Showing papers by "Paul Garner published in 2019"

The ARRIVE guidelines 2019: updated guidelines for reporting animal research

Abstract: Reproducible science requires transparent reporting. The ARRIVE guidelines were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here we introduce ARRIVE 2019. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise the items and split the guidelines into two sets, the ARRIVE Essential 10, which constitute the minimum requirement, and the Recommended Set, which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers to verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document that serves 1) to explain the rationale behind each item in the guidelines, 2) to clarify key concepts and 3) to provide illustrative examples. We aim through these changes to help ensure that researchers, reviewers and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

Guidelines for Malaria Vector Control

Abstract: Malaria remains an important cause of illness and death in children and adults throughout the world, with 87 countries reporting one or more cases of malaria in 2017. Malaria control requires an integrated approach, including prevention (with an emphasis on vector control, plus chemoprevention), early diagnosis and prompt effective treatment. The WHO Guidelines for the treatment of malaria were first developed in 2006 and have been revised periodically, with the most recent edition published in 2015. To date there has been no equivalent comprehensive guidelines document on malaria vector control. WHO guidelines contain recommendations on clinical practice or public health policy intended to guide end-users as to the individual or collective actions that can or should be taken in specific situations to achieve the best possible health outcomes. Such recommendations are also designed to help the user to select and prioritize interventions from a range of potential alternatives. The recommendations in this 1st edition of the Guidelines for malaria vector control are based on a firm evidence base for certain interventions, whereas for other interventions, major information gaps necessitated formulation of guidance based on expert opinion. The Guidelines will therefore remain under regular review; updates are envisioned on an ongoing basis as new evidence becomes available. The recommendations and their rationale presented in the main body of this document are brief so as to facilitate quick reference. More detail on the underlying evidence base is provided in a series of annexes.

Being HIV positive and staying on antiretroviral therapy in Africa: A qualitative systematic review and theoretical model.

Abstract: CITATION: Eshun-Wilson, I. et al. 2019. Being HIV positive and staying on antiretroviral therapy in Africa : a qualitative systematic review and theoretical model. PLoS ONE, 14(1):e0210408, doi:10.1371/journal.pone.0210408.

Indoor residual spraying for preventing malaria in communities using insecticide-treated nets.

Abstract: Background Insecticide‐treated nets (ITNs) and indoor residual spraying (IRS) are used to control malaria vectors. Both strategies use insecticides to kill mosquitoes that bite and rest indoors. For ITNs, the World Health Organization (WHO) only recommended pyrethroids until 2018, but mosquito vectors are becoming resistant to this insecticide. For IRS, a range of insecticides are recommended. Adding IRS to ITNs may improve control, simply because two interventions may be better than one; it may improve malaria control where ITNs are failing due to pyrethroid resistance; and it may slow the emergence and spread of pyrethroid resistance.

Public health deworming programmes for soil‐transmitted helminths in children living in endemic areas

