Wide range of reduced penetrance alleles in spinal and bulbar muscular atrophy: a model-based approach

2020 ◽  
pp. jmedgenet-2020-106963
Author(s):  
Achilleas Laskaratos ◽  
Marianthi Breza ◽  
Georgia Karadima ◽  
Georgios Koutsis
Keyword(s):  
General Population ◽  
Muscular Atrophy ◽  
Meta Analysis ◽  
Cag Repeat ◽  
Gene Coding ◽  
Motor Neuron Disorder ◽  
Wide Range ◽  
Increasing Risk ◽  
Reduced Penetrance ◽  
Asymptomatic Men

BackgroundSpinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s disease, is an X-linked motor neuron disorder caused by an expanded CAG repeat in the gene coding for the androgen receptor (AR). The range and significance of reduced penetrance alleles in SBMA has not been fully determined to date. We presently sought to determine the range of reduced penetrance alleles in SBMA.MethodsThrough systematic literature review and meta-analysis, we collected and analysed data from 2576 patients with SBMA and compared the distributions of the CAG repeat number (CAG)n in the AR gene between patients and 112 248 control alleles of the general population.ResultsOur analysis revealed an unexpectedly high frequency of expanded SBMA-associated alleles, with (CAG)n ≥35 present in 107/100,000 and (CAG)n ≥38 present in 27/100,000 of the general population. Consequently, we suggest an updated model describing the distribution of expanded alleles in the general population. We argue against the established cut-off principle for the penetrance of SBMA and suggest that penetrance gradually increases from 35 to approximately 46 (CAG)n, above which it reaches a plateau approaching maximum value.ConclusionAsymptomatic men of the general population with no/unknown SBMA family history are free of risk when carrying (CAG)n ≤34, are at intermediate but increasing risk for developing SBMA when carrying (CAG)n ≈35–46 and have close to 100% risk of developing the disease when carrying (CAG)n ≥47. The above observations should be helpful and clinically useful when providing genetic counselling to individuals and families bearing SBMA-associated alleles.

scholarly journals Motor function in type 2 and 3 SMA patients treated with Nusinersen: a critical review and meta-analysis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Giorgia Coratti ◽  
Costanza Cutrona ◽  
Maria Carmela Pera ◽  
Francesca Bovis ◽  
Marta Ponzano ◽  
...  
Keyword(s):  
Motor Function ◽  
Real World ◽  
Muscular Atrophy ◽  
Meta Analysis ◽  
Main Body ◽  
Real World Data ◽  
Wide Range ◽  
The Difference ◽  
Reporting Data

Abstract Background There is an increasing number of papers reporting the real world use of Nusinersen in different cohorts of SMA patients. Main body The aim of this paper was to critically review the literature reporting real world data on motor function in type 2 and 3 patients treated with Nusinersen, subdividing the results according to SMA type, age and type of assessment and performing a meta-analysis of the available results. We also report the available data collected in untreated patients using the same measures. Of the 400 papers identified searching for Nusinersen and spinal muscular atrophy, 19 reported motor function in types 2 and 3: 13 in adults, 4 in children and 2 included both. Twelve papers reported untreated patients’ data. All studies reported positive changes on at least one of the functional measures and at every time point while all-untreated cohorts showed negative changes. Conclusion Our review suggests that Nusinersen provides a favorable benefit in motor function across a wide range of SMA type 2 and 3 patients over a 10–14 month observation period. Although a direct comparison with studies reporting data from untreated patients cannot be made, the longitudinal changes in the treated cohorts (consistently positive) are divergent from those observed in the untreated cohorts (consistently negative). The difference could be observed both in the global cohorts and in smaller groups subdivided according to age, type or functional status.

scholarly journals To which extent are per-and poly-fluorinated substances associated to metabolic syndrome?

