Nationally Automated Colonoscopy Performance Feedback Increases Polyp Detection: The NED APRIQOT Randomized Controlled Trial.

BACKGROUND & AIMS: Postcolonoscopy colorectal cancer incidence and mortality rates are higher for endoscopists with low polyp detection rates. Using the UK's National Endoscopy Database (NED), which automatically captures real-time data, we assessed if providing feedback of case-mix-adjusted mean number of polyps (aMNP), as a key performance indicator, improved endoscopists' performance. Feedback was delivered via a theory-informed, evidence-based audit and feedback intervention. METHODS: This multicenter, prospective, NED Automated Performance Reports to Improve Quality Outcomes Trial randomized National Health Service endoscopy centers to intervention or control. Intervention-arm endoscopists were e-mailed tailored monthly reports automatically generated within NED, informed by qualitative interviews and behavior change theory. The primary outcome was endoscopists' aMNP during the 9-month intervention. RESULTS: From November 2020 to July 2021, 541 endoscopists across 36 centers (19 intervention; 17 control) performed 54,770 procedures during the intervention, and 15,960 procedures during the 3-month postintervention period. Comparing the intervention arm with the control arm, endoscopists during the intervention period: aMNP was nonsignificantly higher (7%; 95% CI, -1% to 14%; P = .08). The unadjusted MNP (10%; 95% CI, 1%-20%) and polyp detection rate (10%; 95% CI, 4%-16%) were significantly higher. Differences were not maintained in the postintervention period. In the intervention arm, endoscopists accessing NED Automated Performance Reports to Improve Quality Outcomes Trial webpages had a higher aMNP than those who did not (aMNP, 118 vs 102; P = .03). CONCLUSIONS: Although our automated feedback intervention did not increase aMNP significantly in the intervention period, MNP and polyp detection rate did improve significantly. Engaged endoscopists benefited most and improvements were not maintained postintervention; future work should address engagement in feedback and consider the effectiveness of continuous feedback. CLINICAL TRIALS REGISTRY:  www.isrctn.org ISRCTN11126923 .

Minithoracotomy vs Conventional Sternotomy for Mitral Valve Repair: A Randomized Clinical Trial.

Importance: The safety and effectiveness of mitral valve repair via thoracoscopically-guided minithoracotomy (minithoracotomy) compared with median sternotomy (sternotomy) in patients with degenerative mitral valve regurgitation is uncertain. Objective: To compare the safety and effectiveness of minithoracotomy vs sternotomy mitral valve repair in a randomized trial. Design, Setting, and Participants: A pragmatic, multicenter, superiority, randomized clinical trial in 10 tertiary care institutions in the UK. Participants were adults with degenerative mitral regurgitation undergoing mitral valve repair surgery. Interventions: Participants were randomized 1:1 with concealed allocation to receive either minithoracotomy or sternotomy mitral valve repair performed by an expert surgeon. Main Outcomes and Measures: The primary outcome was physical functioning and associated return to usual activities measured by change from baseline in the 36-Item Short Form Health Survey (SF-36) version 2 physical functioning scale 12 weeks after the index surgery, assessed by an independent researcher masked to the intervention. Secondary outcomes included recurrent mitral regurgitation grade, physical activity, and quality of life. The prespecified safety outcomes included death, repeat mitral valve surgery, or heart failure hospitalization up to 1 year. Results: Between November 2016 and January 2021, 330 participants were randomized (mean age, 67 years, 100 female [30%]); 166 were allocated to minithoracotomy and 164 allocated to sternotomy, of whom 309 underwent surgery and 294 reported the primary outcome. At 12 weeks, the mean between-group difference in the change in the SF-36 physical function T score was 0.68 (95% CI, -1.89 to 3.26). Valve repair rates (≈ 96%) were similar in both groups. Echocardiography demonstrated mitral regurgitation severity as none or mild for 92% of participants at 1 year with no difference between groups. The composite safety outcome occurred in 5.4% (9 of 166) of patients undergoing minithoracotomy and 6.1% (10 of 163) undergoing sternotomy at 1 year. Conclusions and relevance: Minithoracotomy is not superior to sternotomy in recovery of physical function at 12 weeks. Minithoracotomy achieves high rates and quality of valve repair and has similar safety outcomes at 1 year to sternotomy. The results provide evidence to inform shared decision-making and treatment guidelines. Trial Registration: isrctn.org Identifier: ISRCTN13930454.