Abstract: Background The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common. Global advocacy organizations claim routine deworming has substantive health and societal effects beyond the removal of worms. In this update of the 2015 edition we included six new trials, additional data from included trials, and addressed comments and criticisms. Objectives To summarize the effects of public health programmes to regularly treat all children with deworming drugs on child growth, haemoglobin, cognition, school attendance, school performance, physical fitness, and mortality. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; LILACS; the metaRegister of Controlled Trials (mRCT); reference lists; and registers of ongoing and completed trials up to 19 September 2018. Selection criteria We included randomized controlled trials (RCTs) and quasi‐RCTs that compared deworming drugs for soil‐transmitted helminths (STHs) with placebo or no treatment in children aged 16 years or less, reporting on weight, height, haemoglobin, and formal tests of cognition. We also sought data on other measures of growth, school attendance, school performance, physical fitness, and mortality. Data collection and analysis At least two review authors independently assessed the trials for inclusion, 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 stratified the analysis based on the background burden of STH infection. We used outcomes at time of longest follow‐up. We assessed the certainty of the evidence using the GRADE approach. Main results We identified 51 trials, including 10 cluster‐RCTs, that met the inclusion criteria. One trial evaluating mortality included over one million children, and the remaining 50 trials included a total of 84,336 participants. Twenty‐four trials were in populations categorized as high burden, including nine trials in children selected because they were helminth‐stool positive; 18 with intermediate burden; and nine as low burden. First or single dose of deworming drugs Fourteen trials reported on weight after a single dose of deworming drugs (4970 participants, 14 RCTs). The effects were variable. There was little or no effect in studies conducted in low and intermediate worm burden groups. In the high‐burden group, there was little or no effect in most studies, except for a large effect detected from one study area in Kenya reported in two trials carried out over 30 years ago. These trials result in qualitative heterogeneity and uncertainty in the meta‐analysis across all studies (I2 statistic = 90%), with GRADE assessment assessed as very low‐certainty, which means we do not know if a first dose or single dose of deworming impacts on weight. For height, most studies showed little or no effect after a single dose, with one of the two trials in Kenya from 30 years ago showing a large average difference (2621 participants, 10 trials, low‐certainty evidence). Single dose probably had no effect on average haemoglobin (MD 0.10 g/dL, 95% CI 0.03 lower to 0.22 higher; 1252 participants, five trials, moderate‐certainty evidence), or on average cognition (1596 participants, five trials, low‐certainty evidence). The data are insufficient to know if there is an effect on school attendance and performance (304 participants, one trial, low‐certainty evidence), or on physical fitness (280 participants, three trials, very low‐certainty evidence). No trials reported on mortality. Multiple doses of deworming drugs The effect of regularly treating children with deworming drugs given every three to six months on weight was reported in 18 trials, with follow‐up times of between six months and three years; there was little or no effect on average weight in all but two trials, irrespective of worm prevalence‐intensity. The two trials with large average weight gain included one in the high burden area in Kenya carried out over 30 years ago, and one study from India in a low prevalence area where subsequent studies in the same area did not show an effect. This heterogeneity causes uncertainty in any meta‐analysis (I2 = 78%). Post‐hoc analysis excluding trials published prior to 2000 gave an estimate of average difference in weight gain of 0.02 kg (95%CI from 0.04 kg loss to 0.08 gain, I2 = 0%). Thus we conclude that we do not know if repeated doses of deworming drugs impact on average weight, with a fewer older studies showing large gains, and studies since 2000 showing little or no average gain. Regular treatment probably had little or no effect on the following parameters: average height (MD 0.02 cm higher, 95% CI 0.09 lower to 0.13 cm higher; 13,700 participants, 13 trials, moderate‐certainty evidence); average haemoglobin (MD 0.01 g/dL lower; 95% CI 0.05 g/dL lower to 0.07 g/dL higher; 5498 participants, nine trials, moderate‐certainty evidence); formal tests of cognition (35,394 participants, 8 trials, moderate‐certainty evidence); school performance (34,967 participants, four trials, moderate‐certainty evidence). The evidence assessing an effect on school attendance is inconsistent, and at risk of bias (mean attendance 2% higher, 95% CI 5% lower to 8% higher; 20,650 participants, three trials, very low‐certainty evidence). No trials reported on physical fitness. No effect was shown on mortality (1,005,135 participants, three trials, low‐certainty evidence). Authors' conclusions Public health programmes to regularly treat all children with deworming drugs do not appear to improve height, haemoglobin, cognition, school performance, or mortality. We do not know if there is an effect on school attendance, since the evidence is inconsistent and at risk of bias, and there is insufficient data on physical fitness. Studies conducted in two settings over 20 years ago showed large effects on weight gain, but this is not a finding in more recent, larger studies. We would caution against selecting only the evidence from these older studies as a rationale for contemporary mass treatment programmes as this ignores the recent studies that have not shown benefit.

