Knowledge, attitudes and perceptions of Latin American healthcare workers relating to antibiotic stewardship and antibiotic use: a cross-sectional multi-country study.

BACKGROUND: The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers' (HCWs) knowledge, attitudes, and perceptions of antimicrobial stewardship (AS), AMR, and antibiotic use (AU) in the region. METHODS: HCWs from 42 hospitals from 5 Latin American countries were invited to take an electronic, voluntary, anonymous survey regarding knowledge, attitudes, and perceptions of AS, AMR, and AU between March-April 2023. FINDINGS: Overall, 996 HCWs completed the survey (52% physicians, 32% nurses, 11% pharmacists, 3% microbiologists, and 2% "other"). More than 90% of respondents indicated optimizing AU was a priority at their healthcare facility (HCF), 69% stated the importance of AS was communicated at their HCF, and 23% were unfamiliar with the term "antibiotic stewardship". Most (> 95%) respondents acknowledged that appropriate AU can reduce AMR; however, few thought AU (< 30%) or AMR (< 50%) were a problem in their HCF. Lack of access to antibiogram and to locally endorsed guidelines was reported by 51% and 34% of HCWs, respectively. Among prescribers, 53% did not consider non-physicians' opinions to make antibiotic-related decisions, 22% reported not receiving education on how to select antibiotics based on culture results and 60% stated patients and families influence their antibiotic decisions. CONCLUSIONS: Although HCWs perceived improving AU as a priority, they did not perceive AU or AMR as a problem in their HCF. AS opportunities include improved access to guidelines, access to AMR/AU data, teamwork, and education on AS for HCWs and patients and families.

Usefulness of Electoral Models for COVID-19 Vaccine Distribution.

Purpose of Review: In response to the COVID-19 pandemic, there has been a remarkably accelerated development of vaccines worldwide. However, an effective distribution system is crucial for vaccination at a national level. Ecuador was one of the first Latin American countries to be most severely affected by the pandemic. It has been struggling to expand its vaccination drive and requires a strategy that provides an achievable vaccination rate and maintains its primary care services. This study aims to provide an efficient vaccination model to achieve herd immunity by utilizing the country's existing infrastructure (the centralized electoral system) for mass vaccination. Recent Findings: The national electoral data from 2017 and 2021 were used to create estimates for the proposed vaccination model. Two model variations, total personnel, needed, and the number of days needed to vaccinate 50%, 75%, and 100% of the population were considered. The numbers of vaccines needed, and vaccination sites were estimated based on the current number of registered voters and polling stations. The results from the proposed model show that 17,892,353 people can be vaccinated, at 40,093 polling stations, by 90,209 personnel if one vaccinator was available per polling station. Summary: Based on this model, even a conservative estimate shows that 12.56 days are needed to achieve herd immunity, and 16.74 days are needed to vaccinate the entire population of Ecuador. Additionally, we propose that this vaccination model can be used as a blueprint for any country to address similar catastrophes in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s40475-022-00251-y.

Antimicrobial stewardship programs in adult intensive care units in Latin America: Implementation, assessments, and impact on outcomes.

