Calcium channel blockers for antipsychotic-induced tardive dyskinesia (review)

BackgroundSchizophrenia and related disorders affect a sizable proportion of any population. Antipsychotic medications are the primary treatment for these disorders. Antipsychotic medications are associated with a variety of adverse effects including tardive dyskinesia. Dyskinesia is a disfiguring movement disorder of the orofacial region that can be tardive (having a slow or belated onset). Tardive dyskinesia is difficult to treat, despite experimentation with several treatments. Calcium channel blockers (diltiazem, nifedipine, nimodipine, verapamil, flunarizine) have been among these experimental treatments. ObjectivesTo determine the effects of calcium channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic‐induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses. Search methodsWe searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. Selection criteriaWe selected randomised controlled trials comparing calcium channel blockers with placebo, no intervention or any other intervention for people with both tardive dyskinesia and schizophrenia or serious mental illness who remained on their antipsychotic medication. Data collection and analysisWe independently extracted data and estimated risk ratios of dichotomous data or mean differences (MD) of continuous data, with 95% confidence intervals (CI). We assumed that people who left the trials early had no improvement. We also created a 'Summary of findings' table using GRADE. Main resultsPrevious versions of this review included no trials. From the 2015 search, we identified three cross‐over trials that could be included. The 2017 search found no new studies relevant to this review. The included trials randomised 47 inpatients with chronic mental illnesses in the USA and China. Trials were published in the 1990s and were of short duration (six to 10 weeks). Overall, the risk of bias was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, and attrition and outcome data were not fully reported. Findings were sparse, no study reported on the primary outcome 'no clinically important improvement in tardive dyskinesia symptoms,' but two small studies (37 participants) found no difference on the tardive dyskinesia symptoms scale Abnormal Involuntary Movement Scale (AIMS) scores between diltiazem or flunarizine and placebo after three to four weeks' treatment (MD ‐0.71, 95% CI ‐2.68 to 1.26, very low quality evidence). Only one study randomising 20 participants reported on adverse events, and reported that there were no adverse events with flunarizine or with placebo (very low quality evidence). One study with 18 participants reported no events of deterioration in mental state with diltiazem or with placebo (very low quality evidence). No studies reported on acceptability of treatment or on social confidence, social inclusion, social networks or personalised quality of life outcomes designated important to patients. Authors' conclusionsAvailable evidence from randomised controlled trials is extremely limited and very low quality, conclusions cannot be drawn. The effects of calcium channel blockers for antipsychotic‐induced tardive dyskinesia are unknown. Their use is experimental and should only be given in the context of well‐designed randomised trials

Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin and school performance.

