A emergência da nova variante P.1 do SARS-CoV-2 no Amazonas (Brasil) foi temporalmente associada a uma mudança no perfil da mortalidade devido a COVID-19, segundo sexo e idade

Background Since the end of 2020, there has been a great deal of international concern about the variants of SARS-COV-2 B.1.1.7, identified in the United Kingdom; B.1.351 discovered in South Africa and P.1, originating from the Brazilian state of Amazonas. The three variants were associated with an increase in transmissibility and worsening of the epidemiological situation in the places where they expanded. The lineage B.1.1.7 was associated with the increase in case fatality rate in the United Kingdom. There are still no studies on the case fatality rate of the other two variants. The aim of this study was to analyze the mortality profile before and after the emergence of the P.1 strain in the Amazonas state. Methods We analyzed data from the Influenza Epidemiological Surveillance Information System, SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe), comparing two distinct epidemiological periods: during the peak of the first wave, between April and May 2020, and in January 2021 (the second wave), the month in which the new variant came to predominate. We calculated mortality rates, overall case fatality rate and case fatality rate among hospitalized patients; all rates were calculated by age and gender and 95% confidence intervals (95% CI) were determined. Findings We observed that in the second wave there were a higher incidence and an increase in the proportion of cases of COVID-19 in the younger age groups. There was also an increase in the proportion of women among Severe Acute Respiratory Infection (SARI) cases from 40% (2,709) in the first wave to 47% (2,898) in the second wave and in the proportion of deaths due to COVID-19 between the two periods varying from 34% (1,051) to 47% (1,724), respectively. In addition, the proportion of deaths among people between 20 and 59 years old has increased in both sexes. The case fatality rate among those hospitalized in the population between 20 and 39 years old during the second wave was 2.7 times the rate observed in the first wave (female rate ratio = 2.71; 95% CI: 1.9-3.9], p <0.0001; male rate ratio = 2.70, 95%CI:2.0-3.7), and in the general population the rate ratios were 1.15 (95% CI: 1.1-1.2) in females and 0.78 (95% CI: 0.7-0.8) in males]. Interpretation Based on this prompt analysis of the epidemiological scenario in the Amazonas state, the observed changes in the pattern of mortality due to COVID-19 between age groups and gender simultaneously with the emergence of the P.1 strain suggest changes in the pathogenicity and virulence profile of this new variant. Further studies are needed to better understanding of SARS-CoV-2 variants profile and their impact for the health population.Introdução Desde o final de 2020 tem havido grande preocupação internacional com as variantes do SARS-COV-2: B.1.1.7, identificada no Reino Unido; B.1.351, descoberta na África do Sul e P.1, que emergiu inicialmente estado brasileiro do Amazonas. As três variantes foram associadas a aumento na transmissibilidade e piora da situação epidemiológica nos locais onde se expandiram. A linhagem B.1.1.7 foi associada ao aumento da taxa de letalidade no Reino Unido. Ainda não existem estudos conclusivos sobre letalidade das outras duas variantes. O objetivo deste estudo foi analisar o perfil de mortalidade antes e depois da emergência da linhagem P.1 no Amazonas. Métodos Analisamos os dados do sistema nacional de vigilância epidemiológica, comparando dois momentos epidemiológicos distintos: durante o pico da primeira onda, entre abril e maio de 2020, e em janeiro de 2021, mês em que a nova variante passou a predominar. Calculamos as taxas de mortalidade, letalidade e letalidade entre pacientes internados, todas as taxas foram calculadas por idade e por sexo e determinados os intervalos de confiança de 95%. Achados Observamos que na segunda onda houve maior incidência e aumento na proporção de casos de COVID-19 nas faixas etárias mais jovens. Observou-se, também, um aumento na proporção de mulheres entre os casos de SARI de 40% (2.709) na primeira onda para 47% (2.898) na segunda onda e entre mortes por COVID-19 de 34% (1,051) para 47% (1.724), respectivamente. Além disso, a proporção de mortes entre 20 e 59 anos aumentou em ambos os sexos. A letalidade entre os hospitalizados na população entre 20 e 39 anos durante a segunda onda foi 2.7 vezes a primeira onda [razão de taxas sexo feminino=2,71; CI(95%)=1,9-3,9], p<0.0001; razão de taxas sexo masculino=2.70(2.0-3.7)), na população geral as razões de taxa foram 1,15(1,1-1,2) no sexo feminino e 0,78(0,7-0,8) no sexo masculino. Interpretação Observamos mudanças no padrão de mortalidade por COVID-19 entre as faixas etárias e sexo simultaneamente à emergência da linhagem P.1, sugerindo mudanças nos perfis de patogenicidade e virulência, novos estudos são necessários para melhor compreensão das variantes do SARS-CoV-2 e suas consequências na saúde da população

