Cardiac and pulmonary findings in dysferlinopathy: A 3-year, longitudinal study.
Ontology highlight
ABSTRACT: Introduction/aims
There is debate about whether and to what extent either respiratory or cardiac dysfunction occurs in patients with dysferlinopathy. This study aimed to establish definitively whether dysfunction in either system is part of the dysferlinopathy phenotype.Methods
As part of the Jain Foundation's International Clinical Outcome Study (COS) for dysferlinopathy, objective measures of respiratory and cardiac function were collected twice, with a 3-y interval between tests, in 188 genetically confirmed patients aged 11-86 y (53% female). Measures included forced vital capacity (FVC), electrocardiogram (ECG), and echocardiogram (echo).Results
Mean FVC was 90% predicted at baseline, decreasing to 88% at year 3. FVC was less than 80% predicted in 44 patients (24%) at baseline and 48 patients (30%) by year 3, including ambulant participants. ECGs showed P-wave abnormalities indicative of delayed trans-atrial conduction in 58% of patients at baseline, representing a risk for developing atrial flutter or fibrillation. The prevalence of impaired left ventricular function or hypertrophy was comparable to that in the general population.Discussion
These results demonstrate clinically significant respiratory impairment and abnormal atrial conduction in some patients with dysferlinopathy. Therefore, we recommend that annual or biannual follow-up should include FVC measurement, enquiry about arrhythmia symptoms and peripheral pulse palpation to assess cardiac rhythm. However, periodic specialist cardiac review is probably not warranted unless prompted by symptoms or abnormal pulse findings.
SUBMITTER: Moore U
PROVIDER: S-EPMC9311426 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:To assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year. One 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. The 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. Certain functional outcome measures can detect changes over 6 months and 1 year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials. NCT01676077.
| S-EPMC6369904 | biostudies-literature
Project description:BackgroundRecent meta-analyses have raised concerns about the replicability of gene × environment interactions involving the serotonin transporter gene (5-HTTLPR) in moderating the associations between adverse life events and mental disorders.AimsTo use data gathered over the course of a 30-year longitudinal study of a New Zealand birth cohort to test the hypothesis that the presence of short ('s') alleles of 5-HTTLPR are associated with an increased response to life stress.MethodParticipants were 893 individuals from the Christchurch Health and Development Study who had complete data on: the 5-HTTLPR genotype; psychiatric disorders up to the age of 30; and exposure to childhood and adult adverse life events.ResultsA series of 104 regression models were fitted to four mental health outcomes (depressive symptoms, major depression, anxiety disorder and suicidal ideation) observed at ages 18, 21, 25 and 30 using 13 measures of life-course stress that spanned childhood and adult stressors. Both multiplicative and additive models were fitted to the data. No evidence was found that would support the hypothesis that 's' alleles of 5-HTTLPR are associated with increased responsivity to life stressors.ConclusionsThe present findings add to the evidence suggesting that it is unlikely that there is a stable gene × environment interaction involving 5-HTTLPR, life stress and mental disorders.
| S-EPMC3031653 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with an unpredictable course. An observational study was set up using the French hospital discharge database to describe the reasons, outcomes and costs of hospitalisations related to this disease. Patients newly hospitalised for idiopathic pulmonary fibrosis (ICD-10 code: J84.1) in 2008 were identified and followed for 5 years. As J84.1 includes other fibrotic pulmonary diseases, an algorithm excluding age<50 years and presence of a differential diagnosis in the following year was defined. Overall, 6,476 patients were identified; of whom 30% were admitted through the emergency unit and 12% died during their first hospitalisation. Most of patients were hospitalised at least once for one or several acute events (n = 5,635; 87.0% of patients), of whom 36.5% of patients with an acute respiratory worsening (in-hospital mortality of 17.0% and median cost of €3,224; interquartile range (IQR €889-6,092)), 43.7% of patients with a respiratory infection (in-hospital mortality of 29.5% and median cost of €5,432 (IQR, €3,620-9,115)) and 51.7% of patients with a cardiac event (in-hospital mortality of 35.7% and median cost of €4,584 (IQR, €2,803-6,399)); 30.2% of these events occurred during the first hospitalisation. Finally, the 3-year in-hospital mortality crude rate was 36.8%. This study is the first providing extensive data on hospitalisations in patients with pulmonary fibrosis, mostly idiopathic, in France, demonstrating high burden and hospital cost.
| S-EPMC5242514 | biostudies-literature
Project description:To describe the baseline clinical and functional characteristics of an international cohort of 193 patients with dysferlinopathy.The Clinical Outcome Study for dysferlinopathy (COS) is an international multicenter study of this disease, evaluating patients with genetically confirmed dysferlinopathy over 3 years. We present a cross-sectional analysis of 193 patients derived from their baseline clinical and functional assessments.There is a high degree of variability in disease onset, pattern of weakness, and rate of progression. No factor, such as mutation class, protein expression, or age at onset, accounted for this variability. Among patients with clinical diagnoses of Miyoshi myopathy or limb-girdle muscular dystrophy, clinical presentation and examination was not strikingly different. Respiratory impairment and cardiac dysfunction were observed in a minority of patients. A substantial delay in diagnosis was previously common but has been steadily reducing, suggesting increasing awareness of dysferlinopathies.These findings highlight crucial issues to be addressed for both optimizing clinical care and planning therapeutic trials in dysferlinopathy. This ongoing longitudinal study will provide an opportunity to further understand patterns and variability in disease progression and form the basis for trial design.
| S-EPMC4994875 | biostudies-other
Project description:BackgroundAnemia and poor physical growth during adolescence have far-ranging consequences, but limited longitudinal evidence exists on how changes in these factors relate to changes in learning skills as adolescents mature.ObjectivesWe examined the association between changes in anemia and physical growth during adolescence and learning outcomes.MethodsWe used longitudinal data from the Understanding the Lives of Adolescents and Young Adults (UDAYA) project, which surveyed adolescents aged 10-19 y in northern India in 2015-2016 and 2018-2019 (n = 5963). We used multilevel mixed-effects logistic regression models to examine associations between changes in anemia/thinness/stunting status (4 groups: never, improved, new, and persistent) and reading (ability to read a story) and math proficiency (ability to solve division problems) at follow-up.ResultsPersistent anemia and stunting were higher among girls than among boys (46% compared with 8% and 37% compared with 14%, respectively), but persistent thinness was lower (7% compared with 16%). Improvement in anemia, thinness, and stunting was 1.4-1.7 times higher among boys than among girls. Boys who were anemic in both waves were 74% [adjusted odds ratio (AOR): 0.26; 95% CI: 0.12, 0.59] and 65% (AOR: 0.35; 95% CI: 0.16, 0.76) less likely to be able to read a story and solve division problems, respectively, than boys who were nonanemic in both waves. Persistent thinness in boys was negatively associated with both reading (AOR: 0.37; 95% CI: 0.21, 0.66) and math proficiency (AOR: 0.27; 95% CI: 0.16, 0.46). Persistent stunting contributed to lower reading and math proficiency in boys and girls (AORs: 0.29-0.46). Boys whose anemia or thinness status improved and girls whose stunting status improved had similar learning skills at follow-up as those who were never anemic/thin/stunted.ConclusionsPersistent anemia, thinness, and short stature during adolescence were associated with poor learning. Programs targeted at adolescents should contribute to nurturing environments that foster healthy growth and learning.
| S-EPMC9170477 | biostudies-literature
Project description:OBJECTIVES:Few studies have investigated the psychological and health-related outcome after out-of-hospital cardiac arrest (OHCA) over time. This longitudinal study aims to evaluate psychological distress in terms of anxiety and depression, self-assessed health and predictors of these outcomes in survivors of OHCA, 3 and 12 months after resuscitation. METHODS:Recruitment took place from 2008 to 2011 and survivors of OHCA were identified through the national Swedish Cardiopulmonary Resuscitation Registry. Inclusion criteria were age ≥18 years, survival ≥12 months and a Cerebral Performance Category score ≤2. Questionnaires containing the Hospital Anxiety and Depression Scale and European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) were administered at 3 and 12 months after the OHCA. Participants were also asked to report treatment-requiring comorbidities. RESULTS:Of 298 survivors, 85 (29%) were eligible for this study and 74 (25%) responded. Clinically relevant anxiety was reported by 22 survivors at 3 months and by 17 at 12 months, while clinical depression was reported by 10 at 3 months and 4 at 12 months. The mean EQ-5D-3L index value increased from 0.82 (±0.26) to 0.88 (±0.15) over time. There were significantly less symptoms of psychological distress (p=0.01) and better self-assessed health (p=0.003) at 12 months. Treatment-requiring comorbidity predicted anxiety (OR 4.07, p=0.04), while being female and young age predicted poor health (OR 6.33, p=0.04; OR 0.91, p=0.002) at 3 months. At 12 months, being female was linked to anxiety (OR 9.23, p=0.01) and depression (OR 14.78, p=0.002), while young age predicted poor health (OR 0.93, p=0.003). CONCLUSION:The level of psychological distress and self-assessed health improves among survivors of OHCA between 3 and 12 months after resuscitation. Higher levels of psychological distress can be expected among female survivors and those with comorbidity, while survivors of young age and who are female are at greater risk of poor health.
| S-EPMC6615909 | biostudies-other
Project description:ImportanceChronic obstructive pulmonary disease (COPD) is a critical public health burden. The neutrophil to lymphocyte ratio (NLR), an inflammation biomarker, has been associated with COPD morbidity and mortality; however, its associations with lung function decline and COPD development are poorly understood.ObjectiveTo explore the associations of NLR with lung function decline and COPD risks.Design, setting, and participantsThis longitudinal cohort study included white male veterans in the US with more than 30 years of follow-up to investigate the associations of NLR with lung function, COPD, and hypomethylation of cg05575921, the top DNA methylation marker of lung function changes in response to tobacco smoking. This study included 7466 visits from 1549 participants, each examined up to 13 times between 1982 and 2018. A subgroup of 1411 participants without COPD at baseline were selected to analyze the association of NLR with incident COPD. Data were analyzed from September 2019 to January 2020.ExposuresThe primary exposure was NLR, which was estimated using automated whole blood cell counts based on a blood sample collected at each visit. The methylation level of cg05575921 was measured in blood DNA from a subgroup of 1228 visits.Main outcomes and measuresThe outcomes of interest were lung function, measured as forced respiratory volume in the first second (FEV1) in liters, forced vital capacity (FVC) in liters, percentage of FVC exhaled in the first second (FEV1/FVC), and maximal midexpiratory flow rate (MMEF) in liters per minute and COPD status, defined as meeting the Global Initiative for Chronic Obstructive Lung Diseases stage II (or higher) criteria. Both outcomes were measured as each visit.ResultsAmong 1549 included men (mean [SD] age, 68.3 [9.3] years) with 7466 visits from 1982 to 2018, a 1-unit increase in NLR was associated with statistically significant mean (SE) decreases of 0.021 (0.004) L in FEV1, 0.016 (0.005) L in FVC, 0.290% (0.005) L in FVC, 0.290% (0.065%) in FEV1/FVC, and 3.65 (0.916) L/min MMEF. Changes in NLR up to approximately 10 years were associated with corresponding longitudinal changes in lung function. Furthermore, this increase in NLR was associated with 9% higher odds of COPD (odds ratio, 1.09 [95% CI, 1.03-1.15]) for all visits and 27% higher risk of incident COPD (odds ratio, 1.07 [95% CI, 1.07-1.51]) for participants without COPD at baseline. Additionally, a 1-unit increase in NLR was associated with a mean (SE) decrease of 0.0048 (0.0021 in cg05575921 hypomethylation, which may mediate the adverse association of NLR-related inflammation on lung function.Conclusions and relevanceThese findings suggest that NLR may be a clinically relevant biomarker associated with high risk of lung function impairment and COPD alone or in combination with DNA methylation profiles.
