Importance Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.Objective To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.Data Sources Twenty-eight databases from inception to April 2015. Study SelectionRandomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome. Data Extraction and SynthesisStudy quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis. Main Outcomes and MeasuresPatient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs.Results A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], −0.46 [95% CI, −0.80 to −0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, −0.12 [95% CI, −0.24 to 0.01]; 5 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. Conclusions and RelevanceThere was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.

BackgroundDuchenne Muscular Dystrophy (DMD) is a rapidly progressive, lethal neuromuscular disorder, present from birth, which occurs almost exclusively in males. We have reviewed contemporary evidence of burden, epidemiology, illness costs and treatment patterns of DMD.This systematic review adhered to published methods with information also sought from the web and contacting registries. Searches were carried out from 2005 to June 2015. The population of interest was individuals with clearly defined DMD or their carers.ResultsNine thousand eight hundred fifty titles were retrieved from searches. Fifty-eight studies were reviewed with three assessed as high, 33 as medium and 22 as low quality. We found two studies reporting birth and four reporting point prevalence, three reporting mortality, 41 reporting severity and/or progression, 18 reporting treatment patterns, 12 reporting quality of life, two reporting utility measures, three reporting costs of illness and three treatment guidelines.Birth prevalence ranged from 15.9 to 19.5 per 100,000 live births. Point prevalence per 100,000 males was for France, USA, UK and Canada, 10.9, 1.9, 2.2 and 6.1 respectively. A study of adult DMD patients at a centre in France found median survival for those born between 1970 and 1994 was 40.95 years compared to 25.77 years for those born between 1955 and 1969. Loss of ambulation occurred at a median age of 12 and ventilation starts at about 20 years. There was international variation in use of corticosteroids, scoliosis surgery, ventilation and physiotherapy. The economic cost of DMD climbs dramatically with disease progression – rising as much as 5.7 fold from the early ambulatory phase to the non-ambulatory phase in Germany.ConclusionsThis is the first systematic review of treatment, progression, severity and quality of life in DMD. It also provides the most recent description of the burden, epidemiology, illness costs and treatment patterns in DMD. There are evidence gaps, particularly in prevalence and mortality. People with DMD seem to be living longer, possibly due to corticosteroid use, cardiac medical management and ventilation. Future research should incorporate registry data to improve comparability across time and between countries and to investigate the quality of life impact as the condition progresses.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-017-0631-3) contains supplementary material, which is available to authorized users.

BackgroundPatients with substantive bleeding usually require transfusion and/or (re-)operation. Red blood cell (RBC) transfusion is independently associated with a greater risk of infection, morbidity, increased hospital stay and mortality. ROTEM (ROTEM®Delta, TEM International GmbH, Munich, Germany;www.rotem.de), TEG (TEG®5000 analyser, Haemonetics Corporation, Niles, IL, USA;www.haemonetics.com) and Sonoclot (Sonoclot®coagulation and platelet function analyser, Sienco Inc., Arvada, CO) are point-of-care viscoelastic (VE) devices that use thromboelastometry to test for haemostasis in whole blood. They have a number of proposed advantages over standard laboratory tests (SLTs): they provide a result much quicker, are able to identify what part of the clotting process is disrupted, and provide information on clot formation over time and fibrinolysis.ObjectivesThis assessment aimed to assess the clinical effectiveness and cost-effectiveness of VE devices to assist with the diagnosis, management and monitoring of haemostasis disorders during and after cardiac surgery, trauma-induced coagulopathy and post-partum haemorrhage (PPH).MethodsSixteen databases were searched to December 2013: MEDLINE (OvidSP), MEDLINE In-Process and Other Non-Indexed Citations and Daily Update (OvidSP), EMBASE (OvidSP), BIOSIS Previews (Web of Knowledge), Science Citation Index (SCI) (Web of Science), Conference Proceedings Citation Index (CPCI-S) (Web of Science), Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA) database, Latin American and Caribbean Health Sciences Literature (LILACS), International Network of Agencies for Health Technology Assessment (INAHTA), National Institute for Health Research (NIHR) HTA programme, Aggressive Research Intelligence Facility (ARIF), Medion, and the International Prospective Register of Systematic Reviews (PROSPERO). Randomised controlled trials (RCTs) were assessed for quality using the Cochrane Risk of Bias tool. Prediction studies were assessed using QUADAS-2. For RCTs, summary relative risks (RRs) were estimated using random-effects models. Continuous data were summarised narratively. For prediction studies, the odds ratio (OR) was selected as the primary effect estimate. The health-economic analysis considered the costs and quality-adjusted life-years of ROTEM, TEG and Sonoclot compared with SLTs in cardiac surgery and trauma patients. A decision tree was used to take into account short-term complications and longer-term side effects from transfusion. The model assumed a 1-year time horizon.ResultsThirty-one studies (39 publications) were included in the clinical effectiveness review. Eleven RCTs (n = 1089) assessed VE devices in patients undergoing cardiac surgery; six assessed thromboelastography (TEG) and five assessed ROTEM. There was a significant reduction in RBC transfusion [RR 0.88, 95% confidence interval (CI) 0.80 to 0.96; six studies], platelet transfusion (RR 0.72, 95% CI 0.58 to 0.89; six studies) and fresh frozen plasma to transfusion (RR 0.47, 95% CI 0.35 to 0.65; five studies) in VE testing groups compared with control. There were no significant differences between groups in terms of other blood products transfused. Continuous data on blood product use supported these findings. Clinical outcomes did not differ significantly between groups. There were no apparent differences between ROTEM or TEG; none of the RCTs evaluated Sonoclot. There were no data on the clinical effectiveness of VE devices in trauma patients or women with PPH. VE testing was cost-saving and more effective than SLTs. For the cardiac surgery model, the cost-saving was £43 for ROTEM, £79 for TEG and £132 for Sonoclot. For the trauma population, the cost-savings owing to VE testing were more substantial, amounting to per-patient savings of £688 for ROTEM compared with SLTs, £721 for TEG, and £818 for Sonoclot. This finding was entirely dependent on material costs, which are slightly higher for ROTEM. VE testing remained cost-saving following various scenario analyses.ConclusionsVE testing is cost-saving and more effective than SLTs, in both patients undergoing cardiac surgery and trauma patients. However, there were no data on the clinical effectiveness of Sonoclot or of VE devices in trauma patients.Study registrationThis study is registered as PROSPERO CRD42013005623.FundingThe NIHR Health Technology Assessment programme.

A systematic review was conducted, summarizing international BRCA 1 or 2 ( BRCA1/2 ) mutation prevalence in breast cancer. Databases (eg, Medline and Embase; N=7) and conferences were searched (January 2012 to December 2017). From 17,872 records, 70 studies were included. In 58 large (N>100) studies, BRCA1/2 mutation prevalence varied widely from 1.8% (Spain) in sporadic breast cancer to 36.9% (United States) in estrogen receptor/progesterone receptor low+ (1–9% on immunohistochemistry/human epidermal growth factor receptor 2–negative [HER2-]) breast cancer. In 2 large studies unselected for family history, ethnicity, sex, or age and no/unclear selection by breast cancer stage or hormone receptor (HR) status, germline BRCA (g BRCA ) mutation prevalence was 2.9% (Italy) to 3.0% (South Korea). In the 4 large unselected triple-negative breast cancer studies, g BRCA mutation prevalence varied from 9.3% (Australia) to 15.4% (United States). g BRCA mutation prevalence in 1 large unselected HR positive/HER2- early breast cancer study was 5% (United States). In 2 large unselected metastatic breast cancer studies, g BRCA mutation prevalence was 2.7% (France) and 4.3% (Germany). Locally advanced breast cancer studies were small and not in unselected populations. Poor reporting of g BRCA status and basis of selection implies a need for further large well-reported BRCA mutation prevalence studies in breast cancer.

