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

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

To GP or not to GP: a natural experiment in children triaged to see a GP in a tertiary paediatric emergency department (ED)

Objective: To evaluate the impact of integrating a general practitioner (GP) into a tertiary paediatric emergency department (ED) on admissions, waiting times and antibiotic prescriptions. Design: Retrospective cohort study. Setting: Alder Hey Children’s NHS Foundation Trust, a tertiary paediatric hospital in Liverpool, UK. Participants: From October 2014, a GP was colocated within the ED, from 14:00 to 22:00 hours, 7 days a week. Children triaged green on the Manchester Triage System without any comorbidities were classed as ‘GP appropriate’. The natural experiment compared patients triaged as ‘GP appropriate’ and able to be seen by a GP between 14:00 and 22:00 hours (GP group) to patients triaged as ‘GP appropriate’ seen outside of the hours when a GP was available (ED group). Intention-to-treat (ITT) analysis was used to assess the main outcomes. Results: 5223 patients were designated as ‘GP appropriate’—18.2% of the total attendances to the ED over the study period. There were 2821 (54%) in the GP group and 2402 (46%) in the ED group. The median duration of stay in the ED was 94 min (IQR 63–141) for the GP group compared with 113 min (IQR 70–167) for the ED group (p<0.0005). Using the ITT analysis equivalent, we demonstrated that the GP group were less likely to: be admitted to hospital (2.2% vs 6.5%, OR 0.32, 95% CI 0.24 to 0.44), wait longer than 4 hours (2.3% vs 5.1%, OR 0.45, 95% CI 0.33 to 0.61) or leave before being seen (3.1% vs 5.7%, OR 0.53, 95% CI 0.41 to 0.70), but more likely to receive antibiotics (26.1% vs 20.5%, OR 1.37, 95% CI 1.10 to 1.56). Sensitivity analyses yielded similar results. Conclusions: Introducing a GP to a paediatric ED service can significantly reduce waiting times and admissions, but may lead to more antibiotic prescribing. This study demonstrates a novel, potentially more efficient ED care pathway in the current context of rising demand for children’s emergency services

Effects of ecstasy/polydrug use on memory for associative information

Rationale Associative learning underpins behaviours that are fundamental to the everyday functioning of the individual. Evidence pointing to learning deficits in recreational drug users merits further examination. Objectives A word pair learning task was administered to examine associative learning processes in ecstasy/polydrug users. Methods After assignment to either single or divided attention conditions, 44 ecstasy/polydrug users and 48 non-users were presented with 80 word pairs at encoding. Following this, four types of stimuli were presented at the recognition phase: the words as originally paired (old pairs), previously presented words in different pairings (conjunction pairs), old words paired with new words, and pairs of new words (not presented previously). The task was to identify which of the stimuli were intact old pairs. Results Ecstasy/ploydrug users produced significantly more false-positive responses overall compared to non-users. Increased long-term frequency of ecstasy use was positively associated with the propensity to produce false-positive responses. It was also associated with a more liberal signal detection theory decision criterion value. Measures of long term and recent cannabis use were also associated with these same word pair learning outcome measures. Conjunction word pairs, irrespective of drug use, generated the highest level of false-positive responses and significantly more false-positive responses were made in the divided attention condition compared to the single attention condition. Conclusions Overall, the results suggest that long-term ecstasy exposure may induce a deficit in associative learning and this may be in part a consequence of users adopting a more liberal decision criterion value

Do early-life exposures explain why more advantaged children get eczema? Findings from the UK Millennium Cohort Study

Background: Atopic dermatitis (eczema) in childhood is socially patterned, with higher incidence in more advantaged populations. However, it is unclear what factors explain the social differences. Objectives: To identify early‐life risk factors for eczema, and to explore how early‐life risk factors explain any differences in eczema. Methods: We estimated odds ratios (ORs) for ever having had eczema by age 5 years in 14 499 children from the U.K. Millennium Cohort Study (MCS), with a focus on maternal, antenatal and early‐life risk factors and socioeconomic circumstances (SECs). Risk factors were explored to assess whether they attenuated associations between SECs and eczema. Results Overall 35·1% of children had ever had eczema by age 5 years. Children of mothers with degree‐level qualifications vs. no educational qualifications were more likely to have eczema (OR 1·52, 95% confidence interval 1·31–1·76), and there was a gradient across the socioeconomic spectrum. Maternal atopy, breastfeeding (1–6 weeks and ≥ 6 months), introduction of solids under 4 months or cow's milk under 9 months, antibiotic exposure in the first year of life and grime exposure were associated with an increased odds of having eczema. Female sex, Pakistani and Bangladeshi ethnicity, smoking during pregnancy, exposure to environmental tobacco smoke and having more siblings were associated with reduced odds for eczema. Controlling for maternal, antenatal and early‐life characteristics (particularly maternal smoking during pregnancy, breastfeeding and number of siblings) reduced the OR for eczema to 1·26 (95% confidence interval 1·03–1·50) in the group with the highest educational qualifications compared with the least. Conclusions: In a representative U.K. child cohort, eczema was more common in more advantaged children. This was explained partially by early‐life factors including not smoking during pregnancy, breastfeeding and having fewer siblings

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

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

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

State-space Manifold and Rotating Black Holes

We study a class of fluctuating higher dimensional black hole configurations obtained in string theory/ $M$-theory compactifications. We explore the intrinsic Riemannian geometric nature of Gaussian fluctuations arising from the Hessian of the coarse graining entropy, defined over an ensemble of brane microstates. It has been shown that the state-space geometry spanned by the set of invariant parameters is non-degenerate, regular and has a negative scalar curvature for the rotating Myers-Perry black holes, Kaluza-Klein black holes, supersymmetric $AdS_5$ black holes, $D_1$-$D_5$ configurations and the associated BMPV black holes. Interestingly, these solutions demonstrate that the principal components of the state-space metric tensor admit a positive definite form, while the off diagonal components do not. Furthermore, the ratio of diagonal components weakens relatively faster than the off diagonal components, and thus they swiftly come into an equilibrium statistical configuration. Novel aspects of the scaling property suggest that the brane-brane statistical pair correlation functions divulge an asymmetric nature, in comparison with the others. This approach indicates that all above configurations are effectively attractive and stable, on an arbitrary hyper-surface of the state-space manifolds. It is nevertheless noticed that there exists an intriguing relationship between non-ideal inter-brane statistical interactions and phase transitions. The ramifications thus described are consistent with the existing picture of the microscopic CFTs. We conclude with an extended discussion of the implications of this work for the physics of black holes in string theory.Comment: 44 pages, Keywords: Rotating Black Holes; State-space Geometry; Statistical Configurations, String Theory, M-Theory. PACS numbers: 04.70.-s Physics of black holes; 04.70.Bw Classical black holes; 04.70.Dy Quantum aspects of black holes, evaporation, thermodynamics; 04.50.Gh Higher-dimensional black holes, black strings, and related objects. Edited the bibliograph