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Background: Dengue is a global health problem of high significance, with 3.9 billion people at risk of infection. The geographic expansion of dengue virus (DENV) infection has resulted in increased frequency and severity of the disease, and the number of deaths has increased in recent years. Wolbachia,an intracellular bacterial endosymbiont, has been under investigation for several years as a novel dengue-control strategy. Some dengue vectors (Aedes mosquitoes) can be transinfected with specific strains of Wolbachia, which decreases their fitness (ability to survive and mate) and their ability to reproduce, inhibiting the replication of dengue. Both laboratory and field studies have demonstrated the potential effect of Wolbachia deployments on reducing dengue transmission, and modelling studies have suggested that this may be a self-sustaining strategy for dengue prevention, although long-term effects are yet to be elucidated., Objectives: To assess the efficacy of Wolbachia-carrying Aedes speciesdeployments (specifically wMel-, wMelPop-, and wAlbB- strains of Wolbachia) for preventing dengue virus infection., Search Methods: We searched CENTRAL, MEDLINE, Embase, four other databases, and two trial registries up to 24 January 2024., Selection Criteria: Randomized controlled trials (RCTs), including cluster-randomized controlled trials (cRCTs), conducted in dengue endemic or epidemic-prone settings were eligible. We sought studies that investigated the impact of Wolbachia-carrying Aedes deployments on epidemiological or entomological dengue-related outcomes, utilizing either the population replacement or population suppression strategy., Data Collection and Analysis: Two review authors independently selected eligible studies, extracted data, and assessed the risk of bias using the Cochrane RoB 2 tool. We used odds ratios (OR) with the corresponding 95% confidence intervals (CI) as the effect measure for dichotomous outcomes. For count/rate outcomes, we planned to use the rate ratio with 95% CI as the effect measure. We used adjusted measures of effect for cRCTs. We assessed the certainty of evidence using GRADE., Main Results: One completed cRCT met our inclusion criteria, and we identified two further ongoing cRCTs. The included trial was conducted in an urban setting in Yogyakarta, Indonesia. It utilized a nested test-negative study design, whereby all participants aged three to 45 years who presented at healthcare centres with a fever were enrolled in the study provided they had resided in the study area for the previous 10 nights. The trial showed that wMel-Wolbachia infected Ae aegypti deployments probably reduce the odds of contracting virologically confirmed dengue by 77% (OR 0.23, 95% CI 0.15 to 0.35; 1 trial, 6306 participants; moderate-certainty evidence). The cluster-level prevalence of wMel Wolbachia-carrying mosquitoes remained high over two years in the intervention arm of the trial, reported as 95.8% (interquartile range 91.5 to 97.8) across 27 months in clusters receiving wMel-Wolbachia Ae aegypti deployments, but there were no reliable comparative data for this outcome. Other primary outcomes were the incidence of virologically confirmed dengue, the prevalence of dengue ribonucleic acid in the mosquito population, and mosquito density, but there were no data for these outcomes. Additionally, there were no data on adverse events., Authors' Conclusions: The included trial demonstrates the potential significant impact of wMel-Wolbachia-carrying Ae aegypti mosquitoes on preventing dengue infection in an endemic setting, and supports evidence reported in non-randomized and uncontrolled studies. Further trials across a greater diversity of settings are required to confirm whether these findings apply to other locations and country settings, and greater reporting of acceptability and cost are important., (Copyright © 2024 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Trypanosoma cruzi infection is diagnosed by parasitological, molecular, and serological tests. Molecular methods based on DNA amplification provide a more sensitive alternative to classical parasitological techniques for detecting evidence of T. cruzi parasitemia, and are the preferred tests for congenital and oral transmission cases and parasite reactivation in chronically infected immunosuppressed individuals. In newborns at risk of vertical transmission, simplified diagnostic algorithms that provide timely results can reduce the high follow-up losses observed with current algorithms. Molecular methods have also proved useful for monitoring T. cruzi infection in solid organ transplantation recipients, regardless of host immune status, allowing parasite detection even before symptom manifestation. Furthermore, in the absence of other biomarkers and a practical test of cure, and given the limitations of serological methods, recent clinical guidelines have included polymerase chain reaction (PCR) to detect therapeutic failure after antiparasitic treatment in chronically infected adults. Increasing evidence supports the use of molecular tests in a clinical context, given the improved sensitivity and specificity of current assays - characteristics which largely depend on epidemiological factors and genetic and antigenic variability among T. cruzi strains. Further development and registration of commercial PCR kits will improve the use of molecular tests. We discuss the attributes of PCR and other molecular tests for clinical management in people with T. cruzi infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors MS and FB declared that they were editorial board members of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Pinazo, Forsyth, Lopez-Albizu, Bisio, González-Martínez, Bohorquez, Pinto, Molina, Marchiol, Herazo, Galván, Marques, Barreira, Villar, Sguassero, Santini, Altcheh, Alarcón de Noya and Sosa-Estani.)

Background: It has been reported that people with COVID-19 and pre-existing autoantibodies against type I interferons are likely to develop an inflammatory cytokine storm responsible for severe respiratory symptoms. Since interleukin 6 (IL-6) is one of the cytokines released during this inflammatory process, IL-6 blocking agents have been used for treating people with severe COVID-19., Objectives: To update the evidence on the effectiveness and safety of IL-6 blocking agents compared to standard care alone or to a placebo for people with COVID-19., Search Methods: We searched the World Health Organization (WHO) International Clinical Trials Registry Platform, the Living OVerview of Evidence (L·OVE) platform, and the Cochrane COVID-19 Study Register to identify studies on 7 June 2022., Selection Criteria: We included randomized controlled trials (RCTs) evaluating IL-6 blocking agents compared to standard care alone or to placebo for people with COVID-19, regardless of disease severity., Data Collection and Analysis: Pairs of researchers independently conducted study selection, extracted data and assessed risk of bias. We assessed the certainty of evidence using the GRADE approach for all critical and important outcomes. In this update we amended our protocol to update the methods used for grading evidence by establishing minimal important differences for the critical outcomes., Main Results: This update includes 22 additional trials, for a total of 32 trials including 12,160 randomized participants all hospitalized for COVID-19 disease. We identified a further 17 registered RCTs evaluating IL-6 blocking agents without results available as of 7 June 2022.  The mean age range varied from 56 to 75 years; 66.2% (8051/12,160) of enrolled participants were men. One-third (11/32) of included trials were placebo-controlled. Twenty-two were published in peer-reviewed journals, three were reported as preprints, two trials had results posted only on registries, and results from five trials were retrieved from another meta-analysis. Eight were funded by pharmaceutical companies.  Twenty-six included studies were multicenter trials; four were multinational and 22 took place in single countries. Recruitment of participants occurred between February 2020 and June 2021, with a mean enrollment duration of 21 weeks (range 1 to 54 weeks). Nineteen trials (60%) had a follow-up of 60 days or more. Disease severity ranged from mild to critical disease. The proportion of participants who were intubated at study inclusion also varied from 5% to 95%. Only six trials reported vaccination status; there were no vaccinated participants included in these trials, and 17 trials were conducted before vaccination was rolled out. We assessed a total of six treatments, each compared to placebo or standard care. Twenty trials assessed tocilizumab, nine assessed sarilumab, and two assessed clazakizumab. Only one trial was included for each of the other IL-6 blocking agents (siltuximab, olokizumab, and levilimab). Two trials assessed more than one treatment. Efficacy and safety of tocilizumab and sarilumab compared to standard care or placebo for treating COVID-19 At day (D) 28, tocilizumab and sarilumab probably result in little or no increase in clinical improvement (tocilizumab: risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.11; 15 RCTs, 6116 participants; moderate-certainty evidence; sarilumab: RR 0.99, 95% CI 0.94 to 1.05; 7 RCTs, 2425 participants; moderate-certainty evidence). For clinical improvement at ≥ D60, the certainty of evidence is very low for both tocilizumab (RR 1.10, 95% CI 0.81 to 1.48; 1 RCT, 97 participants; very low-certainty evidence) and sarilumab (RR 1.22, 95% CI 0.91 to 1.63; 2 RCTs, 239 participants; very low-certainty evidence). The effect of tocilizumab on the proportion of participants with a WHO Clinical Progression Score (WHO-CPS) of level 7 or above remains uncertain at D28 (RR 0.90, 95% CI 0.72 to 1.12; 13 RCTs, 2117 participants; low-certainty evidence) and that for sarilumab very uncertain (RR 1.10, 95% CI 0.90 to 1.33; 5 RCTs, 886 participants; very low-certainty evidence). Tocilizumab reduces all cause-mortality at D28 compared to standard care/placebo (RR 0.88, 95% CI 0.81 to 0.94; 18 RCTs, 7428 participants; high-certainty evidence). The evidence about the effect of sarilumab on this outcome is very uncertain (RR 1.06, 95% CI 0.86 to 1.30; 9 RCTs, 3305 participants; very low-certainty evidence). The evidence is uncertain for all cause-mortality at ≥ D60 for tocilizumab (RR 0.91, 95% CI 0.80 to 1.04; 9 RCTs, 2775 participants; low-certainty evidence) and very uncertain for sarilumab (RR 0.95, 95% CI 0.84 to 1.07; 6 RCTs, 3379 participants; very low-certainty evidence). Tocilizumab probably results in little to no difference in the risk of adverse events (RR 1.03, 95% CI 0.95 to 1.12; 9 RCTs, 1811 participants; moderate-certainty evidence). The evidence about adverse events for sarilumab is uncertain (RR 1.12, 95% CI 0.97 to 1.28; 4 RCT, 860 participants; low-certainty evidence).  The evidence about serious adverse events is very uncertain for tocilizumab (RR 0.93, 95% CI 0.81 to 1.07; 16 RCTs; 2974 participants; very low-certainty evidence) and uncertain for sarilumab (RR 1.09, 95% CI 0.97 to 1.21; 6 RCTs; 2936 participants; low-certainty evidence). Efficacy and safety of clazakizumab, olokizumab, siltuximab and levilimab compared to standard care or placebo for treating COVID-19 The evidence about the effects of clazakizumab, olokizumab, siltuximab, and levilimab comes from only one or two studies for each blocking agent, and is uncertain or very uncertain., Authors' Conclusions: In hospitalized people with COVID-19, results show a beneficial effect of tocilizumab on all-cause mortality in the short term and probably little or no difference in the risk of adverse events compared to standard care alone or placebo. Nevertheless, both tocilizumab and sarilumab probably result in little or no increase in clinical improvement at D28. Evidence for an effect of sarilumab and the other IL-6 blocking agents on critical outcomes is uncertain or very uncertain. Most of the trials included in our review were done before the waves of different variants of concern and before vaccination was rolled out on a large scale. An additional 17 RCTs of IL-6 blocking agents are currently registered with no results yet reported. The number of pending studies and the number of participants planned is low. Consequently, we will not publish further updates of this review., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The diagnostic challenges associated with the COVID-19 pandemic resulted in rapid development of diagnostic test methods for detecting SARS-CoV-2 infection. Serology tests to detect the presence of antibodies to SARS-CoV-2 enable detection of past infection and may detect cases of SARS-CoV-2 infection that were missed by earlier diagnostic tests. Understanding the diagnostic accuracy of serology tests for SARS-CoV-2 infection may enable development of effective diagnostic and management pathways, inform public health management decisions and understanding of SARS-CoV-2 epidemiology., Objectives: To assess the accuracy of antibody tests, firstly, to determine if a person presenting in the community, or in primary or secondary care has current SARS-CoV-2 infection according to time after onset of infection and, secondly, to determine if a person has previously been infected with SARS-CoV-2. Sources of heterogeneity investigated included: timing of test, test method, SARS-CoV-2 antigen used, test brand, and reference standard for non-SARS-CoV-2 cases., Search Methods: The COVID-19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) was searched on 30 September 2020. We included additional publications from the Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre) 'COVID-19: Living map of the evidence' and the Norwegian Institute of Public Health 'NIPH systematic and living map on COVID-19 evidence'. We did not apply language