering-Sorensen F. et al. Reduction of common synaptic drive to ankle dorsiflexor motoneurons during walking in patients with spinal cord lesion. J Neurophysiol. 2005; 94(2): 934–42. No relevant outcomes. [PubMed]

251.

Harris S, Chen D, Green D. Enoxaparin for thromboembolism prophylaxis in spinal injury: preliminary report on experience with 105 patients. Am J Phys Med Rehabil. 1996 Sep–Oct;75(5): 326–7. Not eligible target population. [PubMed]

252.

Hart KA, Rintala DH, Fuhrer MJ. Educational interests of individuals with spinal cord injury living in the community: medical, sexuality, and wellness topics. Rehabil Nurs. 1996; 21(2): 82–90. No exercise program or physical activity. [PubMed]

253.

Hartkopp A, Harridge SD, Mizuno M, Ratkevicius A, Quistorff B, Kjaer M. et al. Effect of training on contractile and metabolic properties of wrist extensors in spinal cord-injured individuals. Muscle Nerve. 2003; 27(1): 72–80. No relevant outcomes. [PubMed]

254.

Harvey L, de Jong I, Goehl G, Mardwedel S. Twelve weeks of nightly stretch does not reduce thumb web-space contractures in people with a neurological condition: a randomised controlled trial. Aust J Physiother. 2006; 52(4): 251–8. Not eligible outcomes. [PubMed]

255.

Harvey LA, McQuade L, Hawthorne S, Byak A. Quantifying the magnitude of torque physiotherapists apply when stretching the hamstring muscles of people with spinal cord injury. Arch Phys Med Rehabil. 2003; 84(7): 1072–5. No relevant outcomes. [PubMed]

256.

Hashimoto H, Iida J, Shin Y, Hironaka Y, Sakaki T. Spinal dural arteriovenous fistula with perimesencephalic subarachnoid haemorrhage. J Clin Neurosci. 2000; 7(1): 64–6. Not adult chronic SCI patients. [PubMed]

257.

Hautvast RW, Blanksma PK, DeJongste MJ, Pruim J, van der Wall EE, Vaalburg W. et al. Effect of spinal cord stimulation on myocardial blood flow assessed by positron emission tomography in patients with refractory angina pectoris. Am J Cardiol. 1996; 77(7): 462–7. Not adult chronic SCI patients. [PubMed]

258.

Hautvast RW, Brouwer J, DeJongste MJ, Lie KI. Effect of spinal cord stimulation on heart rate variability and myocardial ischemia in patients with chronic intractable angina pectoris—a prospective ambulatory electrocardiographic study. Clin Cardiol. 1998; 21(1): 33–8. Not adult chronic SCI patients. [PubMed]

259.

Hautvast RW, DeJongste MJ, Staal MJ, van Gilst WH, Lie KI. Spinal cord stimulation in chronic intractable angina pectoris: a randomized, controlled efficacy study. Am Heart J. 1998; 136(6): 1114–20. Not adult chronic SCI patients. [PubMed]

260.

He Q, Li J, Bettiol E, Jaconi ME. Embryonic stem cells: new possible therapy for degenerative diseases that affect elderly people. Journals of Gerontology Series A-Biological Sciences & Medical Sciences. 2003; 58(3): 279–87. No relevant data.

261.

Healy ME, Hesselink JR, Ostrup RC, Alksne JF. Demonstration by magnetic resonance of symptomatic spinal epidural lipomatosis. Neurosurgery. 1987; 21(3): 414–5. Not adult spinal cord injury patients. [PubMed]

262.

Heilbrun MP, Davis DO. Spastic paraplegia secondary to cord constriction by the dura. Case report. Journal of Neurosurgery. 1973; 39(5): 645–7. Not adult spinal cord injury patients. [PubMed]

263.

Heimbach RD. Hyperbaric medicine—demonstration cases. Transactions of the Association of Life Insurance Medical Directors of America 67:126–34, 1985 1985;67:126–34. No relevant data.

264.

Henderson CE. Application of ventilatory strategies to enhance functional activities for an individual with spinal cord injury. J Neurol Phys Ther. 2005; 29(2): 107–11. No relevant outcomes. [PubMed]

265.

Henriksen JD. Part V: secondary health problems: Specialized care of the spinal cord injured patient. Journal of Practical Nursing. 1976; 26(10): 21. No relevant data. [PubMed]

266.

Hicks AL, Adams MM, Martin Ginis K, Giangregorio L, Latimer A, Phillips SM. et al. Long-term body-weight-supported treadmill training and subsequent follow-up in persons with chronic SCI: effects on functional walking ability and measures of subjective well-being. Spinal Cord. 2005; 43(5): 291–8. No relevant outcomes. [PubMed]

267.

Hicks AL, Martin KA, Ditor DS, Latimer AE, Craven C, Bugaresti J. et al. Long-term exercise training in persons with spinal cord injury: effects on strength, arm ergometry performance and psychological well-being. Spinal Cord. 2003; 41(1): 34–43. No relevant outcomes. [PubMed]

268.

Higuchi Y, Kitamura S, Kawashima N, Nakazawa K, Iwaya T, Yamasaki M. Cardiorespiratory responses during passive walking-like exercise in quadriplegics. Spinal Cord. 2006; 44(8): 480–6. No relevant outcomes. [PubMed]

269.

Hirsh EH, Brandenburg D, Hersh T, Brooks WS Jr. Chronic intestinal pseudo-obstruction. Journal of Clinical Gastroenterology. 1981; 3(3): 247–54. Not adult spinal cord injury patients. [PubMed]

270.

Hjeltnes N, Aksnes AK, Birkeland KI, Johansen J, Lannem A, Wallberg-Henriksson H. Improved body composition after 8 wk of electrically stimulated leg cycling in tetraplegic patients. Am J Physiol. 1997; 273(3): R1072–9. No relevant outcomes. [PubMed]

271.

Hjeltnes N, Wallberg-Henriksson H. Improved work capacity but unchanged peak oxygen uptake during primary rehabilitation in tetraplegic patients. Spinal Cord. 1998; 36(10): 691–8. No relevant outcomes. [PubMed]

272.

Ho MH, Bhatia NN, Khorram O. Physiologic role of nitric oxide and nitric oxide synthase in female lower urinary tract. [Review] [42 refs]. Current Opinion in Obstetrics & Gynecology. 2004; 16(5): 423–9. No relevant data. [PubMed]

273.

Ho RM, Freed MM. Persistent hypertension in young spinal cord injured individuals resulting from aortic repair. Arch Phys Med Rehabil. 1991 Sep;72(10): 743–6. Not eligible target population. [PubMed]

274.

Hopman MT, Groothuis JT, Flendrie M, Gerrits KH, Houtman S. Increased vascular resistance in paralyzed legs after spinal cord injury is reversible by training. J Appl Physiol. 2002; 93(6): 1966–72. No relevant outcomes. [PubMed]

275.

Hopman MT, Houtman S, Groothuis JT, Folgering HT. The effect of varied fractional inspired oxygen on arm exercise performance in spinal cord injury and able-bodied persons. Arch Phys Med Rehabil. 2004; 85(2): 319–23. No relevant outcomes. [PubMed]

276.

Hopman MT, Monroe M, Dueck C, Phillips WT, Skinner JS. Blood redistribution and circulatory responses to submaximal arm exercise in persons with spinal cord injury. Scand J Rehabil Med. 1998; 30(3): 167–74. No relevant outcomes. [PubMed]

277.

Hopman MT, van der Woude LH, Dallmeijer AJ, Snoek G, Folgering HT. Respiratory muscle strength and endurance in individuals with tetraplegia. Spinal Cord. 1997; 35(2): 104–8. No relevant outcomes. [PubMed]

278.

Hornby TG, Zemon DH, Campbell D. Robotic-assisted, body-weight-supported treadmill training in individuals following motor incomplete spinal cord injury. Phys Ther. 2005; 85(1): 52–66. No relevant outcomes. [PubMed]

279.

Houtman S, Colier WN, Oeseburg B, Hopman MT. Systemic circulation and cerebral oxygenation during head-up tilt in spinal cord injured individuals. Spinal Cord. 2000 Mar;38(3): 158–63. Not eligible outcomes. [PubMed]

280.

Houtman S, Thielen JJ, Binkhorst RA, Hopman MT. Effect of a pulsating anti-gravity suit on peak exercise performance in individual with spinal cord injuries. Eur J Appl Physiol Occup Physiol. 1999; 79(2): 202–4. No relevant outcomes. [PubMed]

281.

Hubault A. Nervous arthropathies. Revue Neurologique. 1982; 138(12): 1009–17. Not english language. [PubMed]

282.

Hunt KJ, Ferrario C, Grant S, Stone B, McLean AN, Fraser MH. et al. Comparison of stimulation patterns for FES-cycling using measures of oxygen cost and stimulation cost. Med Eng Phys. 2006; 28(7): 710–8. No relevant outcomes. [PubMed]

283.

Huntoon E, Sinaki M. Thoracic osteoporotic fracture without upper back pain. Am J Phys Med Rehabil. 2004; 83(9): 729. Not adult chronic SCI patients. [PubMed]

284.

Hutzler Y, Ochana S, Bolotin R, Kalina E. Aerobic and anaerobic arm-cranking power outputs of males with lower limb impairments: relationship with sport participation intensity, age, impairment and functional classification. Spinal Cord. 1998; 36(3): 205–12. No relevant outcomes. [PubMed]

285.

Hwang WS, Roh SI, Lee BC, Kang SK, Kwon DK, Kim S. et al. Patient-specific embryonic stem cells derived from human SCNT blastocysts. Science. 2005; 308(5729): 1777–83. No relevant data. [PubMed]

286.

Ide M, Ogata H, Kobayashi M, Wada F. Muscle damage occurring in wheelchair sports people. Spinal Cord. 1997; 35(4): 234–7. No relevant outcomes. [PubMed]

287.

Ide M, Tajima F, Furusawa K, Mizushima T, Ogata H. Wheelchair marathon racing causes striated muscle distress in individuals with spinal cord injury. Arch Phys Med Rehabil. 1999 Mar;80(3): 324–7. Not eligible outcomes. [PubMed]

288.

Iida H, Tachibana S, Kitahara T, Horiike S, Ohwada T, Fujii K. Association of head trauma with cervical spine injury, spinal cord injury, or both. J Trauma. 1999 Mar;46(3): 450–2. Not eligible outcomes. [PubMed]

289.

Iles JF, Ali A, Pardoe J. Task-related changes of transmission in the pathway of heteronymous spinal recurrent inhibition from soleus to quadriceps motor neurones in man. Brain. 2000; 123( Pt 11): 2264–72. Not adult chronic SCI patients. [PubMed]

290.

Illman A, Stiller K, Williams M. The prevalence of orthostatic hypotension during physiotherapy treatment in patients with an acute spinal cord injury. Spinal Cord. 2000 Dec;38(12): 741–7. Not eligible target population. [PubMed]

291.

Iseli E, Cavigelli A, Dietz V, Curt A. Prognosis and recovery in ischaemic and traumatic spinal cord injury: clinical and electrophysiological evaluation. J Neurol Neurosurg Psychiatry. 1999 Nov;67(5): 567–71. Not eligible target population. [PubMed] [Free Full text in PMC]

292.

Israel JF, Campbell DD, Kahn JH, Hornby TG. Metabolic costs and muscle activity patterns during robotic- and therapist-assisted treadmill walking in individuals with incomplete spinal cord injury. Phys Ther. 2006; 86(11): 1466–78. No relevant outcomes. [PubMed]

293.

Iversen PO, Groot PD, Hjeltnes N, Andersen TO, Mowinckel MC, Sandset PM. Impaired circadian variations of haemostatic and fibrinolytic parameters in tetraplegia. Br J Haematol. 2002 Dec;119(4): 1011–6. Not eligible outcomes. [PubMed]

294.

Jacobs PL, Johnson B, Mahoney ET. Physiologic responses to electrically assisted and frame-supported standing in persons with paraplegia. J Spinal Cord Med. 2003; 26(4): 384–9. No relevant outcomes. [PubMed]

295.

Jacobs PL, Johnson B, Somarriba GA, Carter AB. Reliability of upper extremity anaerobic power assessment in persons with tetraplegia. J Spinal Cord Med. 2005; 28(2): 109–13. No relevant outcomes. [PubMed]

296.

Jacobs PL, Mahoney ET. Peak exercise capacity of electrically induced ambulation in persons with paraplegia. Med Sci Sports Exerc. 2002; 34(10): 1551–6. No relevant outcomes. [PubMed]

297.

Jacobs PL, Mahoney ET, Johnson B. Reliability of arm Wingate Anaerobic Testing in persons with complete paraplegia. J Spinal Cord Med. 2003; 26(2): 141–4. No relevant outcomes. [PubMed]

298.

Jacobs PL, Mahoney ET, Nash MS, Green BA. Circuit resistance training in persons with complete paraplegia. J Rehabil Res Dev. 2002; 39(1): 21–8. No relevant outcomes. [PubMed]

299.

