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The management of myeloma is complex and challenging. It increasingly involves the use of expensive drugs. The guideline will aim to raise standards nationally while allowing clinical flexibility and defining a common pathway for patients at various stages of their illness, and of different ages and levels of fitness. Although a consistent approach to management is desirable, it needs to reflect the very different groups of patients with myeloma from the fit and suitable for transplant, fairly fit but not suitable for transplant to patients who are extremely frail and/or unwell.

NICE Guideline - National Collaborating Centre for Cancer (UK).

Version: February 2016

The purpose of this project was to provide national guidance on the optimal use of 99mTc during a situation of reduced supply. To accomplish this, our objective at CADTH was:

Optimal Use Report - Canadian Agency for Drugs and Technologies in Health.

Version: 2012

Allogeneic haematopoietic (blood) stem cell transplantation (HSCT) is a potentially curative therapeutic option for a variety of malignant and some non‐malignant haematological (blood‐related) diseases. For this therapy, blood stem cells are transferred from a healthy person who has compatible tissue markers, so‐called human leukocyte antigen (HLA) markers, to a matched recipient. Even though the donor and the recipient are matched concerning these markers, immune cells that are part of the transferred cells ('the graft') are prone to recognise tissues of the recipient ('the host') as being to some extent incompatible or foreign, which then can induce inflammation ('graft‐versus‐host‐disease' or 'GVHD'). GVHD typically involves the skin, the gastrointestinal tract and the liver. GVHD is divided into acute and chronic forms based on the clinical features and the time of occurrence after transplantation. In order to prevent this potentially life‐threatening condition, reactive immune cells can be depleted in the recipient by administering antibodies which are directed against them. These antibodies are called anti‐thymocyte globulins (ATG) and are derived from animals which were immunised with human thymocytes or T‐cells. Different types of ATG have been used for decades to decrease the occurrence and severity of GVHD but they bear the risk of severe side effects such as increased infection rates or the risk of disease relapse. Also, severe side effects such as allergic reactions or serum sickness with shortness of breath and fever, blood coagulation disturbances or liver failure can harm the patient during the infusion of ATG. So far, no systematic analysis of the advantages and disadvantages of the use of ATG has been done.

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

Version: 2012

Patients with breast cancer receiving chemotherapy have an increased risk of infection mediated through a low number of protective white blood cells (neutropenia). Neutropenia is a common toxicity of many chemotherapy agents and is caused by the suppression of the bone marrow. The first sign of infection is usually a fever, which indicates a potentially life‐threatening condition if it occurs during severe neutropenia (febrile neutropenia (FN)). FN requires hospital care including the administration of intravenous antibiotics and possible delays in the continuation of chemotherapy. Colony‐stimulating factors (CSFs) are drugs administered during chemotherapy in order to prevent or reduce the incidence or duration of FN and neutropenia. This review included eight trials in which 2156 patients with breast cancer had randomly received CSFs or placebo or no treatment during chemotherapy. These trials were carried out between 1995 and 2008. Prophylactic treatment with CSFs significantly reduced the risk of developing FN by 73%. The estimated number of patients needed to be treated with CSFs in order to prevent one event of FN was 12. Although a significant decrease in mortality of all causes during chemotherapy and CSF therapy was noted, there was no reduction in infection‐related mortality. There was no significant effect observed that planned chemotherapy schedules could be better maintained if CSFs were administered or that the number of patients with neutropenia decreased with CSFs. Notably, CSFs significantly reduced the need for hospital care yet frequently caused short‐term adverse effects like bone pain and injection‐site reactions. There were several limitations in this analysis: only a few trials could be included, the number of patients was low in many of these trials, and disease stages and chemotherapy treatments varied considerably. Moreover, the trial authors defined their outcomes differently, making comparisons across studies difficult. Information on the primary and secondary outcomes could not be obtained from all trials and the overall reporting quality was low. Many studies were dated and hence the administration of CSFs did not comply with current recommendations. Overall, CSFs have shown moderate evidence of benefit in the prevention of FN in patients with breast cancer receiving chemotherapy. The evidence that the administration of CSFs could reduce early mortality of all causes was weak and substantiates the need of further studies. There was no reduction in risk of infection‐related mortality with CSF treatment.

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

Version: 2012

Adults with cancer are prone to serious complications from influenza, more than healthy adults. The influenza vaccine protects against influenza and its complications. However, its effectiveness among cancer patients is unclear, as the immune dysfunction that accompanies cancer and as a result of chemotherapy might lower immune response to the vaccine. Cancer patients, therefore, do not have clear information on the importance, need and safety of the vaccine.