OBJECTIVE: To assess the impact of antimicrobial stewardship programs (ASPs) in adult medical-surgical intensive care units (MS-ICUs) in Latin America. DESIGN: Quasi-experimental prospective with continuous time series. SETTING: The study included 77 MS-ICUs in 9 Latin American countries. PATIENTS: Adult patients admitted to an MS-ICU for at least 24 hours were included in the study. METHODS: This multicenter study was conducted over 12 months. To evaluate the ASPs, representatives from all MS-ICUs performed a self-assessment survey (0-100 scale) at the beginning and end of the study. The impact of each ASP was evaluated monthly using the following measures: antimicrobial consumption, appropriateness of antimicrobial treatments, crude mortality, and multidrug-resistant microorganisms in healthcare-associated infections (MDRO-HAIs). Using final stewardship program quality self-assessment scores, MS-ICUs were stratified and compared among 3 groups: ≤25th percentile, >25th to <75th percentile, and ≥75th percentile. RESULTS: In total, 77 MS-ICU from 9 Latin American countries completed the study. Twenty MS-ICUs reached at least the 75th percentile at the end of the study in comparison with the same number who remain within the 25th percentile (score, 76.1 ± 7.5 vs 28.0 ± 7.3; P < .0001). Several indicators performed better in the MS-ICUs in the 75th versus 25th percentiles: antimicrobial consumption (143.4 vs 159.4 DDD per 100 patient days; P < .0001), adherence to clinical guidelines (92.5% vs 59.3%; P < .0001), validation of prescription by pharmacist (72.0% vs 58.0%; P < .0001), crude mortality (15.9% vs 17.7%; P < .0001), and MDRO-HAIs (9.45 vs 10.96 cases per 1,000 patient days; P = .004). CONCLUSION: MS-ICUs with more comprehensive ASPs showed significant improvement in antimicrobial utilization.

Circulating Tumor DNA Genomics Reveal Potential Mechanisms of Resistance to BRAF-Targeted Therapies in Patients with BRAF-Mutant Metastatic Non-Small Cell Lung Cancer.

PURPOSE: The limited knowledge on the molecular profile of patients with BRAF-mutant non-small cell lung cancer (NSCLC) who progress under BRAF-targeted therapies (BRAF-TT) has hampered the development of subsequent therapeutic strategies for these patients. Here, we evaluated the clinical utility of circulating tumor DNA (ctDNA)-targeted sequencing to identify canonical BRAF mutations and genomic alterations potentially related to resistance to BRAF-TT, in a large cohort of patients with BRAF-mutant NSCLC. EXPERIMENTAL DESIGN: This was a prospective study of 78 patients with advanced BRAF-mutant NSCLC, enrolled in 27 centers across France. Blood samples (n = 208) were collected from BRAF-TT-naïve patients (n = 47), patients nonprogressive under treatment (n = 115), or patients at disease progression (PD) to BRAF-TT (24/46 on BRAF monotherapy and 22/46 on BRAF/MEK combination therapy). ctDNA sequencing was performed using InVisionFirst-Lung. In silico structural modeling was used to predict the potential functional effect of the alterations found in ctDNA. RESULTS: BRAFV600E ctDNA was detected in 74% of BRAF-TT-naïve patients, where alterations in genes related with the MAPK and PI3K pathways, signal transducers, and protein kinases were identified in 29% of the samples. ctDNA positivity at the first radiographic evaluation under treatment, as well as BRAF-mutant ctDNA positivity at PD were associated with poor survival. Potential drivers of resistance to either BRAF-TT monotherapy or BRAF/MEK combination were identified in 46% of patients and these included activating mutations in effectors of the MAPK and PI3K pathways, as well as alterations in U2AF1, IDH1, and CTNNB1. CONCLUSIONS: ctDNA sequencing is clinically relevant for the detection of BRAF-activating mutations and the identification of alterations potentially related to resistance to BRAF-TT in BRAF-mutant NSCLC.

Knowledge Extraction and Improved Data Fusion for Sales Prediction in Local Agricultural Markets.

In this paper, a monitoring system of agricultural production is modeled as a Data Fusion System (data from local fairs and meteorological data). The proposal considers the particular information of sales in agricultural markets for knowledge extraction about the associations among them. This association knowledge is employed to improve predictions of sales using a spatial prediction technique, as shown with data collected from local markets of the Andean region of Ecuador. The commercial activity in these markets uses Alternative Marketing Circuits (CIALCO). This market platform establishes a direct relationship between producer and consumer prices and promotes direct commercial interaction among family groups. The problem is presented first as a general fusion problem with a network of spatially distributed heterogeneous data sources, and is then applied to the prediction of products sales based on association rules mined in available sales data. First, transactional data is used as the base to extract the best association rules between products sold in different local markets, knowledge that allows the system to gain a significant improvement in prediction accuracy in the spatial region considered.

