QUESTION: Network meta-analyses (NMAs) of treatment efficacy across different pharmacological treatments help inform clinical decision-making, but their methodological quality may vary a lot depending also on the quality of the included primary studies. We therefore conducted a systematic review of NMAs of pharmacological treatment for common mental disorders in order to assess the methodological quality of these NMAs, and to relate study characteristics to the rankings of efficacy and tolerability.
STUDY SELECTION AND ANALYSIS: We searched three databases for NMAs of pharmacological treatment used in major depression, generalised anxiety disorder (GAD), social anxiety disorder (SAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD) and specific phobia.Studies were appraised using the International Society for Pharmacoeconomics and Outcomes Research checklist of good research practices for indirect-treatment-comparison and network-meta-analysis studies.
FINDINGS: Twenty NMAs were eligible for inclusion. The number of randomised controlled trials per NMA ranged from 11 to 234, and included between 801 to more than 26 000 participants. Overall, antidepressants were found to be efficacious and tolerable agents for several disorders based on rankings (45%) or statistical significance (55%). The majority of NMAs in this review adhered to guidelines by including a network diagram (70%), assessing consistency (75%), making use of a random effects model (75%), providing information on the model used to fit the data (75%) and adjusting for covariates (75%).
CONCLUSIONS: The 20 NMAs of depression and anxiety disorders, PTSD and/or OCD included in this review demonstrate some methodological strengths in comparison with the larger body of published NMAs for medical disorders, support current treatment guidelines and help inform clinical decision-making.
PURPOSE OF REVIEW: Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms. This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects.
RECENT FINDINGS: We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs. Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms. Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.
Objective To map the diverse health outcomes associated with serum uric acid (SUA) levels.Design Umbrella review.Data sources Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references.Eligibility criteria Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes.Results 57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10(-6), 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies.Conclusion Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis.
Multiple beneficial effects have been proposed lately for cannabinoids in different clinical situations. Among them, it has been postulated they would control symptoms of multiple sclerosis. However, there is no consensus about their real clinical role. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple databases. We identified 25 systematic reviews including 35 studies overall, of which 26 were randomized trials. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded cannabinoids in multiple sclerosis do not reduce spasticity or pain, and are probably associated to frequent adverse effects.
BACKGROUND: Falls are common events in older people, which cause considerable morbidity and mortality. Non-pharmacological interventions are an important approach to prevent falls. There are a large number of systematic reviews of non-pharmacological interventions, whose evidence needs to be synthesized in order to facilitate evidence-based clinical decision making. OBJECTIVES: To systematically examine reviews and meta-analyses that evaluated non-pharmacological interventions to prevent falls in older adults in the community, care facilities and hospitals. METHODS: We searched the electronic databases Pubmed, the Cochrane Database of Systematic Reviews, EMBASE, CINAHL, PsycINFO, PEDRO and TRIP from January 2009 to March 2015, for systematic reviews that included at least one comparative study, evaluating any non-pharmacological intervention, to prevent falls amongst older adults. The quality of the reviews was assessed using AMSTAR and ProFaNE taxonomy was used to organize the interventions. RESULTS: Fifty-nine systematic reviews were identified which consisted of single, multiple and multifactorial non-pharmacological interventions to prevent falls in older people. The most frequent ProFaNE defined interventions were exercises either alone or combined with other interventions, followed by environment/assistive technology interventions comprising environmental modifications, assistive and protective aids, staff education and vision assessment/correction. Knowledge was the third principle class of interventions as patient education. Exercise and multifactorial interventions were the most effective treatments to reduce falls in older adults, although not all types of exercise were equally effective in all subjects and in all settings. Effective exercise programs combined balance and strength training. Reviews with a higher AMSTAR score were more likely to contain more primary studies, to be updated and to perform meta-analysis. CONCLUSIONS: The aim of this overview of reviews of non-pharmacological interventions to prevent falls in older people in different settings, is to support clinicians and other healthcare workers with clinical decision-making by providing a comprehensive perspective of findings.
