Wolbachia-carrying Aedes mosquitoes for preventing dengue infection.

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.

Interleukin-6 blocking agents for treating COVID-19: a living systematic review.

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.

Antibody tests for identification of current and past infection with SARS-CoV-2.

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.

Accuracy of measures for antiretroviral adherence in people living with HIV.

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.

Caesarean birth in public maternities in Argentina: a formative research study on the views of obstetricians, midwives and trainees.

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.

Paracetamol/acetaminophen (single administration) for perineal pain in the early postpartum period.

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.

Interleukin-6 blocking agents for treating COVID-19: a living systematic review.

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; I2 = 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; I2 = 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; I2 = 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; I2 = 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; I2 = 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; I2 = 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).

Neumonía por Staphylococcus aureus resistente a meticilina adquirido de la comunidad en un hospital pediátrico. Nuestra experiencia de 10 años / Community-acquired methicillin-resistant Staphylococcusaureus pneumonia in a children's hospital. Our ten-year experience

Introducción. Las infecciones por Staphylococcus aureus resistente a meticilina adquirido de la comunidad (SARM-AC) se han incrementado en los últimos años. Neumonías necrotizantes y empiemas por SARM-AC son cada vez más frecuentes en niños.Objetivos. Determinar la prevalencia de neumonías por SARM-AC y sus características clínico-epidemiológicas, en comparación con las neumonías por Streptococcus pneumoniae (SP) en la misma población.Material y métodos. Estudio descriptivo, observacional, transversal, de pacientes internados con neumonía por SARM-AC en el Hospital de Niños Víctor J. Vilela (período: 1/2008-12/2017).Resultados. De 54 neumonías por Staphylococcus aureus, 46 (el 85 %) fueron SARM-AC. El índice de neumonías por SARM-AC varió de 4,9/10 000 (2008) a 10/10 000 egresos (2017). Presentaron sepsis/shock séptico el 41 %; empiema, el 96 %; neumotórax, el 35 %; requirieron drenaje pleural el 90 % y toilette quirúrgica el 55 %. Ingresaron a Terapia Intensiva el 65 %; la mitad necesitó asistencia respiratoria mecánica. Hubo dos muertes. Resistencia de las cepas: el 17 % a gentamicina, el 13 % a eritromicina, el 11 % a clindamicina. En las neumonías por SARM-AC vs. las neumonías por SP, se observó mayor riesgo de sepsis (IC 95 %; RR 7,38; 3,32-16,38) e ingreso a Terapia Intensiva (RR 4,29; 2,70-6,83). No hubo muertes por SP.Conclusiones. La prevalencia de neumonías por SARM-AC se duplicó durante la última década. Comparadas con las neumonías por SP, las neumonías por SARM-AC se acompañaron, más frecuentemente, de cuadros de sepsis y shockséptico, ingreso a Terapia Intensiva y asistencia respiratoria.

Introduction. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have increased in recent years. CA-MRSA 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, CA-MRSA 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

Optimizing the use of cesarean section in Argentina: design and methodology of a formative research for the development of interventions.

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.

RESUMEN: INTRODUCCIóN: Aun cuando la cesárea es una intervención que puede ser esencial para salvar la vida de una mujer y su hijo, el crecimiento excesivo de su uso  es un problema global. El propósito de esta investigación formativa es recolectar información sobre las instituciones, profesionales de la salud y mujeres acerca del uso de la cesárea en la Argentina. Este artículo describe la metodología del estudio, las características de los hospitales y el perfil de los participantes. METODOLOGíA: Esta investigación formativa usa un diseño mixto aplicado en siete provincias del país. Los criterios de elegibilidad para los hospitales son: (a) uso del Sistema Informático Perinatal, (b) tasa de cesáreas mayor al 27% en 2016, y (c) ≥ 1000 partos por año. Se usarán técnicas cualitativas y cuantitativas para la recolección de datos y el análisis. Los principales temas a indagar son los determinantes del uso de la cesárea, las intervenciones para optimizar su uso y, en el caso de las mujeres, sus preferencias sobre el modo de parto. DISCUSIóN: Se espera que los resultados den lugar a un diagnóstico de situación que permita una implementación de las intervenciones propuesas por la OMS para optimizar el uso de la cesárea más ajustada al contexto. Registro del estudio IS002316.

Community-acquired methicillin-resistant Staphylococcus aureus pneumonia in a children's hospital. Our ten-year experience. / Neumonía por Staphylococcus aureus resistente a meticilina adquirido de la comunidad en un hospital pediátrico. Nuestra experiencia de 10 años.

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.

