Infant mortality in the municipality of São Paulo: trend and social inequality (2006–2019)

OBJETIVO: Considerando as evidências publicadas sobre o impacto de crises econômicas e da implementação de políticas de austeridade fiscal em vários indicadores de saúde, e a ocorrência recente desses eventos no Brasil, o objetivo deste estudo foi analisar o comportamento da tendência e da desigualdade socioespacial da mortalidade infantil no município de São Paulo, entre 2006 e 2019. MÉTODOS: Trata-se d e e studo e cológico d e a nálise d e t endência t emporal, d esenvolvido no município de São Paulo e em três estratos de áreas de residência, diferenciadas segundo nível de vulnerabilidade social, a partir do Índice Paulista de Vulnerabilidade Social de 2010. Calcularam-se as taxas de mortalidade infantil, neonatal e pós-neonatal para cada um dos estratos de vulnerabilidade social, para cada ano do período e para o primeiro e o último triênios. A tendência temporal foi analisada com o modelo de regressão de Prais-Winsten e a magnitude da desigualdade avaliada pelas razões de taxas. RESULTADOS: O declínio das taxas de mortalidade infantil e de seus componentes, observado entre 2006 e 2015, que foi mais elevado no estrato de baixa vulnerabilidade social e no período pós-neonatal em comparação ao neonatal, foi interrompido em 2015, com estagnação das taxas no período subsequente (2016–2019). A análise da desigualdade da mortalidade infantil entre os estratos de vulnerabilidade social revelou aumento significativo entre os triênios inicial e final do período analisado; as razões de taxas cresceram de 1,36 para 1,48 entre o estrato de alta em relação ao de baixa vulnerabilidade social e de 1,19 para 1,32 entre o de média e de baixa vulnerabilidade social. CONCLUSÕES: O estancamento do declínio da taxas de mortalidade infantil em 2015 e o aumento da desigualdade socioespacial observados apontam para a necessidade premente de reformulação das políticas públicas vigentes para reversão desse quadro, visando reduzir a iniquidade presente no risco de morte infantil.OBJECTIVE: Considering the published evidence on the impact of recent economic crises and the implementation of fiscal austerity policies in Brazil on various health indicators, this study aims to analyze how the trend and socio-spatial inequality of infant mortality behaved in the municipality of São Paulo from 2006 to 2019. METHODS: This is an ecological study with a temporal trend analysis that was developed in municipality of São Paulo, using three residence area strata differentiated according to their social vulnerability following the 2010 São Paulo Social Vulnerability Index. Infant mortality rate, as well as neonatal, and post-neonatal mortality rates, were calculated for each social vulnerability stratum, each year in the period, and for the first and last three triennia. Temporal trends were analyzed by the Prais-Winsten regression model and inequality magnitude, by rate ratios. RESULTS: We found a decline in infant mortality rate and its components from 2006 to 2015, greater in the stratum with low social vulnerability and in the post-neonatal period when compared to the neonatal one. This decline ended in 2015, stagnating in the next period (2016–2019). Our analysis of infant mortality inequality across social vulnerability stratum showed a significant increase from the initial to the final triennia in the analyzed period; rate ratios increased from 1.36 to 1.48 in the high stratum (compared to the low social vulnerability stratum), and from 1.19 to 1.32 between the medium and low social vulnerability strata. CONCLUSIONS: The observed stagnation of infant mortality rate decline in 2015 and the increase in socio-spatial inequality point to the urgent need to reformulate current public policies to reverse this situation and reduce inequalities in the risk of infant death

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Studio clinico e strumentale preliminare dell’attività idratante di Cicatridina® compresse assunta per via sistemica