WHAT DO WE WANT TO KNOW?: Delayed diagnosis results in serious consequences for patients and healthcare professionals and can incur substantial financial costs. While research focusing upon cancer suggests that late diagnosis leads to increased morbidity and mortality, the evidence for other conditions is less clear. This systematic rapid evidence assessment (SREA) identifies the nature and extent of the literature on late diagnosis across a range of conditions. We wanted to know:
1. What is the prevalence of late diagnosis?
2. What are the determinants of late diagnosis?
3. What are the outcomes of late diagnosis?
4. What are the cost implications of late diagnosis?
5. Which interventions reduce delays in diagnosis?
WHO WANTS TO KNOW?: Policy makers, clinicians, general practitioners and patients. WHAT DID WE FIND?: • Late diagnosis is of most concern for those with chronic obstructive pulmonary disease (COPD), dementia, human immunodeficiency virus (HIV) and type 1 Diabetes.
• COPD has a high prevalence of late diagnosis, with an estimated 80% of cases remaining undiagnosed. Many of these cases are patients in the milder stages of the disease.
• Early dementia is harder to detect, with doctors acknowledging their difficulties in distinguishing between dementia and ‘normal ageing’.
• The evidence suggested that a substantial proportion (16–51%) of children experience delayed diagnosis in type I diabetes.
• Those engaging in high-risk behaviours were more likely to avoid HIV testing due to fear of a positive diagnosis, with worrying implications regarding onward transmission. Data from the Health Protection Agency indicates that 50% of new diagnoses are late in the UK.
• Broadly, late diagnosis affects vulnerable groups such as older people or those living in poverty.
• Patients delayed seeking help from clinicians for a number of conditions including chronic kidney disease, dementia, HIV, stroke, myocardial infarction, epilepsy and tuberculosis. Late presentation was linked to symptom misinterpretation and lack of knowledge.
• Inadequate knowledge and training of doctors were barriers to prompt diagnosis for chronic kidney disease, COPD, dementia and tuberculosis.
• Restricted access, insufficient consultation time and resource constraints hindered diagnosis.
• There was very little material about the cost implications of delayed diagnosis. WHAT ARE THE IMPLICATIONS?: The training of doctors in the early diagnosis of COPD, dementia and tuberculosis has improved detection. Media campaigns to alert the public to the symptoms of stroke, heart attack and psychosis have had mixed results. Overall, public recognition has increased, but this may not have contributed to shortening patient delay.
This study includes information from health care systems outside the UK. However, policy makers may find future reviews of UK primary research into the late diagnosis of these conditions useful to understand the nature of the problem in a UK context. HOW DID WE GET THESE RESULTS?: We examined evidence from 43 systematic reviews for: chronic kidney disease, dementia, depression, type I diabetes, epilepsy, HIV, myocardial infarction, psychosis, stroke and tuberculosis.
We found 606 UK primary studies on late diagnosis, of which 12 investigated COPD, 12 investigated tuberculosis and 4 investigated epilepsy. While there were systematic reviews to draw on for most conditions, this was not the case for COPD (no systematic reviews), tuberculosis (systematic reviews with limited relevance to UK healthcare system) and epilepsy (systematic reviews focused on over-diagnosis), and so we used evidence from the primary studies.
BACKGROUND: Effective implementation strategies are needed to optimize advancements in the fields of cancer diagnosis, treatment, survivorship, and end-of-life care. We conducted a review of systematic reviews to better understand the evidentiary base of implementation strategies in cancer control.
METHODS: Using three databases, we conducted a search and identified English-language systematic reviews published between 2005 and 2010 that targeted consumer, professional, organizational, regulatory, or financial interventions, tested exclusively or partially in a cancer context (primary focus); generic or non-cancer-specific reviews were also considered. Data were extracted, appraised, and analyzed by members of the research team, and research ideas to advance the field were proposed.