restrictions., Selection Criteria: We included test accuracy studies of any design that evaluated commercially produced serology tests, targeting IgG, IgM, IgA alone, or in combination. Studies must have provided data for sensitivity, that could be allocated to a predefined time period after onset of symptoms, or after a positive RT-PCR test. Small studies with fewer than 25 SARS-CoV-2 infection cases were excluded. We included any reference standard to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction tests (RT-PCR), clinical diagnostic criteria, and pre-pandemic samples)., Data Collection and Analysis: We use standard screening procedures with three reviewers. Quality assessment (using the QUADAS-2 tool) and numeric study results were extracted independently by two people. Other study characteristics were extracted by one reviewer and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and, for meta-analysis, we fitted univariate random-effects logistic regression models for sensitivity by eligible time period and for specificity by reference standard group. Heterogeneity was investigated by including indicator variables in the random-effects logistic regression models. We tabulated results by test manufacturer and summarised results for tests that were evaluated in 200 or more samples and that met a modification of UK Medicines and Healthcare products Regulatory Agency (MHRA) target performance criteria., Main Results: We included 178 separate studies (described in 177 study reports, with 45 as pre-prints) providing 527 test evaluations. The studies included 64,688 samples including 25,724 from people with confirmed SARS-CoV-2; most compared the accuracy of two or more assays (102/178, 57%). Participants with confirmed SARS-CoV-2 infection were most commonly hospital inpatients (78/178, 44%), and pre-pandemic samples were used by 45% (81/178) to estimate specificity. Over two-thirds of studies recruited participants based on known SARS-CoV-2 infection status (123/178, 69%). All studies were conducted prior to the introduction of SARS-CoV-2 vaccines and present data for naturally acquired antibody responses. Seventy-nine percent (141/178) of studies reported sensitivity by week after symptom onset and 66% (117/178) for convalescent phase infection. Studies evaluated enzyme-linked immunosorbent assays (ELISA) (165/527; 31%), chemiluminescent assays (CLIA) (167/527; 32%) or lateral flow assays (LFA) (188/527; 36%). Risk of bias was high because of participant selection (172, 97%); application and interpretation of the index test (35, 20%); weaknesses in the reference standard (38, 21%); and issues related to participant flow and timing (148, 82%). We judged that there were high concerns about the applicability of the evidence related to participants in 170 (96%) studies, and about the applicability of the reference standard in 162 (91%) studies. Average sensitivities for current SARS-CoV-2 infection increased by week after onset for all target antibodies. Average sensitivity for the combination of either IgG or IgM was 41.1% in week one (95% CI 38.1 to 44.2; 103 evaluations; 3881 samples, 1593 cases), 74.9% in week two (95% CI 72.4 to 77.3; 96 evaluations, 3948 samples, 2904 cases) and 88.0% by week three after onset of symptoms (95% CI 86.3 to 89.5; 103 evaluations, 2929 samples, 2571 cases). Average sensitivity during the convalescent phase of infection (up to a maximum of 100 days since onset of symptoms, where reported) was 89.8% for IgG (95% CI 88.5 to 90.9; 253 evaluations, 16,846 samples, 14,183 cases), 92.9% for IgG or IgM combined (95% CI 91.0 to 94.4; 108 evaluations, 3571 samples, 3206 cases) and 94.3% for total antibodies (95% CI 92.8 to 95.5; 58 evaluations, 7063 samples, 6652 cases). Average sensitivities for IgM alone followed a similar pattern but were of a lower test accuracy in every time slot. Average specificities were consistently high and precise, particularly for pre-pandemic samples which provide the least biased estimates of specificity (ranging from 98.6% for IgM to 99.8% for total antibodies). Subgroup analyses suggested small differences in sensitivity and specificity by test technology however heterogeneity in study results, timing of sample collection, and smaller sample numbers in some groups made comparisons difficult. For IgG, CLIAs were the most sensitive (convalescent-phase infection) and specific (pre-pandemic samples) compared to both ELISAs and LFAs (P < 0.001 for differences across test methods). The antigen(s) used (whether from the Spike-protein or nucleocapsid) appeared to have some effect on average sensitivity in the first weeks after onset but there was no clear evidence of an effect during convalescent-phase infection. Investigations of test performance by brand showed considerable variation in sensitivity between tests, and in results between studies evaluating the same test. For tests that were evaluated in 200 or more samples, the lower bound of the 95% CI for sensitivity was 90% or more for only a small number of tests (IgG, n = 5; IgG or IgM, n = 1; total antibodies, n = 4). More test brands met the MHRA minimum criteria for specificity of 98% or above (IgG, n = 16; IgG or IgM, n = 5; total antibodies, n = 7). Seven assays met the specified criteria for both sensitivity and specificity. In a low-prevalence (2%) setting, where antibody testing is used to diagnose COVID-19 in people with symptoms but who have had a negative PCR test, we would anticipate that 1 (1 to 2) case would be missed and 8 (5 to 15) would be falsely positive in 1000 people undergoing IgG or IgM testing in week three after onset of SARS-CoV-2 infection. In a seroprevalence survey, where prevalence of prior infection is 50%, we would anticipate that 51 (46 to 58) cases would be missed and 6 (5 to 7) would be falsely positive in 1000 people having IgG tests during the convalescent phase (21 to 100 days post-symptom onset or post-positive PCR) of SARS-CoV-2 infection., Authors' Conclusions: Some antibody tests could be a useful diagnostic tool for those in whom molecular- or antigen-based tests have failed to detect the SARS-CoV-2 virus, including in those with ongoing symptoms of acute infection (from week three onwards) or those presenting with post-acute sequelae of COVID-19. However, antibody tests have an increasing likelihood of detecting an immune response to infection as time since onset of infection progresses and have demonstrated adequate performance for detection of prior infection for sero-epidemiological purposes. The applicability of results for detection of vaccination-induced antibodies is uncertain., (Copyright © 2022 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Background: Good patient adherence to antiretroviral (ART) medication determines effective HIV viral suppression, and thus reduces the risk of progression and transmission of HIV. With accurate methods to monitor treatment adherence, we could use simple triage to target adherence support interventions that could help in the community or at health centres in resource-limited settings., Objectives: To determine the accuracy of simple measures of ART adherence (including patient self-report, tablet counts, pharmacy records, electronic monitoring, or composite methods) for detecting non-suppressed viral load in people living with HIV and receiving ART treatment., Search Methods: The Cochrane Infectious Diseases Group Information Specialists searched CENTRAL, MEDLINE, Embase, LILACS, CINAHL, African-Wide information, and Web of Science up to 22 April 2021. They also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing studies. No restrictions were placed on the language or date of publication when searching the electronic databases., Selection Criteria: We included studies of all designs that evaluated a simple measure of adherence (index test) such as self-report, tablet counts, pharmacy records or secondary database analysis, or both, electronic monitoring or composite measures of any of those tests, in people living with HIV