Data Association Methodology to Improve Spatial Predictions in Alternative Marketing Circuits in Ecuador.

This work proposes a methodology that reduces the error of future estimations in commercialization based on multivariate spatial prediction techniques (cokriging) considering the products with strong associations. It is based on the Apriori algorithm to find association rules in sales of agricultural products of local markets. Results show the improvement in spatial prediction accuracy after using the best association rules.

Resistencia bacteriana de Escherichia coli uropatogénica en población nativa amerindia Kichwa de Ecuador / Bacterial resistance of uropathogenic Escherichia coli in native Kichwa Amerindian population of Ecuador

Contexto: Escherichia coli uropatógena (ECUP) se presenta como uno de los principales agentes etiológicos en infecciones del tracto urinario (ITUs) no complicadas (70-95%). El objetivo del tratamiento de ITUs no complicadas es obtener curación clínica y microbiológica. Para ello, es de particular importancia el conocimiento de las tasas de resistencia antibiótica local. Objetivo: identificar los perfiles de resistencia a antibióticos de primera línea para ITUs no complicadas en poblaciones nativas amerindias Kichwas ecuatorianas, en donde el tratamiento empírico se basa en trimetoprim/sulfametoxazol, ampicilina, y ciprofloxacina mayoritariamente. Métodos: se analizaron 335 muestras de orina procedentes de las poblaciones de Zumbahua, Colta y Guamote, en un periodo de 4 meses (febrero-mayo 2016). Las muestras fueron incubadas por 24 y 48 horas en agar Eosin Methylene Blue (EMB), para luego ser identificadas en género y especie por pruebas bioquímicas. Para determinar la susceptibilidad antibiótica, se realizó la técnica de difusión en disco de Kirby-Bauer. Para la Concentración Inhibitoria Mínima (CIM), se utilizó la técnica de microdilución en caldo (Vitek 2). El método de doble disco fue la técnica utilizada para la detección de betalactamasas de espectro extendido (BLEE). Resultados: noventa (26,9%) muestras mostraron un recuento significativo de ≥105 (ufc)/ml, compatibles con ITUs. El microorganismo identificado con mayor frecuencia fue E. coli (n=75; 83,3%). La resistencia antibiótica encontrada para los aislados de E. coli fue de 56,7% a trimetoprim/sulfametoxazol, 52,5% a ampicilina, 43.3% a ácido nalidíxico, 32.5% a ciprofloxacina, 28.3% a norfloxacina, 25% a levofloxacina, 15.85% a cefazolina, 17.5% a cefoxitina, 15% a cefuroxima, 15% a ceftazidima, cefotaxima, y ceftriaxona, 15% a cefepima, 7,5% a nitrofurantoina y 1,7% a fosfomicina. Se identificaron 7 aislados productores de betalactamasas de espectro extendido (BLEE). Conclusión: con los resultados obtenidos se recomienda no utilizar ampicilina, trimetoprim/sulfametoxazol, ni quinolonas en la zona estudiada como terapia empírica. Se sugiere instaurar tratamiento empírico con fosfomicina o nitrofurantoina para ITUs no complicadas. (AU)

Who mixes with whom among men who have sex with men? Implications for modelling the HIV epidemic in southern India.