Jacobs PL, Nash MS. Modes, benefits, and risks of voluntary an delectrically induced exercise in persons with spinal cord injury. Journal of Spinal Cord Medicine. 2001; 24(1): 10–8. No relevant data. [PubMed]

300.

Jacobs PL, Nash MS, Klose KJ, Guest RS, Needham-Shropshire BM, Green BA. Evaluation of a training program for persons with SCI paraplegia using the Parastep 1 ambulation system: part 2. Effects on physiological responses to peak arm ergometry. Arch Phys Med Rehabil. 1997; 78(8): 794–8. No relevant outcomes. [PubMed]

301.

Jaconi M. Embryonic stem cells: new possible therapy of degenerative diseases. Therapeutische Umschau. 2002; 59(11): 588–95. Not english language. [PubMed]

302.

Jaeger-Denavit O, Lacert P, Pannier S, Grossiord A. Study of cutaneous blood flow as a function of local skin temperature in paraplegia and guadraplegia due to spinal cord lesions. Revue Europeenne d Etudes Cliniques et Biologiques. 1972; 17(5): 518–24. Not english language.

303.

Jain NB, Brown R, Tun CG, Gagnon D, Garshick E. Determinants of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC in chronic spinal cord injury. Archives of Physical Medicine & Rehabilitation. 2006; 87(10): 1327–33. No relevant data. [PubMed] [Free Full text in PMC]

304.

Jamieson WR, Janusz MT, Gudas VM, Burr LH, Fradet GJ, Henderson C. Traumatic rupture of the thoracic aorta: third decade of experience. Am J Surg. 2002 May;183(5): 571–5. Not eligible target population. [PubMed]

305.

Janosky VJ. Stem cells: potential cures or abortion lures? DePaul Journal of Health Care Law. 2002; 6(1): 111–57. No relevant data. [PubMed]

306.

Janssen TW, Dallmeijer AJ, van der Woude LH. Physical capacity and race performance of handcycle users. J Rehabil Res Dev. 2001; 38(1): 33–40. No relevant outcomes. [PubMed]

307.

Janssen TW, Dallmeijer AJ, Veeger DJ, van der Woude LH. Normative values and determinants of physical capacity in individuals with spinal cord injury. J Rehabil Res Dev. 2002; 39(1): 29–39. No relevant outcomes. [PubMed]

308.

Janssen TW, van Oers CA, Rozendaal EP, Willemsen EM, Hollander AP, van der Woude LH. Changes in physical strain and physical capacity in men with spinal cord injuries. Med Sci Sports Exerc. 1996; 28(5): 551–9. No relevant outcomes. [PubMed]

309.

Janssen TW, van Oers CA, van Kamp GJ, TenVoorde BJ, van der Woude LH, Hollander AP. Coronary heart disease risk indicators, aerobic power, and physical activity in men with spinal cord injuries. Arch Phys Med Rehabil. 1997 Jul;78(7): 697–705. Case-control with <50 cases. [PubMed]

310.

Jaworski TM, Richards JS, Lloyd LK. Retrospective review of sexual and marital satisfaction of spinal cord injury and diabetic males post penile injection or implant. Urology. 1992; 40(2): 127–31. No relevant data. [PubMed]

311.

Jeon JY, Weiss CB, Steadward RD, Ryan E, Burnham RS, Bell G. et al. Improved glucose tolerance and insulin sensitivity after electrical stimulation-assisted cycling in people with spinal cord injury. Spinal Cord. 2002; 40(3): 110–7. Less than 100 patients in study. [PubMed]

312.

Jeremic B, Grujicic D, Cirovic V, Djuric L, Mijatovic L. Radiotherapy of metastatic spinal cord compression. Acta Oncol. 1991; 30(8): 985–6. Not eligible target population. [PubMed]

313.

Jesel M. Anomalies of conduction of the distal segment of nerve fibers in slowly developing neuritic and radiculo-neuritic diseases. Revue Neurologique. 1968; 118(6): 411–8. Not english language. [PubMed]

314.

Jessurun GA, DeJongste MJ, Hautvast RW, Tio RA, Brouwer J, van Lelieveld S. et al. Clinical follow-up after cessation of chronic electrical neuromodulation in patients with severe coronary artery disease: a prospective randomized controlled study on putative involvement of sympathetic activity. Pacing Clin Electrophysiol. 1999; 22(10): 1432–9. Not adult chronic SCI patients. [PubMed]

315.

Jezernik S, Scharer R, Colombo G, Morari M. Adaptive robotic rehabilitation of locomotion: a clinical study in spinally injured individuals. Spinal Cord. 2003; 41(12): 657–66. No relevant outcomes. [PubMed]

316.

Johnson RH, Spaulding JM. Disorders of the autonomic nervous system. Chapter 10. Sweating. Contemporary Neurology Series 1974(11):179–98. No relevant data.

317.

Jones EA, Manaster BJ, May DA, Disler DG. Neuropathic osteoarthropathy: diagnostic dilemmas and differential diagnosis. Radiographics 2000 2000 Oct;20(Spec No):S279–93. No relevant data.

318.

Jones LM, Legge M, Goulding A. Intensive exercise may preserve bone mass of the upper limbs in spinal cord injured males but does not retard demineralisation of the lower body. Spinal Cord. 2002; 40(5): 230–5. No relevant outcomes. [PubMed]

319.

Jones LM, Legge M, Goulding A. Healthy body mass index values often underestimate body fat in men with spinal cord injury. Archives of Physical Medicine & Rehabilitation. 2003; 84(7): 1068–71. Less than 100 patients in study. [PubMed]

320.

Jones LM, Legge M, Goulding A. Factor analysis of the metabolic syndrome in spinal cord-injured men. Metabolism: Clinical & Experimental. 2004; 53(10): 1372–7. Less than 100 patients in study. [PubMed]

321.

Jones T, Ugalde V, Franks P, Zhou H, White RH. Venous thromboembolism after spinal cord injury: incidence, time course, and associated risk factors in 16,240 adults and children. Arch Phys Med Rehabil. 2005 Dec;86(12): 2240–7. Not eligible target population. [PubMed]

322.

Jonsson B, Annertz M, Sjoberg C, Stromqvist B. A prospective and consecutive study of surgically treated lumbar spinal stenosis. Part I: Clinical features related to radiographic findings. Spine. 1997 Dec 15;22(24): 2932–7. Not eligible target population. [PubMed]

323.

Jozsa L, Kannus P, Jarvinen TA, Balint J, Jarvinen M. Number and morphology of mechanoreceptors in the myotendinous junction of paralysed human muscle. J Pathol. 1996 Feb;178(2): 195–200. Not eligible target population. [PubMed]

324.

Kabalin JN, Lennon S, Gill HS, Wolfe V, Perkash I. Incidence and management of autonomic dysreflexia and other intraoperative problems encountered in spinal cord injury patients undergoing extracorporeal shock wave lithotripsy without anesthesia on a second generation lithotriptor. J Urol. 1993 May;149(5): 1064–7. Not eligible outcomes. [PubMed]

325.

Kadyan V, Clinchot DM, Mitchell GL, Colachis SC. Surveillance with duplex ultrasound in traumatic spinal cord injury on initial admission to rehabilitation. J Spinal Cord Med. 2003 Fall;26(3): 231–5. Not eligible target population. [PubMed]

326.

Kahn NN. Platelet-stimulated thrombin and PDGF are normalized by insulin and Ca2+ channel blockers. Am J Physiol. 1999 May;276(5 Pt 1): E856–62. Not eligible outcomes. [PubMed]

327.

Kahn NN, Bauman WA, Sinha AK. Demonstration of a novel circulating anti-prostacyclin receptor antibody. Proc Natl Acad Sci U S A. 1997 Aug 5;94(16): 8779–82. Not eligible outcomes. [PubMed] [Free Full text in PMC]

328.

Kahn NN, Bauman WA, Sinha AK. Circulating heavy chain IgG, a pathological mediator for coronary artery disease, recognizes platelet surface receptors of both prostacyclin and insulin. Platelets. 2003 Jun;14(4): 203–10. Not eligible outcomes. [PubMed]

329.

Kahn NN, Bauman WA, Sinha AK. Appearance of a novel prostacyclin receptor antibody and duration of spinal cord injury. J Spinal Cord Med. 2005; 28(2): 97–102. Not eligible outcomes. [PubMed]

330.

Kameyama J, Handa Y, Hoshimiya N, Sakurai M. Restoration of shoulder movement in quadriplegic and hemiplegic patients by functional electrical stimulation using percutaneous multiple electrodes. Tohoku J Exp Med. 1999 Apr;187(4): 329–37. Not eligible outcomes. [PubMed]

331.

Kapidzic-Durakovic S, Zonic-Imamovic M, Mulaosmanovic A. Family participation in determination of FIM and Barthel indices. Bosn J Basic Med Sci. 2006 May;6(2): 51–3. Not eligible outcomes. [PubMed]

332.

Karlsson AK. Insulin resistance and sympathetic function in high spinal cord injury. Spinal Cord. 1999; 37(7): 494–500. Less than 100 patients in study. [PubMed]

333.

Karlsson AK, Attvall S, Jansson PA, Sullivan L, Lonnroth P. Influence of the sympathetic nervous system on insulin sensitivity and adipose tissue metabolism: a study in spinal cord-injured subjects. Metabolism: Clinical & Experimental. 1995; 44(1): 52–8. Less than 100 patients in study. [PubMed]

334.

Karlsson AK, Elam M, Friberg P, Biering-Sorensen F, Sullivan L, Lonnroth P. Regulation of lipolysis by the sympathetic nervous system: a microdialysis study in normal and spinal cord-injured subjects. Metabolism: Clinical & Experimental. 1997; 46(4): 388–94. Less than 100 patients in study. [PubMed]

335.

Katz PG, Greenstein A. Urinary incontinence associated with neurologic disorders. [Review] [29 refs]. Seminars in Urology. 1989; 7(2): 133–8. No relevant data. [PubMed]

336.

Kawashima N, Nakazawa K, Ishii N, Akai M, Yano H. Potential impact of orthotic gait exercise on natural killer cell activities in thoracic level of spinal cord-injured patients. Spinal Cord. 2004; 42(7): 420–4. No relevant outcomes. [PubMed]

337.

Kawashima N, Sone Y, Nakazawa K, Akai M, Yano H. Energy expenditure during walking with weight-bearing control (WBC) orthosis in thoracic level of paraplegic patients. Spinal Cord. 2003; 41(9): 506–10. No relevant outcomes. [PubMed]

338.

Kerslake RW, Jaspan T, Worthington BS. Magnetic resonance imaging of spinal trauma. Br J Radiol. 1991 May;64(761): 386–402. Not eligible outcomes. [PubMed]

339.

Kerstin W, Gabriele B, Richard L. What promotes physical activity after spinal cord injury? An interview study from a patient perspective. Disabil Rehabil. 2006; 28(8): 481–8. No relevant outcomes. [PubMed]

340.

Kesiktas N, Paker N, Erdogan N, Gulsen G, Bicki D, Yilmaz H. The use of hydrotherapy for the management of spasticity. Neurorehabil Neural Repair. 2004; 18(4): 268–73. No relevant outcomes. [PubMed]

341.

Ketover SR, Ansel HJ, Goldish G, Roche B, Gebhard RL. Gallstones in chronic spinal cord injury: is impaired gallbladder emptying a risk factor? Archives of Physical Medicine & Rehabilitation. 1996; 77(11): 1136–8. No relevant data. [PubMed]

342.

Keyser RE, Rasch EK, Finley M, Rodgers MM. Improved upper-body endurance following a 12-week home exercise program for manual wheelchair users. J Rehabil Res Dev. 2003; 40(6): 501–10. No relevant outcomes. [PubMed]

343.

Khan SH, Hattingh S, Griebel RW. Spinal epidural abscess. Canadian Journal of Neurological Sciences. 2001; 28(3): 254–5. Not adult spinal cord injury patients. [PubMed]

344.

Khoynezhad A, Donayre CE, Bui H, Kopchok GE, Walot I, White RA. Risk factors of neurologic deficit after thoracic aortic endografting. Ann Thorac Surg. 2007 Feb;83(2): S882–9. discussion S90–2. Not eligible target population. [PubMed]

345.

Kilkens OJ, Dallmeijer AJ, De Witte LP, Van Der Woude LH, Post MW. The Wheelchair Circuit: Construct validity and responsiveness of a test to assess manual wheelchair mobility in persons with spinal cord injury. Arch Phys Med Rehabil. 2004; 85(3): 424–31. No relevant outcomes. [PubMed]

346.

Kim V, Spandorfer J. Epidemiology of venous thromboembolic disease. Emergency Medicine Clinics of North America. 2001; 19(4): 839–59. Not adult spinal cord injury patients. [PubMed]

347.

King ML, Lichtman SW, Pellicone JT, Close RJ, Lisanti P. Exertional hypotension in spinal cord injury. Chest. 1994 Oct;106(4): 1166–71. Not eligible outcomes. [PubMed]

348.

