5 research outputs found
ASPIRE trial: study protocol for a double-blind randomised controlled trial of aspirin for overheating during exercise in multiple sclerosis
Introduction The many benefits of exercise for persons with multiple sclerosis (MS) are well established, yet patients often refrain from exercise due to overheating and exhaustion. The present randomised controlled trial tests aspirin (acetylsalicylic acid (ASA)) as a convenient method to prevent overheating and improve exercise performance in persons with MS. The effects of ASA are compared with those of acetaminophen (APAP) and placebo.Methods and analysis Participants are seen for a laboratory maximal exercise test on 3 separate days separated by at least 1âweek. At each session, body temperature is measured before oral administration of a standard adult dose (650 mg) of ASA, APAP or placebo. One hour after drug administration, participants perform a maximal ramp test on a cycle ergometer. Primary outcomes are (a) time to exhaustion (that is, time spent cycling to peak exertion) and (b) body temperature change. Crossover analyses will include tests for effects of treatment, period, treatmentâperiod interaction (carryover effect) and sequence.Ethics and dissemination Ethical approval was granted by the institutional review board at Columbia University Irving Medical Center (reference: AAAS2529). Results of the trial will be published in peer-reviewed scientific journals and presented at national and international conferences. Neurologists, physiatrists, primary care physicians and physiotherapists are important stakeholders and will be targeted during dissemination. Positive trial results have the potential to promote aspirin therapy, an inexpensive and readily available treatment, to reduce overheating and allow more persons with MS to benefit from exercise.Trial registration number NCT03824938
Manifestations and impact of the COVIDâ19 pandemic in neuroinflammatory diseases
Abstract Objective To report initial results of a planned multicenter yearâlong prospective study examining the risk and impact of COVIDâ19 among persons with neuroinflammatory disorders (NID), particularly multiple sclerosis (MS). Methods In April 2020, we deployed online questionnaires to individuals in their home environment to assess the prevalence and potential risk factors of suspected COVIDâ19 in persons with NID (PwNID) and change in their neurological care. Results Our cohort included 1115 participants (630 NID, 98% MS; 485 reference) as of 30 April 2020. 202 (18%) participants, residing in areas with high COVIDâ19 case prevalence, met the April 2020 CDC symptom criteria for suspected COVIDâ19, but only 4% of all participants received testing given testing shortages. Among all participants, those with suspected COVIDâ19 were younger, more racially diverse, and reported more depression and liver disease. PwNID had the same rate of suspected COVIDâ19 as the reference group. Early changes in disease management included telemedicine visits in 21% and treatment changes in 9% of PwNID. After adjusting for potential confounders, increasing neurological disability was associated with a greater likelihood of suspected COVIDâ19 (ORadj = 1.45, 1.17â1.84). Interpretations Our study of realâtime, patientâreported experience during the COVIDâ19 pandemic complements physicianâreported MS case registries which capture an excess of severe cases. Overall, PwNID seem to have a risk of suspected COVIDâ19 similar to the reference population
Progress in treating inherited retinal diseases: Early subretinal gene therapy clinical trials and candidates for future initiatives
Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
Abstract
Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min Pâ=â8.5âĂâ10â72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (Pâ=â1.7âĂâ10â4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (Pâ=â1.4âĂâ10â5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids