Efficacy and safety of second-generation antipsychotic long-acting injections (SGA LAIs) in maintenance treatment of bipolar disorder:protocol for a systematic review and meta-analysis

INTRODUCTION: Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. METHODS AND ANALYSIS: The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.

Systematic review investigating the reporting of comorbidities and medication in randomized controlled trials of people with dementia

Objectives: dementia is a debilitating condition characterised by global loss of cognitive and intellectual functioning, which reduces social and occupational performance. This population frequently presents with medical co-morbidities such as hypertension, cardiovascular disease and diabetes. The CONSORT statement outlines recommended guidance on reporting of participant characteristics in clinical trials. It is, however, unclear how much these are adhered to in trials assessing people with dementia. This paper assesses the reporting of medical co-morbidities and prescribed medications for people with dementia within randomised controlled trial (RCT) reports. Design: a systematic review of the published literature from the databases AMED, CINAHL, MEDLINE, EMBASE and the Cochrane Clinical Trial Registry from 1 January 1997 to 9 January 2014 was undertaken in order to identify RCTs detailing baseline medical co-morbidities and prescribed medications . Eligible studies were appraised using the Critical Appraisal Skills Programme (CASP) RCT appraisal tool, and descriptive statistical analyses were calculated to determine point prevalence. Results: nine trials, including 1474 people with dementia, were identified presenting medical co-morbidity data. These indicated neurological disorders ( prevalence 91%), vascular disorders (prevalence 91%), cardiac disorders ( prevalence 74%) and ischaemic cerebrovascular disease ( prevalence 53%) were most frequently seen. Conclusions: published RCTs poorly report medical co-morbidities and medications for people with dementia. Future trials should include the report of these items to allow interpretation of whether the results are generalisable to frailer older populations.

How well does the theory of planned behaviour predict alcohol consumption? A systematic review and meta-analysis

This study aimed to quantify correlations between theory of planned behaviour (TPB) variables and (i) intentions to consume alcohol and (ii) alcohol consumption. Systematic literature searches identified 40 eligible studies that were meta-analysed. Three moderator analyses were conducted: pattern of consumption, gender of participants and age of participants. Across studies, intentions had the strongest relationship with attitudes (r+ = .62), followed by subjective norms (r+ = .47) and perceived behavioural control (PBC; r+ = .31). Self-efficacy (SE) had a stronger relationship with intentions (r+ = .48) compared with perceived control (PC; r+ = −.10). Intention had the strongest relationship with alcohol consumption (r+ = .54), followed by SE (r+ = .41). In contrast, PBC and PC had negative relationships with alcohol consumption (r+ = −.05 and −.13, respectively). All moderators affected TPB relationships. Patterns of consumption with clear definitions had stronger TPB relations, females reported stronger attitude–intention relations than males, and adults reported stronger attitude–intention and SE–intention relations than adolescents. Recommendations for future research include targeting attitudes and intentions in interventions to reduce alcohol consumption, using clear definitions of alcohol consumption in TPB items to improve prediction and assessing SE when investigating risk behaviours.

Metformin in patients with type 2 diabetes and kidney disease:a systematic review

IMPORTANCE: Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. OBJECTIVE: To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. EVIDENCE ACQUISITION: In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining tometformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014.We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. RESULTS: Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety ofmetformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus-use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use. CONCLUSIONS AND RELEVANCE: Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function.

Patients’ perceptions and experiences of cardiovascular disease and diabetes prevention programmes:a systematic review and framework synthesis using the Theoretical Domains Framework

Background - This review provides a worked example of ‘best fit’ framework synthesis using the Theoretical Domains Framework (TDF) of health psychology theories as an a priori framework in the synthesis of qualitative evidence. Framework synthesis works best with ‘policy urgent’ questions. Objective - The review question selected was: what are patients’ experiences of prevention programmes for cardiovascular disease (CVD) and diabetes? The significance of these conditions is clear: CVD claims more deaths worldwide than any other; diabetes is a risk factor for CVD and leading cause of death. Method - A systematic review and framework synthesis were conducted. This novel method for synthesizing qualitative evidence aims to make health psychology theory accessible to implementation science and advance the application of qualitative research findings in evidence-based healthcare. Results - Findings from 14 original studies were coded deductively into the TDF and subsequently an inductive thematic analysis was conducted. Synthesized findings produced six themes relating to: knowledge, beliefs, cues to (in)action, social influences, role and identity, and context. A conceptual model was generated illustrating combinations of factors that produce cues to (in)action. This model demonstrated interrelationships between individual (beliefs and knowledge) and societal (social influences, role and identity, context) factors. Conclusion - Several intervention points were highlighted where factors could be manipulated to produce favourable cues to action. However, a lack of transparency of behavioural components of published interventions needs to be corrected and further evaluations of acceptability in relation to patient experience are required. Further work is needed to test the comprehensiveness of the TDF as an a priori framework for ‘policy urgent’ questions using ‘best fit’ framework synthesis.

Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis:implications for aetiology and early prevention

The aim of this review was to quantify the global variation in childhood myopia prevalence over time taking account of demographic and study design factors. A systematic review identified population-based surveys with estimates of childhood myopia prevalence published by February 2015. Multilevel binomial logistic regression of log odds of myopia was used to examine the association with age, gender, urban versus rural setting and survey year, among populations of different ethnic origins, adjusting for study design factors. 143 published articles (42 countries, 374 349 subjects aged 1- 18 years, 74 847 myopia cases) were included. Increase in myopia prevalence with age varied by ethnicity. East Asians showed the highest prevalence, reaching 69% (95% credible intervals (CrI) 61% to 77%) at 15 years of age (86% among Singaporean-Chinese). Blacks in Africa had the lowest prevalence; 5.5% at 15 years (95% CrI 3% to 9%). Time trends in myopia prevalence over the last decade were small in whites, increased by 23% in East Asians, with a weaker increase among South Asians. Children from urban environments have 2.6 times the odds of myopia compared with those from rural environments. In whites and East Asians sex differences emerge at about 9 years of age; by late adolescence girls are twice as likely as boys to be myopic. Marked ethnic differences in age-specific prevalence of myopia exist. Rapid increases in myopia prevalence over time, particularly in East Asians, combined with a universally higher risk of myopia in urban settings, suggest that environmental factors play an important role in myopia development, which may offer scope for prevention.

Beyond BMI: The “Metabolically healthy obese” phenotype & its association with clinical/subclinical cardiovascular disease and all-cause mortality -- a systematic review

Background A subgroup has emerged within the obese that do not display the typical metabolic disorders associated with obesity and are hypothesized to have lower risk of complications. The purpose of this review was to analyze the literature which has examined the burden of cardiovascular disease (CVD) and all-cause mortality in the metabolically healthy obese (MHO) population. Methods Pubmed, Cochrane Library, and Web of Science were searched from their inception until December 2012. Studies were included which clearly defined the MHO group (using either insulin sensitivity and/or components of metabolic syndrome AND obesity) and its association with either all cause mortality, CVD mortality, incident CVD, and/or subclinical CVD. Results A total of 20 studies were identified; 15 cohort and 5 cross-sectional. Eight studies used the NCEP Adult Treatment Panel III definition of metabolic syndrome to define “metabolically healthy”, while another nine used insulin resistance. Seven studies assessed all-cause mortality, seven assessed CVD mortality, and nine assessed incident CVD. MHO was found to be significantly associated with all-cause mortality in two studies (30%), CVD mortality in one study (14%), and incident CVD in three studies (33%). Of the six studies which examined subclinical disease, four (67%) showed significantly higher mean common carotid artery intima media thickness (CCA-IMT), coronary artery calcium (CAC), or other subclinical CVD markers in the MHO as compared to their MHNW counterparts. Conclusions MHO is an important, emerging phenotype with a CVD risk between healthy, normal weight and unhealthy, obese individuals. Successful work towards a universally accepted definition of MHO would improve (and simplify) future studies and aid inter-study comparisons. Usefulness of a definition inclusive of insulin sensitivity and stricter criteria for metabolic syndrome components as well as the potential addition of markers of fatty liver and inflammation should be explored. Clinicians should be hesitant to reassure patients that the metabolically benign phenotype is safe, as increased risk cardiovascular disease and death have been shown.

Pre-eclampsia is associated with a two-fold increase in diabetes : a systematic review and meta-analysis

Peer reviewed

Pre-eclampsia is associated with a two-fold increase in diabetes : a systematic review and meta-analysis

Peer reviewed

Pre-eclampsia is associated with a twofold increase in diabetes : a systematic review and meta-analysis

CSK and RH are funded by National Institute for Health Research Academic Clinical Fellowships. This study was supported by a grant from the North Staffs Heart Committee.

Pre-eclampsia is associated with a twofold increase in diabetes : a systematic review and meta-analysis

CSK and RH are funded by National Institute for Health Research Academic Clinical Fellowships. This study was supported by a grant from the North Staffs Heart Committee.

A systematic review of evidence for silver nanoparticle-induced mitochondrial toxicity

© The Royal Society of Chemistry 2016.Silver nanoparticles (AgNPs) are extensively used for their antibacterial properties in a diverse set of applications, ranging from the treatment of municipal wastewater to infection control in hospitals. However, the properties of AgNPs that render them conducive to bactericidal use in commerce may influence their potential toxicity to non-bacterial organisms. Based on the physiological and phylogenetic similarities between bacteria and mitochondria within eukaryotic cells, mitochondria are a likely intracellular target of AgNP toxicity. Mitochondria-specific outcomes of AgNP exposures have been identified in multiple cell types, including (but not limited to) loss of membrane potential, inhibition of enzymes involved in oxidative phosphorylation, and changes in calcium sequestration. However, the biological significance of mitochondrial toxicity due to AgNP exposure is currently incompletely understood. This review examines the existing evidence of mitochondrial toxicity induced by AgNP exposure, with discussions of the role of the physicochemical properties of the nanoparticles themselves in mitochondrial toxicity. The impacts of potentially differential cell- and tissue-specific significance of AgNP-induced mitochondrial dysfunction are also discussed.