| S-EPMC7358911 | biostudies-literature
Project description:Cumulative risk (CR) models provide some of the most robust findings in the developmental literature, predicting numerous and varied outcomes. Typically, however, these outcomes are predicted one at a time, across different samples, using concurrent designs, longitudinal designs of short duration, or retrospective designs. We predicted that a single CR index, applied within a single sample, would prospectively predict diverse outcomes, i.e., depression, intelligence, school dropout, arrest, smoking, and physical disease from childhood to adulthood. Further, we predicted that number of risk factors would predict number of adverse outcomes (cumulative outcome; CO). We also predicted that early CR (assessed at age 5/6) explains variance in CO above and beyond that explained by subsequent risk (assessed at ages 12/13 and 19/20). The sample consisted of 284 individuals, 48% of whom were diagnosed with a speech/language disorder. Cumulative risk, assessed at 5/6-, 12/13-, and 19/20-years-old, predicted aforementioned outcomes at age 25/26 in every instance. Furthermore, number of risk factors was positively associated with number of negative outcomes. Finally, early risk accounted for variance beyond that explained by later risk in the prediction of CO. We discuss these findings in terms of five criteria posed by these data, positing a "mediated net of adversity" model, suggesting that CR may increase some central integrative factor, simultaneously augmenting risk across cognitive, quality of life, psychiatric and physical health outcomes.
| S-EPMC4452593 | biostudies-other
Project description:There is increasing evidence that leading an active, socially engaged lifestyle might protect against cognitive decline. The arts have been proposed as potentially beneficial activities due to their combination of cognitive complexity and mental creativity. Yet it remains uncertain which types of arts engagement and what level of engagement is required for potential benefits to accrue. This study therefore explored the association between three types of cultural engagement (visiting museums/galleries/exhibitions, going to the theatre/concert/opera and going to the cinema) and change in cognitive function over 10 years amongst adults aged over 52. Our participants (n?=?3,445), drawn from the English Longitudinal Study of Ageing, were assessed in 2004/5 and 2014/15. We measured memory and semantic fluency at baseline and follow-up, analysing results using ordinary least squares regression models. Independent of demographic, health and social confounders, visiting museums/galleries/exhibitions and going to the theatre/concert/opera were associated with a lesser decline in cognitive function. Sensitivity analyses confirmed effects were unaffected by considerations of mobility or dementia diagnoses. However, going to the cinema was found to hold little effect for cognitive preservation. Overall, our results suggest that more frequent cultural engagement is associated with more marked effects, but even annual engagement may be protective.
| S-EPMC6033851 | biostudies-other
Project description:BACKGROUND:Patients who develop horizontal and vertical saccadic palsy after cardiac surgery have rarely been described. Although most such patients exhibit distinct neurological deficits, their brain MRI findings are almost normal. In addition, functional neuroimaging of such patients has never been reported. CASE REPORT:A 43-year-old woman with dysarthria, dysphagia, and horizontal and vertical saccadic palsy after cardiac surgery was followed up for about 6 years; serial brain MRIs has been performed during this period, including susceptibility-weighted imaging (SWI) and [(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Multiple microbleeds in the cerebral cortex, cerebellum, and brainstem, and glucose hypometabolism in the brainstem, cerebellum, and multiple cortical areas. CONCLUSIONS:To the best of our knowledge, this is the first reported case of saccadic palsy after cardiac surgery with serial SWI and [(18)F]-FDG-PET performed to explore the possible cerebral lesions.
| S-EPMC4198721 | biostudies-literature