Introducción. Las infecciones por Staphylococcus aureus resistente a meticilina adquirido de la comunidad (SARM-AC) se han incrementado en los últimos años. Neumonías necrotizantes y empiemas por SARM-AC son cada vez más frecuentes en niños. Objetivos. Determinar la prevalencia de neumonías por SARM-AC y sus características clínico-epidemiológicas, en comparación con las neumonías por Streptococcus pneumoniae (SP) en la misma población. Material y métodos. Estudio descriptivo, observacional, transversal, de pacientes internados con neumonía por SARM-AC en el Hospital de Niños Víctor J. Vilela (período: 1/2008-12/2017). Resultados. De 54 neumonías por Staphylococcus aureus, 46 (el 85 %) fueron SARM-AC. El índice de neumonías por SARM-AC varió de 4,9/10 000 (2008) a 10/10 000 egresos (2017). Presentaron sepsis/shock séptico el 41 %; empiema, el 96 %; neumotórax, el 35 %; requirieron drenaje pleural el 90 % y toilette quirúrgica el 55 %. Ingresaron a Terapia Intensiva el 65 %; la mitad necesitó asistencia respiratoria mecánica. Hubo dos muertes. Resistencia de las cepas: el 17 % a gentamicina, el 13 % a eritromicina, el 11 % a clindamicina. En las neumonías por SARM-AC vs. las neumonías por SP, se observó mayor riesgo de sepsis (IC 95 %; RR 7,38; 3,32-16,38) e ingreso a Terapia Intensiva (RR 4,29; 2,70-6,83). No hubo muertes por SP. Conclusiones. La prevalencia de neumonías por SARM-AC se duplicó durante la última década. Comparadas con las neumonías por SP, las neumonías por SARM-AC se acompañaron, más frecuentemente, de cuadros de sepsis y shock séptico, ingreso a Terapia Intensiva y asistencia respiratoria.

Pandemia pro COVID-19 e infodema: retos y oportunidades para la síntesis confiable y actualizada del conocimiento / COVID-19 pandemic and infodemic: challenges and opportunities for reliable and updated synthesis of knowledge

En paralelo a la pandemia por el nuevo coronavirus (SARS-CoV-2) que causa la enfermedad por coronavirus (COVID-19), emerge otra epidemia denominada infodemia. Esto provoca una saturación y sobreexposición a información de calidad variable y dificulta el acceso a la información confiable por el personal de salud y otros tomadores de decisión. A su vez, existen diversas formas de síntesis de información; entre las más conocidas se encuentran las revisiones sistemáticas, que pueden asistir a los tomadores de decisiones en la formulación de políticas y cuidados basados en la evidencia. En este artículo, se resumen algunas de las limitaciones en las revisiones sistemáticas actuales y los retos que acarrean las nuevas metodologías para la síntesis de la evidencia. Cochrane y otras organizaciones han liderado la innovación metodológica para favorecer el acceso y uso de la síntesis de información en COVID-19. Aparecen en escena las revisiones sistemáticas rápidas para dar respuesta a preguntas de prioridad alta en los diferentes países, se crea un repositorio de ensayos clínicos sobre COVID-19 y se pone en marcha un protocolo a nivel internacional para conducir un metaanálisis en red vivo sobre la efectividad de las intervenciones terapéuticas y de prevención en pacientes infectados por SARS-CoV-2. A nivel regional, se destacan la base de datos COVID-19 de la Organización Panamericana de la Salud y el registro de estudios primarios y revisiones sistemáticas de libre acceso (plataforma Living OVerview of the Evidence, L·OVE).

Validation of the International Guide for Monitoring Child Development demonstrates good sensitivity and specificity in four diverse countries.

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.

Course of serological tests in treated subjects with chronic Trypanosoma cruzi infection: A systematic review and meta-analysis of individual participant data.

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.

Infecciones por Staphylococcus aureus meticilino resistente adquirido en la comunidad: experiencia de 10 años en un hospital pediátrico de Rosario, Argentina / Community-acquired methicillin-resistant Staphylococcus aureus infections: 10-years' experience in a children's hospital in the city of Rosario, Argentina

Introducción: Las infecciones por Staphylococcus aureus meticilino resistente adquirido en la comunidad (SAMR-ac) son motivo de consulta frecuente en pediatría. La mayoría se presentan como infecciones de piel y partes blandas; sin embargo, en la última década, se ha constatado un aumento de las infecciones invasivas. Objetivos: El objetivo principal es describir las características clínico-epidemiológicas de las infecciones producidas por SAMR-ac. El objetivo secundario es comparar la prevalencia, presentación clínica y susceptibilidad antibiótica con un período previo de estudio (1/2004-12/2007). Material y métodos: Estudio descriptivo, prospectivo, de tipo transversal. Criterios de inclusión: niños con diagnóstico de infección por SAMR-ac admitidos en el Hospital de Niños de Rosario, período de enero de 2008 a diciembre de 2014. Criterios de exclusión: internación reciente, antibiótico o cirugía previa, comorbilidades o inmunocompromiso. Resultados: De 728 niños con infecciones por Staphylococcus aureus, 529 (73%) fueron por SAMR-ac. La tasa de incidencia de infecciones por SAMR-ac varió de 12,2/10 000 egresos hospitalarios de 2004 a 145/10 000 del 2014: 75% (391) fueron infecciones de piel y partes blandas; 8% (43), os teo articular es; 6% (30), pleuropulmonares; 5% (24), sepsis. Se observó un aumento en el número de infecciones invasivas en el 2º período sin significancia estadística (OR= 0,895; IC: 0,52-1,53). La resistencia a gentamicina, clindamicina y eritromicina se mantuvo estable en ambos períodos. Conclusión: Las infecciones por SAMR-ac fueron cada vez más frecuentes, principalmente, las de piel y partes blandas. Se observó un aumento en el número de infecciones invasivas sin significancia estadística. La resistencia antibiótica se mantuvo estable.

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.

Community-acquired methicillin-resistant Staphylococcus aureus infections: 10-years' experience in a children's hospital in the city of Rosario, Argentina. / Infecciones por Staphylococcus aureus meticilino resistente adquirido en la comunidad: experiencia de 10 años en un hospital pediátrico de Rosario, Argentina.

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.

INTRODUCCIÓN: Las infecciones por Staphylococcus aureus meticilino resistente adquirido en la comunidad (SAMR-ac) son motivo de consulta frecuente en pediatría. La mayoría se presentan como infecciones de piel y partes blandas; sin embargo, en la última década, se ha constatado un aumento de las infecciones invasivas. OBJETIVOS: El objetivo principal es describir las características clínico-epidemiológicas de las infecciones producidas por SAMR-ac. El objetivo secundario es comparar la prevalencia, presentación clínica y susceptibilidad antibiótica con un período previo de estudio (1/2004-12/2007). MATERIAL Y MÉTODOS: Estudio descriptivo, prospectivo, de tipo transversal. Criterios de inclusión: niños con diagnóstico de infección por SAMR-ac admitidos en el Hospital de Niños de Rosario, período de enero de 2008 a diciembre de 2014. Criterios de exclusión: internación reciente, antibiótico o cirugía previa, comorbilidades o inmunocompromiso. RESULTADOS: De 728 niños con infecciones por Staphylococcus aureus, 529 (73%) fueron por SAMR-ac. La tasa de incidencia de infecciones por SAMR-ac varió de 12,2/10 000 egresos hospitalarios de 2004 a 145/10 000 del 2014: 75% (391) fueron infecciones de piel y partes blandas; 8% (43), os teo articular es; 6% (30), pleuropulmonares; 5% (24), sepsis. Se observó un aumento en el número de infecciones invasivas en el 2o período sin significancia estadística (OR= 0,895; IC: 0,52-1,53). La resistencia a gentamicina, clindamicina y eritromicina se mantuvo estable en ambos períodos. CONCLUSIÓN: Las infecciones por SAMR-ac fueron cada vez más frecuentes, principalmente, las de piel y partes blandas. Se observó un aumento en el número de infecciones invasivas sin significancia estadística. La resistencia antibiótica se mantuvo estable.

Similarities and differences in child development from birth to age 3 years by sex and across four countries: a cross-sectional, observational study.

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.

La visión de médicos pediatras de atención primaria de la salud sobre la anemia infantil y el suplemento con hierro / The perspective of primary health care pediatricians regarding childhood anemia and iron supplementation

