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DEVTA: Results from the biggest clinical trial ever
... Among the studies of MDA [43][44][45][46][47][48] , all involved biannual treatment of PSAC or SAC under-five years of age and a majority were conducted in Uttar Pradesh. A single MDA RCT was conducted in West Bengal 45 . ...
... In addition to these direct effects on treated children, several studies also suggested indirect 'spillover' benefits from deworming programmes that resulted in positive outcomes in siblings of the children who received the drug and positive educational outcomes in untreated children in schools where deworming was done 64,65 . However, the largest clinical trial to date, the DEVTA trial, involving two million children 47,48 , reported negligible weight gain following deworming. In addition, meta-analyses of multiple studies of deworming have failed to demonstrate consistent benefit of deworming on anthropometric and cognitive outcomes 32,34 . ...
Soil-transmitted helminth (STH) infections continue to be a major global cause of morbidity, with a large proportion of the burden of STH infections occurring in India. In addition to direct health impacts of these infections, including anaemia and nutritional deficiencies in children, these infections also significantly impact economic development, as a result of delays in early childhood cognitive development and future income earning potential. The current World Health Organization strategy for STH is focused on morbidity control through the application of mass drug administration to all pre-school-aged and school-aged children. In India, the control of STH-related morbidity requires mobilization of significant human and financial resources, placing additional burdens on limited public resources. Infected adults and untreated children in the community act as a reservoir of infection by which treated children get rapidly reinfected. As a result, deworming programmes will need to be sustained indefinitely in the absence of other strategies to reduce reinfection, including water, hygiene and sanitation interventions (WASH). However, WASH interventions require sustained effort by the government or other agencies to build infrastructure and to promote healthy behavioural modifications, and their effectiveness is often limited by deeply entrenched cultural norms and behaviours. Novel strategies must be explored to provide a lasting solution to the problem of STH infections in India other than the indefinite provision of deworming for morbidity control.
... Among the studies of MDA [43][44][45][46][47][48] , all involved biannual treatment of PSAC or SAC under-five years of age and a majority were conducted in Uttar Pradesh. A single MDA RCT was conducted in West Bengal 45 . ...
... In addition to these direct effects on treated children, several studies also suggested indirect 'spillover' benefits from deworming programmes that resulted in positive outcomes in siblings of the children who received the drug and positive educational outcomes in untreated children in schools where deworming was done 64,65 . However, the largest clinical trial to date, the DEVTA trial, involving two million children 47,48 , reported negligible weight gain following deworming. In addition, meta-analyses of multiple studies of deworming have failed to demonstrate consistent benefit of deworming on anthropometric and cognitive outcomes 32,34 . ...
Soil-transmitted helminth (STH) infections continue to be a major global cause of morbidity, with a large proportion of the burden of STH infections occurring in India. In addition to direct health impacts of these infections, including anaemia and nutritional deficiencies in children, these infections also significantly impact economic development, as a result of delays in early childhood cognitive development and future income earning potential. The current World Health Organization strategy for STH is focused on morbidity control through the application of mass drug administration to all pre-school-aged and school-aged children. In India, the control of STH-related morbidity requires mobilization of significant human and financial resources, placing additional burdens on limited public resources. Infected adults and untreated children in the community act as a reservoir of infection by which treated children get rapidly reinfected. As a result, deworming programmes will need to be sustained indefinitely in the absence of other strategies to reduce reinfection, including water, hygiene and sanitation interventions (WASH). However, WASH interventions require sustained effort by the government or other agencies to build infrastructure and to promote healthy behavioural modifications, and their effectiveness is often limited by deeply entrenched cultural norms and behaviours. Novel strategies must be explored to provide a lasting solution to the problem of STH infections in India other than the indefinite provision of deworming for morbidity control.
... 18 Importantly, although the preliminary results were available in the public domain as early as 2007, the final results were published only in 2013. Commenting on this delay, Garner et al. (2013Garner et al. ( : 1440 ascribe it to 'belief disconfirmation bias', that is: '[w]hen people are faced with evidence that disconfirms their beliefs they subject it to intense critical evaluation; but when exposed to confirming evidence they take the evidence at face value . . . people might reject good science because . . . ...
... While drawing conclusions from meta analysis is not uncommon or outside the norm, Garner et al. (2013Garner et al. ( : 1439 point out that there could be an alternative interpretation: that vitamin A does not affect child mortality in all settings all of the time, and that 'just the size of DEVTA shakes beliefs in current global policies promoting vitamin A and deworming to the core. Ironically, the largest drug trial in the world hasn't settled the policy questions, but has generated uncertainties'. ...
... Vitamin A: Several studies have looked into the effect of vitamin A supplementation in reducing respiratory infection related morbidity and mortality among children from developing counties [39][40][41][42][43]. ...
Malnutrition is a major cause of morbidity and mortality in developing countries and nutrition plays a critical role in both acute and chronic respiratory conditions. Inadequacies in the nutritional requirements of a developing lung in utero and in early life can compromise the respiratory system integrity and result in poor lung function, reduced protection against infections, greater likelihood of acute illnesses in childhood and chronic illness in adulthood. Nutritional interventions harness great potential in reducing respiratory illness related morbidity and mortality in the developing world. In this review we have summarized the findings from published systematic reviews/meta-analysis, experimental and observational studies that looked into different nutritional interventions for preventing respiratory diseases in developing countries.
... Publikasjonsskjevheter er en trussel mot et helhetlig kunnskapsbilde -selve målsetningen med en systema-tisk oversikt. Ikke alle tidsskrifter er så pågående som for eksempel Lancet nylig var for å sørge for at også de ikke-signifikante funnene fra verdens største randomiserte kontrollerte studie ble publisert (26). Forfatterne av studien trengte både tid, motivasjon og kanskje også et lite spark bak for å skrive sammen resultatene de egentlig var skuffet over. ...
p>En god helsetjeneste forutsetter god kunnskap som grunnlag for de valg som gjøres. Systematiske oversikter som sammenfatter tilgjengelig forskningsbasert kunnskap er en viktig del av beslutningsgrunnlaget, enten det er snakk om effektene av tiltak, hvorfor sykdom oppstår, diagnostikk, prognose, eller hvordan sykdom oppleves for dem som rammes.
Systematiske oversikter er blitt en vel anerkjent kilde for kunnskap om effekt av helsetiltak, med bred internasjonal enighet om metodene som bør benyttes ved utvikling av slike oversikter. Når det gjelder systematiske oversikter for å sammenfatte resultater fra epidemiologisk forskning på årsaksspørsmål er erfaringene langt mindre.
Samtidig som systematiske oversikter over epidemiologiske studier i større grad bør inngå i beslutningsprosesser, er det et betydelig behov for metodeutvikling. Dette gjelder særlig kriterier for vurdering av kvalitet på epidemiologiske studier, metoder for sammenfatning av resultater i metaanalyser og kriterier for å gradere tillit til de endelige estimatene. Publikasjonsskjevheter er en utfordring for all forskning, og det er behov for initiativ for å sikre bedre rapportering av funn fra epidemiologiske studier, blant annet publisering av studieprotokoller.
Norderhaug IN. Systematic reviews of epidemiological research . Nor J Epidemiol 2013; 23 (2): 125-130.
ENGLISH SUMMARY
In health care, good knowledge is key to sound decision making. Good management of knowledge can be achieved through systematic reviews for various questions including the effects of health care interventions, causes of disease, how to best diagnose diseases, prognosis, as well as people’s experiences from living with disease.
Systematic reviews are well recognized and valued resources to inform decisions regarding health care interventions. Furthermore there is broad international consensus on methods for conducting systematic reviews on the effects of health care interventions. Although the need for systematic reviews is recognized also for epidemiological questions, such as the causes of disease, the level of experience in this area is far less than for systematic reviews on the effects of interventions.
Thus, alongside the need for better integration of systematic reviews in epidemiology into health care decision making processes, methodological developments are needed, particularly on how to assess the quality of epidemiological studies, methods for combining the results in meta-analyses, and criteria for grading our confidence in the final estimates.
Publication bias is a problem in all research, and initiatives are needed to improve planning and reporting of epidemiological studies, such as publication of study protocols.</p
... ). La méthodologie de l'étude et de l'analyse statistique, le manque de détails, des comparaisons inadéquates, la présence de biais ou de potentielles interactions (statut en vitamine D, vaccinations…) et des conclusions hâtives et globales sont entre autres reprochés à cette publication d'impact majeur dans le domaine. Enfin, bien que le commentaire sur l'étude DEVTA conclue sur le besoin de conduire de nouvelles études randomisées contre placebo, d'autres auteurs soulignent qu'au vu des connaissances actuelles, il n'est plus éthique de développer des interventions n'incluant pas de vitamine A dans le groupe contrôle(Garner et al., 2013;Mannar et al., 2013;Mayo-Wilson et al., 2013).Dans les contextes de diminution du risque de maladies non transmissibles, les caroténoïdes sont souvent administrés en mélange à d'autres micronutriments comme dans les grandes études SU.VI.MAX, CARET et ATBC. Les résultats sont, là encore, très mitigés : un bénéfice a été démontré pour certains sous-groupes ...
Selon la FAO, deux milliards de personnes souffrent de la « faim cachée » qui correspond aux carences en micronutriments incluant la carence en vitamine A, principale cause de cécité dans le monde. Par ailleurs, une alimentation excédentaire est source de stress oxydant pour le corps, facteur de risque de nombreuses maladies non transmissibles comme le diabète et les maladies cardiovasculaires. Contenus dans les produits végétaux, certains caroténoïdes représentent une source indirecte de vitamine A et pourraient participer aux effets bénéfiques de la consommation de fruits et légumes via des propriétés antioxydantes. Dans cette thèse, le comportement in vitro des caroténoïdes et rétinoïdes pendant la digestion a été étudié, depuis leur libération de la matrice alimentaire jusqu'à leurs interactions avec les cellules intestinales. Mes recherches s'articulent autour de la micellisation : processus clé de l'absorption des caroténoïdes et rétinoïdes. Dans un premier temps, la stabilité et la bioaccessibilité en digestion in vitro (DIV) de ces composés purs ont été comparées à celles de leurs homologues issus d'un jus de carotte, d'épinards crus et cuits et d'une farine fortifiée. Dans un deuxième temps, un nouveau modèle d'oxydation de nano-émulsions intestinales à base de sels biliaires (SB) a été développé. Les relations entre structure des micelles mixtes, réactivité à l'oxydation et protection par des antioxydants ont été étudiées grâce notamment au suivi de la dégradation des acides gras. Enfin, des expériences préliminaires ont été menées sur la réactivité enzymatique de cellules coliques (Caco-2) à divers oxydants et aux micelles mixtes. Pendant la DIV, le β-carotène et palmitate de rétinyl purs étaient particulièrement instables contrairement à la lutéine et à l'acétate de rétinyl. De plus, la matrice alimentaire protège ces composés et favorise leur bioaccessibilité surtout lorsqu'elle est broyée ou cuite. En effet, les prétraitements ont un impact conséquent sur la libération des caroténoïdes et doivent être considérés comme des moyens sérieux pour optimiser les apports. Les nano-émulsions intestinales mises au point se composaient de micelles mixtes sphériques ou cylindriques, ces dernières étant les moins résistantes à l'oxydation. En effet, la distribution des molécules de SB doit être différente selon la morphologie de la micelle, impactant ainsi leur réactivité. Dans nos conditions expérimentales, l'AAPH fut le seul oxydant efficace. L'α-tocophérol et la lutéine ont significativement ralenti la dégradation des acides gras contrairement au β-carotène. Leur place au sein de la micelle (coeur ou bordure) pourrait expliquer ces observations. Enfin, aucun des oxydants testés n'a significativement modifié l'activité catalase des cellules Caco-2. En revanche, la mise en contact avec les micelles à base de SB ont significativement diminué l'activité des 3 enzymes suivies. L'effet était positivement corrélé à la concentration en SB dont la conjugaison fut un élément déterminant. Finalement, le β-carotène, la lutéine, et l'acétate de rétinyl présents dans ces micelles ont en partie rétabli l'activité de la catalase contrairement au rétinol, palmitate de rétinyl et à l'α-tocophérol.
... Another trial in India showed benefit, but subsequent trials in the same area failed to show an effect. 4,9 So deworming may have helped in these exceptional, heavily infected, untreated populations from another decade, but this is scarcely a solid base for contemporary policy: public health nutrition has changed, worm burden has declined and this probably accounts for the lack of effect on biomedical outcomes in contemporary studies. 10 We have been perplexed by the unquestioning belief behind deworming in the advocates, and have found it is deep rooted in American history. ...
... When the results from DEVTA are pooled with the other studies reporting on mortality, the resulting effect size of vitamin A supplementation on mortality is reduced from 24 % to 12 % (RR 0.89, 95 % CI, 0.84-0.95). Although DEVTA enrolled 10 times the number of children included in the other studies, the weight of the study in the pooled analysis is reduced by the cluster effect [23]. ...
Diarrhea is one of the leading causes of childhood morbidity and mortality. This review synthesizes the most recent evidence on micronutrients interventions for the prevention and treatment of diarrhea in children in low- and middle-income countries. Systematic reviews and high-quality trials were searched in the Cochrane Library, MEDLINE, and the e-Library of Evidence for Nutrition Actions (eLENA) in January 2014. Evidence supports a benefit of zinc supplementation for prevention and treatment of diarrhea, although this is limited to children over 6 months of age and in countries with moderate to high levels of zinc deficiency. Evidence supports the use of vitamin A supplementation for reducing all-cause mortality as well as diarrhea-related mortality, the substantial heterogeneity of findings in different studies remains unexplained. Multiple micronutrient powders have recently been associated with an increased risk of diarrhea and dysentery, which calls for careful monitoring in future studies as well as in ongoing programs.
... Reactions to the DEVTA report have not focused on the underlying methodologic problem, namely the difference between biological and program efficacy. After stating that the "the trial authors propose that the DEVTA attenuates the global estimates of mortality reduction by half," an accompanying commentary to the DEVTA article claimed that the "DEVTA is a courageous study, and a watershed for best practice in research to inform international development" (22). The commentator, like the authors, confuses biological and program efficacy. ...
The biological efficacy of nutritional supplements to complement usual diets in poor populations is well established. This knowledge rests on decades of methodologic research development and, more recently, on codification of methods to compile and interpret results across studies. The challenge now is to develop implementation (delivery) science knowledge and achieve a similar consensus on efficacy criteria for the delivery of these nutrients by public health and other organizations. This requires analysis of the major policy instruments for delivery and well-designed program delivery studies that examine the flow of a nutrient through a program impact pathway. This article discusses the differences between biological and program efficacy, and why elucidating the fidelity of delivery along the program impact pathways is essential for implementing a program efficacy trial and for assessing its internal and external validity. Research on program efficacy is expanding, but there is a lack of adequate frameworks to facilitate the process of harmonizing concepts and vocabulary, which is essential for communication among scientists, policy planners, and program implementers. There is an urgent need to elaborate these frameworks at national and program levels not only for program efficacy studies but also for the broader research agenda to support and improve the science of delivering adequate nutrition to those who need it most.
