scholarly journals High rates of JCV seroconversion in a large international cohort of natalizumab-treated patients

2021 ◽  
Vol 14 ◽  
pp. 175628642199891
Author(s):  
Christopher M. Dwyer ◽  
Vilija G. Jokubaitis ◽  
Jim Stankovich ◽  
Josephine Baker ◽  
Jodi Haartsen ◽  
...  
Keyword(s):  
Seroconversion Rate ◽  
Epidemiological Studies ◽  
Sensitivity Analyses ◽  
Event Analysis ◽  
Tertiary Centre ◽  
Natalizumab Treatment ◽  
Tertiary Hospitals ◽  
Post Marketing ◽  
Male Sex ◽  
Immune Changes

Aims: To retrospectively assess factors associated with John Cunningham virus (JCV) seroconversion in natalizumab-treated patients. Background: Natalizumab is highly effective for the treatment of relapsing–remitting multiple sclerosis (RRMS), but its use is complicated by opportunistic JCV infection. This virus can result in progressive multifocal leukoencephalopathy (PML). Serial assessment of JCV serostatus is mandated during natalizumab treatment. Methods: Patients treated with natalizumab for RRMS at six tertiary hospitals in Melbourne, Australia ( n = 865) and 11 MS treatment centres in Brazil ( n = 136) were assessed for change in JCV serostatus, duration of exposure to natalizumab and prior immunosuppression. Sensitivity analyses examined whether sex, age, tertiary centre, prior immunosuppression or number of JCV tests affected time to seroconversion. Results: From a cohort of 1001 natalizumab-treated patients, durable positive seroconversion was observed in 83 of 345 initially JCV negative patients (24.1%; 7.3% per year). Conversely, 16 of 165 initially JCV positive patients experienced durable negative seroconversion (9.7%; 3.8% per year). Forty patients (3.9%) had fluctuating serostatus. Time-to-event analysis did not identify a relationship between JCV seroconversion and duration of natalizumab exposure. Prior exposure to immunosuppression was not associated with an increased hazard of positive JCV seroconversion. Male sex was associated with increased JCV seroconversion risk [adjusted hazard ratio 2.09 (95% confidence interval 1.17–3.71) p = 0.012]. Conclusion: In this large international cohort of natalizumab-treated patients we observed an annual durable positive seroconversion rate of 7.3%. This rate exceeds that noted in registration and post-marketing studies for natalizumab. This rate also greatly exceeds that predicted by epidemiological studies of JCV seroconversion in healthy populations. Taken together, our findings support emerging evidence that natalizumab causes off-target immune changes that may be trophic for JCV seroconversion. In addition, male sex may be associated with increased positive JCV seroconversion.

scholarly journals Ambient temperature and subsequent COVID-19 mortality in the OECD countries and individual United States

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Costas A. Christophi ◽  
Mercedes Sotos-Prieto ◽  
Fan-Yun Lan ◽  
Mario Delgado-Velandia ◽  
Vasilis Efthymiou ◽  
...  
Keyword(s):  
United States ◽  
Ambient Temperature ◽  
Negative Binomial ◽  
Negative Binomial Regression ◽  
Weather Conditions ◽  
Oecd Countries ◽  
Epidemiological Studies ◽  
Sociodemographic Factors ◽  
Sensitivity Analyses ◽  
Inverse Association

AbstractEpidemiological studies have yielded conflicting results regarding climate and incident SARS-CoV-2 infection, and seasonality of infection rates is debated. Moreover, few studies have focused on COVD-19 deaths. We studied the association of average ambient temperature with subsequent COVID-19 mortality in the OECD countries and the individual United States (US), while accounting for other important meteorological and non-meteorological co-variates. The exposure of interest was average temperature and other weather conditions, measured at 25 days prior and 25 days after the first reported COVID-19 death was collected in the OECD countries and US states. The outcome of interest was cumulative COVID-19 mortality, assessed for each region at 25, 30, 35, and 40 days after the first reported death. Analyses were performed with negative binomial regression and adjusted for other weather conditions, particulate matter, sociodemographic factors, smoking, obesity, ICU beds, and social distancing. A 1 °C increase in ambient temperature was associated with 6% lower COVID-19 mortality at 30 days following the first reported death (multivariate-adjusted mortality rate ratio: 0.94, 95% CI 0.90, 0.99, p = 0.016). The results were robust for COVID-19 mortality at 25, 35 and 40 days after the first death, as well as other sensitivity analyses. The results provide consistent evidence across various models of an inverse association between higher average temperatures and subsequent COVID-19 mortality rates after accounting for other meteorological variables and predictors of SARS-CoV-2 infection or death. This suggests potentially decreased viral transmission in warmer regions and during the summer season.

scholarly journals Prevalence of personality disorders in the general adult population in Western countries: systematic review and meta-analysis

2018 ◽  
Vol 213 (6) ◽  
pp. 709-715 ◽  
Author(s):  
Jana Volkert ◽  
Thorsten-Christian Gablonski ◽  
Sven Rabung
Keyword(s):  
Personality Disorder ◽  
Personality Disorders ◽  
Meta Analysis ◽  
Adult Population ◽  
Epidemiological Studies ◽  
Sensitivity Analyses ◽  
Prevalence Rates ◽  
Efficient Treatment ◽  
Random Effects Models ◽  
Western Countries

BackgroundPersonality disorder is a severe health issue. However, the epidemiology of personality disorders is insufficiently described and surveys report very heterogeneous rates.AimsWe aimed to conduct a meta-analysis on the prevalence of personality disorders in adult populations and examine potential moderators that affect heterogeneity.MethodWe searched PsycINFO, PSYNDEX and Medline for studies that used standardised diagnostics (DSM-IV/-5, ICD-10) to report prevalence rates of personality disorders in community populations in Western countries. Prevalence rates were extracted and aggregated by random-effects models. Meta-regression and sensitivity analyses were performed and publication bias was assessed.ResultsThe final sample comprised ten studies, with a total of 113 998 individuals. Prevalence rates were fairly high for any personality disorder (12.16%; 95% CI, 8.01–17.02%) and similarly high for DSM Clusters A, B and C, between 5.53 (95% CI, 3.20–8.43%) and 7.23% (95% CI, 2.37–14.42%). Prevalence was highest for obsessive–compulsive personality disorder (4.32%; 95% CI, 2.16–7.16%) and lowest for dependent personality disorder (0.78%; 95% CI, 0.37–1.32%). A low prevalence was significantly associated with expert-rated assessment (versus self-rated) and reporting of descriptive statistics for antisocial personality disorder.ConclusionsEpidemiological studies on personality disorders in community samples are rare, whereas prevalence rates are fairly high and vary substantially depending on samples and methods. Future studies investigating the epidemiology of personality disorders based on the DSM-5 and ICD-11 and models of personality functioning and traits are needed, and efficient treatment should be a priority for healthcare systems to reduce disease burden.Declaration of interestNone.

A Swedish national post-marketing surveillance study of natalizumab treatment in multiple sclerosis

2011 ◽  
Vol 17 (6) ◽  
pp. 708-719 ◽  
Author(s):  
Carolina Holmén ◽  
Fredrik Piehl ◽  
Jan Hillert ◽  
Anna Fogdell-Hahn ◽  
Malin Lundkvist ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Drug Effects ◽  
Surveillance Study ◽  
Serious Adverse Events ◽  
Web Based ◽  
Quality Registry ◽  
Post Marketing Surveillance ◽  
Natalizumab Treatment ◽  
Post Marketing