Background The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common. As the intervention is often claimed to have important health, nutrition, and societal effects beyond the removal of worms, we critically evaluated the evidence on benefits. Objectives To summarize the effects of giving deworming drugs to children to treat soil-transmitted helminths on weight, haemoglobin, and cognition; and the evidence of impact on physical well-being, school attendance, school performance, and mortality. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (14 April 2015); Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library (2015, Issue 4); MEDLINE (2000 to 14 April 2015); EMBASE (2000 to 14 April 2015); LILACS (2000 to 14 April 2015); the metaRegister of Controlled Trials (mRCT); and reference lists, and registers of ongoing and completed trials up to 14 April 2015. Selection criteria We included randomized controlled trials (RCTs) and quasi-RCTs comparing deworming drugs for soil-transmitted helminths with placebo or no treatment in children aged 16 years or less, reporting on weight, haemoglobin, and formal tests of intellectual development. We also sought data on school attendance, school performance, and mortality. We included trials that combined health education with deworming programmes. Data collection and analysis At least two review authors independently assessed the trials, evaluated risk of bias, and extracted data. We analysed continuous data using the mean difference (MD) with 95% confidence intervals (CIs). Where data were missing, we contacted trial authors. We used outcomes at time of longest follow-up. The evidence quality was assessed using GRADE. This edition of the Cochrane Review adds the DEVTA trial from India, and draws on an independent analytical replication of a trial from Kenya. Main results We identified 45 trials, including nine cluster-RCTs, that met the inclusion criteria. One trial evaluating mortality included over one million children, and the remaining 44 trials included a total of 67,672 participants. Eight trials were in children known to be infected, and 37 trials were carried out in endemic areas, including areas of high (15 trials), moderate (12 trials), and low prevalence (10 trials). Treating children known to be infected Treating children known to be infected with a single dose of deworming drugs (selected by screening, or living in areas where all children are infected) may increase weight gain over the next one to six months (627 participants, five trials, low quality evidence). The effect size varied across trials from an additional 0.2 kg gain to 1.3 kg. There is currently insufficient evidence to know whether treatment has additional effects on haemoglobin (247 participants, two trials, very low quality evidence); school attendance (0 trials); cognitive functioning (103 participants, two trials, very low quality evidence), or physical well-being (280 participants, three trials, very low quality evidence). Community deworming programmes Treating all children living in endemic areas with a dose of deworming drugs probably has little or no effect on average weight gain (MD 0.04 kg less, 95% CI 0.11 kg less to 0.04 kg more; trials 2719 participants, seven trials, moderate quality evidence), even in settings with high prevalence of infection (290 participants, two trials). A single dose also probably has no effect on average haemoglobin (MD 0.06 g/dL, 95% CI -0.05 lower to 0.17 higher; 1005 participants, three trials, moderate quality evidence), or average cognition (1361 participants, two trials, low quality evidence). Similiarly, regularly treating all children in endemic areas with deworming drugs, given every three to six months, may have little or no effect on average weight gain (MD 0.08 kg, 95% CI 0.11 kg less to 0.27 kg more; 38,392 participants, 10 trials, low quality evidence). The effects were variable across trials; one trial from a low prevalence setting carried out in 1995 found an increase in weight, but nine trials carried out since then found no effect, including five from moderate and high prevalence areas. There is also reasonable evidence that regular treatment probably has no effect on average height (MD 0.02 cm higher, 95% CI 0.14 lower to 0.17 cm higher; 7057 participants, seven trials, moderate quality evidence); average haemoglobin (MD 0.02 g/dL lower; 95% CI 0.08 g/dL lower to 0.04 g/dL higher; 3595 participants, seven trials, low quality evidence); formal tests of cognition (32,486 participants, five trials, moderate quality evidence); exam performance (32,659 participants, two trials, moderate quality evidence); or mortality (1,005,135 participants, three trials, low quality evidence). There is very limited evidence assessing an effect on school attendance and the findings are inconsistent, and at risk of bias (mean attendance 2% higher, 95% CI 4% lower to 8% higher; 20,243 participants, two trials, very low quality evidence). In a sensitivity analysis that only included trials with adequate allocation concealment, there was no evidence of any effect for the main outcomes. Authors' conclusions Treating children known to have worm infection may have some nutritional benefits for the individual. However, in mass treatment of all children in endemic areas, there is now substantial evidence that this does not improve average nutritional status, haemoglobin, cognition, school performance, or survival

meta-analyses

c i a l D i s t r i b u t i o n U n a u t h o r i z e d u s e p r o h i b i t e d . A u t h o r i s e d u s e r s c a n d o w n l o a d , d i s p l a y , v i e w a n d p r i n t a s i n g l e c o p y f o r p e r s o n a l u s e Current Medical Research & Opinion Vol. 27, No. 7, 2011, 1477-1491 Abstract Objective: For chronic pain treatment many health care authorities consider morphine to be the reference standard for strategic decisions in pain therapy. Although morphine's effectiveness is clear and its cost is low, it's unclear whether morphine should remain the first choice or reference treatment. Research design and methods: We performed a systematic review to evaluate the evidence available to support the position of morphine as the reference standard for step III opioids based on efficacy and tolerability outcomes. Results: The search yielded 5675 titles and 56 studies were included. Considerable heterogeneity precluded pairwise meta-analysis on change of pain intensity and no difference between morphine and other opioids were found for tolerability outcomes. The network meta-analysis showed no statistically significant difference in change of pain intensity between morphine and oxycodone, methadone and oxymorphone. Compared to morphine, patients using buprenorphine are more likely to discontinue treatment due to lack of effect (OR 2.32, 95% CI 1.37 to 3.95). Patients using methadone are more likely to discontinue due to adverse events (OR 3.09, 95% CI 1.14 to 8.36), whereas this risk is decreased for patients using fentanyl (OR 0.29, 95% CI 0.17 to 0.50) or buprenorphine (OR 0.30, 95% CI 0.16 to 0.53). The most important limitation of this review is that the included studies are heterogeneous with regard to study population and intervention, which may affect the pooled effect estimates. The main strength is that we only included parallel RCTs, the strongest design for intervention studies. Conclusions: The current evidence is moderate, both in respect to the number of directly comparative studies and in the quality of reporting of these studies. No clear superiority in efficacy and tolerability of morphine over other opioids was found in pair-wise and network analyses. Based on these results, a justification for the placement of morphine as the reference standard for the treatment of severe chronic pain cannot be supported