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maryam Zare Jeddi ◽  
Rozita Soltanmohammadi ◽  
Giulia Barbieri ◽  
Aline S. C. Fabricio ◽  
Gisella Pitter ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
General Population ◽  
Meta Analysis ◽  
Small Body ◽  
Epidemiological Studies ◽  
Cross Sectional ◽  
Random Effects Models ◽  
Epidemiologic Evidence ◽  
Adults And Children ◽  
Meta Analyses

Abstract Exposure to per- and polyfluoroalkyl substances (PFAS), ubiquitous persistent environmental contaminants, has led to substantial global concern due to their potential environmental and human health effects. Several epidemiological studies have assessed the possible association between PFAS exposure and risk of metabolic syndrome (MetS), however, the results are ambiguous. The aim of this study was to assess the current human epidemiologic evidence on the association between exposure to PFAS and MetS. We performed a systematic search strategy using three electronic databases (PubMed, Scopus, and Web of Science) for relevant studies concerning the associations of PFAS with MetS and its clinical relevance from inception until January 2021. We undertook meta-analyses where there were five or more studies with exposure and outcomes assessments that were reasonably comparable. The pooled odd ratios (ORs) were calculated using random effects models and heterogeneity among studies was assessed by I2 index and Q test. A total of 12 cross-sectional studies (10 studies on the general population and two studies in the occupational settings) investigated the association between PFAS exposure and MetS. We pooled data from seven studies on the general population for perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) and five studies for perfluorohexanesulfonate (PFHxS) and perfluorononanoic acid (PFNA). Predominately, most studies reported no statistically significant association between concentrations of PFAS and MetS. In the meta-analysis, the overall measure of effect was not statistically significant, showing no evidence of an association between concentrations of PFOA, PFOS, PFNA, and PFHxS and the risk of MetS. Based on the results of the meta-analysis, current small body of evidence does not support association between PFAS and MetS. However, due to limited number of studies and substantial heterogeneity, results should be interpreted with caution. Further scrutinizing cohort studies are needed to evaluate the association between various and less well-known PFAS substances and their mixture with MetS and its components in both adults and children in different settings.

scholarly journals Health Consequences of an Elite Sporting Career: Long-Term Detriment or Long-Term Gain? A Meta-Analysis of 165,000 Former Athletes

2020 ◽  
Author(s):  
Adam Runacres ◽  
Kelly A. Mackintosh ◽  
Melitta A. McNarry
Keyword(s):  
General Population ◽  
Cancer Mortality ◽  
English Language ◽  
Meta Analysis ◽  
Premature Mortality ◽  
Epidemiological Studies ◽  
Registration Number ◽  
Mortality Ratio ◽  
Former Elite Athletes

Abstract Introduction Exercise is widely accepted to improve health, reducing the risk of premature mortality, cardiovascular disease (CVD) and cancer. However, several epidemiological studies suggest that the exercise-longevity relationship may be ‘J’ shaped; with elite athlete’s likely training above these intensity and volume thresholds. Therefore, the aim of this meta-analysis was to examine this relationship in former elite athletes. Methods 38,047 English language articles were retrieved from Web of Science, PubMed and SportDiscus databases published after 1970, of which 44 and 24 were included in the systematic review and meta-analysis, respectively. Athletes were split into three groups depending on primary sport: Endurance (END), Mixed/Team, or power (POW). Standard mortality ratio’s (SMR) and standard proportionate mortality ratio (SPMR) were obtained, or calculated, and combined for the meta-analysis. Results Athletes lived significantly longer than the general population (male SMR 0.69 [95% CI 0.61–0.78]; female SMR 0.51 [95% CI 0.40–0.65]; both p < 0.01). There was no survival benefit for male POW athletes compared to the general population (SMR 1.04 [95% CI 0.91–1.12]). Although male athlete’s CVD (SMR 0.73 [95% CI 0.62–0.85]) and cancer mortality (SMR 0.75 [95% CI 0.63–0.89]), were significantly reduced compared to the general population, there was no risk-reduction for POW athletes CVD mortality (SMR 1.10 [0.86–1.40]) or END athletes cancer mortality (SMR 0.73 [0.50–1.07]). There was insufficient data to calculate female sport-specific SMR’s. Discussion Overall, athletes live longer and have a reduced incidence of both CVD and cancer mortality compared to the general population, refuting the ‘J’ shape hypothesis. However, different health risks may be apparent according to sports classification, and between sexes, warranting further investigation. Trial registration PROSPERO (registration number: CRD42019130688).

scholarly journals Long-Term and Short-Term Prognostic Value of Circulating Soluble Suppression of Tumorigenicity-2 Concentration in Chronic Heart Failure: A Systematic Review and Meta-Analysis

Cardiology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Guoqi Dong ◽  
Hao Chen ◽  
Hongru Zhang ◽  
Yihuang Gu
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Prognostic Value ◽  
Web Of Science ◽  
Meta Analysis ◽  
Short Term ◽  
Prisma Statement ◽  
All Cause Mortality ◽  
Increasing Risk

<b><i>Introduction:</i></b> Soluble suppression of tumorigenicity-2 (sST2) has been considered as a prognostic factor of cardiovascular disease. However, the prognostic value of sST2 concentration in chronic heart failure remains to be summarized. <b><i>Methods:</i></b> We searched PubMed, Embase, and Web of Science for eligible studies up to January 1, 2020. Data extracted from articles and provided by authors were used in agreement with the PRISMA statement. The endpoints were all-cause mortality (ACM), cardiovascular mortality (CVM)/heart failure-related hospitalization (HFH), and all-cause mortality (ACM)/heart failure-related readmission (HFR). <b><i>Results:</i></b> A total of 11 studies with 5,121 participants were included in this analysis. Higher concentration of sST2 predicted the incidence of long-term ACM (hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 1.02–1.04), long-term ACM/HFR (HR: 1.42, CI: 1.27–1.59), and long-term CVM/HFH (HR: 2.25, CI: 1.82–2.79), regardless of short-term ACM/HFR (HR: 2.31, CI: 0.71–7.49). <b><i>Conclusion:</i></b> Higher sST2 concentration at baseline is associated with increasing risk of long-term ACM, ACM/HFR, and CVM/HFH and can be a tool for the prognosis of chronic heart failure.

scholarly journals Mental disorders among adults formerly in out-of-home care: a systematic review and meta-analysis of longitudinal studies

2021 ◽  
Author(s):  
Süheyla Seker ◽  
Cyril Boonmann ◽  
Heike Gerger ◽  
Lena Jäggi ◽  
Delfine d’Huart ◽  
...  
Keyword(s):  
Child Welfare ◽  
General Population ◽  
Mental Disorders ◽  
Juvenile Justice ◽  
Meta Analysis ◽  
Prevalence Rates ◽  
Out Of Home Care ◽  
Specific Disorders ◽  
Home Placement ◽  
Care History

AbstractWhile children and adolescents placed in child welfare or juvenile justice out-of-home care show higher prevalence rates of mental disorders compared to the general population, it remains unclear whether this pattern persists into adulthood. A quantitative synthesis of existing studies is lacking. The aim of this meta-analysis was to estimate the prevalence rates for mental disorders among adults with a foster or residential child welfare or juvenile justice care history, comparing them where possible to rates among the general population. PubMed, PsycInfo, EMBASE, and Web of Science were systematically searched for epidemiological studies published up to 28 October 2020. Nineteen studies, totaling 604,257 participants, met our inclusion criteria. Random-effects models were used for prevalence rates and odds ratios (OR) of mental disorders, and study quality was rated. A prevalence rate of 30% [95% CI (23.36, 37.36)] for any mental disorder in adults with a child welfare care history was found (3–17% for specific disorders). A prevalence rate of 45% [95% CI (42.38, 47.38)] for any mental disorder was found in adults with a juvenile justice care history (6–66% for specific disorders). For out-of-home placement history, adult mental disorders were significantly higher than in the general population (OR = 1.33–2.76). Studies differed in terms of methodology and the disorder groups considered, so heterogeneity between effect sizes ranged from low to high. Our findings suggest that the high risk that mental health issues will persist in adults with an out-of-home placement history needs to be taken seriously in the transition from adolescence to adulthood. The care systems involved need to collaborate and to be aware of these risks.

scholarly journals The Comprehensive Autistic Trait Inventory (CATI): development and validation of a new measure of autistic traits in the general population

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michael C. W. English ◽  
Gilles E. Gignac ◽  
Troy A. W. Visser ◽  
Andrew J. O. Whitehouse ◽  
James T. Enns ◽  
...  
Keyword(s):  
Factor Analysis ◽  
General Population ◽  
Measurement Invariance ◽  
High Reliability ◽  
Predictive Ability ◽  
Autistic Traits ◽  
Autism Spectrum ◽  
Autism Spectrum Quotient ◽  
Sensory Sensitivity ◽  
Wide Range