and receiving ART treatment. We used a viral load assay with a limit of detection ranging from 10 copies/mL to 400 copies/mL as the reference standard. We created 2 × 2 tables to calculate sensitivity and specificity., Data Collection and Analysis: We screened studies, extracted data, and assessed risk of bias using QUADAS-2 independently and in duplicate. We assessed the certainty of evidence using the GRADE method. The results of estimated sensitivity and specificity were presented using paired forest plots and tabulated summaries. We encountered a high level of variation among studies which precluded a meaningful meta-analysis or comparison of adherence measures. We explored heterogeneity using pre-defined subgroup analysis., Main Results: We included 51 studies involving children and adults with HIV, mostly living in low- and middle-income settings, conducted between 2003 and 2021. Several studies assessed more than one index test, and the most common measure of adherence to ART was self-report. - Self-report questionnaires (25 studies, 9211 participants; very low-certainty): sensitivity ranged from 10% to 85% and specificity ranged from 10% to 99%. - Self-report using a visual analogue scale (VAS) (11 studies, 4235 participants; very low-certainty): sensitivity ranged from 0% to 58% and specificity ranged from 55% to 100%. - Tablet counts (12 studies, 3466 participants; very low-certainty): sensitivity ranged from 0% to 100% and specificity ranged from 5% to 99%. - Electronic monitoring devices (3 studies, 186 participants; very low-certainty): sensitivity ranged from 60% to 88% and the specificity ranged from 27% to 67%. - Pharmacy records or secondary databases (6 studies, 2254 participants; very low-certainty): sensitivity ranged from 17% to 88% and the specificity ranged from 9% to 95%. - Composite measures (9 studies, 1513 participants; very low-certainty): sensitivity ranged from 10% to 100% and specificity ranged from 49% to 100%. Across all included studies, the ability of adherence measures to detect viral non-suppression showed a large variation in both sensitivity and specificity that could not be explained by subgroup analysis. We assessed the overall certainty of the evidence as very low due to risk of bias, indirectness, inconsistency, and imprecision. The risk of bias and the applicability concerns for patient selection, index test, and reference standard domains were generally low or unclear due to unclear reporting. The main methodological issues identified were related to flow and timing due to high numbers of missing data. For all index tests, we assessed the certainty of the evidence as very low due to limitations in the design and conduct of the studies, applicability concerns and inconsistency of results., Authors' Conclusions: We encountered high variability for all index tests, and the overall certainty of evidence in all areas was very low. No measure consistently offered either a sufficiently high sensitivity or specificity to detect viral non-suppression. These concerns limit their value in triaging patients for viral load monitoring or enhanced adherence support interventions., (Copyright © 2022 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Objectives: To explore obstetricians', midwives' and trainees' perceptions of caesarean section (CS) determinants in the context of public obstetric care services provision in Argentina. Our hypothesis is that known determinants of CS use may differ in settings with limited access to essential obstetric services., Setting: We conducted a formative research study in 19 public maternity hospitals in Argentina. An institutional survey assessed the availability of essential obstetric services. Subsequently, we conducted online surveys and semistructured interviews to assess the opinions of providers on known CS determinants., Results: Obstetric services showed an adequate provision of emergency obstetric care but limited services to support women during birth. Midwives, with some exceptions, are not involved during labour. We received 680 surveys from obstetricians, residents and midwives (response rate of 63%) and interviewed 26 key informants. Six out of 10 providers (411, 61%) indicated that the use of CS is associated with the complexities of our caseload . Limited pain management access was deemed a potential contributing factor for CS in adolescents and first-time mothers. Providers have conflicting views on the adequacy of training to deal with complex or prolonged labour. Obstetricians with more than 10 years of clinical experience indicated that fear of litigation was also associated with CS. Overall, there is consensus on the need to implement interventions to reduce unnecessary CS., Conclusions: Public maternity hospitals in Argentina have made significant improvements in the provision of emergency services. The environment of service provision does not seem to facilitate the physiological process of vaginal birth. Providers acknowledged some of these challenges., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Interleukin 6 (IL-6) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19). Their immunosuppressive effect might be valuable in patients with COVID-19 characterised by substantial immune system dysfunction by controlling inflammation and promoting disease tolerance., Objectives: To assess the effect of IL-6 blocking agents compared to standard care alone or with placebo on efficacy and safety outcomes in COVID-19. We will update this assessment regularly., Search Methods: We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (up to 11 February 2021) and the L-OVE platform, and Cochrane COVID-19 Study Register to identify trials up to 26 February 2021., Selection Criteria: We included randomised controlled trials (RCTs) evaluating IL-6 blocking agents compared with standard care alone or with placebo for people with COVID-19, regardless of disease severity., Data Collection and Analysis: We followed standard Cochrane methodology. The protocol was amended to reduce the number of outcomes considered. Two review authors independently collected data and assessed the risk of bias with the Cochrane Risk of Bias 2 tool. We rated the certainty of evidence with the GRADE approach for the critical outcomes such as clinical improvement (defined as hospital discharge or improvement on the scale used by trialists to evaluate clinical progression or recovery) (day (D) 28 / ≥ D60); WHO Clinical Progression Score of level 7 or above (i.e. the proportion of participants with mechanical ventilation +/- additional organ support OR death) (D28 / ≥ D60); all-cause mortality (D28 / ≥ D60); incidence of any adverse events; and incidence of serious adverse events., Main Results: We identified 10 RCTs with available data including one platform trial comparing tocilizumab and sarilumab with standard of care. These trials evaluated tocilizumab (nine RCTs including two platform trials; seven were reported as peer-reviewed articles, two as preprints; 6428 randomised participants); and two sarilumab (one platform trial reported as peer reviewed article, one reported as preprint, 880 randomised participants). All trials included were multicentre trials. They were conducted in Brazil, China, France, Italy, UK, USA, and four were multi-country trials. The mean age range of participants ranged from 56 to 65 years; 4572 (66.3%) of trial participants were male. Disease severity ranged from mild to critical disease. The reported proportion of participants on oxygen at baseline but not intubated varied from 56% to 100% where reported. Five trials reported the inclusion of intubated patients at baseline. We identified a further 20 registered RCTs of tocilizumab compared to placebo/standard care (five completed without available results, five terminated without available results, eight ongoing, two not recruiting); 11 RCTs of sarilumab (two completed without results, three terminated without available results, six ongoing); six RCTs of clazakisumab (five ongoing, one not