Kishi Y, Robinson RG, Kosier JT. Suicidal ideation among patients with acute life-threatening physical illness: patients with stroke, traumatic brain injury, myocardial infarction, and spinal cord injury. Psychosomatics. 2001 Sep–Oct;42(5): 382–90. Not eligible target population. [PubMed]

349.

Kishi Y, Robinson RG, Kosier JT. Suicidal ideation among patients during the rehabilitation period after life-threatening physical illness. J Nerv Ment Dis. 2001 Sep;189(9): 623–8. Not eligible outcomes. [PubMed]

350.

Kjaer M, Dela F, Sorensen FB, Secher NH, Bangsbo J, Mohr T. et al. Fatty acid kinetics and carbohydrate metabolism during electrical exercise in spinal cord-injured humans. Am J Physiol Regul Integr Comp Physiol. 2001; 281(5): R1492–8. No relevant outcomes. [PubMed]

351.

Kjaer M, Mohr T, Biering-Sorensen F, Bangsbo J. Muscle enzyme adaptation to training and tapering-off in spinal-cord-injured humans. Eur J Appl Physiol. 2001; 84(5): 482–6. No relevant outcomes. [PubMed]

352.

Kjaer M, Pollack SF, Mohr T, Weiss H, Gleim GW, Bach FW. et al. Regulation of glucose turnover and hormonal responses during electrical cycling in tetraplegic humans. Am J Physiol. 1996; 271(1): R191–9. No relevant outcomes. [PubMed]

353.

Kjaer M, Pott F, Mohr T, Linkis P, Tornoe P, Secher NH. Heart rate during exercise with leg vascular occlusion in spinal cord-injured humans. J Appl Physiol. 1999; 86(3): 806–11. No relevant outcomes. [PubMed]

354.

Klokker M, Mohr T, Kjaer M, Galbo H, Pedersen BK. The natural killer cell response to exercise in spinal cord injured individuals. Eur J Appl Physiol Occup Physiol. 1998; 79(1): 106–9. No relevant outcomes. [PubMed]

355.

Knechtle B, Hardegger K, Muller G, Odermatt P, Eser P, Knecht H. Evaluation of sprint exercise testing protocols in wheelchair athletes. Spinal Cord. 2003; 41(3): 182–6. No relevant outcomes. [PubMed]

356.

Knechtle B, Kopfli W. Treadmill exercise testing with increasing inclination as exercise protocol for wheelchair athletes. Spinal Cord. 2001; 39(12): 633–6. No relevant outcomes. [PubMed]

357.

Knechtle B, Muller G, Knecht H. Optimal exercise intensities for fat metabolism in handbike cycling and cycling. Spinal Cord. 2004; 42(10): 564–72. No exercise program or physical activity. [PubMed]

358.

Knechtle B, Muller G, Willmann F, Eser P, Knecht H. Comparison of fat oxidation in arm cranking in spinal cord-injured people versus ergometry in cyclists. Eur J Appl Physiol. 2003; 90(5): 614–9. No relevant outcomes. [PubMed]

359.

Knoller N, Auerbach G, Fulga V, Zelig G, Attias J, Bakimer R. et al. Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg Spine. 2005 Sep;3(3): 173–81. Not eligible target population. [PubMed]

360.

Kocina P. Body composition of spinal cord injured adults. Sports Medicine. 1997; 23(1): 48–60. Review. [PubMed]

361.

Kondo T, Saito K, Nishigami J, Ohshima T. Fatal injuries of the brain stem and/or upper cervical spinal cord in traffic accidents: nine autopsy cases. Sci Justice. 1995 Jul–Sep;35(3): 197–201. Not eligible target population. [PubMed]

362.

Konz KR, Chia JK, Kurup VP, Resnick A, Kelly KJ, Fink JN. Comparison of latex hypersensitivity among patients with neurologic defects. J Allergy Clin Immunol. 1995 May;95(5 Pt 1): 950–4. Not eligible outcomes. [PubMed]

363.

Kooijman M, Rongen GA, Smits P, Hopman MT. Preserved alpha-adrenergic tone in the leg vascular bed of spinal cord-injured individuals. Circulation. 2003 Nov 11;108(19): 2361–7. Not eligible outcomes. [PubMed]

364.

Krassioukov AV, Furlan JC, Fehlings MG. Autonomic dysreflexia in acute spinal cord injury: an under-recognized clinical entity. J Neurotrauma. 2003 Aug;20(8): 707–16. Not eligible target population. [PubMed]

365.

Krause JS, Broderick L. Patterns of recurrent pressure ulcers after spinal cord injury: identification of risk and protective factors 5 or more years after onset. Arch Phys Med Rehabil. 2004; 85(8): 1257–64. No exercise program or physical activity. [PubMed]

366.

Kucukdeveci AA, Yavuzer G, Tennant A, Suldur N, Sonel B, Arasil T. Adaptation of the modified Barthel Index for use in physical medicine and rehabilitation in Turkey. Scand J Rehabil Med. 2000 Jun;32(2): 87–92. Not eligible outcomes. [PubMed]

367.

Kunihara T, Matsuzaki K, Shiiya N, Saijo Y, Yasuda K. Naloxone lowers cerebrospinal fluid levels of excitatory amino acids after thoracoabdominal aortic surgery. J Vasc Surg. 2004 Oct;40(4): 681–90. Not eligible target population. [PubMed]

368.

Kuo HC. Therapeutic effects of suburothelial injection of botulinum a toxin for neurogenic detrusor overactivity due to chronic cerebrovascular accident and spinal cord lesions. Urology. 2006 Feb;67(2): 232–6. Not eligible outcomes. [PubMed]

369.

Lagerquist O, Zehr EP, Docherty D. Increased spinal reflex excitability is not associated with neural plasticity underlying the cross-education effect. J Appl Physiol. 2006; 100(1): 83–90. Not adult chronic SCI patients. [PubMed]

370.

Langmayr JJ, Ortler M, Dessl A, Twerdy K, Aichner F, Felber S. Management of spontaneous extramedullary spinal haematomas: results in eight patients after MRI diagnosis and surgical decompression. J Neurol Neurosurg Psychiatry. 1995 Oct;59(4): 442–7. Not eligible target population. [PubMed] [Free Full text in PMC]

371.

Lanza GA, Sestito A, Sandric S, Cioni B, Tamburrini G, Barollo A. et al. Spinal cord stimulation in patients with refractory anginal pain and normal coronary arteries. Ital Heart J. 2001; 2(1): 25–30. Not adult chronic SCI patients. [PubMed]

372.

Lapides J, Diokno AC, Lowe BS, Kalish MD. Followup on unsterile intermittent self-catheterization. Journal of Urology. 1974; 111(2): 184–7. No relevant data. [PubMed]

373.

Lassau-Wray ER, Ward GR. Varying physiological response to arm-crank exercise in specific spinal injuries. J Physiol Anthropol Appl Human Sci. 2000; 19(1): 5–12. No relevant outcomes.

374.

Lawton MT, Porter RW, Heiserman JE, Jacobowitz R, Sonntag VK, Dickman CA. Surgical management of spinal epidural hematoma: relationship between surgical timing and neurological outcome. J Neurosurg. 1995 Jul;83(1): 1–7. Not eligible target population. [PubMed]

375.

Leaf DA, Bahl RA, Adkins RH. Risk of cardiac dysrhythmias in chronic spinal cord injury patients. Paraplegia. 1993 Sep;31(9): 571–5. Case-series. [PubMed]

376.

Lecouvet F, Richard F, Vande Berg B, Malghem J, Maldague B, Jamart J. et al. Long-term effects of localized spinal radiation therapy on vertebral fractures and focal lesions appearance in patients with multiple myeloma. Br J Haematol. 1997 Mar;96(4): 743–5. Not eligible target population. [PubMed]

377.

Leduc BE, Dagher JH, Mayer P, Bellemare F, Lepage Y. Estimated prevalence of obstructive sleep apnea-hypopnea syndrome after cervical cord injury. Archives of Physical Medicine & Rehabilitation. 2007; 88(3): 333–7. No relevant data. [PubMed]

378.

Lee CS, Lu YH, Lee ST, Lin CC, Ding HJ. Evaluating the prevalence of silent coronary artery disease in asymptomatic patients with spinal cord injury. Int Heart J. 2006 May;47(3): 325–30. Case-series. [PubMed]

379.

Lee MY, Myers J, Hayes A, Madan S, Froelicher VF, Perkash I. et al. C-reactive protein, metabolic syndrome, and insulin resistance in individuals with spinal cord injury. Journal of Spinal Cord Medicine. 2005; 28(1): 20–5. Less than 100 patients in study. [PubMed]

380.

Leist M, Ghezzi P, Grasso G, Bianchi R, Villa P, Fratelli M. et al. Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science. 2004; 305(5681): 239–42. Not adult spinal cord injury patients. [PubMed]

381.

Leite CC, Escobar BE, Bazan C 3rd, Jinkins JR. MRI of cervical facet dislocation. Neuroradiology. 1997 Aug;39(8): 583–8. Not eligible outcomes. [PubMed]

382.

Lena P, Teboul J, Mercier B, Bonnet F. Motor deficit of the lower limbs and urinary incontinence following peridural anesthesia. Annales Francaises d Anesthesie et de Reanimation. 1998; 17(9): 1144–7. Not english language. [PubMed]

383.

Leroux A, Fung J, Barbeau H. Postural adaptation to walking on inclined surfaces: II. Strategies following spinal cord injury. Clin Neurophysiol. 2006; 117(6): 1273–82. No relevant outcomes. [PubMed]

384.

Levi L, Wolf A, Belzberg H. Hemodynamic parameters in patients with acute cervical cord trauma: description, intervention, and prediction of outcome. Neurosurgery. 1993 Dec;33(6): 1007–16. discussion 16–7. Not eligible target population. [PubMed]

385.

Levi R, Hultling C, Nash MS, Seiger A. The Stockholm spinal cord injury study: 1. Medical problems in a regional SCI population. Paraplegia. 1995 Jun;33(6): 308–15. Not eligible target population. [PubMed]

386.

Linden D, Berlit P. Magnetic motor evoked potentials (MEP) in diseases of the spinal cord. Acta Neurol Scand. 1994 Nov;90(5): 348–53. Not eligible outcomes. [PubMed]

387.

Lischke V, Westphal K, Behne M, Wilke HJ, Rosenthal D, Marquardt G. et al. Thoracoscopic microsurgical technique for vertebral surgery—anesthetic considerations. Acta Anaesthesiol Scand. 1998; 42(10): 1199–204. No exercise program or physical activity. [PubMed]

388.

Liu JE, Tahmoush AJ, Roos DB, Schwartzman RJ. Shoulder-arm pain from cervical bands and scalene muscle anomalies. J Neurol Sci. 1995 Feb;128(2): 175–80. Not eligible outcome. [PubMed]

389.

Liusuwan A, Widman L, Abresch RT, McDonald CM. Altered body composition affects resting energy expenditure and interpretation of body mass index in children with spinal cord injury. Journal of Spinal Cord Medicine 27 Suppl 1:S24–8, 2004 2004;27(Suppl 1):S24–8. Not adult spinal cord injury patients.

390.

Logemann JA, Veis S, Colangelo L. A screening procedure for oropharyngeal dysphagia. Dysphagia. 1999 Winter;14(1): 44–51. Not eligible outcomes. [PubMed]

391.

LoPresti EF, Brienza DM. Adaptive software for head-operated computer controls. IEEE Trans Neural Syst Rehabil Eng. 2004; 12(1): 102–11. No exercise program or physical activity. [PubMed]

392.

Loudon JK, Cagle PE, Figoni SF, Nau KL, Klein RM. A submaximal all-extremity exercise test to predict maximal oxygen consumption. Med Sci Sports Exerc. 1998; 30(8): 1299–303. Not adult chronic SCI patients. [PubMed]

393.

Lu K, Lee TC, Liang CL, Chen HJ. Delayed apnea in patients with mid- to lower cervical spinal cord injury. Spine. 2000 Jun 1;25(11): 1332–8. Not eligible outcomes. [PubMed]

394.

Luce JM, Culver BH. Respiratory muscle function in health and disease. Chest. 1982; 81(1): 82–90. Not adult spinal cord injury patients. [PubMed]

395.

Lundgren-Nilsson A, Tennant A, Grimby G, Sunnerhagen KS. Cross-diagnostic validity in a generic instrument: an example from the Functional Independence Measure in Scandinavia. Health Qual Life Outcomes. 2006; 4: 55. Not eligible outcomes. [PubMed] [Free Full text in PMC]

396.

Lunney M. Critical thinking and accuracy of nurses' diagnoses. [Review] [26 refs]. International Journal of Nursing Terminologies & Classifications. 2003; 14(3): 96–107. Not adult spinal cord injury patients. [PubMed]

397.

Luther SL, Nelson A, Powell-Cope G. Provider attitudes and beliefs about clinical practice guidelines. SCI Nurs. 2004 Winter;21(4): 206–12. Not eligible target population. [PubMed]

398.