Individual Proton Pump Inhibitors and Outcomes in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy: A Systematic Review.

BACKGROUND: Observational studies evaluating the possible interaction between proton pump inhibitors (PPIs) and clopidogrel have shown mixed results. We conducted a systematic review comparing the safety of individual PPIs in patients with coronary artery disease taking clopidogrel. METHODS AND RESULTS: Studies performed from January 1995 to December 2013 were screened for inclusion. Data were extracted, and study quality was graded for 34 potential studies. For those studies in which follow-up period, outcomes, and multivariable adjustment were comparable, meta-analysis was performed.The adjusted odds or hazard ratios for the composite of cardiovascular or all-cause death, myocardial infarction, and stroke at 1 year were reported in 6 observational studies with data on individual PPIs. Random-effects meta-analyses of the 6 studies revealed an increased risk for adverse cardiovascular events for those taking pantoprazole (hazard ratio 1.38; 95% CI 1.12-1.70), lansoprazole (hazard ratio 1.29; 95% CI 1.09-1.52), or esomeprazole (hazard ratio 1.27; 95% CI 1.02-1.58) compared with patients on no PPI. This association was not significant for omeprazole (hazard ratio 1.16; 95% CI 0.93-1.44). Sensitivity analyses for the coronary artery disease population (acute coronary syndrome versus mixed) and exclusion of a single study due to heterogeneity of reported results did not have significant influence on the effect estimates for any PPIs. CONCLUSIONS: Several frequently used PPIs previously thought to be safe for concomitant use with clopidogrel were associated with greater risk of adverse cardiovascular events. Although the data are observational, they highlight the need for randomized controlled trials to evaluate the safety of concomitant PPI and clopidogrel use in patients with coronary artery disease.

Systematic Review Protocol to Evaluate the Effectiveness and Cost Effectiveness of Personalised Surveillance after Colorectal Adenomatous Polypectomy

Lifetime risk of developing colorectal cancer (CRC) is 5% and five-year survival at early-stage is 92%. CRC risk following index colonoscopy should establish post-screening surveillance benefit, which may be greater in high-risk patients. This review evaluated published cost-effectiveness estimates of post-polypectomy surveillance to assess the potential for personalised recommendations by risk sub-group. Current data suggested colonoscopy identifies those at low-risk of CRC, who may not benefit from intensive surveillance, which risks unnecessary harms and inefficient use of colonoscopy resources. Meta-analyses of incidence of advanced-neoplasia post-polypectomy for low-risk was comparable to those without adenoma; both rates were under the lifetime risk of 5%. Therefore, greater personalisation through de-intensified strategies for low-risk individuals could be beneficial and could employ non-invasive testing such as faecal immunochemical tests (FIT) combined with primary prevention or chemoprevention, thereby reserving colonoscopy for targeted use in personalised risk-stratified surveillance.
This systematic review aims to:
1. Assess if there is evidence supporting a program of personalised surveillance in patients with colorectal adenoma according to risk sub-group.
2. Compare the effectiveness of surveillance colonoscopy with alternative prevention strategies.
3. Assess trade-off between costs, benefits and adverse effects which must be considered in a decision to adopt or reject personalised surveillance.

Behaviour change techniques in home-based cardiac rehabilitation: a systematic review

BACKGROUND: Cardiac rehabilitation (CR) programmes offering secondary prevention for cardiovascular disease (CVD) advise healthy lifestyle behaviours, with the behaviour change techniques (BCTs) of goals and planning, feedback and monitoring, and social support recommended. More information is needed about BCT use in home-based CR to support these programmes in practice.

AIM: To identify and describe the use of BCTs in home-based CR programmes.

DESIGN AND SETTING: Randomised controlled trials of home-based CR between 2005 and 2015 were identified by searching MEDLINE(®), Embase, PsycINFO, Web of Science, and Cochrane Database.

METHOD: Reviewers independently screened titles and abstracts for eligibility. Relevant data, including BCTs, were extracted from included studies. A meta-analysis studied risk factor change in home-based and comparator programmes.

RESULTS: From 2448 studies identified, 11 of good methodological quality (10 on post-myocardial infarction, one on heart failure, 1907 patients) were included. These reported the use of 20 different BCTs. Social support (unspecified) was used in all studies and goal setting (behaviour) in 10. Of the 11 studies, 10 reported effectiveness in reducing CVD risk factors, but one study showed no improvement compared to usual care. This study differed from effective programmes in that it didn't include BCTs that had instructions on how to perform the behaviour and monitoring, or a credible source.

CONCLUSION: Social support and goal setting were frequently used BCTs in home-based CR programmes, with the BCTs related to monitoring, instruction on how to perform the behaviour, and credible source being included in effective programmes. Further robust trials are needed to determine the relative value of different BCTs within CR programmes.