Introducción. La anemia ferropénica es más frecuente en los países de bajos y medianos ingresos. La evidencia sugiere que el impacto del suplemento con sulfato ferroso en la población infantil es bajo. Nuestro objetivo fue analizar la visión de los pediatras en torno a la problemática de la anemia y al suplemento con hierro. Población y métodos. Estudio cualitativo, exploratorio. Se realizaron entrevistas semiestructuradas a los pediatras del primer nivel de atención de Rosario. Se incluyeron tres ejes de indagación: "relevancia del problema", "práctica clínica" y "representaciones sobre el suplemento con hierro". El análisis consistió en sistematizar la información obtenida mediante la transcripción de entrevistas grabadas y anotaciones. Resultados. Se realizaron 32 entrevistas. Todos los entrevistados pensaban que la anemia era un problema relevante. Actualmente, se la asocia con una alimentación de mala calidad. Los hallazgos llevan a considerar que la práctica pediátrica sigue las normativas nacionales. Hay acuerdo en que la baja adherencia es un obstáculo para el manejo clínico de la anemia ferropénica. Los pediatras expresaron ideas potencialmente beneficiosas para el contexto local, que incluían la organización de talleres sobre anemia y la distribución gratuita de preparados con hierro de mejor sabor. Conclusiones. La anemia por déficit de hierro se consideró un problema grave. En atención primaria, las intervenciones destacadas fueron la organización de talleres y el acceso a preparados con hierro de sabor más agradable.

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.

The perspective of primary health care pediatricians regarding childhood anemia and iron supplementation. / La visión de médicos pediatras de atención primaria de la salud sobre la anemia infantil y el suplemento con hierro.

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.

INTRODUCCIÓN: La anemia ferropénica es más frecuente en los países de bajos y medianos ingresos. La evidencia sugiere que el impacto del suplemento con sulfato ferroso en la población infantil es bajo. Nuestro objetivo fue analizar la visión de los pediatras en torno a la problemática de la anemia y al suplemento con hierro. POBLACIÓN Y MÉTODOS: Estudio cualitativo, exploratorio. Se realizaron entrevistas semiestructuradas a los pediatras del primer nivel de atención de Rosario. Se incluyeron tres ejes de indagación: "relevancia del problema", "práctica clínica" y "representaciones sobre el suplemento con hierro". El análisis consistió en sistematizar la información obtenida mediante la transcripción de entrevistas grabadas y anotaciones. RESULTADOS: Se realizaron 32 entrevistas. Todos los entrevistados pensaban que la anemia era un problema relevante. Actualmente, se la asocia con una alimentación de mala calidad. Los hallazgos llevan a considerar que la práctica pediátrica sigue las normativas nacionales. Hay acuerdo en que la baja adherencia es un obstáculo para el manejo clínico de la anemia ferropénica. Los pediatras expresaron ideas potencialmente beneficiosas para el contexto local, que incluían la organización de talleres sobre anemia y la distribución gratuita de preparados con hierro de mejor sabor. CONCLUSIONES: La anemia por déficit de hierro se consideró un problema grave. En atención primaria, las intervenciones destacadas fueron la organización de talleres y el acceso a preparados con hierro de sabor más agradable.

Los estándares de crecimiento infantil de la Organización Mundial de la Salud a 10 años de su implementación en la ciudad de Rosario / The child growth standards of the World Health Organization 10 years after its implementation in the city of Rosario

INTRODUCCIÓN El control del crecimiento físico constituye un método válido para determinar el grado en que se satisfacen las necesidades básicas del niño. OBJETIVO Analizar el estado actual de implementación de los estándares de la OMS en el primer nivel de atención de Rosario. MÉTODOS Estudio descriptivo, transversal. Se realizaron encuestas en línea a médicos pediatras y generalistas de centros de atención primaria y se entrevistaron a informantes clave de la Municipalidad de Rosario. La obtención del consentimiento informado fue un requisito para participar del estudio. Los ejes de indagación fueron; valoración de las curvas OMS, actividades de capacitación y acciones para promover su uso e interpretación. Se utilizaron métodos de análisis cuantitativos y cualitativos. RESULTADOS Durante agosto-octubre 2019, se enviaron 180 encuestas en línea a médicos de la red de atención primaria (119 generalistas y 61 pediatras). Se completaron 95 encuestas y se realizaron 8 entrevistas. Los participantes consideraron que la adopción de las curvas OMS ha sido un cambio favorable, aunque menos de la mitad conocía sobre la metodología utilizada para su construcción. Además, alrededor de un tercio de los médicos encuestados refirió utilizar otras curvas. El índice de masa corporal se valoró como un indicador útil particularmente para control del sobrepeso y obesidad. Las intervenciones consideradas de mayor utilidad fueron; promoción de consejería nutricional, impresión de gráficas de crecimiento para uso individual y mantenimiento de los equipos para mediciones antropométricas. Para los entrevistados, la falta de mantenimiento de los equipos no fue visualizada como un problema. Los médicos encuestados opinaron que las intervenciones para capacitación son útiles aunque poco factibles. DISCUSIÓN Sería posible lograr un mayor aprovechamiento del uso de las curvas de crecimiento OMS a través de estrategias tendientes a favorecer la implementación de intervenciones consideradas como útiles por los médicos de la red de atención primaria