Maki KC, Briones ER, Langbein WE, Inman-Felton A, Nemchausky B, Welch M. et al. Associations between serum lipids and indicators of adiposity in men with spinal cord injury. Paraplegia. 1995; 33(2): 102–9. Less than 100 patients in study. [PubMed]

399.

Manns PJ, Chad KE. Determining the relation between quality of life, handicap, fitness, and physical activity for persons with spinal cord injury. Arch Phys Med Rehabil. 1999; 80(12): 1566–71. No relevant outcomes. [PubMed]

400.

Manns PJ, McCubbin JA, Williams DP. Fitness, inflammation, and the metabolic syndrome in men with paraplegia. Archives of Physical Medicine & Rehabilitation. 2005; 86(6): 1176–81. Less than 100 patients in study. [PubMed]

401.

Maranzano E, Latini P, Beneventi S, Perruci E, Panizza BM, Aristei C. et al. Radiotherapy without steroids in selected metastatic spinal cord compression patients. A phase II trial. American Journal of Clinical Oncology. 1996; 19(2): 179–83. Not adult spinal cord injury patients. [PubMed]

402.

Matthews JM. Succinylcholine-induced hyperkalemia and rhabdomyolysis in a patient with necrotizing pancreatitis. Anesthesia & Analgesia. 2000; 91(6): 1552–4. No relevant data. [PubMed]

403.

Maurice-Williams RS. Spinal dural arteriovenous malformations—a treatable cause of progressive paraparesis in elderly people. Age Ageing. 1992 Nov;21(6): 412–6. Not eligible target population. [PubMed]

404.

Maxwell RA, Chavarria-Aguilar M, Cockerham WT, Lewis PL, Barker DE, Durham RM. et al. Routine prophylactic vena cava filtration is not indicated after acute spinal cord injury. J Trauma. 2002 May;52(5): 902–6. Not eligible target population. [PubMed]

405.

Mazzocchio R, Kitago T, Liuzzi G, Wolpaw JR, Cohen LG. Plastic changes in the human H-reflex pathway at rest following skillful cycling training. Clin Neurophysiol. 2006; 117(8): 1682–91. Not adult chronic SCI patients. [PubMed]

406.

McColl MA, Friedland J. The effects of age and disability on social support. Int J Rehabil Res. 1995 Dec;18(4): 325–40. Not eligible outcomes. [PubMed]

407.

McDermott S, Moran R, Platt T, Issac T, Wood H, Dasari S. Depression in adults with disabilities, in primary care. Disabil Rehabil. 2005 Feb 4;27(3): 117–23. Not eligible outcomes. [PubMed]

408.

McGirt MJ, Woodworth GF, Lynch JR, Laskowitz DT. Synthes Award for Resident Research in Spinal Cord & Spinal Column Injury: Statins for the treatment of neurological injury: a role beyond cholesterol lowering. Clinical Neurosurgery. 2004; 51: 320–8. No relevant data. [PubMed]

409.

Meggiorin G, Onali A, Manduco G, Coraddu M. Continuous epidural anesthesia with a double catheter for sedation for surgery of the vertebral dorsolumbar column. Minerva Anestesiologica. 1999; 65(9): 653–8. Not english language. [PubMed]

410.

Mello MT, Silva AC, Rueda AD, Poyares D, Tufik S. Correlation between K complex, periodic leg movements (PLM), and myoclonus during sleep in paraplegic adults before and after an acute physical activity. Spinal Cord. 1997; 35(4): 248–52. No relevant outcomes. [PubMed]

411.

Melman A. Pathophysiologic basis of erectile dysfunction. What can we learn from animal models?. [Review] [27 refs]. International Journal of Impotence Research. 2001; 13(3): 140–2. Not adult spinal cord injury patients. [PubMed]

412.

Menssen HD, Sakalova A, Fontana A, Herrmann Z, Boewer C, Facon T. et al. Effects of long-term intravenous ibandronate therapy on skeletal-related events, survival, and bone resorption markers in patients with advanced multiple myeloma. J Clin Oncol. 2002 May 1;20(9): 2353–9. Not eligible target population. [PubMed]

413.

Merli GJ, Crabbe S, Doyle L, Ditunno JF, Herbision GJ. Mechanical plus pharmacological prophylaxis for deep vein thrombosis in acute spinal cord injury. Paraplegia. 1992 Aug;30(8): 558–62. Not eligible target population. [PubMed]

414.

Mersdorf A, Goldsmith PC, Diederichs W, Padula CA, Lue TF, Fishman IJ. et al. Ultrastructural changes in impotent penile tissue: a comparison of 65 patients. Journal of Urology. 1991; 145(4): 749–58. No relevant data. [PubMed]

415.

Mirvis SE, Geisler FH. Intraoperative sonography of cervical spinal cord injury: results in 30 patients. AJR Am J Roentgenol. 1990 Sep;155(3): 603–9. Not eligible outcomes. [PubMed]

416.

Miyakoshi N, Shimada Y, Suzuki T, Hongo M, Itoi E. Magnetic resonance imaging of spinal involvement by hematopoietic malignancies requiring surgical decompression. J Orthop Sci. 2003; 8(2): 207–12. Not eligible target population. [PubMed]

417.

Mohr T, Andersen JL, Biering-Sorensen F, Galbo H, Bangsbo J, Wagner A. et al. Long-term adaptation to electrically induced cycle training in severe spinal cord injured individuals. Spinal Cord. 1997; 35(1): 1–16. No relevant outcomes. [PubMed]

418.

Mohr T, Dela F, Handberg A, Biering-Sorensen F, Galbo H, Kjaer M. Insulin action and long-term electrically induced training in individuals with spinal cord injuries. Medicine & Science in Sports & Exercise. 2001; 33(8): 1247–52. Less than 100 patients in study. [PubMed]

419.

Mohr T, Podenphant J, Biering-Sorensen F, Galbo H, Thamsborg G, Kjaer M. Increased bone mineral density after prolonged electrically induced cycle training of paralyzed limbs in spinal cord injured man. Calcif Tissue Int. 1997; 61(1): 22–5. No relevant outcomes. [PubMed]

420.

Monroe MB, Tataranni PA, Pratley R, Manore MM, Skinner JS, Ravussin E. Lower daily energy expenditure as measured by a respiratory chamber in subjects with spinal cord injury compared with control subjects. Am J Clin Nutr. 1998; 68(6): 1223–7. No exercise program or physical activity. [PubMed]

421.

Morse JM, Mitcham C. The experience of agonizing pain and signals of disembodiment. J Psychosom Res. 1998 Jun;44(6): 667–80. Not eligible outcomes. [PubMed]

422.

Morton SM, Bastian AJ. Cerebellar contributions to locomotor adaptations during splitbelt treadmill walking. J Neurosci. 2006; 26(36): 9107–16. Not adult chronic SCI patients. [PubMed]

423.

Mostwin JL. Urinary incontinence.[comment]. Journal of Urology. 1995; 153(2): 352–3. No relevant data. [PubMed]

424.

Moynahan M, Mullin C, Cohn J, Burns CA, Halden EE, Triolo RJ. et al. Home use of a functional electrical stimulation system for standing and mobility in adolescents with spinal cord injury. Arch Phys Med Rehabil. 1996; 77(10): 1005–13. Not adult chronic SCI patients. [PubMed]

425.

Muller G, Odermatt P, Perret C. A new test to improve the training quality of wheelchair racing athletes. Spinal Cord. 2004; 42(10): 585–90. No relevant outcomes. [PubMed]

426.

Munakata M, Kameyama J, Kanazawa M, Nunokawa T, Moriai N, Yoshinaga K. Circadian blood pressure rhythm in patients with higher and lower spinal cord injury: simultaneous evaluation of autonomic nervous activity and physical activity. J Hypertens. 1997; 15(12): 1745–9. No relevant outcomes. [PubMed]

427.

Muraki S, Yamasaki M, Ehara Y, Kikuchi K, Seki K. Cardiovascular and respiratory responses to passive leg cycle exercise in people with spinal cord injuries. Eur J Appl Physiol Occup Physiol. 1996; 74(1): 23–8. No relevant outcomes. [PubMed]

428.

Muraki S, Yamasaki M, Ehara Y, Kikuchi K, Seki K. Effect of maximal arm exercise on skin blood flux in the paralyzed lower limbs in persons with spinal cord injury. Eur J Appl Physiol Occup Physiol. 1996; 74(5): 481–3. No relevant outcomes. [PubMed]

429.

Muraki S, Yamasaki M, Ishii K, Kikuchi K, Seki K. Relationship between core temperature and skin blood flux in lower limbs during prolonged arm exercise in persons with spinal cord injury. Eur J Appl Physiol Occup Physiol. 1996; 72(4): 330–4. No relevant outcomes. [PubMed]

430.

Murphy RJ, Hartkopp A, Gardiner PF, Kjaer M, Beliveau L. Salbutamol effect in spinal cord injured individuals undergoing functional electrical stimulation training. Arch Phys Med Rehabil. 1999; 80(10): 1264–7. No relevant outcomes. [PubMed]

431.

Murray S, Collins PD, James MA. An investigation into the ‘carry over’ effect of neurostimulation in the treatment of angina pectoris. Int J Clin Pract. 2004; 58(7): 669–74. Not adult chronic SCI patients. [PubMed]

432.

Mutton DL, Scremin AM, Barstow TJ, Scott MD, Kunkel CF, Cagle TG. Physiologic responses during functional electrical stimulation leg cycling and hybrid exercise in spinal cord injured subjects. Arch Phys Med Rehabil. 1997; 78(7): 712–8. No relevant outcomes. [PubMed]

433.

Myllynen P, Koivisto VA, Nikkila EA. Glucose intolerance and insulin resistance accompany immobilization. Acta Medica Scandinavica. 1987; 222(1): 75–81. Less than 100 patients in study. [PubMed]

434.

Naaman SC, Stein RB, Thomas C. Minimizing discomfort with surface neuromuscular stimulation. Neurorehabil Neural Repair. 2000; 14(3): 223–8. Not eligible outcomes. [PubMed]

435.

Nash MS, DeGroot J, Martinez-Arizala A, Mendez AJ. Evidence for an exaggerated postprandial lipemia in chronic paraplegia. Journal of Spinal Cord Medicine. 2005; 28(4): 320–5. Less than 100 patients in study. [PubMed] [Free Full text in PMC]

436.

Nash MS, Jacobs PL, Mendez AJ, Goldberg RB. Circuit resistance training improves the atherogenic lipid profiles of persons with chronic paraplegia. Journal of Spinal Cord Medicine. 2001; 24(1): 2–9. Less than 100 patients in study. [PubMed]

437.

Nash MS, Jacobs PL, Montalvo BM, Klose KJ, Guest RS, Needham-Shropshire BM. Evaluation of a training program for persons with SCI paraplegia using the Parastep 1 ambulation system: part 5. Lower extremity blood flow and hyperemic responses to occlusion are augmented by ambulation training. Arch Phys Med Rehabil. 1997; 78(8): 808–14. No relevant outcomes. [PubMed]

438.

Nash MS, Johnson BM, Jacobs PL. Combined hyperlipidemia in a single subject with tetraplegia: ineffective risk reduction after atorvastatin monotherapy. Journal of Spinal Cord Medicine. 2004; 27(5): 484–7. Less than 100 patients in study. [PubMed]

439.

Nash MS, Montalvo BM, Applegate B. Lower extremity blood flow and responses to occlusion ischemia differ in exercise-trained and sedentary tetraplegic persons. Arch Phys Med Rehabil. 1996; 77(12): 1260–5. No relevant outcomes. [PubMed]

440.

Nehra A, Moreland RB. Neurologic erectile dysfunction. [Review] [202 refs]. Urologic Clinics of North America. 2001; 28(2): 289–308. No relevant data. [PubMed]

441.

New PW, Rawicki HB, Bailey MJ. Nontraumatic spinal cord injury: demographic characteristics and complications. Archives of Physical Medicine & Rehabilitation. 2002; 83(7): 996–1001. No relevant data. [PubMed]

442.

Nicolle LE. Asymptomatic bacteriuria: when to screen and when to treat. Infectious Disease Clinics of North America. 2003; 17(2): 367–94. No relevant data. [PubMed]

443.

Nieshoff EC, Birk TJ, Birk CA, Hinderer SR, Yavuzer G. Double-blinded, placebo-controlled trial of midodrine for exercise performance enhancement in tetraplegia: a pilot study. J Spinal Cord Med. 2004; 27(3): 219–25. No relevant outcomes. [PubMed]

444.

Noel P. Study of afferent conduction in the external saphenous nerve using the method of evoked cerebral potentials. Revue Neurologique. 1975; 131(3): 193–210. Not english language. [PubMed]

445.

Nomura K, Takei Y, Yanagida Y. Comparison of cardio-locomotor synchronization during running and cycling. Eur J Appl Physiol. 2003; 89(3): 221–9. Not adult chronic SCI patients. [PubMed]

446.

Norman KE, Pepin A, Barbeau H. Effects of drugs on walking after spinal cord injury. Spinal Cord. 1998; 36(10): 699–715. No relevant outcomes. [PubMed]

447.

Norton JA, Gorassini MA. Changes in cortically related intermuscular coherence accompanying improvements in locomotor skills in incomplete spinal cord injury. J Neurophysiol. 2006; 95(4): 2580–9. No relevant outcomes. [PubMed]

448.

O'Connor RJ, Cano SJ, Thompson AJ, Hobart JC. Exploring rating scale responsiveness: does the total score reflect the sum of its parts? Neurology. 2004 May 25;62(10): 1842–4. Not eligible target population. [PubMed]

449.

O'Connor TJ, Cooper RA, Fitzgerald SG, Dvorznak MJ, Boninger ML, VanSickle DP. et al. Evaluation of a manual wheelchair interface to computer games. Neurorehabil Neural Repair. 2000; 14(1): 21–31. No relevant outcomes. [PubMed]

450.

O'Connor TJ, Fitzgerald SG, Cooper RA, Thorman TA, Boninger ML. Does computer game play aid in motivation of exercise and increase metabolic activity during wheelchair ergometry? Med Eng Phys. 2001; 23(4): 267–73. No relevant outcomes. [PubMed]

451.

Oester YT, Zalis AW, Rodriquez AA. Possible diagnostic applications of sensory evoked potentials. Archives of Physical Medicine & Rehabilitation. 1972; 53(1): 21–7. Not adult spinal cord injury patients. [PubMed]

452.

Ogino H, Sasaki H, Minatoya K, Matsuda H, Yamada N, Kitamura S. Combined use of adamkiewicz artery demonstration and motor-evoked potentials in descending and thoracoabdominal repair. Ann Thorac Surg. 2006 Aug;82(2): 592–6. Not eligible target population. [PubMed]

453.

Ohta Y, Hayashi T, Sasaki C, Shiote M, Manabe Y, Shoji M. et al. Cauda equina syndrome caused by idiopathic sacral epidural lipomatosis. Intern Med. 2002; 41(7): 593–4. Not adult chronic SCI patients. [PubMed]

454.

Okawa H, Tajima F, Makino K, Kawazu T, Mizushima T, Monji K. et al. Kinetic factors determining wheelchair propulsion in marathon racers with paraplegia. Spinal Cord. 1999; 37(8): 542–7. No relevant outcomes. [PubMed]

455.

Okita Y, Takamoto S, Ando M, Morota T, Yamaki F, Matsukawa R. et al. Repair for aneurysms of the entire descending thoracic aorta or thoracoabdominal aorta using a deep hypothermia. Eur J Cardiothorac Surg. 1997 Jul;12(1): 120–6. Not eligible target population. [PubMed]

456.

Oku Y, Kurusu M, Hara Y, Sugita M, Muro S, Chin K. et al. Ventilatory responses and subjective sensations during arm exercise and hypercapnia in patients with lower-cervical and upper-thoracic spinal cord injuries. Intern Med. 1997; 36(11): 776–80. No relevant outcomes. [PubMed]

457.

Olive JL, McCully KK, Dudley GA. Blood flow response in individuals with incomplete spinal cord injuries. Spinal Cord. 2002; 40(12): 639–45. No exercise program or physical activity. [PubMed]

458.

Olive JL, Slade JM, Bickel CS, Dudley GA, McCully KK. Increasing blood flow before exercise in spinal cord-injured individuals does not alter muscle fatigue. J Appl Physiol. 2004; 96(2): 477–82. No relevant outcomes. [PubMed]

459.

Olive JL, Slade JM, Dudley GA, McCully KK. Blood flow and muscle fatigue in SCI individuals during electrical stimulation. J Appl Physiol. 2003; 94(2): 701–8. No relevant outcomes. [PubMed]

460.

Orlandi G, Fanucchi S, Strata G, Pataleo L, Landucci Pellegrini L, Prontera C. et al. Transient autonomic nervous system dysfunction during hyperacute stroke. Acta Neurol Scand. 2000 Nov;102(5): 317–21. Not eligible target population. [PubMed]

461.

Osaka T, Endo M, Yamakawa M, Inoue S. Energy expenditure by intravenous administration of glucagon-like peptide-1 mediated by the lower brainstem and sympathoadrenal system. Peptides. 2005; 26(9): 1623–31. Not human subjects. [PubMed]

462.

Ozgurtas T, Alaca R, Gulec M, Kutluay T. Do spinal cord injuries adversely affect serum lipoprotein profiles? Military Medicine. 2003; 168(7): 545–7. Less than 100 patients in study. [PubMed]

463.

Pacher P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacological Reviews. 2006; 58(3): 389–462. Not adult spinal cord injury patients. [PubMed] [Free Full text in PMC]

464.

Pahl MV, Vaziri ND, Gonzales E. Coagulation profile in persons with long-standing spinal cord injury. J Am Paraplegia Soc. 1994 Jul;17(3): 133–5. Case-series. [PubMed]

465.

Papadopoulos A, Wright S, Ensor J. Evaluation and attributional analysis of an aromatherapy service for older adults with physical health problems and carers using the service. Complement Ther Med. 1999 Dec;7(4): 239–44. Not eligible target population. [PubMed]

466.

Parke WW, Whalen JL, Bunger PC, Settles HE. Intimal musculature of the lower anterior spinal artery. Spine. 1995 Oct 1;20(19): 2073–9. Not eligible target population. [PubMed]

467.

Peng CT, Ger J, Yang CC, Tsai WJ, Deng JF, Bullard MJ. Prolonged severe withdrawal symptoms after acute-on-chronic baclofen overdose. J Toxicol Clin Toxicol. 1998; 36(4): 359–63. Not adult chronic SCI patients. [PubMed]

468.

Pepin A, Ladouceur M, Barbeau H. Treadmill walking in incomplete spinal-cord-injured subjects: 2. Factors limiting the maximal speed. Spinal Cord. 2003; 41(5): 271–9. No relevant outcomes. [PubMed]

469.

Pepin A, Norman KE, Barbeau H. Treadmill walking in incomplete spinal-cord-injured subjects: 1. Adaptation to changes in speed. Spinal Cord. 2003; 41(5): 257–70. No relevant outcomes. [PubMed]

470.

Perell K, Scremin A, Scremin O, Kunkel C. Quantifying muscle tone in spinal cord injury patients using isokinetic dynamometric techniques. Paraplegia. 1996; 34(1): 46–53. No relevant outcomes. [PubMed]

471.

Perkash A, Sullivan G, Toth L, Bradleigh LH, Linder SH, Perkash I. Persistent hypercoagulation associated with heterotopic ossification in patients with spinal cord injury long after injury has occurred. Paraplegia. 1993 Oct;31(10): 653–9. Case-series. [PubMed]

472.

Perkins TA, de NDN, Hatcher NA, Swain ID, Wood DE. Control of leg-powered paraplegic cycling using stimulation of the lumbo-sacral anterior spinal nerve roots. IEEE Trans Neural Syst Rehabil Eng. 2002; 10(3): 158–64. No relevant outcomes. [PubMed]

473.

Peterson C. The use of electrical stimulation and taping to address shoulder subluxation for a patient with central cord syndrome. Phys Ther. 2004; 84(7): 634–43. No relevant outcomes. [PubMed]

474.

Petrofsky JS, Laymon M. Blood pressure and heart rate responses during a fatiguing isometric exercise in paraplegic men with hypertension. Eur J Appl Physiol. 2000; 83(4): 274–82. No relevant outcomes. [PubMed]

475.

Petrofsky JS, Stacy R, Laymon M. The relationship between exercise work intervals and duration of exercise on lower extremity training induced by electrical stimulation in humans with spinal cord injuries. Eur J Appl Physiol. 2000; 82(5): 504–9. No relevant outcomes. [PubMed]

476.

Phillips SM, Stewart BG, Mahoney DJ, Hicks AL, McCartney N, Tang JE. et al. Body-weight-support treadmill training improves blood glucose regulation in persons with incomplete spinal cord injury. Journal of Applied Physiology. 2004; 97(2): 716–24. Less than 100 patients in study. [PubMed]

477.

Phillips WT, Burkett LN. Augmented upper body contribution to oxygen uptake during upper body exercise with concurrent leg functional electrical stimulation in persons with spinal cord injury. Spinal Cord. 1998; 36(11): 750–5. No relevant outcomes. [PubMed]

478.

Piatt JH Jr. Detected and overlooked cervical spine injury among comatose trauma patients: from the Pennsylvania Trauma Outcomes Study. Neurosurg Focus. 2005 Oct 15;19(4): E6. Not eligible outcomes. [PubMed]

479.

Pongratz G, Zietz B, Gluck T, Scholmerich J, Straub RH. Corticotropin-releasing factor modulates cardiovascular and pupillary autonomic reflexes in man: is there a link to inflammation-induced autonomic nervous hyperreflexia? Ann N Y Acad Sci. 2002 Jun;966: 373–83. Not eligible target population. [PubMed]

480.

Popovic MR, Keller T, Pappas IP, Dietz V, Morari M. Surface-stimulation technology for grasping and walking neuroprosthesis. IEEE Eng Med Biol Mag. 2001 Jan–Feb;20(1): 82–93. Not eligible target population. [PubMed]

481.

Popovic MR, Thrasher TA, Adams ME, Takes V, Zivanovic V, Tonack MI. Functional electrical therapy: retraining grasping in spinal cord injury. Spinal Cord. 2006; 44(3): 143–51. No relevant outcomes. [PubMed]

482.

Post MJ, Becerra JL, Madsen PW, Puckett W, Quencer RM, Bunge RP. et al. Acute spinal subdural hematoma: MR and CT findings with pathologic correlates. AJNR Am J Neuroradiol. 1994 Nov;15(10): 1895–905. Not eligible target population. [PubMed]

483.

Powell M, Kirshblum S, O'Connor KC. Duplex ultrasound screening for deep vein thrombosis in spinal cord injured patients at rehabilitation admission. Arch Phys Med Rehabil. 1999 Sep;80(9): 1044–6. Not eligible target population. [PubMed]

484.

Price MJ, Campbell IG. Thermoregulatory responses of spinal cord injured and able-bodied athletes to prolonged upper body exercise and recovery. Spinal Cord. 1999; 37(11): 772–9. No relevant outcomes. [PubMed]

485.

Price MJ, Campbell IG. Thermoregulatory responses during prolonged upper-body exercise in cool and warm conditions. J Sports Sci. 2002; 20(7): 519–27. No relevant outcomes. [PubMed]

486.

Price MJ, Campbell IG. Effects of spinal cord lesion level upon thermoregulation during exercise in the heat. Med Sci Sports Exerc. 2003; 35(7): 1100–7. No relevant outcomes. [PubMed]

487.

Price R, Lehmann JF, Boswell-Bessette S, Burleigh A, deLateur BJ. Influence of cryotherapy on spasticity at the human ankle. Arch Phys Med Rehabil. 1993 Mar;74(3): 300–4. Not eligible outcomes. [PubMed]

488.

Prophet S. Summary of ICD-9-CM Coordination and Maintenance Committee meeting. Journal of Ahima. 1999; 70(2): 64–70. quiz 5–6. No relevant data. [PubMed]

489.

Protas EJ, Holmes SA, Qureshy H, Johnson A, Lee D, Sherwood AM. Supported treadmill ambulation training after spinal cord injury: a pilot study. Arch Phys Med Rehabil. 2001; 82(6): 825–31. No relevant outcomes. [PubMed]

490.

Quirke TE, Ritota PC, Swan KG. Inferior vena caval filter use in U.S. trauma centers: a practitioner survey. Journal of Trauma-Injury Infection & Critical Care. 1997; 43(2): 333–7. No relevant data.

491.

Rades D, Hoskin PJ, Stalpers LJ, Schulte R, Poortmans P, Veninga T. et al. Short-course radiotherapy is not optimal for spinal cord compression due to myeloma. Int J Radiat Oncol Biol Phys. 2006 Apr 1;64(5): 1452–7. Not eligible target population. [PubMed]

492.

Raymond J, Davis GM, Clarke J, Bryant G. Cardiovascular responses during arm exercise and orthostatic challenge in individuals with paraplegia. Eur J Appl Physiol. 2001; 85(1): 89–95. No relevant outcomes. [PubMed]

493.

Raymond J, Davis GM, Climstein M, Sutton JR. Cardiorespiratory responses to arm cranking and electrical stimulation leg cycling in people with paraplegia. Med Sci Sports Exerc. 1999; 31(6): 822–8. No relevant outcomes. [PubMed]

494.

Raymond J, Davis GM, Fahey A, Climstein M, Sutton JR. Oxygen uptake and heart rate responses during arm vs combined arm/electrically stimulated leg exercise in people with paraplegia. Spinal Cord. 1997; 35(10): 680–5. No relevant outcomes. [PubMed]

495.

Raymond J, Davis GM, van der Plas M. Cardiovascular responses during submaximal electrical stimulation-induced leg cycling in individuals with paraplegia. Clin Physiol Funct Imaging. 2002; 22(2): 92–8. No relevant outcomes. [PubMed]

496.

Raymond J, Schoneveld K, Van Kemenade CH, Davis GM. Onset of electrical stimulation leg cycling in individuals with paraplegia. Med Sci Sports Exerc. 2002; 34(10): 1557–62. No relevant outcomes. [PubMed]

497.

Razdan S, Kaul RL, Motta A, Kaul S, Bhatt RK. Prevalence and pattern of major neurological disorders in rural Kashmir (India) in 1986. Neuroepidemiology. 1994; 13(3): 113–9. Not eligible outcomes. [PubMed]

498.

Rena F, Moshe S, Abraham O. Couples' adjustment to one partner's disability: the relationship between sense of coherence and adjustment. Soc Sci Med. 1996 Jul;43(2): 163–71. Not eligible outcomes. [PubMed]

499.

Rendeli C, Castorina M, Ausili E, Girardi E, Fundaro C, Caldarelli M. et al. Risk factors for atherogenesis in children with spina bifida. Childs Nervous System. 2004; 20(6): 392–6. Not adult spinal cord injury patients.

500.

Rieder HP, Peyer C. Sex differences in the serum lipoprotein relations of normal persons and multiple sclerosis patients. Clinica Chimica Acta. 1970; 30(2): 305–10. Not adult spinal cord injury patients.

501.

Rittenberg JD, Burns SP, Little JW. Worsening myelopathy masked by peripheral nerve disorders. Journal of Spinal Cord Medicine. 2004; 27(1): 72–7. Less than 100 patients in study. [PubMed]

502.

Rodgers MM, Keyser RE, Gardner ER, Russell PJ, Gorman PH. Influence of trunk flexion on biomechanics of wheelchair propulsion. J Rehabil Res Dev. 2000; 37(3): 283–95. No relevant outcomes. [PubMed]

503.

Rodgers MM, Keyser RE, Rasch EK, Gorman PH, Russell PJ. Influence of training on biomechanics of wheelchair propulsion. J Rehabil Res Dev. 2001; 38(5): 505–11. No relevant outcomes. [PubMed]

504.

Rohde V, Kuker W, Reinges MH, Gilsbach JM. Microsurgical treatment of spontaneous and non-spontaneous spinal epidural haematomas: neurological outcome in relation to aetiology. Acta Neurochir (Wien). 2000; 142(7): 787–92. discussion 92–3. Not eligible target population. [PubMed]

505.

Roig RL, Worsowicz GM, Stewart DG, Cifu DX. Geriatric rehabilitation. 3. Physical medicine and rehabilitation interventions for common disabling disorders. Archives of Physical Medicine & Rehabilitation. 2004; 85(7 Suppl 3): S12–7. quiz S27–30. No relevant data. [PubMed]

506.

Rosche J, Paulus C, Maisch U, Kaspar A, Mauch E, Kornhuber HH. The effects of therapy on spasticity utilizing a motorized exercise-cycle. Spinal Cord. 1997; 35(3): 176–8. No relevant outcomes. [PubMed]

507.

Rotter KP, Larrain CG. Gallstones in spinal cord injury (SCI): a late medical complication? Spinal Cord. 2003; 41(2): 105–8. No relevant data. [PubMed]

508.

Rousseau MC, Guillotel B. Risk factors for deep venous thrombosis in tetraparesic mentally retarded patients. Brain Inj. 2001 Dec;15(12): 1041–4. Not eligible target population. [PubMed]

509.

Roussi J, Bentolila S, Boudaoud L, Casadevall N, Vallee C, Carlier R. et al. Contribution of D-Dimer determination in the exclusion of deep venous thrombosis in spinal cord injury patients. Spinal Cord. 1999 Aug;37(8): 548–52. Not eligible outcomes. [PubMed]

510.

Rubenstein JN, Schaeffer AJ. Managing complicated urinary tract infections: the urologic view. Infectious Disease Clinics of North America. 2003; 17(2): 333–51. No relevant data. [PubMed]

511.

Rutchik A, Weissman AR, Almenoff PL, Spungen AM, Bauman WA, Grimm DR. Resistive inspiratory muscle training in subjects with chronic cervical spinal cord injury. Arch Phys Med Rehabil. 1998; 79(3): 293–7. No relevant outcomes. [PubMed]

512.

Sabatier MJ, Stoner L, Mahoney ET, Black C, Elder C, Dudley GA. et al. Electrically stimulated resistance training in SCI individuals increases muscle fatigue resistance but not femoral artery size or blood flow. Spinal Cord. 2006; 44(4): 227–33. No relevant outcomes. [PubMed]

513.

Sabick MB, Kotajarvi BR, An KN. A new method to quantify demand on the upper extremity during manual wheelchair propulsion. Arch Phys Med Rehabil. 2004 Jul;85(7): 1151–9. Not eligible outcomes. [PubMed]

514.

Saenz de Tejada I, Goldstein I. Diabetic penile neuropathy. Urologic Clinics of North America. 1988; 15(1): 17–22. Not adult spinal cord injury patients. [PubMed]

515.

Sae-Sia W, Wipke-Tevis DD, Williams DA. Elevated sacral skin temperature (T(s)): a risk factor for pressure ulcer development in hospitalized neurologically impaired Thai patients. Appl Nurs Res. 2005 Feb;18(1): 29–35. Not eligible outcomes. [PubMed]

516.

Safi HJ, Miller CC 3rd. Spinal cord protection in descending thoracic and thoracoabdominal aortic repair. Ann Thorac Surg. 1999 Jun;67(6): 1937–9. discussion 53–8. Not eligible target population. [PubMed]

517.

Sairyo K, Katoh S, Sakai T, Mishiro T, Ikata T. Characteristics of velocity-controlled knee movement in patients with cervical compression myelopathy: what is the optimal rehabilitation exercise for spastic gait? Spine. 2001; 26(23): E535–8. Not adult chronic SCI patients. [PubMed]

518.

Saltzstein RJ, Hardin S, Hastings J. Osteoporosis in spinal cord injury: using an index of mobility and its relationship to bone density. J Am Paraplegia Soc. 1992 Oct;15(4): 232–4. Not eligible outcomes. [PubMed]

519.

Salvador de la Barrera S, Barca-Buyo A, Montoto-Marques A, Ferreiro-Velasco ME, Cidoncha-Dans M, Rodriguez-Sotillo A. Spinal cord infarction: prognosis and recovery in a series of 36 patients. Spinal Cord. 2001 Oct;39(10): 520–5. Not eligible target population. [PubMed]

520.

Sampson EE, Burnham RS, Andrews BJ. Functional electrical stimulation effect on orthostatic hypotension after spinal cord injury. Arch Phys Med Rehabil. 2000 Feb;81(2): 139–43. Not eligible outcomes. [PubMed]

521.

Sankale M, Diop B, Quenum C, Ancelle JP, Frament V. 4 atypical cases of primary carcinoma of the liver. Semaine des Hopitaux. 1969; 45(5): 301–8. Not english language. [PubMed]

522.

Scalzitti DA. Because of the risk of developing heterotopic ossification, are passive range of motion exercises contraindicated following traumatic injuries? Phys Ther. 2003; 83(7): 659–7. No relevant outcomes. [PubMed]

523.

Scelsi R, Scelsi L, Bocchi R, Lotta S. Morphological changes in the skin microlymphatics in recently injured paraplegic patients with ilio-femoral venous thrombosis. Paraplegia. 1995 Aug;33(8): 472–5. Not eligible target population. [PubMed]

524.

Scelza WM, Kalpakjian CZ, Zemper ED, Tate DG. Perceived barriers to exercise in people with spinal cord injury. Am J Phys Med Rehabil. 2005; 84(8): 576–83. No relevant outcomes. [PubMed]

525.

Schalow G. Partial cure of spinal cord injury achieved by 6 to 13 months of coordination dynamic therapy. Electromyogr Clin Neurophysiol. 2003; 43(5): 281–92. No relevant outcomes. [PubMed]

526.

Schalow G, Blanc Y, Jeltsch W, Zach GA. Electromyographic identification of spinal oscillator patterns and recouplings in a patient with incomplete spinal cord lesion: oscillator formation training as a method to improve motor activities. Gen Physiol Biophys. 1996; 15(Suppl 1): 121–220. No relevant outcomes. [PubMed]

527.

Schalow G, Paasuke M. Low-load coordination dynamics in athletes, physiotherapists, gymnasts, musicians and patients with spinal cord injury, after stroke, traumatic brain lesion and with cerebral palsy. Electromyogr Clin Neurophysiol. 2003; 43(4): 195–201. No relevant outcomes. [PubMed]

528.

Schalow G, Paasuke M, Kolts I. High-load coordination dynamics in athletes, physiotherapists, gymnasts, musicians and patients with CNS injury. Electromyogr Clin Neurophysiol. 2003; 43(6): 353–65. No relevant outcomes. [PubMed]

529.

Schizas C, Ballesteros C, Roy P. Cauda equina compression after trauma: an unusual presentation of spinal epidural lipoma. Spine. 2003; 28(8): E148–51. Less than 100 patients in study. [PubMed]

530.

Schmid A, Halle M, Stutzle C, Konig D, Baumstark MW, Storch MJ. et al. Lipoproteins and free plasma catecholamines in spinal cord injured men with different injury levels. Clin Physiol. 2000 Jul;20(4): 304–10. Not eligible outcomes. [PubMed]

531.

Schmid A, Huonker M, Barturen JM, Stahl F, Schmidt-Trucksass A, Konig D. et al. Catecholamines, heart rate, and oxygen uptake during exercise in persons with spinal cord injury. J Appl Physiol. 1998; 85(2): 635–41. No relevant outcomes. [PubMed]

532.

Schmid A, Huonker M, Stahl F, Barturen JM, Konig D, Heim M. et al. Free plasma catecholamines in spinal cord injured persons with different injury levels at rest and during exercise. J Auton Nerv Syst. 1998; 68(1): 96–100. No relevant outcomes. [PubMed]

533.

Schmid A, Huonker M, Stober P, Barturen JM, Schmidt-Trucksass A, Durr H. et al. Physical performance and cardiovascular and metabolic adaptation of elite female wheelchair basketball players in wheelchair ergometry and in competition. Am J Phys Med Rehabil. 1998; 77(6): 527–33. No relevant outcomes. [PubMed]

534.

Schmid A, Schmidt-Trucksass A, Huonker M, Konig D, Eisenbarth I, Sauerwein H. et al. Catecholamines response of high performance wheelchair athletes at rest and during exercise with autonomic dysreflexia. Int J Sports Med. 2001; 22(1): 2–7. No relevant outcomes. [PubMed]

535.

Schmitt AB, Buss A, Breuer S, Brook GA, Pech K, Martin D. et al. Major histocompatibility complex class II expression by activated microglia caudal to lesions of descending tracts in the human spinal cord is not associated with a T cell response. Acta Neuropathol (Berl). 2000 Nov;100(5): 528–36. Not eligible target population. [PubMed]

536.

Schneider DA, Sedlock DA, Gass E, Gass G. VO2peak and the gas-exchange anaerobic threshold during incremental arm cranking in able-bodied and paraplegic men. Eur J Appl Physiol Occup Physiol. 1999; 80(4): 292–7. No relevant outcomes. [PubMed]

537.

Schubert V, Fagrell B. Postocclusive reactive hyperemia and thermal response in the skin microcirculation of subjects with spinal cord injury. Scand J Rehabil Med. 1991; 23(1): 33–40. Not eligible outcomes. [PubMed]

538.

Scott CI Jr. Medical and social adaptation in dwarfing conditions. Birth Defects: Original Article Series. 1977; 13(3C): 29–43. Not adult spinal cord injury patients. [PubMed]

539.

Scott D, Papa MZ, Sareli M, Velano A, Ben-Ari GY, Koller M. Management of hemorrhoidal disease in patients with chronic spinal cord injury. Tech Coloproctol. 2002 Apr;6(1): 19–22. Not eligible outcomes. [PubMed]

540.

Scremin AM, Kurta L, Gentili A, Wiseman B, Perell K, Kunkel C. et al. Increasing muscle mass in spinal cord injured persons with a functional electrical stimulation exercise program. Arch Phys Med Rehabil. 1999; 80(12): 1531–6. No relevant outcomes. [PubMed]

541.

Sedlock DA, Schneider DA, Gass E, Gass G. Excess post-exercise oxygen consumption in spinal cord-injured men. Eur J Appl Physiol. 2004; 93(1): 231–6. No relevant outcomes. [PubMed]

542.

Seelen HA, Potten YJ, Drukker J, Reulen JP, Pons C. Development of new muscle synergies in postural control in spinal cord injured subjects. J Electromyogr Kinesiol. 1998; 8(1): 23–34. No relevant outcomes. [PubMed]

543.

Selmi F, Davies KG, Sharma RR, Redfern RM. Idiopathic spinal extradural lipomatosis in a non-obese otherwise healthy man. British Journal of Neurosurgery. 1994; 8(3): 355–8. Not adult spinal cord injury patients. [PubMed]

544.

Sencer W. THE CEREBROSPINAL FLUID IN MYELORADICULOPATHIES ASSOCIATED WITH DIABETES MELLITUS. Journal of the Mount Sinai Hospital, New York. 1964 May–Jun;31: 202–11. Not adult spinal cord injury patients.

545.

Seymour RJ, Lacefield WE. Wheelchair cushion effect on pressure and skin temperature. Archives of Physical Medicine & Rehabilitation. 1985; 66(2): 103–8. No relevant data. [PubMed]

546.

Shaffer EA. Gallstone disease: Epidemiology of gallbladder stone disease. Best Practice & Research in Clinical Gastroenterology. 2006; 20(6): 981–96. Not adult spinal cord injury patients.

547.

Shetty KR, Sutton CH, Rudman IW, Rudman D. Lipid and lipoprotein abnormalities in young quadriplegic men. American Journal of the Medical Sciences. 1992; 303(4): 213–6. Less than 100 patients in study. [PubMed]

548.

Shiiya N, Kunihara T, Matsuzaki K, Yasuda K. Evolving strategy and results of spinal cord protection in type I and II thoracoabdominal aortic aneurysm repair. Ann Thorac Cardiovasc Surg. 2005 Jun;11(3): 178–85. Not eligible target population. [PubMed]

549.

Shimizu T, Shimada H, Shirakura K. Scapulohumeral reflex (Shimizu). Its clinical significance and testing maneuver. Spine. 1993 Nov;18(15): 2182–90. Not eligible outcomes. [PubMed]

550.

Shiraishi N, Matsumura G. Prevention of vascular injury to the spinal cord incidence of a great posterior radicular artery. Okajimas Folia Anat Jpn. 2005 Mar;81(6): 143–6. Not eligible target population. [PubMed]

551.

Sidman JM. Sexual functioning and the physically disabled adult. American Journal of Occupational Therapy. 1977; 31(2): 81–5. No relevant data. [PubMed]

552.

Silva AC, Neder JA, Chiurciu MV, Pasqualin DC, da Silva RC, Fernandez AC. et al. Effect of aerobic training on ventilatory muscle endurance of spinal cord injured men. Spinal Cord. 1998; 36(4): 240–5. No relevant outcomes. [PubMed]

553.

Silver JR, Noori Z. Pulmonary embolism following anticoagulation therapy. International Disability Studies. 1991; 13(1): 16–9. Less than 100 patients in study. [PubMed]

554.

Sinderby C, Weinberg J, Sullivan L, Borg J, Lindstrom L, Grassino A. Diaphragm function in patients with cervical cord injury or prior poliomyelitis infection. Spinal Cord. 1996; 34(4): 204–13. No relevant outcomes. [PubMed]

555.

Sinderby C, Weinberg J, Sullivan L, Lindstrom L, Grassino A. Electromyographical evidence for exercise-induced diaphragm fatigue in patients with chronic cervical cord injury or prior poliomyelitis infection. Spinal Cord. 1996; 34(10): 594–601. No relevant outcomes. [PubMed]

556.

Singh A, Crockard HA. Quantitative assessment of cervical spondylotic myelopathy by a simple walking test. Lancet. 1999; 354(9176): 370–3. Not adult chronic SCI patients. [PubMed]

557.

Slade JM, Bickel CS, Dudley GA. The effect of a repeat bout of exercise on muscle injury in persons with spinal cord injury. Eur J Appl Physiol. 2004; 92(3): 363–6. No relevant outcomes. [PubMed]

558.

Sliwa JA, Mason K, Yarkony G, Press J, Lovell L. The value of routine chest roentgenograms on admission for rehabilitation after traumatic spinal cord injury. Am J Phys Med Rehabil. 1994 Apr;73(2): 84–8. Not eligible target population. [PubMed]

559.

Smals AG. Impotence: organic causes. Nederlands Tijdschrift voor Geneeskunde. 1986; 130(15): 675–80. Not english language. [PubMed]

560.

Smith HC, Davey NJ, Savic G, Maskill DW, Ellaway PH, Frankel HL. Motor unit discharge characteristics during voluntary contraction in patients with incomplete spinal cord injury. Exp Physiol. 1999 Nov;84(6): 1151–60. Not eligible outcomes. [PubMed]

561.

Smith J, Caldwell E, Sugrue M. Difference in trauma team activation criteria between hospitals within the same region. Emerg Med Australas. 2005 Oct–Dec;17(56): 480–7. Not eligible target population. [PubMed]

562.

Stanghelle JK, Festvag LV. Postpolio syndrome: a 5 year follow-up. Spinal Cord. 1997; 35(8): 503–8. Not adult chronic SCI patients. [PubMed]

563.

Steers WD. Rat: overview and innervation. [Review] [112 refs]. Neurourology & Urodynamics. 1994; 13(2): 97–118. Not human subjects. [PubMed]

564.

Stein RB, Chong SL, James KB, Bell GJ. Improved efficiency with a wheelchair propelled by the legs using voluntary activity or electric stimulation. Arch Phys Med Rehabil. 2001; 82(9): 1198–203. No exercise program or physical activity. [PubMed]

565.

Stein RB, Zehr EP, Lebiedowska MK, Popovic DB, Scheiner A, Chizeck HJ. Estimating mechanical parameters of leg segments in individuals with and without physical disabilities. IEEE Trans Rehabil Eng. 1996 Sep;4(3): 201–11. Not eligible outcomes. [PubMed]

566.

Steinberg LL, Lauro FA, Sposito MM, Tufik S, Mello MT, Naffah-Mazzacoratti MG. et al. Catecholamine response to exercise in individuals with different levels of paraplegia. Braz J Med Biol Res. 2000; 33(8): 913–8. No relevant outcomes. [PubMed]

567.

Steinberg LL, Sposito MM, Lauro FA, Tufik S, Mello MT, Naffah-Mazzacoratti MG. et al. Serum level of serotonin during rest and during exercise in paraplegic patients. Spinal Cord. 1998; 36(1): 18–20. No relevant outcomes. [PubMed]

568.

Sterbis JR, Lewis VL, Bushman W. Urologic and plastic surgical collaboration for continent diversion when urine leakage is complicated by pressure ulcers or obesity. Journal of Spinal Cord Medicine. 2003; 26(2): 124–8. No relevant data. [PubMed]

569.

Stoner L, Sabatier M, VanhHiel L, Groves D, Ripley D, Palardy G. et al. Upper vs lower extremity arterial function after spinal cord injury. J Spinal Cord Med. 2006; 29(2): 138–46. Not eligible outcomes. [PubMed] [Free Full text in PMC]

570.

Strachan RK, Cook J, Wilkie W, Kennedy NS. An evaluation of pneumatic orthoses in thoracic paraplegia. Paraplegia. 1985; 23(5): 295–305. Less than 100 patients in study. [PubMed]

571.

Stroman PW, Nance PW, Ryner LN. BOLD MRI of the human cervical spinal cord at 3 tesla. Magn Reson Med. 1999; 42(3): 571–6. Not adult chronic SCI patients. [PubMed]

572.

Subbotin AV, Kovalenko VN, Apasova NA. The clinical picture and differential diagnosis of spinal strokes. Zhurnal Nevropatologii i Psikhiatrii Imeni S - S - Korsakova. 1970; 70(6): 824–8. Not english language. [PubMed]

573.

Sugiyama T, Fugelso P, Avon M. Extracorporeal shock wave lithotripsy in neurologically impaired patients. Semin Urol. 1992 May;10(2): 109–11. Not eligible outcomes. [PubMed]

574.

Sutbeyaz ST, Koseoglu BF, Gokkaya NK. The combined effects of controlled breathing techniques and ventilatory and upper extremity muscle exercise on cardiopulmonary responses in patients with spinal cord injury. Int J Rehabil Res. 2005; 28(3): 273–6. No relevant outcomes. [PubMed]

575.

Swarczinski C, Dijkers M. The value of serial leg measurements for monitoring deep vein thrombosis in spinal cord injury. J Neurosci Nurs. 1991 Oct;23(5): 306–14. Not eligible target population. [PubMed]

576.

Sytin LV, Slepushkin VD, Zoloev GK, Argintaev ES, Lasukova TV. Disorders of metabolism and their pathogenesis in patients with spinal cord injuries. Ortopediia Travmatologiia i Protezirovanie 1989(5):16–8. Not english language.

577.

Szlachcic Y, Adkins RH, Adal T, Yee F, Bauman W, Waters RL. The effect of dietary intervention on lipid profiles in individuals with spinal cord injury. J Spinal Cord Med. 2001 Spring;24(1): 26–9. Not eligible exposure. [PubMed]

578.

Szlachcic Y, Adkins RH, Waters RL, Govindarajan S, Wang J, Yee F. et al. Incidence and clinical correlates of increased serum creatine kinase levels in persons with spinal cord injury. J Spinal Cord Med. 2002; 25(3): 156–60. No exercise program or physical activity. [PubMed]

579.

Taira T, Kawamura H, Tanikawa T, Iseki H, Kawabatake H, Takakura K. A new approach to control central deafferentation pain: spinal intrathecal baclofen. Stereotact Funct Neurosurg. 1995; 65(14): 101–5. Not eligible outcomes. [PubMed]

580.

Taira T, Kawamura H, Tanikawa T, Kawabatake H, Iseki H, Ueda A. et al. A new approach to the control of central deafferentation pain—spinal intrathecal baclofen. Acta Neurochir Suppl. 1995; 64: 136–8. Not eligible outcomes. [PubMed]

581.

Takahashi M, Sakaguchi A, Matsukawa K, Komine H, Kawaguchi K, Onari K. Cardiovascular control during voluntary static exercise in humans with tetraplegia. J Appl Physiol. 2004; 97(6): 2077–82. No relevant outcomes. [PubMed]

582.

Tarabulcy E. Neurogenic diseases of the bladder in the geriatric population. Geriatrics. 1974; 29(9): 123–8. passim. No relevant data. [PubMed]

583.

Tariq M, Morais C, Kishore PN, Biary N, Al Deeb S, Al Moutaery K. Neurological recovery in diabetic rats following spinal cord injury. Journal of Neurotrauma. 1998; 15(4): 239–51. Not human subjects. [PubMed]

584.

Tator CH, Koyanagi I. Vascular mechanisms in the pathophysiology of human spinal cord injury. J Neurosurg. 1997 Mar;86(3): 483–92. Not eligible target population. [PubMed]

585.

Taylor PN, Burridge JH, Dunkerley AL, Wood DE, Norton JA, Singleton C. et al. Clinical use of the Odstock dropped foot stimulator: its effect on the speed and effort of walking. Arch Phys Med Rehabil. 1999 Dec;80(12): 1577–83. Not eligible outcomes. [PubMed]

586.

Teasell RW, Arnold JM. Alpha-1 adrenoceptor hyperresponsiveness in three neuropathic pain states: complex regional pain syndrome 1, diabetic peripheral neuropathic pain and central pain states following spinal cord injury. Pain Research & Management. 2004; 9(2): 89–97. No relevant data. [PubMed]

587.

Teixeira da Cunha-Filho I, Henson H, Qureshy H, Williams AL, Holmes SA, Protas EJ. Differential responses to measures of gait performance among healthy and neurologically impaired individuals. Arch Phys Med Rehabil. 2003; 84(12): 1774–9. No relevant outcomes. [PubMed]

588.

Telfeian AE, Reiter GT, Durham SR, Marcotte P. Spine surgery in morbidly obese patients. Journal of Neurosurgery. 2002; 97(1 Suppl): 20–4. Less than 100 patients in study. [PubMed]

589.

Ter Woerds W, De Groot PC, van Kuppevelt DH, Hopman MT. Passive leg movements and passive cycling do not alter arterial leg blood flow in subjects with spinal cord injury. Phys Ther. 2006; 86(5): 636–45. No relevant outcomes. [PubMed]

590.

Theisen D, Fornusek C, Raymond J, Davis GM. External power output changes during prolonged cycling with electrical stimulation. J Rehabil Med. 2002; 34(4): 171–5. No relevant outcomes. [PubMed]

591.

Theisen D, Vanlandewijck Y, Sturbois X, Francaux M. Cutaneous vascular response and thermoregulation in individuals with paraplegia during sustained arm-cranking exercise. Int J Sports Med. 2001; 22(2): 97–102. No relevant outcomes. [PubMed]

592.

Thijssen DH, Heesterbeek P, van Kuppevelt DJ, Duysens J, Hopman MT. Local vascular adaptations after hybrid training in spinal cord-injured subjects. Med Sci Sports Exerc. 2005; 37(7): 1112–8. No relevant outcomes. [PubMed]

593.

Thomas AJ Jr. Ejaculatory dysfunction. Fertility & Sterility. 1983; 39(4): 445–54. No relevant data. [PubMed]

594.

Thomas SL, Gorassini MA. Increases in corticospinal tract function by treadmill training after incomplete spinal cord injury. J Neurophysiol. 2005; 94(4): 2844–55. No relevant outcomes. [PubMed]

595.