Community health workers and health equity in low- and middle-income countries: systematic review and recommendations for policy and practice.

BACKGROUND: The deployment of Community Health Workers (CHWs) is widely promoted as a strategy for reducing health inequities in low- and middle-income countries (LMIC). Yet there is limited evidence on whether and how CHW programmes achieve this. This systematic review aimed to synthesise research findings on the following questions: (1) How effective are CHW interventions at reaching the most disadvantaged groups in LMIC contexts? and (2) What evidence exists on whether and how these programmes reduce health inequities in the populations they serve? METHODS: We searched six academic databases for recent (2014-2020) studies reporting on CHW programme access, utilisation, quality, and effects on health outcomes/behaviours in relation to potential stratifiers of health opportunities and outcomes (e.g., gender, socioeconomic status, place of residence). Quantitative data were extracted, tabulated, and subjected to meta-analysis where appropriate. Qualitative findings were synthesised using thematic analysis. RESULTS: One hundred sixty-seven studies met the search criteria, reporting on CHW interventions in 33 LMIC. Quantitative synthesis showed that CHW programmes successfully reach many (although not all) marginalized groups, but that health inequalities often persist in the populations they serve. Qualitative findings suggest that disadvantaged groups experienced barriers to taking up CHW health advice and referrals and point to a range of strategies for improving the reach and impact of CHW programmes in these groups. Ensuring fair working conditions for CHWs and expanding opportunities for advocacy were also revealed as being important for bridging health equity gaps. CONCLUSION: In order to optimise the equity impacts of CHW programmes, we need to move beyond seeing CHWs as a temporary sticking plaster, and instead build meaningful partnerships between CHWs, communities and policy-makers to confront and address the underlying structures of inequity. TRIAL REGISTRATION: PROSPERO registration number CRD42020177333 .

Fecal glucocorticoids and gastrointestinal parasite infections in wild western lowland gorillas (Gorilla gorilla gorilla) involved in ecotourism.

Wildlife ecotourism can offer a source of revenue which benefits local development and conservation simultaneously. However, habituation of wildlife for ecotourism can cause long-term elevation of glucocorticoid hormones, which may suppress immune function and increase an animal's vulnerability to disease. We have previously shown that western lowland gorillas (Gorilla gorilla gorilla) undergoing habituation in Dzanga-Sangha Protected Areas, Central African Republic, have higher fecal glucocorticoid metabolite (FGCM) levels than both habituated and unhabituated gorillas. Here, we tested the relationship between FGCM levels and strongylid infections in the same gorillas. If high FGCM levels suppress the immune system, we predicted that FGCM levels will be positively associated with strongylid egg counts and that gorillas undergoing habituation will have the highest strongylid egg counts, relative to both habituated and unhabituated gorillas. We collected fecal samples over 12 months in two habituated gorilla groups, one group undergoing habituation and completely unhabituated gorillas. We established FGCM levels and fecal egg counts of Necator/Oesophagostomum spp. and Mammomonogamus sp. Controlling for seasonal variation and age-sex category in strongylid infections we found no significant relationship between FGCMs and Nectator/Oesophagostomum spp. or Mammomonogamus sp. egg counts in a within group comparison in either a habituated group or a group undergoing habituation. However, across groups, egg counts of Nectator/Oesophagostomum spp. were lowest in unhabituated animals and highest in the group undergoing habituation, matching the differences in FGCM levels among these gorilla groups. Our findings partially support the hypothesis that elevated glucocorticoids reduce a host's ability to control the extent of parasitic infections, and show the importance of non-invasive monitoring of endocrine function and parasite infection in individuals exposed to human pressure including habituation process and ecotourism.

