Efficacy and safety of a fixed dose artesunate-sulphamethoxypyrazine-pyrimethamine compared to artemether-lumefantrine for the treatment of uncomplicated falciparum malaria across Africa: a randomized multi-centre trial

<p>Abstract</p> <p>Background</p> <p>The efficacy of artemisinin-based combination therapy has already been demonstrated in a number of studies all over the world, and some of them can be regarded as comparably effective. Ease of administration of anti-malarial treatments with shorter courses and fewer tablets may be key determinant of compliance.</p> <p>Methods</p> <p>Patients with uncomplicated falciparum malaria and over six months of age were recruited in Cameroon, Mali, Rwanda and Sudan. 1,384 patients were randomly assigned to receive artesunate-sulphamethoxypyrazine-pyrimethamine (AS-SMP) three-day (once daily for 3 days) regimen (N = 476) or AS-SMP 24-hour (0 h, 12 h, 24 h) regimen (N = 458) or artemether-lumefantrine (AL), the regular 6 doses regimen (N = 450). The primary objective was to demonstrate non-inferiority (using a margin of -6%) of AS-SMP 24 hours or AS-SMP three days versus AL on the PCR-corrected 28-day cure rate.</p> <p>Results</p> <p>The PCR corrected 28-day cure rate on the intention to treat (ITT) analysis population were: 96.0%(457/476) in the AS-SMP three-day group, 93.7%(429/458) in the AS-SMP 24-hour group and 92.0%(414/450) in the AL group. Likewise, the cure rates on the PP analysis population were high: 99.3%(432/437) in the AS-SMP three-day group, 99.5%(416/419) in the AS-SMP 24-hour group and 99.7(391/394)% in the AL group. Most common drug-related adverse events were gastrointestinal symptoms (such as vomiting and diarrhea) which were slightly higher in the AS-SMP 24-hour group.</p> <p>Conclusion</p> <p>AS-SMP three days or AS-SMP 24 hours are safe, are as efficacious as AL, and are well tolerated.</p> <p>Trial registration</p> <p>NCT00484900 <url>http://www.clinicaltrials.gov</url>.</p

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05-1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4-7 days or ≥ 8 days of 1.25 (1.04-1.48), p = 0.015 and 1.31 (1.11-1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care

Clinical predictors of abnormal esophageal pH monitoring in preterm infants Preditores clínicos para pHmetria esofágica anormal em prematuros

BACKGROUND: Risk factors for gastroesophageal reflux disease in preterm neonates have not been yet clearly defined. AIM: To identify factors associated with increased esophageal acid exposition in preterm infants during the stay in the neonatal unit. METHODS: A case-control study in preterm infants who had undergone prolonged monitoring of distal esophageal pH, following clinical indication. Eighty-seven preterms with reflux index (percentage of total time of esophageal pHmetry) >10% (cases) and 87 unpaired preterms were selected with reflux index <10% (controls). Demographic variables, signs and symptoms, main diagnoses and some aspects of treatment were studied. Simple and multiple logistic regression analysis adjusted for birthweight and postconceptional age at the pH study were used. RESULTS: The factors associated with a greater chance of reflux index >10% in preterms were: vomiting, regurgitation, Apnea, female gender. The variables that were associated with a lower frequency of increased reflux index were: volume of enteral intake at the onset of symptoms >147 mL/kg/day, and postnatal corticoid use. CONCLUSIONS: Vomiting, regurgitation, apnea, female gender and acute respiratory distress during the first week of life were variables predictive of increased esophageal acid exposition in preterm infants with birthweight <2000 g. Bronchopulmonary dysplasia and use of caffeine were not associated with reflux index >10%.<br>RACIONAL: Os fatores de risco para a doença pelo refluxo gastroesofágico em recém-nascidos prematuros não foram, até momento, claramente estabelecidos. OBJETIVO: Identificar fatores associados ao aumento da exposição ácida intra-esofágica em prematuros durante o período de internação em unidade neonatal. MÉTODOS: Realizou-se estudo de caso controle com prematuros que realizaram monitorização prolongada do pH esofágico por suspeita clínica de doença do refluxo. Foram selecionados 87 recém-nascidos com valor do índice de refluxo (percentual do tempo total do exame com pH abaixo de 4) >10% (casos) e 87 recém-nascidos com índice de refluxo <10% (controles). Casos e controles não foram emparelhados. As variáveis estudadas foram as demográficas, os sinais e sintomas clínicos, os principais diagnósticos e alguns aspectos da terapêutica. Foram utilizadas as análises de regressão logística uni e multivariada, ambas ajustadas pelo peso ao nascimento e pela idade pós-conceptual no momento do estudo de pH. RESULTADOS: Os fatores que se associaram a maior chance de índice de refluxo >10% foram: vômitos, regurgitações, apnéia, sexo feminino e insuficiência respiratória na 1ª semana de vida. As variáveis que se associaram a menor freqüência de índice de refluxo <10% foram: volume de mamada ao início dos sintomas >147mL/kg/d e uso de corticóide pós-natal. CONCLUSÕES: Vômitos, regurgitações, apnéia, sexo feminino e a insuficiência respiratória na primeira semana de vida foram variáveis preditoras para elevada exposição ácida do esôfago em prematuros com peso ao nascer <2000 g. A displasia broncopulmonar e o uso de cafeína não se associaram ao índice de refluxo >10%