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Limited evidence of effectiveness of physostigmine for the symptomatic treatment of Alzheimer's disease

Physostigmine is an acetylcholinesterase inhibitor; it works by obstructing the enzyme responsible for ACh destruction in the synaptic cleft. Studies conducted more than 20 years ago suggested that physostigmine could improve memory in people with or without dementia. Investigation of this property has been limited by the very short half‐life of physostigmine. Various forms of administering the drug have been tried to overcome this problem, most recently a controlled‐release (CR) oral formulation, and a skin patch. An additional limiting factor has been a high incidence of adverse effects, including nausea, vomiting and diarrhoea. Physostigmine appears to have no advantage over some newer anticholinesterase drugs. The short half‐life remains a serious disadvantage and requires complex forms of administration. There is no reason to recommend further research into this drug.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2008

[Therapy of cognitive deficits in schizophrenia with acetylcholinesterase inhibitors: a systematic overview]

Patients with schizophrenia suffer from cognitive deficits which are important predictors of functional outcome. Alterations such as reduced muscarinic and nicotinic receptors in the central cholinergic system in patients with schizophrenia may contribute to these cognitive impairments. Because such deficits do not respond to neuroleptic treatment, different approaches have been developed regarding pharmacological treatments that enhance central cholinergic transmission, e.g. with acetylcholinesterase inhibitors. In this review the pathophysiology of cognitive impairment in schizophrenia, results of studies using acetylcholinesterase inhibitors (donepezil, rivastigmine, physostigmine, and galantamine), and future research strategies are presented. Till now randomized, placebo-controlled studies exist only for donepezil and rivastigmine, and none could replicate the positive results of previous trials with open designs. More trials with higher numbers of patients are needed, particularly for substances with more complex mechanisms of action (e.g. galantamine).

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2008

The Management of Inadvertent Perioperative Hypothermia in Adults [Internet]

Inadvertent perioperative hypothermia is a common but preventable complication of perioperative procedures, which is associated with poor outcomes for patients. Inadvertent perioperative hypothermia should be distinguished from the deliberate induction of hypothermia for medical reasons, which is not covered by this guideline.

NICE Clinical Guidelines - National Collaborating Centre for Nursing and Supportive Care (UK).

Version: April 2008
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Dementia: A NICE-SCIE Guideline on Supporting People With Dementia and Their Carers in Health and Social Care

This guideline has been developed to advise on supporting people with dementia and their carers in health and social care. The guideline recommendations have been developed by a multidisciplinary team of health and social care professionals, a person with dementia, carers and guideline methodologists after careful consideration of the best available evidence. It is intended that the guideline will be useful to practitioners and service commissioners in providing and planning high-quality care for those with dementia while also emphasising the importance of the experience of care for people with dementia and carers.

NICE Clinical Guidelines - National Collaborating Centre for Mental Health (UK).

Version: 2007
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Delirium: Screening, Prevention, and Diagnosis – A Systematic Review of the Evidence [Internet]

Delirium is a common syndrome in hospitalized or institutionalized adults. It is characterized by the acute onset of altered mental status, hallmarked by difficulty sustaining attention and a fluctuating course. Delirium frequently causes patients, families, and health care providers considerable distress. The incidence varies widely based on patient population, setting, and intensity of diagnostic ascertainment with reported values of 10% to over 80%. Delirium is associated with multiple serious outcomes including increased morbidity, length of hospital stay, healthcare costs, institutionalization, and mortality. In surgical settings, older adults and those with multiple medical conditions are at increased risk for postoperative delirium. Delirium may be under-recognized by healthcare providers and it can be difficult to resolve. Several brief “bedside” questionnaires and checklists exist that can help detect delirium earlier and among those with milder symptoms. Additionally, efforts to prevent the development of delirium in those at risk have been advocated. Medications (including sedatives, narcotics, and anticholinergic drugs), diseases and intercurrent illnesses (e.g., stroke, infection, shock, anemia), surgical procedures (especially orthopedic and cardiac surgery), and environmental factors (e.g., use of a bladder catheter, pain, and emotional stress) are all associated with delirium. Therefore, identifying and implementing effective strategies to prevent and detect delirium could improve clinical outcomes and resource utilization. Suggested strategies to prevent delirium include avoidance of psychoactive medications, pharmacologic interventions to decrease risk, and single- or multi-component non-pharmacologic interventions (including use of music, mobilization, fluid and nutrition management, and orientation and cognitive stimulation).

Evidence-based Synthesis Program - Department of Veterans Affairs (US).

Version: September 2011
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Cholinergic medication for neuroleptic‐induced tardive dyskinesia

Drug‐induced tardive dyskinesia is a common adverse effect of some antipsychotics, especially when these are given for an extended period of time. Tardive dyskinesia consists of involuntary repetitive movements, mainly in the oral region, but sometimes also in the limbs. It may become persistent. Cholinergic drugs, such as deanol, lecithin and meclofenoxate, have been used to treat tardive dyskinesia. This review did not identify any evidence to suggest that they are effective and found some to suggest that these old drugs may be toxic. New cholinergic drugs have been developed for the treatment of Alzheimer's disease, and it will be of interest to know if these drugs have an effect on the movements of tardive dyskinesia. We found one ongoing randomised trial.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

A systematic review of the clinical effectiveness and cost-effectiveness of sensory, psychological and behavioural interventions for managing agitation in older adults with dementia

The study found that supervised person-centred care, communication skills and dementia-care mapping, as well as sensory therapy activities and structured music therapies, reduce agitation in care-home dementia residents. Health and social care costs were between £7000 and £15,000 depending on the severity of agitation. Further work is required to investigate interventions for agitation for use with people with dementia living in their own homes.

Health Technology Assessment - NIHR Journals Library.

Version: June 2014
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Screening for Cognitive Impairment in Older Adults: An Evidence Update for the U.S. Preventive Services Task Force [Internet]

We conducted this systematic review to support the U.S. Preventive Services Task Force (USPSTF) in updating its recommendation on screening for cognitive impairment in older adults. Our review addresses five questions: 1) Does screening for cognitive impairment in community-dwelling older adults improve decisionmaking, patient, family/caregiver, or societal outcomes?; 2) What is the test performance of screening instruments to detect dementia or mild cognitive impairment (MCI) in community-dwelling older adult primary care patients?; 3) What are the harms of screening for cognitive impairment?; 4) Do interventions for early dementia or MCI in older adults improve decisionmaking, patient, family/caregiver, or societal outcomes?; and 5) What are the harms of interventions for cognitive impairment?

Evidence Syntheses - Agency for Healthcare Research and Quality (US).

Version: November 2013
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Single-dose parenteral pharmacological interventions for the prevention of postoperative shivering: a quantitative systematic review of randomized controlled trials

Shivering is a frequent complication in the postoperative period. The relative efficacy of pharmacological interventions to prevent this phenomenon is not well understood. We performed a systematic search for full reports of randomized comparisons of prophylactic, parenteral, single-dose antishivering interventions with inactive control (placebo or no treatment). Variable doses were converted to fixed doses. Dichotomous data on the absence of shivering were analyzed by using relative benefit (RB) and number needed to treat (NNT) with 95% confidence intervals (CI). Data from 27 trials (1348 adults received an antishivering intervention; 931 were controls) were analyzed. The average incidence of shivering in controls was extremely frequent (52%). Clonidine 65-300 microg (1078 patients), meperidine 12.5-35 mg (250 patients), tramadol 35-220 mg (250 patients), and nefopam 6.5-11 mg (204 patients) were tested in at least 3 trials each. All were more effective than control. For clonidine, meperidine, and nefopam, there was some weak evidence of dose responsiveness. For small-dose clonidine (65-110 microg), the RB compared with control was 1.32 (95% CI, 1.16-1.51); for medium-dose clonidine (140-150 microg), the RB was 1.83 (95% CI, 1.47-2.27); and for large-dose clonidine (220-300 microg), the RB was 1.52 (95% CI, 1.30-1.78). For all clonidine regimens combined, the RB was 1.58 (95% CI, 1.43-1.74), with an NNT of 3.7. For all meperidine regimens combined, the RB was 1.67 (95% CI, 1.37-2.03), with an NNT of 3. For all tramadol regimens combined, the RB was 1.93 (95% CI, 1.56-2.39), with an NNT of 2.2. For all nefopam regimens combined, the RB was 2.62 (95% CI, 2.02-3.40), with an NNT of 1.7. Methylphenidate, midazolam, dolasetron, ondansetron, physostigmine, urapidil, and flumazenil were tested in no more than 3 trials each, with a limited number of patients.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2004

Cholinomimetic agents and neurocognitive impairment following head injury: a systematic review

This review assessed the role of cholinomimetic agents in the treatment of neurocognitive impairment following head injury. Due to the methodological limitations and heterogeneity of the included studies, the authors concluded that there was insufficient evidence to support the use of these agents in practice. The authors' conclusions and recommendations for further research were likely to be reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2008

Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence

This review concluded that of the drugs used for treating neuropsychiatric symptoms of dementia, risperidone and olanzapine had the best evidence for efficacy although their effect sizes were modest and they increased the risk of stroke. This conclusion appears reasonable. However, there was only a small evidence base for most of the drugs considered in the review.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2005

Pharmacotherapy for treatment of attention deficits after non-progressive acquired brain injury: a systematic review

This review concluded that there was a lack of robust evidence that medication improved attention after traumatic brain injury or stroke, but there was evidence of potential benefit for some patients and further research was warranted. In light of the heterogeneity between studies and a paucity of high-quality evidence, the authors' cautious conclusions are justified.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2010

Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis

The review assessed the efficacy of cholinesterase inhibitors (ChIs) for neuropsychiatric symptoms and functional impairment in Alzheimer disease. The authors concluded that ChIs have a modest beneficial impact on these outcomes. Their conclusions seem reliable. However, the clinical meaningfulness of the benefit observed is debatable, and some of the analyses upon which the conclusions were based were not statistically significant.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2003

Pharmacological treatment of dementia

The authors concluded that pharmacotherapy can improve cognitive symptoms and outcomes, there is some evidence for delay in disease progression, and some agents were shown to be effective in patients with vascular dementia. However, few head-to-head studies were found and there were insufficient data relating to efficacy in different subgroups of patients. Despite some minor limitations, the authors' conclusions are likely to be reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2004

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