Thorfinn J, Sjoberg F, Sjostrand L, Lidman D. Perfusion of the skin of the buttocks in paraplegic and tetraplegic patients, and in healthy subjects after a short and long load. Scand J Plast Reconstr Surg Hand Surg. 2006; 40(3): 153–60. Not eligible outcomes. [PubMed]

596.

Thrasher TA, Flett HM, Popovic MR. Gait training regimen for incomplete spinal cord injury using functional electrical stimulation. Spinal Cord. 2006; 44(6): 357–61. No relevant outcomes. [PubMed]

597.

Thyberg M, Ertzgaard P, Gylling M, Granerus G. Blood pressure response to detrusor pressure elevation in patients with a reflex urinary bladder after a cervical or high thoracic spinal cord injury. Scand J Rehabil Med. 1992 Dec;24(4): 187–93. Not eligible outcomes. [PubMed]

598.

Tomaio A, Kirshblum SC, O'Connor KC, Johnston M. Treatment of acute deep vein thrombosis in spinal cord injured patients with enoxaparin: a cost analysis. J Spinal Cord Med. 1998 Jul;21(3): 205–10. Not eligible target population. [PubMed]

599.

Trimble MH, Kukulka CG, Behrman AL. The effect of treadmill gait training on low-frequency depression of the soleus H-reflex: comparison of a spinal cord injured man to normal subjects. Neurosci Lett. 1998; 246(3): 186–8. No relevant outcomes. [PubMed]

600.

Trumbower RD, Faghri PD. Kinematic analyses of semireclined leg cycling in able-bodied and spinal cord injured individuals. Spinal Cord. 2005; 43(9): 543–9. No relevant outcomes. [PubMed]

601.

Truss MC, Djamilian MH, Tan HK, Hinrichs H, Feistner H, Stief CG. et al. Single potential analysis of cavernous electrical activity. Four years' experience in more than 500 patients with erectile dysfunction. European Urology. 1993; 24(3): 358–65. No relevant data. [PubMed]

602.

Tsuji M, Kurihara A, Uratsuji M, Shoda E. Cervical myelopathy with Prader-Willi syndrome in a 13-year-old boy. A case report. Spine. 1991; 16(11): 1342–4. Not adult spinal cord injury patients. [PubMed]

603.

Uijl SG, Houtman S, Folgering HT, Hopman MT. Training of the respiratory muscles in individuals with tetraplegia. Spinal Cord. 1999; 37(8): 575–9. No relevant outcomes. [PubMed]

604.

Unsal A, Yilmaz B, Turgut AT, Taskin F, Alaca R, Karaman CZ. Evaluation of varicocele frequency of patients with spinal cord injury by color Doppler ultrasonography: a new etiological factor for varicocele? Eur J Radiol. 2006 Jan;57(1): 154–7. Not eligible outcomes. [PubMed]

605.

Vale FL, Oliver M, Cahill DW. Rigid occipitocervical fusion. J Neurosurg. 1999 Oct;91(2 Suppl): 144–50. Not eligible outcomes. [PubMed]

606.

van Dijk JM, Lubout CM, Brouwer PA. Cervical high-intensity intramedullary lesions without spinal cord compression in achondroplasia. J Neurosurg Spine. 2007 Apr;6(4): 304–8. Not eligible target population. [PubMed]

607.

van Hedel HJ, Waldvogel D, Dietz V. Learning a high-precision locomotor task in patients with Parkinson's disease. Mov Disord. 2006; 21(3): 406–11. Not adult chronic SCI patients. [PubMed]

608.

van Hedel HJ, Wirth B, Dietz V. Limits of locomotor ability in subjects with a spinal cord injury. Spinal Cord. 2005; 43(10): 593–603. No relevant outcomes. [PubMed]

609.

Vaziri ND, Gordon S, Nikakhtar B. Lipid abnormalities in chronic renal failure associated with spinal cord injury. Paraplegia. 1982; 20(3): 183–9. Less than 100 patients in study. [PubMed]

610.

Vemireddi NK. Sexual counseling for chronically disabled patients. Geriatrics. 1978; 33(7): 65–9. No relevant data. [PubMed]

611.

Ventimiglia B, Patti F, Reggio E, Failla G, Morana C, Lopes M. et al. Disorders of micturition in neurological patients. A clinical study of 786 patients. J Neurol. 1998 Mar;245(3): 173–7. Not eligible outcomes. [PubMed]

612.

Verellen J, Theisen D, Vanlandewijck Y. Influence of crank rate in hand cycling. Med Sci Sports Exerc. 2004; 36(10): 1826–31. No relevant outcomes. [PubMed]

613.

Veron JP, Escourolle R. Current data on orthostatic hypotension. Presse Medicale. 1968; 76(49): 2343–6. Not english language. [PubMed]

614.

Vestergaard P, Krogh K, Rejnmark L, Mosekilde L. Fracture rates and risk factors for fractures in patients with spinal cord injury. Spinal Cord. 1998; 36(11): 790–6. No exercise program or physical activity. [PubMed]

615.

Vidal J, Javierre C, Curia FJ, Garrido E, Lizarraga MA, Segura R. Long-term evolution of blood lipid profiles and glycemic levels in patients after spinal cord injury. Spinal Cord. 2003; 41(3): 178–81. No relevant data. [PubMed]

616.

Vidal J, Javierre C, Segura R, Lizarraga A, Barbany JR, Perez A. Physiological adaptations to exercise in people with spinal cord injury. J Physiol Biochem. 2003; 59(1): 11–8. No relevant outcomes. [PubMed]

617.

Vinet A, Bernard PL, Poulain M, Varray A, Le Gallais D, Micallef JP. Validation of an incremental field test for the direct assessment of peak oxygen uptake in wheelchair-dependent athletes. Spinal Cord. 1996; 34(5): 288–93. No relevant outcomes. [PubMed]

618.

Vinet A, Le Gallais D, Bouges S, Bernard PL, Poulain M, Varray A. et al. Prediction of VO(2peak) in wheelchair-dependent athletes from the adapted Leger and Boucher test. Spinal Cord. 2002; 40(10): 507–12. No relevant outcomes. [PubMed]

619.

Vitenzon AS, Mironov EM, Petrushanskaya KA. Functional electrostimulation of muscles as a method for restoring motor functions. Neurosci Behav Physiol. 2005 Sep;35(7): 709–14. Not eligible outcomes. [PubMed]

620.

Vogel G. Cell biology. Still waiting their turn. Science. 2005; 308(5728): 1536–7. No relevant data. [PubMed]

621.

Wade TP, Andrus CH. Cardiorespiratory effects of laparotomy in patients with spinal cord injury. Am Surg. 1993 Oct;59(10): 689–91. Not eligible exposure. [PubMed]

622.

Wald A. Systemic diseases causing disorders of defecation and continence. Seminars in Gastrointestinal Disease. 1995; 6(4): 194–202. No relevant data. [PubMed]

623.

Walker WA, Evans BJ, Pate JW, Weiman DS, Riddle JC. Coronary operations in patients with spinal cord injury. Ann Thorac Surg. 1996 Mar;61(3): 789–94. Case-series. [PubMed]

624.

Wall BM, Huch KM, Runyan KR, Williams HH, Gavras H, Cooke CR. Effects of vasopressin V1-receptor blockade during acute and sustained hypovolemic hypotension. Am J Physiol. 1996 Feb;270(2 Pt 2): R356–64. Not eligible exposure. [PubMed]

625.

Wallington M, Mendis S, Premawardhana U, Sanders P, Shahsavar-Haghighi K. Local control and survival in spinal cord compression from lymphoma and myeloma. Radiother Oncol. 1997 Jan;42(1): 43–7. Not eligible target population. [PubMed]

626.

Walterbusch G, Fromke J, Sydow M. A simple method to reduce ischemic time of the spinal cord in extensive thoracoabdominal aneurysm operations. Thorac Cardiovasc Surg. 2003 Feb;51(1): 46–8. Not eligible target population. [PubMed]

627.

Wang H, Hiatt WR, Barstow TJ, Brass EP. Relationships between muscle mitochondrial DNA content, mitochondrial enzyme activity and oxidative capacity in man: alterations with disease. Eur J Appl Physiol Occup Physiol. 1999; 80(1): 22–7. No relevant outcomes. [PubMed]

628.

Wang JS, Yang CF, Wong MK. Effect of strenuous arm crank exercise on platelet function in patients with spinal cord injury. Arch Phys Med Rehabil. 2002; 83(2): 210–6. No relevant outcomes. [PubMed]

629.

Wang JS, Yang CF, Wong MK, Chow SE, Chen JK. Effect of strenuous arm exercise on oxidized-LDL-potentiated platelet activation in individuals with spinal cord injury. Thromb Haemost. 2000; 84(1): 118–23. No relevant outcomes. [PubMed]

630.

Waring WP, Karunas RS. Acute spinal cord injuries and the incidence of clinically occurring thromboembolic disease. Paraplegia. 1991 Jan;29(1): 8–16. Not eligible target population. [PubMed]

631.

Warms CA, Belza BL, Whitney JD, Mitchell PH, Stiens SA. Lifestyle physical activity for individuals with spinal cord injury: a pilot study. Am J Health Promot. 2004; 18(4): 288–91. No relevant outcomes. [PubMed]

632.

Washburn RA, Zhu W, McAuley E, Frogley M, Figoni SF. The physical activity scale for individuals with physical disabilities: development and evaluation. Arch Phys Med Rehabil. 2002; 83(2): 193–200. No exercise program or physical activity. [PubMed]

633.

Waters JH, Watson TB, Ward MG. Conus medullaris injury following both tetracaine and lidocaine spinal anesthesia. Journal of Clinical Anesthesia. 1996; 8(8): 656–8. Not adult spinal cord injury patients. [PubMed]

634.

Waters RL, Meyer PR Jr, Adkins RH, Felton D. Emergency, acute, and surgical management of spine trauma. Arch Phys Med Rehabil. 1999 Nov;80(11): 1383–90. Not eligible target population. [PubMed]

635.

Webborn N, Price MJ, Castle PC, Goosey-Tolfrey VL. Effects of two cooling strategies on thermoregulatory responses of tetraplegic athletes during repeated intermittent exercise in the heat. J Appl Physiol. 2005; 98(6): 2101–7. No relevant outcomes. [PubMed]

636.

Weck M, Pause M, Pinzer T. Spinal meningioma as differential diagnosis of diabetic polyneuropathy. Deutsche Medizinische Wochenschrift. 2001; 126(20): 590–2. Not english language. [PubMed]

637.

Weigang E, Hartert M, von Samson P, Pechstein U, Genstorfer J, Pitzer K. et al. Improved spinal cord perfusion during thoracoabdominal aortic repair. Thorac Cardiovasc Surg. 2005 Apr;53(2): 69–73. Not eligible target population. [PubMed]

638.

Weiss HD. Mechanism of erection. Medical Aspects of Human Sexuality. 1973; 7(2): 28. No relevant data. [PubMed]

639.

Wekre LL, Stanghelle JK, Lobben B, Oyhaugen S. The Norwegian Polio Study 1994: a nation-wide survey of problems in long-standing poliomyelitis. Spinal Cord. 1998; 36(4): 280–4. Not adult chronic SCI patients. [PubMed]

640.

Wernig A, Nanassy A, Muller S. Maintenance of locomotor abilities following Laufband (treadmill) therapy in para- and tetraplegic persons: follow-up studies. Spinal Cord. 1998; 36(11): 744–9. No relevant outcomes. [PubMed]

641.

Wernig A, Nanassy A, Muller S. Laufband (treadmill) therapy in incomplete paraplegia and tetraplegia. J Neurotrauma. 1999; 16(8): 719–26. No relevant outcomes. [PubMed]

642.

Wheeler GD, Andrews B, Lederer R, Davoodi R, Natho K, Weiss C. et al. Functional electric stimulation-assisted rowing: Increasing cardiovascular fitness through functional electric stimulation rowing training in persons with spinal cord injury. Arch Phys Med Rehabil. 2002; 83(8): 1093–9. No relevant outcomes. [PubMed]

643.

Wheeler GD, Ashley EA, Harber V, Laskin JJ, Olenik LM, Sloley D. et al. Hormonal responses to graded-resistance, FES-assisted strength training in spinal cord-injured. Spinal Cord. 1996; 34(5): 264–7. No relevant outcomes. [PubMed]

644.

Whitehouse FW. Two minutes with diabetes. Medical Times. 1967; 95(3): 354–5. Not adult spinal cord injury patients. [PubMed]

645.

Widerstrom-Noga EG, Felipe-Cuervo E, Yezierski RP. Chronic pain after spinal injury: interference with sleep and daily activities. Arch Phys Med Rehabil. 2001; 82(11): 1571–7. No exercise program or physical activity. [PubMed]

646.

Wieler M, Stein RB, Ladouceur M, Whittaker M, Smith AW, Naaman S. et al. Multicenter evaluation of electrical stimulation systems for walking. Arch Phys Med Rehabil. 1999 May;80(5): 495–500. Not eligible outcomes. [PubMed]

647.

Wien MF, Garshick E, Tun CG, Lieberman SL, Kelley A, Brown R. Breathlessness and exercise in spinal cord injury.