Informal mhealth at scale in Africa: Opportunities and challenges.

The extraordinary global growth of digital connectivity has generated optimism that mobile technologies can help overcome infrastructural barriers to development, with 'mobile health' (mhealth) being a key component of this. However, while 'formal' (top-down) mhealth programmes continue to face challenges of scalability and sustainability, we know relatively little about how health-workers are using their own mobile phones informally in their work. Using data from Ghana, Ethiopia and Malawi, we document the reach, nature and perceived impacts of community health-workers' (CHWs') 'informal mhealth' practices, and ask how equitably these are distributed. We implemented a mixed-methods study, combining surveys of CHWs across the three countries, using multi-stage proportional-to-size sampling (N = 2197 total), with qualitative research (interviews and focus groups with CHWs, clients and higher-level stake-holders). Survey data were weighted to produce nationally- or regionally-representative samples for multivariate analysis; comparative thematic analysis was used for qualitative data. Our findings confirm the limited reach of 'formal' compared with 'informal' mhealth: while only 15% of CHWs surveyed were using formal mhealth applications, over 97% reported regularly using a personal mobile phone for work-related purposes in a range of innovative ways. CHWs and clients expressed unequivocally enthusiastic views about the perceived impacts of this 'informal health' usage. However, they also identified very real practical challenges, financial burdens and other threats to personal wellbeing; these appear to be borne disproportionately by the lowest-paid cadre of health-workers, especially those serving rural areas. Unlike previous small-scale, qualitative studies, our work has shown that informal mhealth is already happening at scale, far outstripping its formal equivalent. Policy-makers need to engage seriously with this emergent health system, and to work closely with those on the ground to address sources of inequity, without undermining existing good practice.

Does Blood Transfusion Have an Effect on Outcomes After Aortic Valve Replacement Surgery?

OBJECTIVE: Long-term outcomes following surgical aortic valve replacement (AVR) are excellent. However, there is a significant early morbidity burden. Red cell transfusion is common in the perioperative period and deleterious effects of receiving a transfusion on early postoperative morbidity are well described in observational studies. This study aimed to assess the effect of transfusion on ischaemic or infective outcomes after aortic valve replacement. METHODS: Data from 270 patients enrolled in the Manubrium-limited ministernotomy versus conventional sternotomy for aortic valve replacement (MAVRIC) randomised controlled trial was used to create two cohorts, patients that received red cell transfusions following AVR and those that did not. Propensity score matching was performed to limit the effect of confounding variables. Strict transfusion thresholds were maintained, with patients receiving a transfusion if haemoglobin concentration fell below 80 g/L, or if significant bleeding or haemodynamic instability occurred. The primary outcome was a composite of ischaemic event (myocardial infarction, permanent stroke, gut ischaemia or acute kidney injury) or serious infection (sepsis, endocarditis, respiratory tract or wound infection). Patients were followed for 12 weeks following surgery. RESULTS: Sixty-three (63) of 270 patients received a red cell transfusion (23.3%). Transfused patients had significantly lower body mass index (BMI), a higher proportion of females, a lower preoperative haemoglobin and haematocrit, a higher EuroSCORE II score, worse renal function and were more likely to have undergone urgent surgery compared to the unadjusted control cohort. Once matched, there was no difference in the primary outcome between cohorts. There was a significantly increased length of hospital stay in the transfused group (median 7 days transfused, median 5 days not-transfused, p=0.001). CONCLUSIONS: Red cell transfusion, using a transfusion threshold of 80 g/L, does not appear to be associated with adverse ischaemic or infective outcomes after aortic valve replacement.

Missed opportunities: unnecessary medicine use in patients with lung cancer at the end of life - an international cohort study.

AIMS: The aims of the current study were: (i) to examine the prescribing of preventative medication in a cohort of people with advanced lung cancer on hospital admission and discharge across different healthcare systems; and (ii) to explore the factors that influence preventative medication prescribing at hospital discharge. METHODS: A retrospective cohort study was conducted across two centres in the UK and the US. The prescribing of preventative medication was examined at hospital admission and discharge for patients who died of lung cancer. A zero-inflated negative binomial regression model was used to examine the association between preventative medications at discharge and patient- and hospital-based factors. The classes of preventative medication prescribed included were: vitamins and minerals, and antidiabetic, antihypertensive, antihyperlipidaemic and antiplatelet medications. RESULTS: In the UK site (n = 125), the mean number of preventative medications prescribed was 1.9 [standard deviation (SD) 1.7) on admission, and 1.7 (SD 1.7) on discharge, and in the US site (n = 191) the mean was 2.6 (SD 2.2) on admission and 1.9 (SD 2.2) on discharge. The model found a significant association between the number of preventative drugs prescribed on admission and the number on discharge; it also found a significant association between the total number of drugs prescribed on discharge and the number of preventative medications on discharge. Other indicators related to patient and hospital factors were not significantly associated with the number of preventative medications supplied on discharge. CONCLUSIONS: The use of preventative medication was common in lung cancer patients, despite undergoing discharge. Patient- and hospital-based factors did not influence the prescribing of preventative medication.

A random effects model for the identification of differential splicing (REIDS) using exon and HTA arrays.

BACKGROUND: Alternative gene splicing is a common phenomenon in which a single gene gives rise to multiple transcript isoforms. The process is strictly guided and involves a multitude of proteins and regulatory complexes. Unfortunately, aberrant splicing events do occur which have been linked to genetic disorders, such as several types of cancer and neurodegenerative diseases (Fan et al., Theor Biol Med Model 3:19, 2006). Therefore, understanding the mechanism of alternative splicing and identifying the difference in splicing events between diseased and healthy tissue is crucial in biomedical research with the potential of applications in personalized medicine as well as in drug development. RESULTS: We propose a linear mixed model, Random Effects for the Identification of Differential Splicing (REIDS), for the identification of alternative splicing events. Based on a set of scores, an exon score and an array score, a decision regarding alternative splicing can be made. The model enables the ability to distinguish a differential expressed gene from a differential spliced exon. The proposed model was applied to three case studies concerning both exon and HTA arrays. CONCLUSION: The REIDS model provides a work flow for the identification of alternative splicing events relying on the established linear mixed model. The model can be applied to different types of arrays.

A joint modeling approach for uncovering associations between gene expression, bioactivity and chemical structure in early drug discovery to guide lead selection and genomic biomarker development.

The modern drug discovery process involves multiple sources of high-dimensional data. This imposes the challenge of data integration. A typical example is the integration of chemical structure (fingerprint features), phenotypic bioactivity (bioassay read-outs) data for targets of interest, and transcriptomic (gene expression) data in early drug discovery to better understand the chemical and biological mechanisms of candidate drugs, and to facilitate early detection of safety issues prior to later and expensive phases of drug development cycles. In this paper, we discuss a joint model for the transcriptomic and the phenotypic variables conditioned on the chemical structure. This modeling approach can be used to uncover, for a given set of compounds, the association between gene expression and biological activity taking into account the influence of the chemical structure of the compound on both variables. The model allows to detect genes that are associated with the bioactivity data facilitating the identification of potential genomic biomarkers for compounds efficacy. In addition, the effect of every structural feature on both genes and pIC50 and their associations can be simultaneously investigated. Two oncology projects are used to illustrate the applicability and usefulness of the joint model to integrate multi-source high-dimensional information to aid drug discovery.

Multi-state models for the analysis of time-to-treatment modification among HIV patients under highly active antiretroviral therapy in Southwest Ethiopia.

BACKGROUND: Highly active antiretroviral therapy (HAART) has shown a dramatic change in controlling the burden of HIV/AIDS. However, the new challenge of HAART is to allow long-term sustainability. Toxicities, comorbidity, pregnancy, and treatment failure, among others, would result in frequent initial HAART regimen change. The aim of this study was to evaluate the durability of first line antiretroviral therapy and to assess the causes of initial highly active antiretroviral therapeutic regimen changes among patients on HAART. METHODS: A Hospital based retrospective study was conducted from January 2007 to August 2013 at Jimma University Hospital, Southwest Ethiopia. Data on the prescribed ARV along with start date, switching date, and reason for change was collected. The primary outcome was defined as the time-to-treatment change. We adopted a multi-state survival modeling approach assuming each treatment regimen as state. We estimate the transition probability of patients to move from one regimen to another. RESULT: A total of 1284 ART naive patients were included in the study. Almost half of the patients (41.2%) changed their treatment during follow up for various reasons; 442 (34.4%) changed once and 86 (6.69%) changed more than once. Toxicity was the most common reason for treatment changes accounting for 48.94% of the changes, followed by comorbidity (New TB) 14.31%. The HAART combinations that were robust to treatment changes were tenofovir (TDF) + lamivudine (3TC)+ efavirenz (EFV), tenofovir + lamivudine (3TC) + nevirapine (NVP) and zidovudine (AZT) + lamivudine (3TC) + nevirapine (NVP) with 3.6%, 4.5% and 11% treatment changes, respectively. CONCLUSION: Moving away from drugs with poor safety profiles, such as stavudine(d4T), could reduce modification rates and this would improve regimen tolerability, while preserving future treatment options.

Identification of the minimum effective dose for normally distributed data using a Bayesian variable selection approach.

The identification of the minimum effective dose is of high importance in the drug development process. In early stage screening experiments, establishing the minimum effective dose can be translated into a model selection based on information criteria. The presented alternative, Bayesian variable selection approach, allows for selection of the minimum effective dose, while taking into account model uncertainty. The performance of Bayesian variable selection is compared with the generalized order restricted information criterion on two dose-response experiments and through the simulations study. Which method has performed better depends on the complexity of the underlying model and the effect size relative to noise.

Predictive validity of the UKCAT for medical school undergraduate performance: a national prospective cohort study.

BACKGROUND: The UK Clinical Aptitude Test (UKCAT) has been shown to have a modest but statistically significant ability to predict aspects of academic performance throughout medical school. Previously, this ability has been shown to be incremental to conventional measures of educational performance for the first year of medical school. This study evaluates whether this predictive ability extends throughout the whole of undergraduate medical study and explores the potential impact of using the test as a selection screening tool. METHODS: This was an observational prospective study, linking UKCAT scores, prior educational attainment and sociodemographic variables with subsequent academic outcomes during the 5 years of UK medical undergraduate training. The participants were 6812 entrants to UK medical schools in 2007-8 using the UKCAT. The main outcome was academic performance at each year of medical school. A receiver operating characteristic (ROC) curve analysis was also conducted, treating the UKCAT as a screening test for a negative academic outcome (failing at least 1 year at first attempt). RESULTS: All four of the UKCAT scale scores significantly predicted performance in theory- and skills-based exams. After adjustment for prior educational achievement, the UKCAT scale scores remained significantly predictive for most years. Findings from the ROC analysis suggested that, if used as a sole screening test, with the mean applicant UKCAT score as the cut-off, the test could be used to reject candidates at high risk of failing at least 1 year at first attempt. However, the 'number needed to reject' value would be high (at 1.18), with roughly one candidate who would have been likely to pass all years at first sitting being rejected for every higher risk candidate potentially declined entry on this basis. CONCLUSIONS: The UKCAT scores demonstrate a statistically significant but modest degree of incremental predictive validity throughout undergraduate training. Whilst the UKCAT could be considered a fairly crude screening tool for future academic performance, it may offer added value when used in conjunction with other selection measures. Future work should focus on the optimum role of such tests within the selection process and the prediction of post-graduate performance.

Recommodification, Unemployment, and Health Inequalities: Trends in England and Sweden 1991-2011.

Recommodification, the withdrawal of social welfare, has been going on for some decades in both Sweden and England. Recommodification disproportionately affects the unemployed because of their weak market position. We investigated the impact recommodification has had on health inequalities between the employed and unemployed in Sweden and England. Using national surveys, odds ratios for the likelihood of reporting less than good health between the employed and unemployed were computed annually between 1991 and 2011. The correlation between these odds ratios and net replacement rates was then examined. Health inequalities between the employed and unemployed were greater in 2011 than in 1991 in both countries. Sweden began with smaller health inequalities, but by 2011, they were in line with those in England. Sweden experienced more recommodification than England during this period, although it started from a much less commodified position. Correspondingly, correlation between unemployment benefit generosity and health inequalities was stronger in Sweden than in England. Recommodification is linked to ill health among the unemployed and to the health gap between the employed and unemployed. We propose that further recommodification will be associated with increased health inequalities between the employed and unemployed.

Identification of in vitro and in vivo disconnects using transcriptomic data.

BACKGROUND: Integrating transcriptomic experiments within drug development is increasingly advocated for the early detection of toxicity. This is partly to reduce costs related to drug failures in the late, and expensive phases of clinical trials. Such an approach has proven useful both in the study of toxicology and carcinogenicity. However, general lack of translation of in vitro findings to in vivo systems remains one of the bottle necks in drug development. This paper proposes a method for identifying disconnected genes between in vitro and in vivo toxicogenomic rat experiments. The analytical framework is based on the joint modeling of dose-dependent in vitro and in vivo data using a fractional polynomial framework and biclustering algorithm. RESULTS: Most disconnected genes identified belonged to known pathways, such as drug metabolism and oxidative stress due to reactive metabolites, bilirubin increase, glutathion depletion and phospholipidosis. We also identified compounds that were likely to induce disconnect in gene expression between in vitro and in vivo toxicogenomic rat experiments. These compounds include: sulindac and diclofenac (both linked to liver damage), naphtyl isothiocyanate (linked to hepatoxocity), indomethacin and naproxen (linked to gastrointestinal problem and damage of intestines). CONCLUSION: The results confirmed that there are important discrepancies between in vitro and in vivo toxicogenomic experiments. However, the contribution of this paper is to provide a tool to identify genes that are disconnected between the two systems. Pathway analysis of disconnected genes may improve our understanding of uncertainties in the mechanism of actions of drug candidates in humans, especially concerning the early detection of toxicity.

Grim up North or Northern grit? Recessions and the English spatial health divide (1991-2010).

BACKGROUND: Previous research suggests that the health effects of recessions are mixed and vary spatially between countries. Using the North-South English health divide as an example, this paper examines whether there are also spatial variations within countries. METHODS: Cross-sectional data on self-reported 'not good health' was obtained from the British Household Panel Survey and the Health Survey for England from 1991 to 2010. Age-adjusted generalized linear models were used to examine the effects of recessions (1990/91 and 2008/09) on self-reported health in the four English NHS Commissioning Regions (North, South, Midlands and London) with stratification by gender. RESULTS: Over the 20-year study period, the North had consistently higher rates of 'not good health' than the South [OR 1.50 (1.46-1.55) outside recessions and OR 1.29 (1.19-1.39) during recessions]. However, during periods of recession, this health divide narrowed slightly with a 2% decrease in the prevalence of 'not good health' in the North [OR 0.91 (0.86, 0.96)]. CONCLUSION: This study is evidence of spatial variations in the health effects of recessions within England and the North-South divide appears to slightly reduce during recessions. Health in the North remains worse than the South.

ALL IN IT TOGETHER? THE EFFECTS OF RECESSION ON POPULATION HEALTH AND HEALTH INEQUALITIES IN ENGLAND AND SWEDEN, 1991-2010.