Producing Cochrane systematic reviews—a qualitative study of current approaches and opportunities for innovation and improvement

Background: Producing high-quality, relevant systematic reviews and keeping them up to date is challenging. Cochrane is a leading provider of systematic reviews in health. For Cochrane to continue to contribute to improvements in heath, Cochrane Reviews must be rigorous, reliable and up to date. We aimed to explore existing models of Cochrane Review production and emerging opportunities to improve the efficiency and sustainability of these processes. Methods: To inform discussions about how to best achieve this, we conducted 26 interviews and an online survey with 106 respondents. Results: Respondents highlighted the importance and challenge of creating reliable, timely systematic reviews. They described the challenges and opportunities presented by current production models, and they shared what they are doing to improve review production. They particularly highlighted significant challenges with increasing complexity of review methods; difficulty keeping authors on board and on track; and the length of time required to complete the process. Strong themes emerged about the roles of authors and Review Groups, the central actors in the review production process. The results suggest that improvements to Cochrane's systematic review production models could come from improving clarity of roles and expectations, ensuring continuity and consistency of input, enabling active management of the review process, centralising some review production steps; breaking reviews into smaller "chunks", and improving approaches to building capacity of and sharing information between authors and Review Groups. Respondents noted the important role new technologies have to play in enabling these improvements. Conclusions: The findings of this study will inform the development of new Cochrane Review production models and may provide valuable data for other systematic review producers as they consider how best to produce rigorous, reliable, up-to-date reviews

Children in reviews: Methodological issues in child-relevant evidence syntheses

BACKGROUND: The delivery of optimal medical care to children is dependent on the availability of child relevant research. Our objectives were to: i) systematically review and describe how children are handled in reviews of drug interventions published in the Cochrane Database of Systematic Reviews (CDSR); and ii) determine when effect sizes for the same drug interventions differ between children and adults. METHODS: We systematically identified all of the reviews relevant to child health in the CDSR 2002, Issue 4. Reviews were included if they investigated the efficacy or effectiveness of a drug intervention for a condition that occurs in both children and adults. Information was extracted on review characteristics including study methods, results, and conclusions. RESULTS: From 1496 systematic reviews, 408 (27%) were identified as relevant to both adult and child health; 52% (213) of these included data from children. No significant differences were found in effect sizes between adults and children for any of the drug interventions or conditions investigated. However, all of the comparisons lacked the power to detect a clinically significant difference and wide confidence intervals suggest important differences cannot be excluded. A large amount of data was unavailable due to inadequate reporting at the trial and systematic review level. CONCLUSION: Overall, the findings of this study indicate there is a paucity of child-relevant and specific evidence generated from evidence syntheses of drug interventions. The results indicate a need for a higher standard of reporting for participant populations in studies of drug interventions

Making progress with the automation of systematic reviews: Principles of the International Collaboration for the Automation of Systematic Reviews (ICASR)

Systematic reviews (SR) are vital to health care, but have become complicated and time-consuming, due to the rapid expansion of evidence to be synthesised. Fortunately, many tasks of systematic reviews have the potential to be automated or may be assisted by automation. Recent advances in natural language processing, text mining and machine learning have produced new algorithms that can accurately mimic human endeavour in systematic review activity, faster and more cheaply. Automation tools need to be able to work together, to exchange data and results. Therefore, we initiated the International Collaboration for the Automation of Systematic Reviews (ICASR), to successfully put all the parts of automation of systematic review production together. The first meeting was held in Vienna in October 2015. We established a set of principles to enable tools to be developed and integrated into toolkits. This paper sets out the principles devised at that meeting, which cover the need for improvement in efficiency of SR tasks, automation across the spectrum of SR tasks, continuous improvement, adherence to high quality standards, flexibility of use and combining components, the need for a collaboration and varied skills, the desire for open source, shared code and evaluation, and a requirement for replicability through rigorous and open evaluation. Automation has a great potential to improve the speed of systematic reviews. Considerable work is already being done on many of the steps involved in a review. The 'Vienna Principles' set out in this paper aim to guide a more coordinated effort which will allow the integration of work by separate teams and build on the experience, code and evaluations done by the many teams working across the globe

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson