Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura

Publisher Copyright: © 2023, The Author(s).Migraine is a complex neurovascular disease with a range of severity and symptoms, yet mostly studied as one phenotype in genome-wide association studies (GWAS). Here we combine large GWAS datasets from six European populations to study the main migraine subtypes, migraine with aura (MA) and migraine without aura (MO). We identified four new MA-associated variants (in PRRT2, PALMD, ABO and LRRK2) and classified 13 MO-associated variants. Rare variants with large effects highlight three genes. A rare frameshift variant in brain-expressed PRRT2 confers large risk of MA and epilepsy, but not MO. A burden test of rare loss-of-function variants in SCN11A, encoding a neuron-expressed sodium channel with a key role in pain sensation, shows strong protection against migraine. Finally, a rare variant with cis-regulatory effects on KCNK5 confers large protection against migraine and brain aneurysms. Our findings offer new insights with therapeutic potential into the complex biology of migraine and its subtypes.Peer reviewe

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

One-year trial of 12-hour shifts in a non-intensive care unit and an intensive care unit in a public hospital: a qualitative study of 24 nurses’ experiences

Download PDFPDF Qualitative research Research One-year trial of 12-hour shifts in a non-intensive care unit and an intensive care unit in a public hospital: a qualitative study of 24 nurses’ experiences Solveig Osborg Ose, Maria Suong Tjønnås, Silje Lill Kaspersen, Hilde Færevik Author affiliations Abstract Objectives The aim of this study was to provide recommendations to hospital owners and employee unions about developing efficient, sustainable and safe work-hour agreements. Employees at two clinics of a hospital, one a non-intensive care and the other a newborn intensive care unit (ICU), trialled 12-hour shifts on weekends for 1 year. Methods We systematically recorded the experiences of 24 nurses’ working 12-hour shifts, 16 in the medical unit and 8 in the ICU for 1 year. All were interviewed before, during and at the end of the trial period. The interview material was recorded, transcribed to text and coded systematically. Results The experiences of working 12-hour shifts differed considerably between participants, especially those in the ICU. Their individual experiences differed in terms of health consequences, effects on their family, appreciation of extra weekends off, perceived effects on patients and perceived work task flexibility. Conclusions The results indicate that individual preference for working 12-hour shifts is a function of own health situation, family situation, work load tolerance, degree of sleep problems, personality and other factors. If the goal is to recruit and retain nurses, nurses should be free to choose to work 12-hour shifts

COVID-19 concerns among old age Psychiatric In- and out-patients and the employees caring for them, a preliminary study

A questionnaire was administered to 14 patients admitted at the Department of Old Age Psychiatric 24-h unit at Oslo University Hospital with questions about experiences and fears regarding COVID-19. A similar adjusted questionnaire was administered to 19 outpatients. The purpose was to investigate if the patients had fears, anxieties, and quality of life issues related to COVID-19 that could affect their treatment. A quest back questionnaire with similar questions about patient care and work conditions was sent to the personnel working with these patients, and 46 of 81 responded. Most patients welcomed the strict measures that were applied, including a visitation ban for inpatients and a reduction in consultations for the outpatients. Most patients reported that they were not very scared of getting COVID-19, nor did many believe that they would die if they were infected. A minority of patients reported being very worried. The patients also differed on other issues related to the COVID-19 situation. A minority were negative to the interventions, rules, and regulations, and/or considered the risk of infection to be elevated at the clinic, and/or that the quality of their daily life was negatively impacted. Employees more often than patients were concerned about the COVID-19 influence on their health. They were also concerned about being at work amid the crisis. About half of their comments were related to the fear of inadvertently infecting patients with COVID-19. Also, a majority complained about aspects related to the implemented COVID-19 guidelines. This study is explorative in nature, mainly due to its small sample size, which makes it difficult to draw conclusions from the results. However, the results imply a need for addressing the COVID-19 concerns of both patients and employees, to prevent potential negative effects on treatment and overall life quality. Future research should investigate the self-reported effects of the pandemic situation on a larger sample size of elderly psychiatric patients