Abstract Background Traits and characteristics qualitatively similar to those seen in diagnosed autism spectrum disorder can be found to varying degrees in the general population. To measure these traits and facilitate their use in autism research, several questionnaires have been developed that provide broad measures of autistic traits [e.g. Autism-Spectrum Quotient (AQ), Broad Autism Phenotype Questionnaire (BAPQ)]. However, since their development, our understanding of autism has grown considerably, and it is arguable that existing measures do not provide an ideal representation of the trait dimensions currently associated with autism. Our aim was to create a new measure of autistic traits that reflects our current understanding of autism, the Comprehensive Autism Trait Inventory (CATI). Methods In Study 1, 107 pilot items were administered to 1119 individuals in the general population and exploratory factor analysis of responses used to create the 42-item CATI comprising six subscales: Social Interactions, Communication, Social Camouflage, Repetitive Behaviours, Cognitive Rigidity, and Sensory Sensitivity. In Study 2, the CATI was administered to 1068 new individuals and confirmatory factor analysis used to verify the factor structure. The AQ and BAPQ were administered to validate the CATI, and additional autistic participants were recruited to compare the predictive ability of the measures. In Study 3, to validate the CATI subscales, the CATI was administered to 195 new individuals along with existing valid measures qualitatively similar to each CATI subscale. Results The CATI showed convergent validity at both the total-scale (r ≥ .79) and subscale level (r ≥ .68). The CATI also showed superior internal reliability for total-scale scores (α = .95) relative to the AQ (α = .90) and BAPQ (α = .94), consistently high reliability for subscales (α > .81), greater predictive ability for classifying autism (Youden’s Index = .62 vs .56–.59), and demonstrated measurement invariance for sex. Limitations Analyses of predictive ability for classifying autism depended upon self-reported diagnosis or identification of autism. The autistic sample was not large enough to test measurement invariance of autism diagnosis. Conclusions The CATI is a reliable and economical new measure that provides observations across a wide range of trait dimensions associated with autism, potentially precluding the need to administer multiple measures, and to our knowledge, the CATI is also the first broad measure of autistic traits to have dedicated subscales for social camouflage and sensory sensitivity.

scholarly journals COVID-19 in People Living with HIV: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 18 (7) ◽  
pp. 3554
Author(s):  
Kai Wei Lee ◽  
Sook Fan Yap ◽  
Yun Fong Ngeow ◽  
Munn Sann Lye
Keyword(s):  
Systematic Review ◽  
Laboratory Testing ◽  
Meta Analysis ◽  
Clinical Signs ◽  
Adverse Outcomes ◽  
People Living With Hiv ◽  
Common Symptom ◽  
Chest Imaging ◽  
Wide Range ◽  
Epidemiological Characteristics

COVID-19 is a global health emergency. People living with human immunodeficiency virus (PLHIV) have concerns about whether they have a higher risk of getting the infection and suffer worse COVID-19 outcomes. Findings from studies on these questions have largely been inconsistent. We aimed to determine the epidemiological characteristics, clinical signs and symptoms, blood parameters, and clinical outcomes among PLHIV who contracted COVID-19. Relevant studies were identified through Medline, Cinahl, and PubMed databases. A random-effects model was used in meta-analyses with a 95% confidence interval. Eighty-two studies were included in the systematic review and sixty-seven studies for the meta-analysis. The pooled incidence proportion of COVID-19 among PLHIV was 0.9% (95% CI 0.6%, 1.1%) based on the data from seven cohort studies. Overall, 28.4% were hospitalised, of whom, 2.5% was severe-critical cases and 3.5% needed intensive care. The overall mortality rate was 5.3%. Hypertension was the most commonly reported comorbidity (24.0%). Fever (71.1%) was the most common symptom. Chest imaging demonstrated a wide range of abnormal findings encompassing common changes such as ground glass opacities and consolidation as well as a spectrum of less common abnormalities. Laboratory testing of inflammation markers showed that C-reactive protein, ferritin, and interleukin-6 were frequently elevated, albeit to different extents. Clinical features as well as the results of chest imaging and laboratory testing were similar in highly active antiretroviral therapy (HAART)-treated and non-treated patients. PLHIV were not found to be at higher risk for adverse outcomes of COVID-19. Hence, in COVID-19 management, it appears that they can be treated the same way as HIV negative individuals. Nevertheless, as the pandemic situation is rapidly evolving, more evidence may be needed to arrive at definitive recommendations.

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