This “case study” documents the ways in which a variety of epidemiologic studies and the data they generated (which challenged existing beliefs and public health constructs) were greeted by established “experts” in relevant fields. Just as Virchow described over a century ago, results of an initial observational study, which raised the issues, were entirely ignored. Prominent publication of a randomized clinical trial, which both supported the observational study’s associations and proved that they were causal, was greeted with intense hostility, disbelief, and rejection. Only the subsequent accrual of additional, similar RCTs slowly changed scientific opinion, especially when replications were eventually conducted by others than the original investigators. A halt was brought to this slowly changing scientific climate by the timely gathering of those involved in a week-long meeting that evaluated the quality and interpretation of all available data and discussed their relevance and validity. That many investigators had not understood the importance of the context in which their own studies had been conducted was startling, particularly regarding the two variables of greatest relevance: the study population’s baseline risk of vitamin A deficiency and mortality. Investigators of some of the best conducted studies misinterpreted their own data. The resulting 10-year effort eventually changed global health policy, but some “deniers,” without a shred of evidence to back their claims, still refuse to accept this outcome.
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 drugsFourteen 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 drugsThe 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.The conclusions of the 2015 edition have not changed in this update.
Background
The impact of deworming on parasite load, nutritional status and other health outcomes of non-pregnant adolescent girls and adult women is uncertain.
Methods
MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform, the Cochrane Database of Systematic Reviews and Food and Technology Abstracts databases were searched until 24 September 2018. Studies were included if they were randomised controlled trials (RCTs), controlled before and after studies or interrupted time studies comparing deworming with no intervention or placebo in non-pregnant adolescent girls and women 10 to 49 years old. Outcomes of interest included parasite load, reinfection, anaemia, severe anaemia, iron deficiency, diarrhoea or all-cause morbidity. Risk of bias was assessed using the Cochrane risk of bias tool.
Results
We included four RCTs of mass deworming involving 1086 participants, in the analyses. Mass deworming probably reduces the prevalence of roundworm infection (RR 0.29; 95% CI 0.14 to 0.62; 2 trials; 1498 participants, moderate certainty evidence), prevalence of hookworm infection (RR 0.32; 95% CI 0.18 to 0.59; 2 trials; 1498 participants, moderate certainty evidence), prevalence of whipworm infection (RR 0.77; 95% CI 0.65 to 0.91; 2 trials; 1498 participants, moderate certainty evidence) compared to the control group. Deworming may make little or no difference in prevalence of anaemia (RR 0.82; 95% CI 0.60 to 1.11, 3 studies, 683 participants, low certainty evidence) and prevalence of iron-deficiency (RR 0.89; 95% CI 0.64 to 1.23, 1 study, 186 participants, low certainty evidence) compared to control. We are uncertain whether deworming reduces the prevalence of severe anaemia compared to control as the certainty of evidence was very low. None of the included studies assessed screen and treat deworming or reported reinfection, diarrhoea or adverse events.
Conclusions
Mass deworming probably reduces the prevalence of soil-transmitted helminth infections but may have little or no effect on anaemia and iron-deficiency in adolescent girls and non-pregnant women in comparison to no intervention or placebo. We are uncertain about the effect on severe anaemia. These results are limited by sparse data and the moderate to very low quality of evidence available.
Systematic review registration
The protocol was registered in PROSPERO (registration number: CRD42016039557).
Primary source of funding: Evidence and Programme Guidance unit, Department of Nutrition for Health and Development, World Health Organization (WHO).
Electronic supplementary material
The online version of this article (10.1186/s13643-018-0859-6) contains supplementary material, which is available to authorized users.
In health care, good knowledge is key to sound decision making. Good management of knowledge can be achieved through systematic reviews for various questions including the effects of health care interventions, causes of disease, how to best diagnose diseases, prognosis, as well as people's experiences from living with disease. Systematic reviews are well recognized and valued resources to inform decisions regarding health care interventions. Furthermore there is broad international consensus on methods for conducting systematic reviews on the effects of health care interventions. Although the need for systematic reviews is recognized also for epidemiological questions, such as the causes of disease, the level of experience in this area is far less than for systematic reviews on the effects of interventions. Thus, alongside the need for better integration of systematic reviews in epidemiology into health care decision making processes, methodological developments are needed, particularly on how to assess the quality of epidemiological studies, methods for combining the results in meta-analyses, and criteria for grading our confidence in the final estimates. Publication bias is a problem in all research, and initiatives are needed to improve planning and reporting of epidemiological studies, such as publication of study protocols.
The report of DEVTA 1 was the 44th published trial of vitamin A. 2 The eff ect on its primary outcome, mortality, is noticeably smaller than the results of 15 previous trials including more than 200 000 participants. 3 In view of problems with the delivery of the intervention in DEVTA, 4 meta-analyses of previous high-quality trials might more accurately show the effi cacy of vitamin A. In a meta-analysis using a fixed-effect model, DEVTA accounts for 65% of the weight and reduces the average eff ect by half (risk ratio [RR] 0·88, 95% CI 0·84–0·94; I²=64%), 2 consistent with the meta-analysis reported by Awasthi and colleagues. 1 Using random-eff ects, which might be a more appropriate model in view of diff erences between the included trials, DEVTA accounts for 14% of the overall eff ect, which suggests a 26% average reduction in mortality (RR 0·74, 95% CI 0·64–0·87). Since model choice meaningfully changes the outcome, both averages should be interpreted with caution. Continued research to improve the delivery of vitamin A remains important, but further trials are not needed. Because of the size of DEVTA and the stability of previous estimates, average eff ects are highly unlikely to change. We believe that the meta-analysis by Awasthi and colleagues underestimates the eff ect of vitamin A when delivered faithfully to children at high risk of deficiency; however, their report affirms that vitamin A supplementation prevents death, illness, and blindness for children who are defi cient and cannot obtain enough vitamin A through diet alone. It would no longer be ethical to compare vitamin A with a placebo or with a nutritional intervention that lacks this essential nutrient. DEVTA should be the last trial of this kind. We declare that we have no confl icts of interest.