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BackgroundDetermination of the presence or absence of bacterial infection is important to guide appropriate therapy and reduce antibiotic exposure. Procalcitonin (PCT) is an inflammatory marker that has been suggested as a marker for bacterial infection.ObjectivesTo assess the clinical effectiveness and cost-effectiveness of adding PCT testing to the information used to guide antibiotic therapy in adults and children (1) with confirmed or highly suspected sepsis in intensive care and (2) presenting to the emergency department (ED) with suspected bacterial infection.MethodsTwelve databases were searched to June 2014. Randomised controlled trials were assessed for quality using the Cochrane Risk of Bias tool. Summary relative risks (RRs) and weighted mean differences (WMDs) were estimated using random-effects models. Heterogeneity was assessed visually using forest plots and statistically using theI2andQstatistics and investigated through subgroup analysis. The cost-effectiveness of PCT testing in addition to current clinical practice was compared with current clinical practice using a decision tree with a 6 months’ time horizon.ResultsEighteen studies (36 reports) were included in the systematic review. PCT algorithms were associated with reduced antibiotic duration [WMD –3.19 days, 95% confidence interval (CI) –5.44 to –0.95 days,I2 = 95.2%; four studies], hospital stay (WMD –3.85 days, 95% CI –6.78 to –0.92 days,I2 = 75.2%; four studies) and a trend towards reduced intensive care unit (ICU) stay (WMD –2.03 days, 95% CI –4.19 to 0.13 days,I2 = 81.0%; four studies). There were no differences for adverse clinical outcomes. PCT algorithms were associated with a reduction in the proportion of adults (RR 0.77, 95% CI 0.68 to 0.87; seven studies) and children (RR 0.86, 95% CI 0.80 to 0.93) receiving antibiotics, reduced antibiotic duration (two studies). There were no differences for adverse clinical outcomes. All but one of the studies in the ED were conducted in people presenting with respiratory symptoms.Cost-effectiveness: the base-case analyses indicated that PCT testing was cost-saving for (1) adults with confirmed or highly suspected sepsis in an ICU setting; (2) adults with suspected bacterial infection presenting to the ED; and (3) children with suspected bacterial infection presenting to the ED. Cost-savings ranged from £368 to £3268. Moreover, PCT-guided treatment resulted in a small quality-adjusted life-year (QALY) gain (ranging between < 0.001 and 0.005). Cost-effectiveness acceptability curves showed that PCT-guided treatment has a probability of ≥ 84% of being cost-effective for all settings and populations considered (at willingness-to-pay thresholds of £20,000 and £30,000 per QALY).ConclusionsThe limited available data suggest that PCT testing may be effective and cost-effective when used to guide discontinuation of antibiotics in adults being treated for suspected or confirmed sepsis in ICU settings and initiation of antibiotics in adults presenting to the ED with respiratory symptoms and suspected bacterial infection. However, it is not clear that observed costs and effects are directly attributable to PCT testing, are generalisable outside people presenting with respiratory symptoms (for the ED setting) and would be reproducible in the UK NHS. Further studies are needed to assess the effectiveness of adding PCT algorithms to the information used to guide antibiotic treatment in children with suspected or confirmed sepsis in ICU settings. Additional research is needed to examine whether the outcomes presented in this report are fully generalisable to the UK.Study registrationThis study is registered as PROSPERO CRD42014010822.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Based on this systematic review, there is no strong evidence to support one therapy over another as EBRT, BT and RP can all be considered as effective monotherapies for localised disease with EBRT also effective for post-operative management. All treatments have unique adverse events profiles. Further large, robust RCTs which report treatment-specific and treatment combination-specific outcomes in defined prostate cancer risk groups following established reporting standards are needed. These will strengthen the evidence base for newer technologies, help reinforce current consensus guidelines and establish greater standardisation across practices.