Albendazole alone or in combination with microfilaricidal drugs for lymphatic filariasis

Abstract: Background The Global Programme to Eliminate Lymphatic Filariasis recommends mass treatment of albendazole co‐administered with the microfilaricidal (antifilarial) drugs diethylcarbamazine (DEC) or ivermectin; and recommends albendazole alone in areas where loiasis is endemic. Objectives To assess the effects of albendazole alone, and the effects of adding albendazole to DEC or ivermectin, in people and communities with lymphatic filariasis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), Embase (OVID), LILACS (BIREME), and reference lists of included trials. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov to identify ongoing trials. We performed all searches up to 15 January 2018. Selection criteria We included randomized controlled trials (RCTs) and cluster‐RCTs that compared albendazole to placebo or no placebo, or compared albendazole combined with a microfilaricidal drug to a microfilaricidal drug alone, given to people known to have lymphatic filariasis or communities where lymphatic filariasis was known to be endemic. We sought data on measures of transmission potential (microfilariae (mf) prevalence and density); markers of adult worm infection (antigenaemia prevalence and density, and adult worm prevalence detected by ultrasound); and data on clinical disease and adverse events. Data collection and analysis At least two review authors independently assessed the trials, evaluated the risks of bias, and extracted data. The main analysis examined albendazole overall, whether given alone or added to a microfilaricidal drug. We used data collected from all randomized individuals at time of longest follow‐up (up to 12 months) for meta‐analysis of outcomes. We evaluated mf density data up to six months and at 12 months follow‐up to ensure that we did not miss any subtle temporal effects. We conducted additional analyses for different follow‐up periods and whether trials reported on individuals known to be infected or both infected and uninfected. We analysed dichotomous data using the risk ratio (RR) with a 95% confidence interval (CI). We could not meta‐analyse data on parasite density outcomes and we summarized them in tables. Where data were missing, we contacted trial authors. We used GRADE to assess the certainty of evidence. Main results We included 13 trials (12 individually‐randomized and one small cluster‐randomized trial) with 8713 participants in total. No trials evaluated population‐level effects of albendazole in mass drug administration programmes. Seven trials enrolled people with a variety of inclusion criteria related to filarial infection, and six trials enrolled individuals from endemic areas. Outcomes were reported as end or change values. Mf and antigen density data were reported using the geometric mean, log mean and arithmetic mean, and reductions in density were variously calculated. Two trials discounted any increases in mf density in individuals at follow‐up by setting any density increase to zero. For mf prevalence over two weeks to 12 months, albendazole alone or added to another microfilaricidal drug makes little or no difference (RR 0.95, 95% CI 0.85 to 1.07; 5027 participants, 12 trials, high‐certainty evidence). For mf density there is no trend, with some trials reporting a greater reduction in mf density with albendazole and others a greater reduction with the control group. For mf density up to six months and at 12 months, we do not know if albendazole has an effect (one to six months: 1216 participants, 10 trials, very low‐certainty evidence; at 12 months: 1052 participants, 9 trials, very low‐certainty evidence). For antigenaemia prevalence between six to 12 months, albendazole alone or added to another microfilaricidal drug makes little or no difference (RR 1.04, 95% CI 0.97 to 1.12; 3774 participants, 7 trials, high‐certainty evidence). For antigen density over six to 12 months, the trend shows little or no effect of albendazole; but we do not know if albendazole has an effect on antigen density (1374 participants, 5 trials, very low‐certainty evidence). For adult worm prevalence detected by ultrasound at 12 months, albendazole added to a microfilaricidal drug may make little or no difference (RR 1.16, 95% CI 0.72 to 1.86; 165 participants, 3 trials, low‐certainty evidence). For people reporting adverse events, albendazole makes little or no difference (RR 0.97, 95% CI 0.84 to 1.13; 2894 participants, 6 trials, high‐certainty evidence). We also provide meta‐analyses and GRADE tables by drug, as operationally this may be of interest: for albendazole versus placebo (4 trials, 1870 participants); for albendazole with DEC compared to DEC alone (8 trials, 3405 participants); and albendazole with ivermectin compared to ivermectin alone (4 trials, 3438 participants). Authors' conclusions There is good evidence that albendazole makes little difference to clearing microfilaraemia or adult filarial worms in the 12 months post‐treatment. This finding is consistent in trials evaluating albendazole alone, or added to DEC or ivermectin. Trials reporting mf density included small numbers of participants, calculated density data variously, and gave inconsistent results. The review raises questions over whether albendazole has any important contribution to the elimination of lymphatic filariasis. To inform policy for areas with loiasis where only albendazole can be used, it may be worth conducting placebo‐controlled trials of albendazole alone.

Low carbohydrate versus balanced carbohydrate diets for reducing weight and cardiovascular risk

Abstract: This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To compare the effects of low carbohydrate weight-reducing diets to weight-reducing diets with balanced ranges of carbohydrates, in relation to changes in weight and cardiovascular risk, in overweight and obese adults without type 2 diabetes (comparison 1) and with type 2 diabetes (comparison 2).

Community drug distributors for mass drug administration in neglected tropical disease programmes: systematic review and analysis of policy documents.

Abstract: Background Mass drug administration (MDA) programmes for neglected tropical diseases (NTDs) depend on voluntary community drug distributors (CDDs) to deliver drugs, and these volunteer schemes need regular training and supervision. NTD policy now includes integration of multiple disease programmes, but we are unsure if there is clarity in what is currently expected of CDDs and how they are managed. We therefore analysed World Health Organization (WHO) policy, strategy and implementation guidance, and select national NTD programme implementation plans. Methods Included are a) WHO global and WHO-Regional Office for Africa guidelines, strategies, operational manuals and meeting reports published between January 2007 to February 2018 that included policy and plans for CDDs; and b) national NTD programme master plans for Cameroon, Ghana, Liberia and Nigeria. For both review components, we examined the CDD responsibilities through a framework developed iteratively against the documents and prepared a narrative synthesis. Results Twenty WHO policy documents met the inclusion criteria. In the twelve global and eight regional documents, the CDD role was not explicitly or comprehensively defined. Three documents mentioned CDDs will distribute drugs; some mentioned health promotion, data handling and engagement in clinical care. Four WHO documents noted a need for CDD training or management, eight detailed some aspect of this, and one regional document provided a comprehensive overview. In the national plans, additional responsibilities included case management in two countries and transmission control in two countries. Every plan included training and supervision, but this was not always explicit, and details of the purpose and frequency varied. In all national plans, CDD motivation was identified as a challenge but not comprehensively addressed, although one document mentioned provision of bicycles. Conclusions WHO and national policies and plans assume CDDs will implement NTD programmes. However, there is almost no clear delineation of responsibilities, nor is there up-to-date practical guidance to guide managers. This ambiguity, in relation to the lack of explicit policies or programmatic guidance, probably impairs the effectiveness of NTD programmes.

Gut mucosal colonisation with extended-spectrum beta-lactamase producing Enterobacteriaceae in sub-Saharan Africa: a systematic review and meta-analysis.