The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common. The WHO state this will improve nutritional status, haemoglobin, and cognition and thus will improve health, intellect, and school attendance. Consequently, it is claimed that school performance will improve, child mortality will decline, and economic productivity will increase. Given the important health and societal benefits attributed to this intervention, we sought to determine whether they are based on reliable evidence.
To summarize the effects of giving deworming drugs to children to treat soil-transmitted intestinal worms (nematode geohelminths) on weight, haemoglobin, and cognition; and the evidence of impact on physical well being, school attendance, school performance, and mortality.
In February 2012, we searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, EMBASE, LILACS, mRCT, and reference lists, and registers of ongoing and completed trials.
We selected randomized controlled trials (RCTs) and quasi-RCTs comparing deworming drugs for geohelminth worms with placebo or no treatment in children aged 16 years or less, reporting on weight, haemoglobin, and formal test of intellectual development. In cluster-RCTs treating communities or schools, we also sought data on school attendance, school performance, and mortality. We included trials that included health education with deworming.
At least two authors independently assessed the trials, evaluated risk of bias, and extracted data. Continuous data were analysed using the mean difference (MD) with 95% confidence intervals (CI). Where data were missing, we contacted trial authors. We used GRADE to assess evidence quality, and this is reflected in the wording we used: high quality ("deworming improves...."); moderate quality ("deworming probably improves..."); low quality ("deworming may improve...."); and very low quality ("we don't know if deworming improves....").
We identified 42 trials, including eight cluster trials, that met the inclusion criteria. Excluding one trial where data are awaited, the 41 trials include 65,168 participants.For programmes that treat only children detected as infected (by screening), a single dose of deworming drugs probably increased weight (0.58 kg, 95% CI 0.40 to 0.76, three trials, 139 participants; moderate quality evidence) and may have increased haemoglobin (0.37 g/dL, 95% CI 0.1 to 0.64, two trials, 108 participants; low quality evidence), but we do not know if there is an effect on cognitive functioning (two trials, very low quality evidence).For a single dose of deworming drugs given to all children in endemic areas, there were mixed effects on weight, with no effects evident in seven trials, but large effects in two. Overall our analysis indicated that we are uncertain whether there was an effect on weight (nine trials, 3058 participants; very low quality evidence). For haemoglobin, deworming made little or no difference (0.02 g/dL, 95% CI -0.05 to 0.09, four trials, 1992 participants; low quality evidence), and we don't know if it improves cognition (one trial, very low quality evidence).For multiple doses of deworming drugs with follow up for up to one year given to all children in endemic areas, we are uncertain if there is an effect on weight (0.06 kg, 95% CI -0.17 to 0.30; seven trials, 2460 participants; very low quality evidence); cognition (three trials, very low quality evidence); or school attendance (4% higher attendance; 95% CI -6 to 14; two trials, 75 clusters and 143 individually randomized participants, very low quality evidence). For haemoglobin, the intervention may have little or no effect (mean 0.01 g/dL lower; 95% CI 0.14 lower to 0.13 higher; four trials, 807 participants; low quality evidence).For multiple doses of deworming drugs with follow up beyond one year given to all children in endemic areas there were five trials with weight measures. One cluster-RCT of 3712 children in a low prevalence area showed a large effect (average gain of 0.98kg), whilst the other four trials did not show an effect, including a cluster-RCT of 27,995 children in a moderate prevalence area. Overall, we are uncertain if there is an effect for weight (five trials, 302 clusters and 1045 individually randomized participants; very low quality evidence). For other outcomes, we are uncertain whether deworming affects height (-0.26 cm; 95%CI -0.84 to 0.31, three trials, 1219 participants); haemoglobin (0.02 g/dL, 95%CI 0.3 to 0.27, two trials, 1365 participants); cognition (two trials), or school attendance (mean attendance 5% higher, 95% CI -0.5 to 10.5, one trial, 50 clusters).Stratified analysis to seek subgroup effects into low, medium and high helminth endemicity areas did not demonstrate any pattern of effect. We did not detect any significant effects for any primary outcomes in a sensitivity analysis only including trials with adequate allocation concealment.One million children were randomized in a deworming trial from India with mortality as the primary outcome. This was completed in 2005 but the authors have not published the results.
Screening children for intestinal helminths and then treating infected children appears promising, but the evidence base is small. Routine deworming drugs given to school children has been more extensively investigated, and has not shown benefit on weight in most studies, except for substantial weight changes in three trials conducted 15 years ago or more. Two of these trials were carried out in the same high prevalence setting. For haemoglobin, community deworming seems to have little or no effect, and the evidence in relation to cognition, school attendance, and school performance is generally poor, with no obvious or consistent effect. Our interpretation of this data is that it is probably misleading to justify contemporary deworming programmes based on evidence of consistent benefit on nutrition, haemoglobin, school attendance or school performance as there is simply insufficient reliable information to know whether this is so.
Background: Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time.
Methods: We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights.
Findings: Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions.
Interpretation: Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results.
Funding: Bill & Melinda Gates Foundation.
Background: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex.
Methods: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions.
Findings: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted.
Conclusions: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis.
Funding: Bill & Melinda Gates Foundation.
People who hold strong opinions on complex social issues are likely to examine relevant empirical evidence in a biased manner. They are apt to accept "confirming" evidence at face value while subjecting "disconfirming" evidence to critical evaluation, and, as a result, draw undue support for their initial positions from mixed or random empirical findings. Thus, the result of exposing contending factions in a social dispute to an identical body of relevant empirical evidence may be not a narrowing of disagreement but rather an increase in polarization. To test these assumptions, 48 undergraduates supporting and opposing capital punishment were exposed to 2 purported studies, one seemingly confirming and one seemingly disconfirming their existing beliefs about the deterrent efficacy of the death penalty. As predicted, both proponents and opponents of capital punishment rated those results and procedures that confirmed their own beliefs to be the more convincing and probative ones, and they reported corresponding shifts in their beliefs as the various results and procedures were presented. The net effect of such evaluations and opinion shifts was the postulated increase in attitude polarization. (28 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
More than 2·3 million children died in India in 2005; however, the major causes of death have not been measured in the country. We investigated the causes of neonatal and child mortality in India and their differences by sex and region.
The Registrar General of India surveyed all deaths occurring in 2001-03 in 1·1 million nationally representative homes. Field staff interviewed household members and completed standard questions about events that preceded the death. Two of 130 physicians then independently assigned a cause to each death. Cause-specific mortality rates for 2005 were calculated nationally and for the six regions by combining the recorded proportions for each cause in the neonatal deaths and deaths at ages 1-59 months in the study with population and death totals from the United Nations.
There were 10,892 deaths in neonates and 12,260 in children aged 1-59 months in the study. When these details were projected nationally, three causes accounted for 78% (0·79 million of 1·01 million) of all neonatal deaths: prematurity and low birthweight (0·33 million, 99% CI 0·31 million to 0·35 million), neonatal infections (0·27 million, 0·25 million to 0·29 million), and birth asphyxia and birth trauma (0·19 million, 0·18 million to 0·21 million). Two causes accounted for 50% (0·67 million of 1·34 million) of all deaths at 1-59 months: pneumonia (0·37 million, 0·35 million to 0·39 million) and diarrhoeal diseases (0·30 million, 0·28 million to 0·32 million). In children aged 1-59 months, girls in central India had a five-times higher mortality rate (per 1000 livebirths) from pneumonia (20·9, 19·4-22·6) than did boys in south India (4·1, 3·0-5·6) and four-times higher mortality rate from diarrhoeal disease (17·7, 16·2-19·3) than did boys in west India (4·1, 3·0-5·5).
Five avoidable causes accounted for nearly 1·5 million child deaths in India in 2005, with substantial differences between regions and sexes. Expanded neonatal and intrapartum care, case management of diarrhoea and pneumonia, and addition of new vaccines to immunisation programmes could substantially reduce child deaths in India.
US National Institutes of Health, International Development Research Centre, Canadian Institutes of Health Research, Li Ka Shing Knowledge Institute, and US Fund for UNICEF.
Guidance on publishing results and how we operate evidence-based policy - Volume 11 Issue 7 - Agneta Yngve, Barrie Margetts, H.P.S. Sachdev
Background:
Vitamin A deficiency (VAD) is a major public health problem in low and middle income countries affecting 190 million children under 5. VAD can lead to many adverse health consequences, including death.
Objectives:
To evaluate the effect of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged 6 months to 5 years.
Search strategy:
We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2010 Issue 2), MEDLINE (1950 to April Week 2 2010), EMBASE (1980 to 2010 Week 16), Global Health (1973 to March 2010), Latin American and Caribbean Health Sciences (LILACS), metaRegister of Controlled Trials and African Index Medicus (27 April 2010).
Selection criteria:
Randomised controlled trials (RCTs) and cluster RCTs evaluating the effect of synthetic VAS in children aged 6 months to 5 years living in the community. We excluded studies concerned with children in hospital and children with disease or infection. We excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods or beta-carotene supplementation.
Data collection and analysis:
Two review authors independently assessed studies for inclusion. Data were double abstracted and discrepancies were resolved by discussion. Meta-analyses were performed for outcomes including all-cause and cause-specific mortality, disease, vision, and side-effects.
Main results:
43 trials involving 215,633 children were included. A meta-analysis for all-cause mortality included 17 trials comprising 194,795 children with 3536 deaths in both groups. At follow-up, there was a 24% observed reduction in the risk of all-cause mortality for Vitamin A compared with Control (Relative risk (RR) = 0.76 [95% confidence interval (CI) 0.69, 0.83]). Seven trials reported diarrhoea mortality and a 28% overall reduction for VAS (RR = 0.72 [0.57, 0.91]). There was no significant effect of VAS on cause specific mortality of measles, respiratory disease and meningitis. VAS reduced incidence of diarrhoea (RR = 0.85 [0.82, 0.87]) and measles morbidity (RR = 0.50 [0.37, 0.67]); however, there was no significant effect on incidence of respiratory disease or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR = 2.75 [1.81, 4.19]).
Authors' conclusions:
VAS is effective in reducing all-cause mortality by about 24% compared to no treatment. In our opinion, given the evidence that VAS causes considerable reduction in child mortality, further placebo-controlled trials of VAS in children between 6 months and 5 years of age are not required. There is a need for further studies comparing different doses and delivery mechanisms (for example, fortification).
Two BMJ campaigns coincide this week: for publication of all results from clinical trials, and against overdiagnosis and overtreatment.Sentinel node biopsy (removal of the sentinel lymph node) is widely used to stage disease in patients with breast cancer and malignant melanoma. It carries a risk of lymphoedema and other complications, which increases if patients with positive sentinel nodes go on to have further lymph nodes removed in an effort to improve their survival. Evidence from several large trials has saved women with breast cancer from having axillary lymph node dissection if they have no clinical signs of axillary involvement: the trials found no significant difference in overall or disease free survival when axillary dissection was added to sentinel node biopsy.But as Ingrid Torjesen reports, patients in the United Kingdom, the United States, and elsewhere who have malignant melanoma are routinely undergoing sentinel node biopsy, followed by regional lymphadenectomy if the biopsy is positive (doi:10.1136/bmj.e8645). This is despite guidance from the UK’s National Institute for Health and Clinical Excellence that there is, as yet, no published evidence from randomised controlled trials that sentinel node biopsy improves survival.What trial evidence there is comes from the Multicenter Selective Lymphadenectomy trial (MSLT-1). Five year follow-up data published in the New England Journal of Medicine in 2006 found no overall survival advantage in patients who had sentinel node biopsy compared with those who didn’t. But controversy has arisen over the authors’ claims of improved disease free survival. These claims are based on a lower rate of nodal recurrence in the biopsy group, but critics say this finding is unsurprising, since the patients in the intervention group who are most at risk—those with a positive sentinel node—have had their regional nodes removed.The researchers promised further analyses after 10 years of follow-up and at an interim point, and had these been published as expected in 2008 and 2011, the controversy might have been resolved by now. But these data have not yet been published. The authors say they are working on their analysis. Meanwhile, sentinel node biopsy has become the standard of care in many countries. NICE says the procedure is justified only in the context of clinical trials, but Torjesen has learnt that it is carried out in at least 19 trusts in England, only two of which are involved in ongoing trials. Is this another example of harmful overtreatment? Only the trial data will tell.This is not the only case in which clinical trial data have been published late or not at all. In addition to the well documented suppression of data by drug companies, there are clear examples of delayed or non-publication in non-industry sponsored trials. Last week we reported on the long delay in publication of a trial of deworming and vitamin A that was completed in 2005 (BMJ 2013;346:e8558). This week in an editorial we reference a large trial of adenoidectomy that has only just reported after nearly a decade (doi:10.1136/bmj.f105). The editorial calls for ethics committees, funders, and institutions to take responsibility for ensuring that the trials they approve, support, and host are published in full and in good time. Working with others, we are taking the campaign to patients and the public. If you agree that all clinical trials should be published, sign the petition at alltrials.net.NotesCite this as: BMJ 2013;346:f159
The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common. The WHO state this will improve nutritional status, haemoglobin, and cognition and thus will improve health, intellect, and school attendance. Consequently, it is claimed that school performance will improve, child mortality will decline, and economic productivity will increase. Given the important health and societal benefits attributed to this intervention, we sought to determine whether they are based on reliable evidence.
To summarize the effects of giving deworming drugs to children to treat soil-transmitted intestinal worms (nematode geohelminths) on weight, haemoglobin, and cognition; and the evidence of impact on physical well being, school attendance, school performance, and mortality.
In February 2012, we searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, EMBASE, LILACS, mRCT, and reference lists, and registers of ongoing and completed trials.
We selected randomized controlled trials (RCTs) and quasi-RCTs comparing deworming drugs for geohelminth worms with placebo or no treatment in children aged 16 years or less, reporting on weight, haemoglobin, and formal test of intellectual development. In cluster-RCTs treating communities or schools, we also sought data on school attendance, school performance, and mortality. We included trials that included health education with deworming.
At least two authors independently assessed the trials, evaluated risk of bias, and extracted data. Continuous data were analysed using the mean difference (MD) with 95% confidence intervals (CI). Where data were missing, we contacted trial authors. We used GRADE to assess evidence quality, and this is reflected in the wording we used: high quality ("deworming improves...."); moderate quality ("deworming probably improves..."); low quality ("deworming may improve...."); and very low quality ("we don't know if deworming improves....").
We identified 42 trials, including eight cluster trials, that met the inclusion criteria. Excluding one trial where data are awaited, the 41 trials include 65,168 participants.For programmes that treat only children detected as infected (by screening), a single dose of deworming drugs probably increased weight (0.58 kg, 95% CI 0.40 to 0.76, three trials, 139 participants; moderate quality evidence) and may have increased haemoglobin (0.37 g/dL, 95% CI 0.1 to 0.64, two trials, 108 participants; low quality evidence), but we do not know if there is an effect on cognitive functioning (two trials, very low quality evidence).For a single dose of deworming drugs given to all children in endemic areas, there were mixed effects on weight, with no effects evident in seven trials, but large effects in two. Overall our analysis indicated that we are uncertain whether there was an effect on weight (nine trials, 3058 participants; very low quality evidence). For haemoglobin, deworming made little or no difference (0.02 g/dL, 95% CI -0.05 to 0.09, four trials, 1992 participants; low quality evidence), and we don't know if it improves cognition (one trial, very low quality evidence).For multiple doses of deworming drugs with follow up for up to one year given to all children in endemic areas, we are uncertain if there is an effect on weight (0.06 kg, 95% CI -0.17 to 0.30; seven trials, 2460 participants; very low quality evidence); cognition (three trials, very low quality evidence); or school attendance (4% higher attendance; 95% CI -6 to 14; two trials, 75 clusters and 143 individually randomized participants, very low quality evidence). For haemoglobin, the intervention may have little or no effect (mean 0.01 g/dL lower; 95% CI 0.14 lower to 0.13 higher; four trials, 807 participants; low quality evidence).For multiple doses of deworming drugs with follow up beyond one year given to all children in endemic areas there were five trials with weight measures. One cluster-RCT of 3712 children in a low prevalence area showed a large effect (average gain of 0.98kg), whilst the other four trials did not show an effect, including a cluster-RCT of 27,995 children in a moderate prevalence area. Overall, we are uncertain if there is an effect for weight (five trials, 302 clusters and 1045 individually randomized participants; very low quality evidence). For other outcomes, we are uncertain whether deworming affects height (-0.26 cm; 95%CI -0.84 to 0.31, three trials, 1219 participants); haemoglobin (0.02 g/dL, 95%CI 0.3 to 0.27, two trials, 1365 participants); cognition (two trials), or school attendance (mean attendance 5% higher, 95% CI -0.5 to 10.5, one trial, 50 clusters).Stratified analysis to seek subgroup effects into low, medium and high helminth endemicity areas did not demonstrate any pattern of effect. We did not detect any significant effects for any primary outcomes in a sensitivity analysis only including trials with adequate allocation concealment.One million children were randomized in a deworming trial from India with mortality as the primary outcome. This was completed in 2005 but the authors have not published the results.
Screening children for intestinal helminths and then treating infected children appears promising, but the evidence base is small. Routine deworming drugs given to school children has been more extensively investigated, and has not shown benefit on weight in most studies, except for substantial weight changes in three trials conducted 15 years ago or more. Two of these trials were carried out in the same high prevalence setting. For haemoglobin, community deworming seems to have little or no effect, and the evidence in relation to cognition, school attendance, and school performance is generally poor, with no obvious or consistent effect. Our interpretation of this data is that it is probably misleading to justify contemporary deworming programmes based on evidence of consistent benefit on nutrition, haemoglobin, school attendance or school performance as there is simply insufficient reliable information to know whether this is so.
Information about the distribution of causes of and time trends for child mortality should be periodically updated. We report the latest estimates of causes of child mortality in 2010 with time trends since 2000.
Updated total numbers of deaths in children aged 0-27 days and 1-59 months were applied to the corresponding country-specific distribution of deaths by cause. We did the following to derive the number of deaths in children aged 1-59 months: we used vital registration data for countries with an adequate vital registration system; we applied a multinomial logistic regression model to vital registration data for low-mortality countries without adequate vital registration; we used a similar multinomial logistic regression with verbal autopsy data for high-mortality countries; for India and China, we developed national models. We aggregated country results to generate regional and global estimates.
Of 7·6 million deaths in children younger than 5 years in 2010, 64·0% (4·879 million) were attributable to infectious causes and 40·3% (3·072 million) occurred in neonates. Preterm birth complications (14·1%; 1·078 million, uncertainty range [UR] 0·916-1·325), intrapartum-related complications (9·4%; 0·717 million, 0·610-0·876), and sepsis or meningitis (5·2%; 0·393 million, 0·252-0·552) were the leading causes of neonatal death. In older children, pneumonia (14·1%; 1·071 million, 0·977-1·176), diarrhoea (9·9%; 0·751 million, 0·538-1·031), and malaria (7·4%; 0·564 million, 0·432-0·709) claimed the most lives. Despite tremendous efforts to identify relevant data, the causes of only 2·7% (0·205 million) of deaths in children younger than 5 years were medically certified in 2010. Between 2000 and 2010, the global burden of deaths in children younger than 5 years decreased by 2 million, of which pneumonia, measles, and diarrhoea contributed the most to the overall reduction (0·451 million [0·339-0·547], 0·363 million [0·283-0·419], and 0·359 million [0·215-0·476], respectively). However, only tetanus, measles, AIDS, and malaria (in Africa) decreased at an annual rate sufficient to attain the Millennium Development Goal 4.
Child survival strategies should direct resources toward the leading causes of child mortality, with attention focusing on infectious and neonatal causes. More rapid decreases from 2010-15 will need accelerated reduction for the most common causes of death, notably pneumonia and preterm birth complications. Continued efforts to gather high-quality data and enhance estimation methods are essential for the improvement of future estimates.
The Bill & Melinda Gates Foundation.
Development controversy a sign of sophistication
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- C Fiennes
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Six-monthly vitamin A from 1 to 6 years of age. DEVTA: cluster randomised trial in 1 million children in North India
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- R Peto
- S Read
- D Bundy
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