Assessment of disease progression in dysferlinopathy: A 1-year cohort study

ObjectiveTo assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year.MethodsOne hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, and hand-held dynamometry. Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant [mild, moderate, or severe based on a-NSAA score] or nonambulant [unable to complete a 10-meter walk]) and clinical diagnosis.ResultsThe functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate groups, while the 6MWT was most sensitive in the severe group. The 10-meter walk test was the only test showing significant change across all ambulant severity groups. In nonambulant patients, the MFM domain 3, wrist flexion strength, and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1-year clinical trial based on the a-NSAA as a clinical endpoint.ConclusionCertain functional outcome measures can detect changes over 6 months and 1 year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials.ClinicalTrials.gov identifier:NCT01676077

Assessing the relationship of patient reported outcome measures with functional status in dysferlinopathy: a Rasch analysis approach

Dysferlinopathy is a muscular dystrophy with a highly variable functional disease progression in which the relationship of function to some patient reported outcome measures (PROMs) has not been previously reported. This analysis aims to identify the suitability of PROMs and their association with motor performance.Two-hundred and four patients with dysferlinopathy were identified in the Jain Foundation's Clinical Outcome Study in Dysferlinopathy from 14 sites in 8 countries. All patients completed the following PROMs: Individualized Neuromuscular Quality of Life Questionnaire (INQoL), International Physical Activity Questionnaire (IPAQ), and activity limitations for patients with upper and/or lower limb impairments (ACTIVLIMs). In addition, nonambulant patients completed the Egen Klassifikation Scale (EK). Assessments were conducted annually at baseline, years 1, 2, 3, and 4. Data were also collected on the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) and Performance of Upper Limb (PUL) at these time points from year 2. Data were analyzed using descriptive statistics and Rasch analysis was conducted on ACTIVLIM, EK, INQoL. For associations, graphs (NSAD with ACTIVLIM, IPAQ and INQoL and EK with PUL) were generated from generalized estimating equations (GEE). The ACTIVLIM appeared robust psychometrically and was strongly associated with the NSAD total score (Pseudo R(2) 0.68). The INQoL performed less well and was poorly associated with the NSAD total score (Pseudo R(2) 0.18). EK scores were strongly associated with PUL (Pseudo R(2) 0.69). IPAQ was poorly associated with NSAD scores (Pseudo R(2) 0.09). This study showed that several of the chosen PROMs demonstrated change over time and a good association with functional outcomes. An alternative quality of life measure and method of collecting data on physical activity may need to be selected for assessing dysferlinopathy

State of wildfires 2023–24

Climate change is increasing the frequency and intensity of wildfires globally, with significant impacts on society and the environment. However, our understanding of the global distribution of extreme fires remains skewed, primarily influenced by media coverage and regional research concentration. This inaugural State of Wildfires report systematically analyses fire activity worldwide, identifying extreme events from the March 2023–February 2024 fire season. We assess the causes, predictability, and attribution of these events to climate change and land use, and forecast future risks under different climate scenarios. During the 2023–24 fire season, 3.9 million km2 burned globally, slightly below the average of previous seasons, but fire carbon (C) emissions were 16 % above average, totaling 2.4 Pg C. This was driven by record emissions in Canadian boreal forests (over 9 times the average) and dampened by reduced activity in African savannahs. Notable events included record-breaking wildfire extent and emissions in Canada, the largest recorded wildfire in the European Union (Greece), drought-driven fires in western Amazonia and northern parts of South America, and deadly fires in Hawai’i (100 deaths) and Chile (131 deaths). Over 232,000 people were evacuated in Canada alone, highlighting the severity of human impact. Our analyses revealed that multiple drivers were needed to cause areas of extreme fire activity. In Canada and Greece a combination of high fire weather and an abundance of dry fuels increased the probability of fires by 4.5-fold and 1.9–4.1-fold, respectively, whereas fuel load and direct human suppression often modulated areas with anomalous burned area. The fire season in Canada was predictable three months in advance based on the fire weather index, whereas events in Greece and Amazonia had shorter predictability horizons. Formal attribution analyses indicated that the probability of extreme events has increased significantly due to anthropogenic climate change, with a 2.9–3.6-fold increase in likelihood of high fire weather in Canada and a 20.0–28.5-fold increase in Amazonia. By the end of the century, events of similar magnitude are projected to occur 2.22–9.58 times more frequently in Canada under high emission scenarios. Without mitigation, regions like Western Amazonia could see up to a 2.9-fold increase in extreme fire events. For the 2024–25 fire season, seasonal forecasts highlight moderate positive anomalies in fire weather for parts of western Canada and South America, but no clear signal for extreme anomalies is present in the forecast. This report represents our first annual effort to catalogue extreme wildfire events, explain their occurrence, and predict future risks. By consolidating state-of-the-art wildfire science and delivering key insights relevant to policymakers, disaster management services, firefighting agencies, and land managers, we aim to enhance society’s resilience to wildfires and promote advances in preparedness, mitigation, and adaptation