Abstract: Background : Extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) threaten human health; and, in areas of sub-Saharan Africa (sSA) where carbapenems are not available, may render ESBL-E infections untreatable. Gut mucosal colonisation probably occurs before infection, making prevention of colonisation an attractive target for intervention, but the epidemiology of ESBL-E in sSA is poorly described. Objectives : Describe ESBL-E colonisation prevalence in sSA and risk factors associated with colonisation. Methods: Studies included were prospective cross-sectional or cohort studies reporting gut mucosal ESBL-E colonisation in any population in sSA. We searched PubMed and Scopus on 18 December 2018. We summarise the range of prevalence across sites and tabulated risk factors for colonisation. The protocol was registered (Prospero ID CRD42019123559 ). Results: From 2975 abstracts we identified 32 studies including a total of 8619 participants from a range of countries and settings. Six studies were longitudinal; no longitudinal studies followed patients beyond hospital discharge. Prevalence varied between 5 and 84% with a median of 31%, with a relationship to setting: pooled ESBL-E colonisation in community studies was 18% (95% CI 12 to 28, 12 studies); in studies recruiting people at admission to hospital colonisation was 32% (95% CI 24 to 41% 8 studies); and for inpatients, colonisation was 55% (95% CI 49 to 60%, 7 studies). Antimicrobial use was associated with increased risk of ESBL-E colonisation, and protected water sources or water treatment by boiling may reduce risk. Conclusions: ESBL-E colonisation is common in sSA, but how people become carriers and why is not well understood. To inform the design of interventions to interrupt transmission in this setting requires longitudinal, community studies.

WHO guidance for refugees in camps: systematic review.

Abstract: Objectives The circumstances of people living in refugee camps means that they have distinct medical care requirements. Our objective is to describe clinical guidance in published WHO guidelines that refer to people living in refugee camps; and how evidence and context are used and reported in making recommendations. Design Systematic review and analysis of WHO guidelines approved by the organisation’s quality oversight body and published between 2007 and 2018. We sought for key terms related to camps and humanitarian settings, and identified text that included guidance. We compared this to Medecins Sans Frontiers (MSF) guidelines. Results No WHO guideline published in the last 10 years focused exclusively on clinical guidance for healthcare in camp settings. Seven guidelines contained guidance about camps; three made recommendations for camps—but only two used formal evidence summaries. We did not find any structured consideration of the situation in camps used in the decision-making process. We examined seven WHO guidelines and six chapters within guidelines that concerned humanitarian settings: none of these documents contained recommendations based on formal evidence summaries for camp settings. One of the eight MSF guidelines was devoted to clinical care in refugees and the authors had clearly linked the health problems and recommendations to the setting, but this guideline is now >20 years old. Conclusions There is an absence of up-to-date, evidence-based medical treatment guidelines from WHO and MSF that comprehensively address the clinical needs for people living in camps; and there is no common framework to help guideline groups formulate recommendations in these settings. WHO may wish to consider context of special populations more formally in the evidence to decision-making approach for clinical guidelines relevant to primary care.

Reporting animal research: Explanation and Elaboration for the ARRIVE guidelines 2019

Abstract: Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting are vital to this process; it allows readers to assess the reliability of the findings, and repeat or build upon the work of other researchers. The NC3Rs developed the ARRIVE guidelines in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments. Despite widespread endorsement by the scientific community, the impact of the ARRIVE guidelines on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This Explanation and Elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2019, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature.

Housing interventions for preventing malaria (protocol)

Abstract: This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: Primary To assess the effects of different structural house modifications on malaria disease burden. Secondary To explore whether effects vary with level of transmission

Maintaining relevance in HIV systematic reviews: an evaluation of Cochrane reviews

Abstract: Research turnover in the HIV field is rapid, and as a result, maintaining high-quality, up-to-date, and relevant systematic reviews is a challenge. One approach is to frequently update published reviews. We evaluated the methods and relevance of all HIV systematic reviews and protocols published in the Cochrane Library over a 16-year period (2000–2016) to determine the need to update published reviews or complete of reviews in progress. Of 148 published reviews and protocols, 129 (87%) were identified as not for updating or progression to publication, mostly due to research questions which were either entirely outdated or addressed questions in an outdated manner (N = 89; 60%); this was anticipated for older reviews, but was found also to be the case for recent publications. Some research questions were also inadequately conceptualized, particularly when complex pragmatic trials or behavioral interventions were included. We suggest that authors clearly characterize interventions and synthesis approaches in their review protocols. In research fields, such as HIV, where questions change frequently, systematic reviews and protocols should be regularly re-evaluated to ensure relevance to current questions. This process of re-evaluation should be incorporated into the methods of living systematic reviews.