Tezacaftor/ivacaftor in people with cystic fibrosis who stopped lumacaftor/ivacaftor due to respiratory adverse events

BackgroundIncreased rates of respiratory adverse events have been observed in people ≥12 years of age with cystic fibrosis homozygous for the Phe508del-CFTR mutation treated with lumacaftor/ivacaftor, particularly in those with percent predicted forced expiratory volume in 1 s (ppFEV₁) of <40%. We evaluated the safety, tolerability, and efficacy of tezacaftor/ivacaftor in people with cystic fibrosis homozygous for Phe508del-CFTR who discontinued lumacaftor/ivacaftor due to treatment-related respiratory signs or symptoms.MethodsParticipants ≥12 years of age with cystic fibrosis homozygous for Phe508del-CFTR with ppFEV₁ of ≥25% and ≤90% were randomized 1:1 and treated with tezacaftor/ivacaftor or placebo for 56 days.ResultsOf 97 participants, 94 (96.9%) completed the study. The primary endpoint was incidence of predefined respiratory adverse events of special interest (chest discomfort, dyspnea, respiration abnormal, asthma, bronchial hyperreactivity, bronchospasm, and wheezing): tezacaftor/ivacaftor, 14.0%; placebo, 21.3%. The adverse events were mild or moderate in severity. None were serious or led to treatment interruption or discontinuation. Overall, the discontinuation rate was similar between groups. The mean (SD) ppFEV₁ at baseline was 44.6% (16.1%) with tezacaftor/ivacaftor and 48.0% (18.1%) with placebo. The posterior mean difference in absolute change in ppFEV₁ from baseline to the average value of days 28 and 56 was 2.7 percentage points with tezacaftor/ivacaftor vs placebo.ConclusionsTezacaftor/ivacaftor was generally safe, well tolerated, and efficacious in people ≥12 years of age with cystic fibrosis homozygous for Phe508del-CFTR with ppFEV₁ of ≥25% and ≤90% who previously discontinued lumacaftor/ivacaftor due to treatment-related respiratory signs or symptoms.     

基于笔形束散射核的非均匀模体透射平面散射线分析

目的:利用蒙特卡罗方法分析透射平面上散射光子的物理性质以及非均匀模体厚度对散射核的影响,为基于电子射野影像设备（EPID）的在体剂量验证研究提供基础。方法:利用EGSnrc建立笔形束散射核模型,并模拟获得X射线穿过非均匀模体（水肺水/水骨水模体）以及相应等效厚度水模后30 cm处透射平面上的多种散射线能量注量分布,并分析水肺水/水骨水模体与其等效厚度水模体在散射线能量注量分布上的差异。结果:散射核中一阶康普顿散射线最大能量注量在1×10-4 MeV·cm-2数量级,当离轴距离为8~12 cm时下降至最大值的一半,而散射核中其它散射线能量注量最大值在1×10-5 MeV·cm-2数量级附近或以下。对于水肺水/水骨水模体,散射核能量注量相对偏差变化为±1.2%~±11.5%,且随模体非均匀层厚度增大而增大。结论:散射核中一阶康普顿散射线占比最大,同时也贡献了大部分能量注量相对偏差,在通过散射核来重建非均匀模体后EPID平面上的射线分布时,应着重考虑一阶康普顿散射线对重建结果的影响,并对其进行有效的修正。     

Internal carotid artery vasculitis originated by cervicofacial actinomycosis as a predisponing factor to stroke

Actinomycosis is a chronic, suppurative, fibrotic infection produced by a gram-positive anaerobic bacteria of the normal mouth flora, the infection having tendency to fistulate and to extend without respecting tissue layers. Initial diagnosis is usually delayed due to its painless evolution. Three clinical forms are known: cervicofacial, abdominal and thoracic. Occasionally, there is vascular involvement which is mainly associated with venous thrombotic phenomena with low clinical expresion and hematogenous dissemination that can result in a formation of abscess or meningitis in the central nervous system. We report the case of a 28 year old female patient with type I diabetes and microangiopathyc complication with a internal carotid artery stenosis adjacent to mandibular angle actinomicosis. A few months later and after a miscarriage she suffered from ischemic stroke. The anticardiolipin antibody were positive at the time of stroke with post-operative period and over the next two years. To our knowledge (Medline, 1984-2004), it is the first report of internal carotid vasculitis originated by cervicofacial actinomicosis. We discuss the neuroradiological aspects of our case.     

The effect of duodenal exclusion on the cellular endocrine adaptation of the duodenum after performing an antrectomy. An experimental study in the rat]

We present an experimental study in rats with the aim to value the adaptative variations over the duodenal gastrin and somatostatin cell producing populations after antrectomy and gastrojejunostomy. 30 animals were distributed into two groups of 15 animals each. Group 1 rats underwent antrectomy and gastrojejunostomy, the animals of group 2 were considered as a controls. The results obtained show that after antrectomy and gastrojejunostomy an increase of gastrin producing cells is produced as well as decrease of somatostatin producing cells, both figures are statistically significant, concluding that the duodenum is able to supply the gastric antrum in gastrin production while the duodenal somatostatin cell producing population is negative influenced by the absence of alimentary stimuli and gastric secretions.     

Gender and socio-economic patterning of self-reported sleep problems in Britain

Sleep is fundamental to health and well-being, yet relatively little research attention has been paid to sleep quality. This paper addresses how socio-economic circumstances and gender are associated with sleep problems. We examine (i) socio-economic status (SES) patterning of reported sleep problems, (ii) whether SES differences in sleep problems can be explained by socio-demographic characteristics, smoking, worries, health and depression, and (iii) gender differences in sleep problems, addressing the relative contribution of SES, smoking, worries, health and depression in explaining these differences. Logistic regression is used to analyse the British Psychiatric Morbidity Survey 2000, which interviewed 8578 men and women aged 16–74. Strong independent associations are found between sleep problems and four measures of SES: household income, educational qualifications, living in rented housing and not being in paid employment. Income differences in sleep problems were no longer significant when health and other characteristics were adjusted. The higher odds of sleep problems among the unemployed and adults with low education remained significant following adjustment. Women reported significantly more sleep problems than men, as did the divorced and widowed compared with married respondents. Gender differences in sleep problems were halved following adjustment for socio-economic characteristics, suggesting that SES inequalities play a major part in accounting for gender differences in sleep problems. Our study casts doubt on the primacy of physiological explanations underlying these gender differences. Since disadvantaged socio-economic characteristics are strongly associated with sleep problems, we conclude that disrupted sleep may be a mechanism through which low SES is linked to poor health.     

Decadal Change in Seroprevalence of Chikungunya Virus Infection in Pune City,India

Chikungunya virus (CHIKV) is an arthropod-borne virus capable of causing large outbreaks. We aimed to determine the decadal change in the extent of chikungunya virus infection from 2009 to 2019. We implemented a prospective cross-sectional survey in Pune City using a 30-cluster approach with probability-proportion-to-size (PPS) sampling, with blood samples collected from 1654 participants in early 2019. The study also included an additional 799 blood samples from an earlier serosurvey in late 2009. The samples were tested by an in-house anti-CHIKV IgG ELISA assay. The overall seroprevalence in 2019 was 53.2% (95% CI 50.7–55.6) as against 8.5% (95% CI 6.5–10.4) in 2009. A fivefold increase in seroprevalence was observed in a decade (p < 0.00001). The seroprevalence increased significantly with age; however, it did not differ between genders. Modeling of age-stratified seroprevalence data from 2019 coincided with a recent outbreak in 2016 followed by the low-level circulation. The mean estimated force of infection during the outbreak was 35.8% (95% CI 2.9–41.2), and it was 1.2% after the outbreak. To conclude, the study reports a fivefold increase in the seroprevalence of chikungunya infection over a decade in Pune City. The modeling approach considering intermittent outbreaks with continuous low-level circulation was a better fit and coincided with a recent outbreak reported in 2016. Community engagement and effective vector control measures are needed to avert future chikungunya outbreaks.     