In India, the identity of men who have sex with men (MSM) is closely related to the role taken in anal sex (insertive, receptive or both), but little is known about sexual mixing between identity groups. Both role segregation (taking only the insertive or receptive role) and the extent of assortative (within-group) mixing are known to affect HIV epidemic size in other settings and populations. This study explores how different possible mixing scenarios, consistent with behavioural data collected in Bangalore, south India, affect both the HIV epidemic, and the impact of a targeted intervention. Deterministic models describing HIV transmission between three MSM identity groups (mostly insertive Panthis/Bisexuals, mostly receptive Kothis/Hijras and versatile Double Deckers), were parameterised with behavioural data from Bangalore. We extended previous models of MSM role segregation to allow each of the identity groups to have both insertive and receptive acts, in differing ratios, in line with field data. The models were used to explore four different mixing scenarios ranging from assortative (maximising within-group mixing) to disassortative (minimising within-group mixing). A simple model was used to obtain insights into the relationship between the degree of within-group mixing, R0 and equilibrium HIV prevalence under different mixing scenarios. A more complex, extended version of the model was used to compare the predicted HIV prevalence trends and impact of an HIV intervention when fitted to data from Bangalore. With the simple model, mixing scenarios with increased amounts of assortative (within-group) mixing tended to give rise to a higher R0 and increased the likelihood that an epidemic would occur. When the complex model was fit to HIV prevalence data, large differences in the level of assortative mixing were seen between the fits identified using different mixing scenarios, but little difference was projected in future HIV prevalence trends. An oral pre-exposure prophylaxis (PrEP) intervention was modelled, targeted at the different identity groups. For intervention strategies targeting the receptive or receptive and versatile MSM together, the overall impact was very similar for different mixing patterns. However, for PrEP scenarios targeting insertive or versatile MSM alone, the overall impact varied considerably for different mixing scenarios; more impact was achieved with greater levels of disassortative mixing.

Rates and determinants of HIV-attributable mortality among rural female sex workers in Northern Karnataka, India.

Female sex workers (FSWs) have among the highest rates of HIV infection in India. However, little is known about their HIV-specific mortality rates. In total, 1561 FSWs participated in a cohort study in Karnataka. Outcome data (mortality) were available on 1559 women after 15 months of follow-up. To gather details on deaths, verbal autopsy (VA) questionnaires were administered to key informants. Two physicians reviewed the VA reports and assigned underlying causes of death. Forty-seven deaths were reported during the follow-up (overall mortality rate was 2.44 per 100 person-years), with VA data available on 45 women. Thirty-five (75.6%) of these women were known to be HIV-positive, but only 42.5% were on antiretroviral therapy (ART). Forty deaths were assessed to be HIV-related, for an HIV-attributable mortality rate of 2.11 deaths per 100 person-years. Absence of a current regular partner (incidence rate ratio: 2.79; 95% confidence interval [CI]: 1.39-5.60) and older age (1.06; 1.01-1.11) were associated with increased HIV-attributable mortality. Reported duration in sex work was not related to HIV-attributable mortality. We found a high HIV-related mortality rate among this cohort of FSWs; nearly 10 times that of national mortality rates among women of a similar age group. Older age, but not reported duration in sex work, was associated with increased mortality, and suggests HIV acquisition prior to self-reported initiation into sex work. Despite significant efforts, there remain considerable gaps in HIV prevention near or before entry into sex work, as well as access and uptake of HIV treatment among FSWs.

Pro-inflammatory cytokine production in chagasic mothers and their uninfected newborns.

The levels of IFN-gamma, TNF-alpha, IL-10, and TGF-beta1 cytokines associated with Trypanosoma cruzi during pregnancy were determined by enzyme-linked immunosorbent assay (ELISA) in serum samples from peripheral, placental, and cord blood of chronic infected mothers with detectable and undetectable parasitemia, and in their uninfected newborns. Compared to uninfected pregnant women and mothers with undetectable parasitemia, the concentrations of IFN-gamma were higher at the 3 sites in mothers with detectable parasitemia. In these mothers and their newborns, the TNF-alpha concentrations were higher in the periphery and cord in comparison to serum samples from non-chagasic pregnant women. TNF-alpha levels were higher in newborns of mothers with detectable parasitemia than in newborns of mothers with undetectable parasitemia. IL-10 and TGF-beta1 levels at the 3 sites were unchanged and diminished, respectively, in samples from infected mothers with patent parasitemia in comparison with uninfected pregnant women. Cytokine concentrations did not change significantly in all samples from mothers with undetectable parasitemia; however, the concentration of TGF-beta1 was significantly reduced in their peripheral samples but significantly higher in the placenta in comparison with uninfected mothers and mothers with detectable parasitemia, respectively. These results suggest that elevated numbers of circulating parasites in vivo elicit production of pro-inflammatory cytokines that control congenital T. cruzi infection.