L’utilizzo di un prodotto assunto per via sistemica a base di acido ialuronico può svolgere un ruolo significativo nel migliorare il grado di idratazione cutanea. Lo scopo dello studio è stato quello di valutare l’efficacia e la tollerabilità di un prodotto (Cicatridina® compresse) a base di acido ialuronico in soggetti con xerosi cutanea moderata-severa. Allo studio in aperto hanno partecipato 30 pazienti (età media 48,4). Sono state somministrate per via orale 2 compresse al giorno per un mese ed 1 compressa al giorno per altri due mesi. Al termine del trattamento è stato registrato un significativo miglioramento dei parametri clinico-morfologici esaminati, confermato dall’indagine corneometrica, nonché l’assenza di effetti collaterali significativi. In conclusione questo studio ha evidenziato la buona tollerabilità del prodotto in esame e la sua efficacia nel migliorare il grado di idratazione cutanea in soggetti con xerosi cutanea moderata-sever

Keratinocyte dysfunction in vitiligo epidermis: cytokine microenvironment and correlation to keratinocyte apoptosis

Vitiligo is a skin disorder characterized by loss of functional melanocytes. Keratinocytes contribute to melanocyte homeostasis, and keratinocyte alteration may play a role in melanocyte dysfunction in vitiligo. In particular, the release of melanogenic mediators and the level of functioning keratinocytes may affect melanocyte dysfunction in vitiligo epidermis. Keratinocyte-derived mediators involved in pigmentation, analysed by in situ hybridization, and epidermal apoptosis, detected by TUNEL assay and electron microscopy, were evaluated in lesional and perilesional skin biopsies from 15 patients with active vitiligo and in 5 control subjects. Among the melanogenic mediators, stem cell factor (SCF) and endothelin-1 (ET-1) mRNA were significantly reduced in lesional as compared to perilesional epidermis, whereas no difference was observed in mRNA of basic fibroblastic growth factor (bFGF) and granulocyte-monocyte colony stimulating factor (GM-CSF). The expression of mRNA for tumor necrosis factor (TNF)-α and interleukin-6 (IL-6), two pro-inflammatory cytokines with an inhibitory effect on pigmentation, was increased in the epidermis from vitiligo biopsies, whereas their expression was practically undetectable in the skin of control subjects. Apoptotic keratinocytes were more abundant in lesional vs. perilesional skin of vitiligo patients and were absent in the epidermis of control subjects. Changes in expression of keratinocyte-derived mediators observed in the present study are consistent with their differential functions in melanocyte regulation. In particular, increased TNF-α could contribute to keratinocyte apoptosis, which results in reduced release of melanogenic cytokines and ultimately in melanocyte disappearance

Activation of blood coagulation in two prototypic autoimmune skin diseases: A possible link with thrombotic risk

Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1 +2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/ L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease

Organized Hybrid Molecular Films from Natural Phospholipids and Synthetic Block Copolymers: A Physicochemical Investigation

International audienceIn the last few years, hybrid lipid-copolymer assemblies have attracted increasing attention as possible two-dimensional (2D) membrane platforms, combining the biorelevance of the lipid building blocks with the stability and chemical tunability of copolymers. The relevance of these systems varies from fundamental studies on biological membrane-related phenomena to the construction of 2D complex devices for material science and biosensor technology. Both the fundamental understanding and the application of hybrid lipid-copolymer-supported bilayers require thorough physicochemical comprehension and structural control. Herein, we report a comprehensive physicochemical and structural characterization of hybrid monolayers at the air/water interface and of solid-supported hybrid membranes constituted by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and the block copolymer poly(butadiene-b-ethyleneoxide) (PBD-b-PEO). Hybrid lipid-copolymer supported bilayers (HSLBs) with variable copolymer contents were prepared through spontaneous rupture and fusion of hybrid vesicles onto a hydrophilic substrate. The properties of the thin films and the parent vesicles were probed through dynamic light scattering (DLS), differential scanning calorimetry (DSC), optical ellipsometry, quartz crystal microbalance with dissipation monitoring (QCM-D), and confocal scanning laser microscopy (CSLM). Stable, hybrid lipid/copolymer systems were obtained for a copolymer content of 10−65 mol %. In particular, DSC and CSLM show lateral phase separation in these hybrid systems. These results improve our fundamental understanding of HSLBs, which is necessary for future applications of hybrid systems as biomimetic membranes or as drug delivery systems, with additional properties with respect to phospholipid liposomes