Small bowel obstruction caused by appendiceal tourniquet

True mechanical small bowel obstruction because of appendicitis is extremely rare. A case is presented, and diagnosis and treatment principles are discussed.     

Impact of COVID-19 Lockdown on Non-Alcoholic Fatty Liver Disease and Insulin Resistance in Adults: A before and after Pandemic Lockdown Longitudinal Study

Background: Non-alcoholic fatty liver disease is a chronic disease caused by the accumulation of fat in the liver related to overweight and obesity, insulin resistance, hyperglycemia, and high levels of triglycerides and leads to an increased cardiovascular risk. It is considered a global pandemic, coinciding with the pandemic in 2020 caused by the “coronavirus disease 2019” (COVID-19). Due to COVID-19, the population was placed under lockdown. The aim of our study was to evaluate how these unhealthy lifestyle modifications influenced the appearance of metabolic alterations and the increase in non-alcoholic fatty liver disease. Methods: A prospective study was carried out on 6236 workers in a Spanish population between March 2019 and March 2021. Results: Differences in the mean values of anthropometric and clinical parameters before and after lockdown were revealed. There was a statistically significant worsening in non-alcoholic fatty liver disease (NAFLD) and in the insulin resistance scales, with increased body weight, BMI, cholesterol levels with higher LDL levels, and glucose and a reduction in HDL levels. Conclusions: Lockdown caused a worsening of cardiovascular risk factors due to an increase in liver fat estimation scales and an increased risk of presenting with NAFLD and changes in insulin resistance.     

“We are part of a family”. Benefits and limitations of community ART groups (CAGs) in Thyolo,Malawi: a qualitative study

Introduction : In 2012 Community ART Groups (CAGs), a community‐based model of antiretroviral therapy (ART) delivery were piloted in Thyolo District, Malawi as a way to overcome patient barriers to accessing treatment, and to decrease healthcare workers’ workload. CAGs are self‐formed groups of patients on ART taking turns to collect ART refills for all group members from the health facility. We conducted a qualitative study to assess the benefits and challenges of CAGs from patients’ and healthcare workers’ (HCWs) perspectives. Methods : Data were collected by means of 15 focus group discussions, 15 individual in‐depth interviews, and participant observation in 2 health centres. The 94 study participants included CAG members, ART patients eligible for CAGs who remained in conventional care, former CAG members who returned to conventional care and HCWs responsible for providing HIV care. Patient participants were purposively selected from ART registers, taking into account age and gender. Narratives were audio‐recorded, transcribed, and translated from Chichewa to English. Data were analyzed through a thematic analysis. Results : Patients and HCWs spoke favourably about the practical benefits of CAGs. Patient benefits included a reduced frequency of clinic visits, resulting in reduced transportation costs and time savings. HCW benefits included a reduced workload. Additionally peer support was perceived as an added value of the groups allowing not only sharing of the logistical constraints of drugs refills, but also enhanced emotional support. Identified barriers to joining a CAG included a lack of information on CAGs, unwillingness to disclose one's HIV status, change of residence and conflicts among CAG members. Participants reported that HIV‐related stigma persists and CAGs were seen as an effective strategy to reduce exposure to discriminatory labelling by community members. Conclusions : In this setting, patients and HCWs perceived CAGs to be an acceptable model of ART delivery. Despite addressing important practical barriers to accessing ART, and providing peer support, CAGs were not well known by patients and had a limited impact on reducing HIV‐related stigma. The CAG model of ART delivery should be considered in similar settings. Further measures need to be devised and implemented to address HIV‐related stigma.