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

Version: 2016

The model suggested that a particular strategy (systematic antibiotics, antibiotic impregnated cement and conventional ventilation) would prevent many deep infections and save the NHS the most money

Health Technology Assessment - NIHR Journals Library.

Version: July 2016

This guideline offers best practice advice on the identification and care of patients with chronic obstructive pulmonary disease (COPD). It aims to define the symptoms, signs and investigations required to establish a diagnosis of COPD. It also aims to define the factors that are necessary to assess its severity, provide prognostic information and guide best management. It gives guidance on the pharmacological and non-pharmacological treatment of patients with stable COPD, and on the management of exacerbations. The interface with surgery and intensive therapy units (ITU) are also discussed.

NICE Clinical Guidelines - National Clinical Guideline Centre (UK).

Version: June 2010

In the United States, coronary heart disease and cardiovascular disease account for nearly 40% of deaths each year. An individual’s estimated risk for coronary heart disease events, often based on factors incorporated into the Framingham risk score, guides the intensity of risk reduction interventions. We conducted a systematic review of epidemiologic studies to help the U.S. Preventive Services Task Force determine which, if any, of 9 additional risk factors should be considered for incorporation into guidelines for coronary and cardiovascular risk assessment in primary care.

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

Version: October 2009

Study found that for the treatment of rheumatoid arthritis, biologic disease-modifying antirheumatic drugs had cost per quality-adjusted life-year values greater than the thresholds stated by the National Institute for Health and Care Excellence and could not be considered cost-effective.

Health Technology Assessment - NIHR Journals Library.

Version: April 2016

Anaemia is defined internationally as a state in which the quality and/or quantity of circulating red blood cells is below normal. Blood haemoglobin (Hb) concentration serves as the key indicator for anaemia because it can be measured directly and has an international standard. In response to low tissue oxygen levels in anaemia the kidney produces the hormone erythropoietin which stimulates the bone marrow to produce red blood cells. A major cause of the anaemia of chronic kidney disease (CKD) is a reduction in erythropoietin production due to kidney damage.

NICE Guideline - National Clinical Guideline Centre (UK).

Version: June 2015

These guidelines provide guidance on the diagnosis of human immunodeficiency virus (HIV) infection, the use of antiretroviral (ARV) drugs for treating and preventing HIV infection and the care of people living with HIV. They are structured along the continuum of HIV testing, prevention, treatment and care.

World Health Organization.

Version: 2016

Only a few studies have investigated the use of PCT in the diagnosis of bone and joint infection, and these studies have had relatively small sample sizes. We performed a systematic review and meta-analysis of the diagnostic performance of serum procalcitonin (PCT) in the identification of osteomyelitis and septic arthritis in patients who present with fever and orthopedic symptoms. EMBASE, MEDLINE, and Cochrane databases and the reference lists of relevant articles were searched, with no language restrictions, through February 2012. All original studies that reported the use of serum PCT alone or in comparison with other biomarkers for diagnosis of osteomyelitis and septic arthritis were included. Seven studies qualified for inclusion. These studies enrolled a total of 583 patients with suspected bone or joint infection, 131 of whom had confirmed osteomyelitis or septic arthritis. Analysis of the PCT data indicated a bivariate pooled sensitivity of 0.67 (95 % CI: 0.37-0.88), specificity of 0.90 (95 % CI: 0.78-0.96), a positive likelihood ratio (LR+) of 6.48 (95 % CI: 2.28-14.6), and a negative likelihood ratio (LR-) of 0.37 (95 % CI: 0.16-0.84). Use of a lower PCT cut-off value (0.2-0.3 ng/mL) improved the LR + to 6.66 and the LR- to 0.15. Analysis of the three studies that also measured serum C-reactive protein (CRP) indicated that CRP had an LR + of 1.39 (95 % CI: 1.17-1.65) and an LR- of 0.40 (95 % CI: 0.12-1.36). Our results indicate that PCT may be more suitable as an aid for rule-in diagnosis rather than for exclusion of septic arthritis or osteomyelitis and that use of a lower cut-off value for serum PCT may improve its diagnostic performance.

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

Version: 2013

We reviewed the evidence to determine whether antibiotics (alone or in combination) given to people with sickle cell disease who have osteomyelitis (a bone infection) before the specific bacterium causing an infection is known is effective and safe as compared to bacterium‐directed antibiotic treatment and whether this effectiveness and safety is dependent on different treatment regimens, age or setting. This is an update of a previously published Cochrane Review.