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Evaluation of pelvic varicose veins using color Doppler ultrasound: comparison of results obtained with ultrasound of the lower limbs, transvaginal ultrasound, and phlebography Avaliação de varizes pélvicas por Doppler colorido: comparação dos resultados obtidos com ultrassom dos membros inferiores, ultrassom transvaginal e flebografia

Introduction: Pelvic varicose veins, one of the main causes of chronic pelvic pain and dyspareunia, are an important source of reflux for lower limb varicose veins, especially in recurrent cases. Color Doppler ultrasound of the lower limbs and transvaginal ultrasound are the noninvasive diagnostic methods most commonly used to assess pelvic venous insufficiency, whereas phlebography is still considered as the gold standard. Objectives: To determine the prevalence of lower limb varicose veins originating from the pelvis in a group of female patients and to determine the agreement between results obtained via color Doppler ultrasound of the lower limbs, transvaginal ultrasound, and phlebography. Methods: The sample comprised female patients referred to a vascular laboratory for lower limb screening. Patients diagnosed with deep venous thrombosis were excluded. Data analysis included kappa coefficient of agreement, McNemar's test, sensitivity and specificity values. Results: Of a total of 1,020 patients, 124 (12.2%) had findings compatible with reflux of pelvic origin. Among these patients, 51 (41.2%) were recurrent cases. A total of 249 were submitted to transvaginal ultrasound. There was significant agreement between lower limb ultrasonographic findings and transvaginal findings. Phlebography was performed in 54 patients. The comparison between transvaginal ultrasound and phlebography was associated with a 96.2% sensitivity and 100% specificity. Conclusions: The authors draw attention to the relatively high prevalence of lower limb varicose veins originating from the pelvis, suggesting an important but underdiagnosed cause of recurrent varicose veins.<br>Introdução: AS VARIZES Pélvicas, uma das principais causas de dor pélvica crônica e dispareunia, são uma importante fonte de refluxo para as varizes dos membros inferiores, especialmente em casos recorrentes. O Doppler colorido dos membros inferiores e o ultrassom transvaginal são os métodos diagnósticos não-invasivos mais comumente usados para avaliar a insuficiência venosa pélvica, enquanto a flebografia ainda é considerada como o padrão-ouro. Objetivos: Determinar a prevalência de varizes dos membros inferiores originadas na pélvis em um grupo de pacientes do sexo feminino e determinar a concordância entre os resultados obtidos por Doppler colorido dos membros inferiores, ultrassom transvaginal e flebografia. Métodos: A AMOstra incluiu pacientes do sexo feminino encaminhadas para o laboratório vascular para triagem dos membros inferiores. As pacientes diagnosticadas com trombose venosa profunda foram excluídas. A análise dos dados incluiu o coeficiente de concordância kappa, o teste de McNemar e os valores de sensibilidade e especificidade. Resultados: De um total de 1.020 pacientes, 124 (12.2%) tiveram achados compatíveis com refluxo de origem pélvica. Entre essas pacientes, 51 (41.2%) eram casos recorrentes. Um total de 249 foram submetidas a ultrassom transvaginal. Houve concordância significativa entre os achados ultrassonográficos dos membros inferiores e os achados transvaginais. A flebografia foi realizada em 54 pacientes. A comparação entre o ultrassom transvaginal e a flebografia foi associada a 96.2% de sensibilidade e 100% de especificidade. Conclusões: OS AUTores chamam a atenção para a prevalência relativamente alta de varizes dos membros inferiores originadas na pélvis, sugerindo uma importante, embora subdiagnosticada, causa de varizes recorrentes

Apoplexia pituitária seguida de remissão endócrina: relato de dois casos Pituitary apoplexy followed by endocrine remission: report of two cases