Concepts and strategies for scaling up focused prevention for sex workers in India.

OBJECTIVES: To describe the concepts, strategies and field results of a project to scale up prevention programmes and services for female sex workers (FSWs) in Karnataka, India. METHODS: A strategy was developed to scale up urban sex worker interventions in 18 districts in the southern Indian state of Karnataka. Macro-level coverage objectives were defined by mapping the urban locations where FSWs operate and estimating their population size. Prevention programmes were initiated in the urban locations that contained at least 90% of the estimated urban FSW population in each district. Within each location, a micro-planning process was used by FSW peer educators and outreach workers to design local outreach and service delivery plans. RESULTS: An estimated 48 973 FSWs were distributed across 1551 locations and 6232 spots. Outreach was conducted by 1043 peer educators. Services were provided through 170 drop-in centres, 93 programme-run clinics, 110 outreach clinics and 157 referral clinics. Within the first 3 years of the programme the cumulative number of individual FSWs contacted at least once was >78 000, with monthly contact established with 81% of the in situ population; >45 000 FSWs had visited a clinic and >10 000 visited monthly. Direct and indirect condom distribution by the programme amounted to more than 30 per contacted FSW, which is estimated to meet the condom requirement. CONCLUSIONS: A strategy that involves geographically defined coverage and micro-level outreach planning can rapidly and effectively provide outreach and services to large dispersed FSW populations.

Evaluating large-scale HIV prevention interventions: study design for an integrated mathematical modelling approach.

BACKGROUND: There is an urgent need to evaluate HIV prevention interventions, thereby improving our understanding of what works, under what circumstances and what is cost effective. OBJECTIVES: To describe an integrated mathematical evaluation framework designed to assess the population-level impact of large-scale HIV interventions and applied in the context of Avahan, the Indian AIDS Initiative, in southern India. The Avahan Initiative is a large-scale HIV prevention intervention, funded by the Bill & Melinda Gates Foundation, which targets high-risk groups in selected districts of the six states most affected by the HIV/AIDS epidemic (Maharashtra, Karnataka, Tamil Nadu, Andhra Pradesh, Nagaland and Manipur) and along the national highways. METHODS: One important component of the monitoring and evaluation of Avahan relies on an integrated mathematical framework that combines empirical biological and behavioural data from different subpopulations in the intervention areas, with the use of tailor-made transmission dynamics models embedded within a Bayesian framework. RESULTS: An overview of the Avahan Initiative and the objectives of the monitoring and evaluation of the intervention is given. The rationale for choosing this evaluation design compared with other possible designs is presented, and the different components of the evaluation framework are described and its advantages and challenges are discussed, with illustrated examples. CONCLUSIONS: This is the first time such an approach has been applied on such a large scale. Lessons learnt from the CHARME project could help in the design of future evaluations of large-scale interventions in other settings, whereas the results of the evaluation will be of programmatic and public health relevance.

Enhancement of a TH1 immune response in amphotericin B-treated mucocutaneous leishmaniasis.

In an attempt to investigate the effects of treatment of human leishmaniasis, the cytokines produced by peripheral blood mononuclear cells (PBMCs) of patients with cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL) under treatment with amphotericin B were determined during the active disease from cocultures of cells and Leishmania (Viannia) braziliensis antigens. PBMC of these patients exhibited a nonsignificant marginal increased production of TNF-alpha upon antigen stimulation. However, under the same antigenic stimulus, patients with active MCL presented higher IFN-gamma production compared to patients with CL. This increased IFN-gamma production was accompanied by a drastically augmented IL-12 synthesis from cells of MCL patients. The highlighted T cell responses could be relevant for sound control measures of protozoan infections with emphasis on the combined usage of immunoenhancing agents and antiprotozoal drugs.