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

Version: 2016

Coeliac disease is an autoimmune condition associated with chronic inflammation of the small intestine, which can lead to malabsorption of nutrients. Dietary proteins, known as glutens, which are present in wheat, barley and rye activate an abnormal mucosal immune response. Clinical and histological improvements usually follow when gluten is excluded from the diet.

NICE Guideline - Internal Clinical Guidelines Team (UK).

Version: September 2015

This guideline covers bacterial meningitis and meningococcal septicaemia, focusing on management of these conditions in children and young people aged younger than 16 years in primary and secondary care, and using evidence of direct relevance to these age groups where available.

NICE Clinical Guidelines - National Collaborating Centre for Women's and Children's Health (UK).

Version: 2010

Patients who have suspected inflammatory disease or serious infection may undergo a diagnostic workup that involves multiple laboratory tests. Two such laboratory tests are erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), non-specific blood tests often ordered together that are well established and widely used to aid the diagnosis of numerous conditions. The simultaneous and widespread use of both tests has raised concerns about their potential overuse, particularly if they provide little valuable information regarding patient management and outcomes.

Cadth Health Technology Assessment - Canadian Agency for Drugs and Technologies in Health.

Version: November 2015

The term “cancer of unknown primary” refers to a condition in which a patient has metastatic malignancy without an identified primary source. This is a very heterogeneous disease in which the type of tumour, the extent of spread, and the outcome of treatment all vary widely. When categorising patients with cancer of unknown primary, one important factor initially considered is the cell type of origin of the metastatic disease. The majority of patients have malignancy which appears to derive from epithelial cells, and hence are regarded as having carcinoma of unknown primary. Patients with tumours of non-epithelial lineage (melanoma, sarcoma, lymphoma, germ-cell) form a distinct and important minority, since subsequent management can often be satisfactorily undertaken even in the absence of an identifiable primary source. Such patients are not considered in this guideline, since their care is adequately defined in existing guidelines for their specific tumour type. The term “carcinoma of unknown primary” (CUP) is used henceforth to refer to those patients with metastatic malignancy of epithelial, neuroendocrine or undifferentiated lineage whose investigation and management is considered within the scope of this guideline.

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

Version: July 2010

Many people naturally assume that the claims made for foods and nutritional supplements have the same degree of scientific grounding as those for medication, but that is not always the case. The IOM recommends that the FDA adopt a consistent scientific framework for biomarker evaluation in order to achieve a rigorous and transparent process.

National Academies Press (US).

Version: 2010

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic interstitial lung disease (ILD) of unknown origin. It is a difficult disease to diagnose and often requires the collaborative expertise of a chest physician, radiologist and histopathologist to reach a consensus diagnosis. Most people with idiopathic pulmonary fibrosis experience symptoms of breathlessness, which may initially be only on exertion. Cough, with or without sputum is a common symptom. Over time, these symptoms are associated with a decline in lung function, reduced quality of life and ultimately death. Specific pharmacological therapies for IPF are limited but the last decade has seen more trials of new drugs which have had a variable impact on clinical practice. A number of difficulties arise when undertaking clinical trials in IPF in terms of defining precise, diagnostic inclusion criteria and clinically meaningful end-points. However, such trials are the only way by which promising new treatments will come to benefit patients. Furthermore, it is only by performing rigorous clinical trials, we have learned that drugs once widely used to treat IPF may in fact have been harmful. The limitations of current pharmacological therapies for IPF highlight the importance of other forms of treatment including lung transplantation and best supportive care such as oxygen therapy, pulmonary rehabilitation and palliation of symptoms. These are interventions which justifiably require scrutiny in the context of healthcare delivery by the modern NHS. Despite the significant burden of disease caused by IPF, there is currently no established framework within the NHS for its diagnosis and management thus creating an environment in which significant variations in clinical care may occur. In recognition of this, the Department of Health commissioned the National Institute of Health and Care Excellence (NICE) to produce a guideline aimed at improving the care of people with IPF.

NICE Clinical Guidelines - National Clinical Guideline Centre (UK).

Version: June 2013

Study found that supporting self-management is inseparable from the high-quality care for long-term conditions. Commissioners and health-care providers should promote a culture of actively supporting self-management as a normal, expected, monitored and rewarded aspect of care.

Health Services and Delivery Research - NIHR Journals Library.

Version: December 2014

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