RESULTS: Thirty-four systematic reviews providing 41 summaries of evidence on 19 unique interventions comprised the evidence base. AMSTAR quality ratings ranged between 2 and 10. Team members rated most of the interventions as promising and in need of further research, and 64 research ideas were identified.
CONCLUSIONS: While many interventions show promise of effectiveness in the cancer-control context, few reviews were able to conclude definitively in favor of or against a specific intervention. We discuss the complexity of implementation research and offer suggestions to advance the science in this area.
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.
BACKGROUND: Several World Health Organisation reports over recent years have highlighted the high incidence of chronic diseases such as diabetes, coronary heart disease and cancer. Contributory factors include unhealthy diets, alcohol and tobacco use and sedentary lifestyles. This paper reports the findings of a review of reviews of behavioural change interventions to reduce unhealthy behaviours or promote healthy behaviours. We included six different health-related behaviours in the review: healthy eating, physical exercise, smoking, alcohol misuse, sexual risk taking (in young people) and illicit drug use. We excluded reviews which focussed on pharmacological treatments or those which required intensive treatments (e.g. for drug or alcohol dependency).
METHODS: The Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE) and several Ovid databases were searched for systematic reviews of interventions for the six behaviours (updated search 2008). Two reviewers applied the inclusion criteria, extracted data and assessed the quality of the reviews. The results were discussed in a narrative synthesis.
RESULTS: We included 103 reviews published between 1995 and 2008. The focus of interventions varied, but those targeting specific individuals were generally designed to change an existing behaviour (e.g. cigarette smoking, alcohol misuse), whilst those aimed at the general population or groups such as school children were designed to promote positive behaviours (e.g. healthy eating). Almost 50% (n = 48) of the reviews focussed on smoking (either prevention or cessation). Interventions that were most effective across a range of health behaviours included physician advice or individual counselling, and workplace- and school-based activities. Mass media campaigns and legislative interventions also showed small to moderate effects in changing health behaviours.Generally, the evidence related to short-term effects rather than sustained/longer-term impact and there was a relative lack of evidence on how best to address inequalities.
CONCLUSIONS: Despite limitations of the review of reviews approach, it is encouraging that there are interventions that are effective in achieving behavioural change. Further emphasis in both primary studies and secondary analysis (e.g. systematic reviews) should be placed on assessing the differential effectiveness of interventions across different population subgroups to ensure that health inequalities are addressed.
Network meta-analyses (NMAs) of treatment efficacy across different pharmacological treatments help inform clinical decision-making, but their methodological quality may vary a lot depending also on the quality of the included primary studies. We therefore conducted a systematic review of NMAs of pharmacological treatment for common mental disorders in order to assess the methodological quality of these NMAs, and to relate study characteristics to the rankings of efficacy and tolerability.
STUDY SELECTION AND ANALYSIS:
We searched three databases for NMAs of pharmacological treatment used in major depression, generalised anxiety disorder (GAD), social anxiety disorder (SAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD) and specific phobia.Studies were appraised using the International Society for Pharmacoeconomics and Outcomes Research checklist of good research practices for indirect-treatment-comparison and network-meta-analysis studies.
FINDINGS:
Twenty NMAs were eligible for inclusion. The number of randomised controlled trials per NMA ranged from 11 to 234, and included between 801 to more than 26 000 participants. Overall, antidepressants were found to be efficacious and tolerable agents for several disorders based on rankings (45%) or statistical significance (55%). The majority of NMAs in this review adhered to guidelines by including a network diagram (70%), assessing consistency (75%), making use of a random effects model (75%), providing information on the model used to fit the data (75%) and adjusting for covariates (75%).
CONCLUSIONS:
The 20 NMAs of depression and anxiety disorders, PTSD and/or OCD included in this review demonstrate some methodological strengths in comparison with the larger body of published NMAs for medical disorders, support current treatment guidelines and help inform clinical decision-making.