This article is the first to comparatively examine the effects of two recessions on population health and health inequalities in the two historically contrasting welfare states of England and Sweden. Data from 1991-2010 on self-reported general health, age, gender, and educational status were obtained from the Health Survey for England, the Swedish Survey of Living Conditions, and the European Union Survey of Income and Living Conditions, for individuals aged over 16. Generalized linear models were used to test the effects of recessions on self-reported health and educational inequalities in health. Overall, recessions had a significant positive effect on the health of women--but not men-in both England (4%) and Sweden (7%). In England, this improvement was only enjoyed by the most educated women, with the health of less educated women declining during recession. In contrast, in Sweden, the health of all women improved significantly during recession regardless of their educational status, although the most educated benefitted the most. Relative educational inequalities in self-reported health therefore increased during recessions in both countries by 14 percent (England) and 17 percent (Sweden) but for different reasons. This study suggests that Sweden's welfare state protects the health of all during recessions.

Long-term effectiveness of first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy in Ghana.

OBJECTIVES: Information on the long-term effectiveness and tolerability of efavirenz- or nevirapine-based antiretroviral therapy (ART) in Africa is lacking. The primary objective of this retrospective observational study was to compare the long-term clinical and immunological outcomes of efavirenz- versus nevirapine-based first-line ART in a large government clinic in Ghana. PATIENTS AND METHODS: The main outcomes were AIDS, death, ART-related toxicity, discontinuation of ART and a composite endpoint of death, AIDS or ART discontinuation. These time-to-event outcomes were compared using a Cox proportional hazards regression model. CD4 counts on ART were compared using a mixed-effects model. RESULTS: A total of 3990 patients started non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART between 2004 and 2010, of which 2369 (59%) were on efavirenz. No significant differences were apparent between each NNRTI for subsequent risk of AIDS, death or the composite of treatment failure; however, stavudine use was independently associated with an increased risk of death [adjusted hazard ratio (HR) 1.60 (95% CI: 1.21-2.11)]. There was an increased risk of early toxicity with nevirapine leading to discontinuation [adjusted HR 1.53 (95% CI: 1.23-1.97)], mostly due to excess skin rashes in the first 2 months of treatment; however, overall discontinuation rates were low. CONCLUSIONS: There was no difference in the long-term effectiveness of efavirenz- and nevirapine-based ART in this population; however, patients initiating nevirapine were more likely to develop early toxicity and discontinue this drug. The excess mortality observed in patients taking stavudine is of concern and should prompt increased efforts to replace it with alternative antiretroviral drugs in developing countries.

A systematic review of the effectiveness of individual, community and societal level interventions at reducing socioeconomic inequalities in obesity amongst children.

BACKGROUND: Tackling childhood obesity is one of the major contemporary public health policy challenges and vital in terms of addressing socioeconomic health inequalities.We aimed to systematically review studies of the effectiveness of interventions (individual, community and societal) operating via different approaches (targeted or universal) in reducing socio-economic inequalities in obesity-related outcomes amongst children. METHODS: Nine electronic databases were searched from start date to October 2012 along with website and grey literature searches. The review examined the best available international evidence from interventions that aimed to prevent obesity, treat obesity, or improve obesity-related behaviours (diet and/or physical activity) amongst children (aged 0-18 years) in any setting and country, so long as they provided relevant information and analysis on both socioeconomic status and obesity-related outcomes. Data extraction and quality appraisal were conducted using established mechanisms and narrative synthesis was conducted. RESULTS: We located 23 studies that provided the 'best available' (strongest methodologically) international evidence. At the individual level (n = 4), there was indicative evidence that screen time reduction and mentoring health promotion interventions could be effective in reducing inequalities in obesity. For the community level interventions (n = 17), evidence was inconclusive - with some studies suggesting that school-based health promotion activities and community-based group-based programmes were effective in reducing obesity - others not. Societal level evaluations were few (n = 1). However, there was no evidence to suggest that any of these intervention types increase inequalities and several studies found that interventions could at least prevent the widening of inequalities in obesity. The majority of studies were from America and were of 6-12 year old children. CONCLUSIONS: The review has found only limited evidence although some individual and community based interventions may be effective in reducing socio-economic inequalities in obesity-related outcomes amongst children but further research is required, particularly of more complex, societal level interventions and amongst adolescents.