Formal and informal sector health providers in southern India: role in the prevention and care of sexually transmitted infections, including HIV/AIDS.

Healthcare providers (HCPs) play a central role in the provision of prevention and care services for people with sexually transmitted infections (STIs), including HIV/AIDS. However, the degree of readiness for this role through appropriate training and experience is not clear. In the case of both the urban and rural areas of the state of Karnataka, India, primary and secondary healthcare is provided by practitioners who can be categorised into three major groups: qualified allopathic physicians, qualified non-allopathic doctors (homeopathic and Ayurvedic) and registered medical practitioners. In 2002, the India-Canada Collaborative HIV/AIDS Project conducted a study in an urban area and a rural district of the state of Karnataka, collecting information from 998 care providers regarding attitudes, knowledge and practices related to STI care and HIV/AIDS care in particular. This paper analyses and compares the three different types of HCPs with respect to these parameters and discusses implications for STI/HIV/AIDS prevention and care programs.

Serum immunologic markers in multiple sclerosis patients on continuous combined therapy with beta-interferon 1a, prednisone and azathioprine.

Break-through symptoms (BTS) in multiple sclerosis (MS) patients on beta-interferon (beta-IFN) monotherapy are most frequently treated with a brief administration of steroids. Here, we report the results of monitoring serum immunologic markers recorded at three-month intervals for 1.5 years in responders to beta-INF 1a (Avonex) monotherapy (n =21) and MS patients placed on Avonex with prednisone (n =83) and Avonex, prednisone and azathioprine (AZA) (n =21) because of BTS. Compared to 23 healthy controls, patients on Avonex monotherapy and Avonex with prednisone, in individuals on Avonex, prednisone and AZA, a significant decrease in serum concentration of soluble intercellular adhesion molecule-1 (sICAM-1) (P=0.001) was established. Combined therapy with Avonex, prednisone and AZA was associated with a significant increase in the serum level of interleukin (IL)10 (P <0.001). Compared to Avonex monotherapy, combined therapy suppressed the serum level of IL12p40, antagonized elevation in the serum concentration of soluble IL2 receptor (sIL2R) and inhibited an increase in the serum soluble CD95 (sCD95) molecule. In patients studied, no significant differences in the serum level of IL18 and tumor necrosis factor-alpha (TNF-alpha) were established. These findings are important in understanding some of the immunoregulatory mechanisms induced by combined therapy in MS.

What is the achievable effectiveness of the India AIDS Initiative intervention among female sex workers under target coverage? Model projections from southern India.

BACKGROUND: The India AIDS Initiative (Avahan) prevention programme funded by the Bill and Melinda Gates Foundation aims to reduce HIV prevalence in high risk groups such as female and male sex workers and their clients, to limit HIV transmission in the general population. OBJECTIVES: To assess the potential effectiveness of the Avahan intervention at the level of coverage targeted, in different epidemiological settings in India. METHODS: A deterministic compartmental model of the transmission dynamics of HIV and two sexually transmitted infections, and sensitivity analysis techniques, were used, in combination with available behavioural and epidemiological data from Mysore and Bagalkot districts in the Indian state of Karnataka, to evaluate the syndromic sexually transmitted infection (STI) management (STI treatment), periodic presumptive treatment of STI (PPT), and condom components of the Avahan intervention targeted to female sex workers (FSW). RESULTS: If all components of the intervention reach target coverage (that is, PPT, STI treatment and condom use), the intervention is expected to prevent 22-35% of all new HIV infections in FSW and in the total population over 5 years in a low transmission setting like Mysore, and to be half as effective in high transmission settings such as Bagalkot. The results were sensitive to small variations in intervention coverage. The condom component alone is expected to prevent around 20% of all new HIV infections over 5 years in Mysore and around 6% for the STI component alone; compared with 7%-14% for the PPT component alone. Multivariate sensitivity analyses suggested that interventions may be more effective in settings with low FSW HIV prevalence and small FSW populations, whereas HIV prevalence was most influenced by sexual behaviour and condom use parameters for FSW. CONCLUSION: The Avahan intervention is expected to be effective. However, to be able to demonstrate effectiveness empirically in the different settings, it is important to achieve target coverage or higher, which in the case of PPT could take a number of years to achieve. These preliminary model predictions need to be validated with more detailed mathematical models, as better data on sexual behaviour, condom use, STI and HIV trends over time, and intervention coverage data accumulate over the course of the programme.