A apoplexia pituitária é evento raro e a ocorrência de remissão endócrina em pacientes portadores de tumores secretores é ainda mais incomum. O presente estudo relata os casos de dois pacientes portadores de macroadenomas (um com doença de Cushing e outro com acromegalia) nos quais houve remissão endócrina após apoplexia tumoral. A primeira paciente era portadora de doença de Cushing e teve episódio ictal espontâneo de cefaléia e vômitos, após o qual iniciou remissão endócrina. Como houvesse persistência de imagem de macroadenoma à ressonância magnética, a paciente foi submetida a cirurgia transesfenoidal, sendo encontrado apenas cisto hemorrágico hipertensivo, sem sinais de tumor. O segundo paciente apresentava acromegalia e enquanto realizava um teste de LHRH teve evento agudo de cefaléia e vômitos, sem perda visual e instalação de diabetes insipidus. A tomografia computadorizada de sela túrcica mostrou sinais de sangue. Como não houve quadro visual agudo, o paciente foi seguido com exames de imagens seriadas, que demonstraram o desaparecimento completo da lesão e o aparecimento de sela vazia. A avaliação endócrina mostrou remissão da acromegalia. Tendo em vista a tendência à recidiva já documentada na literatura, esses pacientes devem continuar em seguimento a longo prazo.<br>Pituitary apoplexy is rare and endocrine remission in patients with apopletic secreting pituitary adenomas is even rarer. This study reports on two patients with pituitary macroadenomas (one with Cushing's disease and the other with acromegaly) in whom endocrine remission occurred after apoplexy. The first patient had Cushing's disease and had an ictus of headache and vomiting after which she started a progressive remission of hypercortisolism. A post-apoplexy MRI disclosed persistence of a sellar and supra-sellar mass. She was submitted to transesphenoidal surgery. An hypertensive hemorhagic cyst was found with no tumor. The second patient had acromegaly. While performing a LHRH-stimulation test he had an ictus of headache, vomiting, no visual loss and appearance of diabetes insipidus. A CT scan disclosed an intrasellar hematoma. Despite the size of the tumor and since there was no visual impairment, this patient was followed up without surgery. Imaging follow-up showed a progressive shrinkage and disappearance of the mass, which was corroborated by endocrine remission. A high rate of recurrence is reported in such patients in the literature. Both patients are being currently followed-up on a long-term basis

What works? Strategies to increase reproductive, maternal and child health in difficult to access mountainous locations: a systematic literature review

Background: Geography poses serious challenges to delivery of health services and is a well documented marker of inequity. Maternal, newborn and child health (MNCH) outcomes are poorer in mountainous regions of low and lower-middle income countries due to geographical inaccessibility combined with other barriers: poorer quality services, persistent cultural and traditional practices and lower socioeconomic and educational status. Reaching universal coverage goals will require attention for remote mountain settings. This study aims to identify strategies to address barriers to reproductive MNCH (RMNCH) service utilisation in difficult-to-reach mountainous regions in low and lower-middle income settings worldwide. Methods: A systematic literature review drawing from MEDLINE, Web of Science, Scopus, Google Scholar, and Eldis. Inclusion was based on; testing an intervention for utilisation of RMNCH services; remote mountain settings of low- and lower-middle income countries; selected study designs. Studies were assessed for quality and analysed to present a narrative review of the key themes. Findings: From 4,130 articles 34 studies were included, from Afghanistan, Bolivia, Ethiopia, Guatemala, Indonesia, Kenya, Kyrgyzstan, Nepal, Pakistan, Papua New Guinea and Tajikistan. Strategies fall into four broad categories: improving service delivery through selected, trained and supported community health workers (CHWs) to act alongside formal health workers and the distribution of critical medicines to the home; improving the desirability of existing services by addressing the quality of care, innovative training and supervision of health workers; generating demand by engaging communities; and improving health knowledge for timely care-seeking. Task shifting, strengthened roles of CHWs and volunteers, mobile teams, and inclusive structured planning forums have proved effective. Conclusions: The review highlights where known evidence-based strategies have increased the utilisation of RMNCH services in low income mountainous areas. While these are known strategies in public health, in such disadvantaged settings additional supports are required to address both supply and demand barriers