The role of constraints and information gaps in driving risky medicine purchasing practices in four African countries.

Substandard and falsified (SF) medical products pose a major threat to public health and socioeconomic development, particularly in low- and middle-income countries. In response, public education campaigns have been developed to alert consumers about the risks of SF medicines and provide guidance on 'safer' practices, along with other demand- and supply-side measures. However, little is currently known about the potential effectiveness of such campaigns while structural constraints to accessing quality-assured medicines persist. This paper analyses survey data on medicine purchasing practices, information and constraints from four African countries (Ghana, Nigeria, Sierra Leone and Uganda; n > 1000 per country). Using multivariate regression and structural equation modelling, we present what we believe to be the first attempt to tease apart, statistically, the effects of an information gap vs structural constraints in driving potential public exposure to SF medicines. The analysis confirms that less privileged groups (including, variously, those in rural settlements, with low levels of formal education, not in paid employment, often women and households with a disability or long-term sickness) are disproportionately potentially exposed to SF medicines; these same demographic groups also tend to have lower levels of awareness and experience greater levels of constraint. Despite the constraints, our models suggest that public health education may have an important role to play in modifying some (but not all) risky practices. Appropriately targeted public messaging can thus be a useful part of the toolbox in the fight against SF medicines, but it can only work effectively in combination with wider-reaching reforms to address higher-level vulnerabilities in pharmaceutical supply chains in Africa and expand access to quality-assured public-sector health services.

Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial.

Background: Cardiotoxicity is a concern for cancer survivors undergoing anthracycline chemotherapy. Enalapril has been explored for its potential to mitigate cardiotoxicity in cancer patients. The dose-dependent cardiotoxicity effects of anthracyclines can be detected early through the biomarker cardiac troponin. Objectives: The PROACT (Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma) clinical trial assessed the effectiveness of enalapril in preventing cardiotoxicity, manifesting as myocardial injury and cardiac function impairment, in patients undergoing high-dose anthracycline-based chemotherapy for breast cancer or non-Hodgkin lymphoma. Methods: This prospective, multicenter, open-label, randomized controlled trial employed a superiority design with observer-blinded endpoints. A total of 111 participants, scheduled for 6 cycles of chemotherapy with a planned dose of ≥300 mg/m2 doxorubicin equivalents, were randomized to receive either enalapril (titrated up to 20 mg daily) or standard care without enalapril. Results: Myocardial injury, indicated by cardiac troponin T (≥14 ng/L), during and 1 month after chemotherapy, was observed in 42 (77.8%) of 54 patients in the enalapril group vs 45 (83.3%) of 54 patients in the standard care group (OR: 0.65; 95% CI: 0.23-1.78). Injury detected by cardiac troponin I (>26.2 ng/L) occurred in 25 (47.2%) of 53 patients on enalapril compared with 24 (45.3%) of 53 in standard care (OR: 1.10; 95% CI: 0.50-2.38). A relative decline of more than 15% from baseline in left ventricular global longitudinal strain was observed in 10 (21.3%) of 47 patients on enalapril and 9 (21.9%) of 41 in standard care (OR: 0.95; 95% CI: 0.33-2.74). An absolute decline of >10% to <50% in left ventricular ejection fraction was seen in 2 (4.1%) of 49 patients on enalapril vs none in patients in standard care. Conclusions: Adding enalapril to standard care during chemotherapy did not prevent cardiotoxicity in patients receiving high-dose anthracycline-based chemotherapy. (PROACT: Can we prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?; NCT03265574).