recruiting); two RCTs of olokizumab (one completed, one not recruiting); one of siltuximab (ongoing) and one RCT of levilimab (completed without available results). Of note, three were cancelled (2 tocilizumab, 1 clazakisumab). One multiple-arm RCT evaluated both tocilizumab and sarilumab compared to standard of care, one three-arm RCT evaluated tocilizumab and siltuximab compared to standard of care and consequently they appear in each respective comparison. Tocilizumab versus standard care alone or with placebo a. Effectiveness of tocilizumab for patients with COVID-19 Tocilizumab probably results in little or no increase in the outcome of clinical improvement at D28 (RR 1.06, 95% CI 1.00 to 1.13; I 2 = 40.9%; 7 RCTs, 5585 participants; absolute effect: 31 more with clinical improvement per 1000 (from 0 fewer to 67 more); moderate-certainty evidence). However, we cannot exclude that some subgroups of patients could benefit from the treatment. We did not obtain data for longer-term follow-up (≥ D60). The effect of tocilizumab on the proportion of participants with a WHO Clinical Progression Score of level of 7 or above is uncertain at D28 (RR 0.99, 95% CI 0.56 to 1.74; I 2 = 64.4%; 3 RCTs, 712 participants; low-certainty evidence). We did not obtain data for longer-term follow-up (≥ D60). Tocilizumab reduces all-cause mortality at D28 compared to standard care alone or placebo (RR 0.89, 95% CI 0.82 to 0.97; I 2 = 0.0%; 8 RCTs, 6363 participants; absolute effect: 32 fewer deaths per 1000 (from 52 fewer to 9 fewer); high-certainty evidence). The evidence suggests uncertainty around the effect on mortality at ≥ D60 (RR 0.86, 95% CI 0.53 to 1.40; I 2 = 0.0%; 2 RCTs, 519 participants; low-certainty evidence). b. Safety of tocilizumab for patients with COVID-19 The evidence is very uncertain about the effect of tocilizumab on adverse events (RR 1.23, 95% CI 0.87 to 1.72; I 2 = 86.4%; 7 RCTs, 1534 participants; very low-certainty evidence). Nevertheless, tocilizumab probably results in slightly fewer serious adverse events than standard care alone or placebo (RR 0.89, 95% CI 0.75 to 1.06; I 2 = 0.0%; 8 RCTs, 2312 participants; moderate-certainty evidence). Sarilumab versus standard care alone or with placebo The evidence is uncertain about the effect of sarilumab on all-cause mortality at D28 (RR 0.77, 95% CI 0.43 to 1.36; 2 RCTs, 880 participants; low certainty), on all-cause mortality at ≥ D60 (RR 1.00, 95% CI 0.50 to 2.0; 1 RCT, 420 participants; low certainty), and serious adverse events (RR 1.17, 95% CI 0.77 to 1.77; 2 RCTs, 880 participants; low certainty). It is unlikely that sarilumab results in an important increase of adverse events (RR 1.05, 95% CI 0.88 to 1.25; 1 RCT, 420 participants; moderate certainty). However, an increase cannot be excluded No data were available for other critical outcomes., Authors' Conclusions: On average, tocilizumab reduces all-cause mortality at D28 compared to standard care alone or placebo and probably results in slightly fewer serious adverse events than standard care alone or placebo. Nevertheless, tocilizumab probably results in little or no increase in the outcome clinical improvement (defined as hospital discharge or improvement measured by trialist-defined scales) at D28. The impact of tocilizumab on other outcomes is uncertain or very uncertain. With the data available, we were not able to explore heterogeneity. Individual patient data meta-analyses are needed to be able to identify which patients are more likely to benefit from this treatment. Evidence for an effect of sarilumab is uncertain and evidence for other anti-IL6 agents is unavailable. Thirty-nine RCTs of IL-6 blocking agents with no results are currently registered, of which nine are completed and seven trials were terminated with no results available. The findings of this review will be updated as new data are made available on the COVID-NMA platform (covid-nma.com)., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction: Community-acquired methicillinresistant Staphylococcus aureus (CA-MRSA) infections have increased in recent years. CAMRSA necrotizing pneumonia and empyema are now more common in children., Objectives: To determine the prevalence of CA-MRSA pneumonia and its clinical and epidemiological characteristics compared to Streptococcus pneumoniae (SP) pneumonia in the same population., Material and Methods: Descriptive, observational, cross-sectional study of patients hospitalized due to CA-MRSA pneumonia at Hospital de Niños Víctor J. Vilela (period: January 2008-December 2017)., Results: Out of 54 Staphylococcus aureus pneumonia cases, 46 (85 %) corresponded to CA-MRSA. The rate of CA-MRSA pneumonia ranged from 4.9/10 000 (2008) to 10/10 000 hospital discharges (2017). Sepsis/septic shock was observed in 41 %; empyema, in 96 %; pneumothorax, in 35 %; 90 % of cases required pleural drainage and 55 %, surgical debridement. Also, 65 % of patients were admitted to the intensive care unit (ICU); half of them required assisted mechanical ventilation. Two patients died. Strain resistance: 17 %, gentamicin; 13 %, erythromycin; and 11 %, clindamycin. Compared to SP pneumonia, CAMRSA pneumonia showed a higher risk for sepsis (95 % confidence interval; relative risk: 7.38; 3.32- 16.38) and admission to the ICU (RR: 4.29; 2.70- 6.83). No patient died due to SP pneumonia., Conclusions: The prevalence of CA-MRSA pneumonia doubled in the past decade. Compared to SP pneumonia, CA-MRSA pneumonia was more commonly accompanied by sepsis and septic shock, admission to the ICU, and ventilatory support requirement., Competing Interests: None, (Sociedad Argentina de Pediatría.)

Background: While cesarean section is an essential life-saving strategy for women and newborns, its current overuse constitutes a global problem. The aim of this formative research is to collect information from hospitals, health professionals and women regarding the use of cesarean section in Argentina. This article describes the methodology of the study, the characteristics of the hospitals and the profile of the participants., Methods: This formative research is a mixed-method study that will be conducted in seven provinces of Argentina. The eligibility criteria for the hospitals are (a) use of the Perinatal Information System, (b) cesarean section rate higher than 27% in 2016, (c) ≥ 1000 deliveries per year. Quantitative and qualitative research techniques will be used for data collection and analysis. The main inquiry points are the determining factors for the use of cesarean section, the potential interventions to optimize the use of cesarean section and, in the case of women, their preferred type of delivery., Discussion: It is expected that the findings will provide a situation diagnosis to help a context-sensitive implementation of the interventions recommended by the World Health Organization to optimize cesarean section use. Trial registration IS002316 Cesarean section is an essential medical tool for mothers and their children, but nowadays its overuse is a problem worldwide. Our purpose is to get information from hospitals, health professionals and women about how cesarean section is used in Argentina. In this protocol we describe how we will carry out the study and the characteristics of the hospitals and participants. We will implement this study in seven provinces of Argentina, in hospitals that have more than 1,000 births each year, had a cesarean section rate higher than 27% in 2016 and use the Perinatal Information System. We will gather information using forms, surveys and interviews. We want to identify the factors that decide the use of a cesarean section, the potential interventions that can improve the use of cesarean section and, in the case of women, the type of delivery they prefer. We expect that this study will give us a diagnosis of how cesarean section is used in Argentina, and that this will help to apply the interventions that the World Health Organization recommends to optimize the use of cesarean section in our specific context.

Background: Perineal pain is a common but poorly studied adverse outcome following childbirth. Pain may result from perineal trauma due to bruising, spontaneous tears, surgical incisions (episiotomies), or in association with operative vaginal births (ventouse or forceps-assisted births). This is an update of a review last published in 2013., Objectives: To determine the efficacy of a single administration of paracetamol (acetaminophen) used in the relief of acute postpartum perineal pain., Search Methods: For this update, we searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (9 December 2019), and reference lists of retrieved studies., Selection Criteria: Randomised controlled trials (RCTs), including cluster-RCTs, comparing paracetamol to placebo. We excluded quasi-RCTs and cross-over trials. Data from abstracts would be included only if authors had confirmed in writing that the data to be included in the review had come from the final analysis and would not change., Data Collection and Analysis: Two review authors assessed each study for inclusion and extracted data. One review author reviewed the decisions and confirmed calculations for pain relief scores. We assessed the certainty of the evidence using the GRADE approach., Main Results: This update identified no new trials so the results remain unchanged. However, by applying the GRADE assessment of the evidence, the interpretation of main results differed from previous version of this review. We identified 10 studies involving 2044 women, but all these studies involved either three or four groups, looking at differing drugs or doses. We have only included the 1301 women who were in the paracetamol versus placebo arms of the studies. Of these, five studies (482 women) assessed 500 mg to 650 mg and six studies (797 women) assessed 1000 mg of paracetamol. One study assessed 650 mg and 1000 mg compared with placebo and contributed to both comparisons. We used a random-effects meta-analysis because of the clinical variability among studies. Studies were from the 1970s to the early 1990s, and there was insufficient information to assess the risk of bias adequately, hence the findings need to be interpreted within this context. The certainty of the evidence for the two primary outcomes on which data were available was assessed as low, downgraded for overall unclear risk of bias and for heterogeneity (I² statistic 60% or greater). More women may experience pain relief with paracetamol compared with placebo (average risk ratio (RR) 2.14, 95% confidence interval (CI) 1.59 to 2.89; 10 trials, 1279 women), and fewer women may need additional pain relief with paracetamol compared with placebo (average RR 0.34, 95% CI 0.21 to 0.55; 8 trials, 1132 women). However, the certainty of the evidence was low, downgraded for unclear overall risk of bias and substantial heterogeneity. One study used the higher dose of paracetamol (1000 mg) and reported maternal drug adverse effects. There may be little or no difference in the incidence of nausea (average RR 0.18, 95% CI 0.01 to 3.66; 1 trial, 232 women; low-certainty evidence), or sleepiness (average RR 0.89, 95% CI 0.18 to 4.30; 1 trial, 232 women; low-certainty evidence). No other maternal adverse events were reported. None of the studies assessed neonatal drug adverse effects., Authors' Conclusions: A single dose of paracetamol may improve perineal pain relief following vaginal birth, and may reduce the need for additional pain relief. Potential adverse effects for both women and neonates were not appropriately assessed. Any further trials should also address the gaps in evidence concerning maternal outcomes such as satisfaction with postnatal care, maternal functioning/well-being (emotional attachment, self-efficacy, competence, autonomy, confidence, self-care, coping skills) and neonatal drug adverse effects., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Aim: It is of critical importance to have internationally constructed tools to address early childhood development. The aim of this second phase of a two-phase study was to examine the sensitivity and specificity of the Guide for Monitoring Child Development (GMCD) in identifying developmental delay in four diverse countries., Methods: The first phase of this 2011-2015 back-to-back study included 4949 children up to 42 months of age from primary healthcare centres in Argentina, India, South Africa and Turkey. Distribution curves were generated to show the ages when the children attained GMCD milestones and those that could be used across sexes and countries were placed in age ranges corresponding to the 85th and 97th percentile point estimates. Phase two examined a separately recruited sample of children in those countries to determine sensitivity and specificity of the GMCD., Results: The validation phase of the 85 milestones in the GMCD identified delayed development in 30% of the 1731 children in the four countries. The sensitivity and specificity ranged from 0.71-0.94 and 0.69-0.82, respectively, for the total sample and the different age groups., Conclusion: The GMCD standardised in four diverse countries has appropriate accuracy for identification of children with developmental delay., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: To determine the course of serological tests in subjects with chronic Trypanosoma cruzi infection treated with anti-trypanosomal drugs., Methods: A systematic review and meta-analysis was conducted using individual participant data. Survival analysis and the Cox proportional hazards regression model with random effects to adjust for covariates were applied. The protocol was registered in the PROSPERO database (http://www.crd.york.ac.uk/PROSPERO; CRD42012002162)., Results: A total of 27 studies (1296 subjects) conducted in eight countries were included. The risk of bias was low for all domains in 17 studies (63.0%). Nine hundred and thirteen subjects were assessed (149 seroreversion events, 83.7% censored data) for enzyme-linked immunosorbent assay (ELISA), 670 subjects (134 events, 80.0% censored) for indirect immunofluorescence assay (IIF), and 548 subjects (99 events, 82.0% censored) for indirect hemagglutination assay (IHA). A higher probability of seroreversion was observed within a shorter time span in subjects aged 1-19 years compared to adults. The chance of seroreversion also varied according to the country where the infection might have been acquired. For instance, the pooled adjusted hazard ratio between children/adolescents and adults for the IIF test was 1.54 (95% confidence interval 0.64-3.71) for certain countries of South America (Argentina, Bolivia, Chile, and Paraguay) and 9.37 (95% confidence interval 3.44-25.50) for Brazil., Conclusions: The disappearance of anti-T. cruzi antibodies was demonstrated along the course of follow-up. An interaction between age at treatment and country setting was found., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are a common reason for consultation in pediatrics. Most of them present as skin and soft tissue infections; however, invasive infections have increased during the last decade., Objectives: The main objective was to describe the clinical-epidemiological characteristics of CA-MRSA infections. The secondary objective was to compare prevalence, clinical presentation and antibiotic susceptibility with a pre-study period (1/2004-12/2007)., Material and Methods: This is a descriptive, prospective, cross-sectional study. Inclusion criteria: children who have been diagnosed with CA-MRSA infection and admitted to Hospital de Niños de Rosario between January 2008 and December 2014. Exclusion criteria: recent hospitalization, previous antibiotic treatment or surgery, comorbidities or immune compromise., Results: Out of 728 cases of children with Staphylococcus aureus infections, 529 (73%) were due to CA-MRSA. The incidence rate of CA-MRSA infections varied from 12.2/10 000 hospital discharges in 2004 to 145/10 000 in 2014: 75% (391) were skin and soft tissue infections; 8% (43) were osteoarticular infections; 6% (30), pleuropulmonary infections; 5% (24), sepsis. There was an increase in the number of invasive infections in the second period, with no statistical significance (OR= 0.895; CI: 0.52-1.53). Gentamicin, clindamycin and erythromycin resistance remained stable throughout both periods., Conclusion: CA-MRSA infections were increasingly more frequent, mainly skin and soft tissue infections. An increase was observed in the number of invasive infections, with no statistical significance. Antibiotic resistance remained stable., (Sociedad Argentina de Pediatría.)

Background: Knowledge about typical development is of fundamental importance for understanding and promoting child health and development. We aimed to ascertain when healthy children in four culturally and linguistically different countries attain developmental milestones and to identify similarities and differences across sexes and countries., Methods: In this cross-sectional, observational study, we recruited children aged 0-42 months and their caregivers between March 3, 2011, and May 18, 2015, at 22 health clinics in Argentina, India, South Africa, and Turkey. We obtained a healthy subsample, which excluded children with a low birthweight, perinatal complications, chronic illness, undernutrition, or anaemia, and children with missing health data. Using the Guide for Monitoring Child Development, caregivers described their child's development in seven domains: expressive and receptive language, gross and fine motor, play, relating, and self-help. Clinicians examining the children also completed a checklist about the child's health status. We used logit and probit regression models based on the lowest deviance information criterion to generate Bayesian point estimates and 95% credible intervals for the 50th percentile ages of attainment of 106 milestones. We assessed the significance of differences between sexes and countries using predefined criteria and regions of practical equivalence., Findings: Of 10 246 children recruited, 4949 children (48·3%) were included in the healthy subsample. For the 106 milestones assessed, the median age of attainment was equivalent for 102 (96%) milestones across sexes and 81 (76%) milestones across the four countries. Across countries, median ages of attainment were equivalent for all play milestones, 20 (77%) of 26 expressive language milestones, ten (67%) of 15 receptive language milestones, nine (82%) of 11 fine motor milestones, 14 (88%) of 16 gross motor milestones, and eight (73%) of 11 relating milestones. However, across the four countries the median age of attainment was equivalent for only two (22%) of nine milestones in the self-help domain., Interpretation: The ages of attainment of developmental milestones in healthy children, and the similarities and differences across sexes and country samples might aid the development of international tools to guide policy, service delivery, and intervention research, particularly in low-income and middle-income countries., Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Iron deficiency anemia is common in low- and middle-income countries. According to the evidence, the impact of ferrous sulfate supplementation in the pediatric population is low. Our objective was to analyze the perspective of pediatricians regarding anemia and iron supplementation., Population and Methods: Qualitative, exploratory study. Semi-structured interviews were conducted with primary health care pediatricians from Rosario. Three core inquiry concepts were included: importance of this problem, clinical practice, and representations about iron supplementation. The analysis consisted in the systematization of the information collected by transcribing the recorded interviews and notes., Results: A total of 32 interviews were conducted. All interviewees considered anemia was a relevant problem. At present, anemia is associated with a poor-quality diet. Based on the findings, pediatric practice follows national standards. There is consensus that low adherence is a barrier for the clinical management of iron deficiency anemia. Pediatricians described concepts that are potentially beneficial for the local setting, including workshops on anemia and free provision of more flavorful iron supplements., Conclusions: Iron deficiency anemia was considered a severe problem. In the primary health care setting, outstanding interventions included workshops and access to more flavorful iron supplements., (Sociedad Argentina de Pediatría)

Background: Chagas disease is caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi). It is endemic in Latin American countries outside the Caribbean. The current criterion for cure in the chronic phase of the disease is the negativization of at least two serological tests such as enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IIF) and indirect hemagglutination assay (IHA). The serological evolution of treated subjects with chronic T. cruzi infection is variable. Treatment failure is indicated by a positive parasitological and/or molecular test (persistence of parasitemia)., Objectives: To summarize the pattern of response to treatment of parasitological, molecular and serological tests performed during the follow-up of subjects with chronic T. cruzi infection., Methods: Electronic searches in relevant databases and screening of citations of potentially eligible articles were accomplished. Organizations focusing on neglected infectious diseases were asked for help in identifying relevant studies. Included studies were randomized controlled trials (RCTs), quasi-RCTs, and cohort studies involving adults and children with chronic infection who received trypanocidal treatment (benznidazole or nifurtimox) and were followed over time. The assessment of risk of bias was performed separately for each study design. The Cochrane Collaboration's tool and the guidelines developed by Hayden et al. were used. Two reviewers extracted all data independently. A third review author was consulted in case of discordant opinion. Additional analyses were defined in ad-hoc basis. Scatter plots for percentage of positive parasitological and molecular tests and for negative serological tests were developed by using the lowess curve technique. Heterogeneity was measured by I2. The protocol was registered in PROSPERO, an international prospective register of systematic review protocols (Registration Number CRD42012002162)., Results: Out of 2,136 citations screened, 54 studies (six RCTs and 48 cohort studies) were included. The smoothed curves for positive xenodiagnosis and positive polymerase chain reaction (PCR) were characterized by a sharp decrease at twelve month posttreatment. Afterwards, they reached 10-20% and 40% for xenodiagnosis and PCR, respectively. The smoothed curves for negative conventional serological tests increased up to 10% after 48 months of treatment. In the long-term, the rate of negativization was between 20% and 45%. The main sources of bias identified across cohort studies were the lack of control for confounding and attrition bias. In general, RCTs were judged as low risk of bias in all domains. The level of heterogeneity across included studies was moderate to high. Additional analysis were incomplete because of the limited availability of data. In this regard, the country of origin of study participants might affect the results of parasitological and molecular tests, while the level of risk of bias might affect serological outcomes. Subgroup analysis suggested that seronegativization occurs earlier in children compared to adults., Conclusions: We acknowledge that there is a dynamic pattern of response based on parasitological, molecular and serological tests in subjects chronically infected with T. cruzi after treatment. Our findings suggest a trypanocidal effect in the long-term follow-up. Further research is needed to explore potential sources of heterogeneity and to conduct reliable subgroup analysis.

Introduction: Medicinal iron supplementation is a free and widely used intervention to prevent and treat childhood anemia., Objectives: To determine the prevalence of anemia in a sample of children from Rosario, to describe the use of iron supplements in children included in the studied sample, and to illustrate variables potentially related to mothers' adherence to oral iron administration., Population and Methods: A cross-sectional study involving mothers and infants younger than 42 months old assisted by the public health network of Rosario from December 2011 to April 2012 was conducted. Sociodemographic variables and data on children's health, growth, anemia, and iron administration were collected. A rapid test was used to determine hemoglobin level., Results: A total of 325 mother-infant dyads were included. The overall prevalence of anemia was 40% (95% CI: 35-45%), and it increased up to 56% in the 6-23 month old group. Fifty-one percent of mothers reported that their children had at some time received iron. Mothers' adherence to oral iron administration was higher in the group of children without anemia in comparison to those with anemia (OR: 0.28; 95% CI: 0.1-0.69). The most common causes for lack of adherence included gastrointestinal intolerance (38%) and forgetfulness (36%)., Conclusions: Prevalence of childhood anemia in the studied sample was high. A lower mothers' adherence to iron administration was observed in the group of children with anemia.