Prenatal cocaine exposure produces consistent developmental alterations in dopamine-rich regions of the cerebral cortex.

Administration of cocaine to pregnant rabbits produces robust and long-lasting anatomical alterations in the dopamine-rich anterior cingulate cortex of offspring. These effects include increased length and decreased bundling of layer III and V pyramidal neuron dendrites, increases in parvalbumin expression in the dendrites of interneurons, and increases in detectable GABAergic neurons. We have now examined multiple cortical regions with varying degrees of catecholaminergic innervation to investigate regional variations in the ability of prenatal cocaine exposure to elicit these permanent changes. All regions containing a high density of tyrosine hydroxylase-immunoreactive fibers, indicative of prominent dopaminergic input, exhibited alterations in GABA and parvalbumin expression by interneurons and microtubule-associated protein-2 labeling of apical dendrites of pyramidal neurons. These regions included the medial prefrontal, entorhinal, and piriform cortices. In contrast, primary somatosensory, auditory and motor cortices exhibited little tyrosine hydroxylase staining and no measurable cocaine-induced changes in cortical structure. From these data we suggest that the presence of dopaminergic afferents contributes to the marked specificity of the altered development of excitatory pyramidal neurons and inhibitory interneurons induced by low dose i.v. administration of cocaine in utero.

Organized sports for children and preadolescents.

Participation in organized sports provides an opportunity for young people to increase their physical activity and develop physical and social skills. However, when the demands and expectations of organized sports exceed the maturation and readiness of the participant, the positive aspects of participation can be negated. The nature of parental or adult involvement can also influence the degree to which participation in organized sports is a positive experience for preadolescents. This updates a previous policy statement on athletics for preadolescents and incorporates guidelines for sports participation for preschool children. Recommendations are offered on how pediatricians can help determine a child's readiness to participate, how risks can be minimized, and how child-oriented goals can be maximized.

Identification of a sensitive period of prenatal cocaine exposure that alters the development of the anterior cingulate cortex.

Administration of cocaine to pregnant rabbits produces robust and long-lasting anatomical, neurochemical and behavioral alterations in their offspring. For example, exposure to cocaine following implantation [embryonic day (E) 8] through gestation (E29) produces increased length and decreased bundling of layer III and V pyramidal neuron dendrites, increased parvalbumin expression in the dendrites of interneurons, and increased GABA levels in the anterior cingulate cortex (ACC) and other dopamine-rich cortical areas. We have investigated the presence of a sensitive period of in utero exposure during specific developmental epochs prior to and during the onset of cortical development that might be capable of producing such effects. Cocaine (3 mg/kg i.v., twice daily) or saline was administered during embryonic days E16-E25 (onset and peak of corticogenesis), E8-E15 (prior to cortical plate formation), E8-E25 or E8-E29 as in earlier studies. Examination of the ACC in offspring exposed from E8 to E25 and from E16 to E25 were found to induce alterations in the development of pyramidal neurons and interneurons that are nearly identical to those induced by the complete exposure (E8-E29) paradigm. No alterations were observed following the E8-E15 cocaine exposure. These data suggest that exposure to cocaine during E16-E25, the time of peak corticogenesis, appearance of cortical monoamines and onset of D(1) dopamine receptor expression, is necessary and sufficient to produce long-term effects on the organization of excitatory pyramidal neurons and inhibitory interneurons in the ACC.