Background: Supplementary feeding is defined as the provision of extra food to children or families beyond the normal ration of their home diets. The impact of food supplementation on child growth merits careful evaluation in view of the reliance of many states and non-governmental organisations on this intervention to improve child health in low and middle income countries (LMIC). This is an update of a Cochrane review first published in 2005., Objectives: To evaluate the effectiveness of community-based supplementary feeding for promoting the physical growth of children under five years of age in LMIC., Search Methods: For this updated review  we searched the following databases on 31 January 2011: CENTRAL (The Cochrane Library), MEDLINE (1948 to January week 3, 2011), EMBASE (1980 to week 3, 2011), CINAHL (1937 to 27 January 2011), LILACS (all years), WorldCat for dissertations and theses (all years) and ClinicalTrials.gov (all years)., Selection Criteria: Randomised controlled trials (RCTs) evaluating supplementary feeding in comparison to a control group (no intervention or a placebo such as food with a very low number of nutrients and calories) in children from birth to five years of age in LMIC., Data Collection and Analysis: Two review authors independently extracted and analysed the data., Main Results: We included eight RCTs (n = 1243 children) that were at relatively high risk of bias. We found high levels of clinical heterogeneity in the participants, interventions and outcome measures across studies. Nevertheless, in order to quantify pooled effects of supplementary feeding, we decided to combine studies according to prespecified characteristics. These were the children's age (younger or older than 24 months), their nutritional status at baseline (stunted or wasted, or not stunted or wasted) and the duration of the intervention (less or more than 12 months). A statistically significant difference of effect was only found for length during the intervention in children aged less than 12 months (two studies; 795 children; mean difference 0.19 cm; 95% confidence interval (CI) 0.07 to 0.31). Based on the summary statistic calculated for each study, the mean difference (MD) between intervention and control groups ranged from 0.48 cm (95% CI 0.07 to 0.89) to 1.3 cm (95% CI 0.03 to 2.57) after 3 and 12 months of intervention, respectively. Data on potential adverse effects were lacking., Authors' Conclusions: The scarcity of available studies and their heterogeneity makes it difficult to reach any firm conclusions. The review findings suggest supplementary feeding has a negligible impact on child growth; however, the pooled results should be interpreted with great caution because the studies included in the review are clinically diverse. Future studies should address issues of research design, including sample size calculation, to detect meaningful clinical effects and adequate intervention allocation concealment. In the meantime, families and children in need should be provided appropriate feeding, health care and sanitation without waiting for new RCTs to establish a research basis for feeding children.

Introduction: The field testing of the preliminary WHO child growth standards was conducted in Rosario, Argentina. The objective of the article is to analyze the anthropometrical outcomes based on the national and international growth references. POPULATION, MATERIALS AND METHODS: Descriptive, cross-sectional study. Healthy children born at term, aged 0 to 5 years, and users of the health care network of the municipality from January to May 2005 were included. A data collection form was designed for the study. The weight (kg) was measured with an electronic scale. The length/height (cm) was taken with instruments constructed locally. The measurements techniques were based on national guidelines. The NUTRI 1.3: 5 and ANTHRO 2005 software were used., Results: A sample of 1.804 boys and girls was analyzed. The prevalence of underweight was 1,7 times higher in children less than 6 months with the application of the new standards compared to the national reference. For the rest of the age groups, the situation was the opposite. A major prevalence of stunting was observed after 6 months of age based on the new standards compared to the national reference. The prevalence of overweight, in comparison with the old growth international reference, increased with the use of the new standards., Conclusions: Differences in underweight, stunting and overweight were found based on the tool used. The prevalence of stunting and overweight may increase with the application of the new growth standard.

In April 2006 the WHO released a set of growth standards for children from birth to the age of 5 y. Prior to their release, the standards were field-tested in 4 countries. The main objective was to compare children's length/height-for-age and weight-for-length/height based on the new standards with clinician assessments of the same children. The study sampled children <5-y-old attending well-child clinics in 2 affluent populations (Argentina and Italy) and 2 less-affluent ones (Maldives and Pakistan). Length/height and weight were measured by doctors and epidemiologists who also recorded a clinical assessment of each child's length/height in relation to age and weight relative to length/height. Anthropometric indicators of nutritional status were generated based on the WHO standards. As expected, Pakistan and the Maldives had higher rates of stunting, wasting, and underweight than Italy and Argentina, and the reverse was true for overweight and obesity. Where stunting was prevalent, the children classified as short were a mean <-2 SD for height-for-age. In all sites, the children classified as thin were indeed wasted (<-2 SD for weight-for-height) and a positive association in trend was evident between weight-for-height and the line-up of groups from thin to obese. The overall concordance between clinical assessments and the WHO standards-based indicators attested to the clinical soundness of the standards.

Background: Supplementary feeding is defined as the provision of extra food to poor children or families beyond the normal ration of their home diets. The impact of food supplementation on child growth merits careful evaluation in view of the reliance of many states and NGOs on this intervention to improve child health in developing countries., Objectives: To evaluate the effectiveness of community-based supplementary feeding for promoting the physical growth of pre-school children in developing countries., Search Strategy: Searches of CENTRAL 2005 (Issue 2), MEDLINE 1966 to 2005, EMBASE 1980 to 2005, CINAHL 1982 to 2005, LILACS 1982 to 2005, Social Science Citation Index 1956 to 2005, and Dissertation Abstracts International (late 1960s to 2005) were conducted., Selection Criteria: Randomised controlled trials evaluating supplementary feeding in children aged 0-5 years old in developing countries., Data Collection and Analysis: Data were extracted and analysed independently by two authors., Main Results: Four trials met the inclusion criteria for this review. No meta-analysis is currently appropriate due to the clinical heterogeneity among the included studies. We group these trials into two categories: a) studies without formally assessment of malnourishment at baseline and, b) studies involving children formally assessed as malnourished.a) A cluster RCT conducted in Indonesia in 1991(20 Day Care Centres, n = 113 children), found no benefit in weight-for-age and height-for-age z-scores of the intervention group compared to the control group after three months of intervention. A study in Guatemala included four villages as unit of analysis (exact sample sizes were not provided). The length of 3-yr-old children was based on a 'before-after comparison' by village size and type of supplement. According to this analysis, the difference in net change in the large villages was 2.55 cm and in the small villages was 2.35 cm. The mean of these differences is 2.45 +- 0.10 cm (mean +- SD).b) A study conducted in Jamaica (n = 65 children) reported a positive effect on length (cm) in the supplemented group compared to controls [WMD 1.3 (0.03 to 2.57)] after 12 months of intervention. A trial from Indonesia (n = 75 children) found no benefit in growth after 12 months of supplementation., Authors' Conclusions: Based on the small number of available trials, no firm conclusions of the effectiveness of supplementary feeding to the growth of pre-school children could be drawn. Issues of research design such as blinding and sample size calculation need to be addressed in future studies.