Background: A post marketing surveillance study was conducted to evaluate safety and efficacy of natalizumab in Swedish multiple sclerosis (MS) patients since its introduction in August 2006 until March 2010. Methods: Patients were registered in the web-based Swedish MS-registry at 40 locations and evaluated every 6 months. Adverse events and clinical outcomes were recorded. Results: One thousand one hundred and fifty-two patients were included (71.4% female) and 149 patients stopped treatment; the main reason was planned pregnancy. Anti-natalizumab antibodies were found in 4.5% (52 patients) of which 1.6% displayed persistent antibodies. Serious adverse events were rare, but included three cases with progressive multifocal leukoencephalopathy (PML). There were seven fatal cases, probably unrelated to the natalizumab treatment. For relapsing–remitting MS patients ( n = 901), mean Expanded Disability Status Scale (EDSS, −10.7%), Multiple Sclerosis Severity Scale (MSSS, −20.4%), Multiple Sclerosis Impact Scale (MSIS-29, physical −9.9%, psychological −13.3%) and Symbol Digit Modalities Test (SDMT, +10.7%) all showed significant improvements during 24 months of treatment with natalizumab. The Swedish web-based MS quality registry proved to function as a platform for post-marketing MS drug surveillance, providing long-term data regarding drug effects and adverse events beyond clinical trials. Conclusions: Our results indicate that natalizumab is generally well tolerated and has sustained efficacy for patients with active MS, though the risk of PML is still an important concern.

scholarly journals Dairy consumption and CVD: a systematic review and meta-analysis

2016 ◽  
Vol 115 (4) ◽  
pp. 737-750 ◽  
Author(s):  
Dominik D. Alexander ◽  
Lauren C. Bylsma ◽  
Ashley J. Vargas ◽  
Sarah S. Cohen ◽  
Abigail Doucette ◽  
...  
Keyword(s):  
Cohort Studies ◽  
Dose Response ◽  
Prospective Cohort ◽  
Meta Analysis ◽  
Epidemiological Studies ◽  
Sensitivity Analyses ◽  
Dairy Intake ◽  
Prospective Cohort Studies ◽  
Dairy Consumption ◽  
Risk Estimates

AbstractInverse associations between dairy consumption and CVD have been reported in several epidemiological studies. Our objective was to conduct a meta-analysis of prospective cohort studies of dairy intake and CVD. A comprehensive literature search was conducted to identify studies that reported risk estimates for total dairy intake, individual dairy products, low/full-fat dairy intake, Ca from dairy sources and CVD, CHD and stroke. Random-effects meta-analyses were used to generate summary relative risk estimates (SRRE) for high v. low intake and stratified intake dose–response analyses. Additional dose–response analyses were performed. Heterogeneity was examined in sub-group and sensitivity analyses. In total, thirty-one unique cohort studies were identified and included in the meta-analysis. Several statistically significant SRRE below 1.0 were observed, namely for total dairy intake and stroke (SRRE=0·91; 95 % CI 0·83, 0·99), cheese intake and CHD (SRRE=0·82; 95 % CI 0·72, 0·93) and stroke (SRRE=0·87; 95 % CI 0·77, 0·99), and Ca from dairy sources and stroke (SRRE=0·69; 95 % CI 0·60, 0·81). However, there was little evidence for inverse dose–response relationships between the dairy variables and CHD and stroke after adjusting for within-study covariance. The results of this meta-analysis of prospective cohort studies have shown that dairy consumption may be associated with reduced risks of CVD, although additional data are needed to more comprehensively examine potential dose–response patterns.

scholarly journals Left-censored recurrent event analysis in epidemiological studies: a proposal for when the number of previous episodes is unknown

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Gilma Hernández-Herrera ◽  
David Moriña ◽  
Albert Navarro
Keyword(s):  
At Risk ◽  
Recurrent Events ◽  
Counting Process ◽  
Frailty Model ◽  
R Package ◽  
Epidemiological Studies ◽  
Recurrent Event ◽  
Event Analysis ◽  
Gap Time

Abstract Background When dealing with recurrent events in observational studies it is common to include subjects who became at risk before follow-up. This phenomenon is known as left censoring, and simply ignoring these prior episodes can lead to biased and inefficient estimates. We aimed to propose a statistical method that performs well in this setting. Methods Our proposal was based on the use of models with specific baseline hazards. In this, the number of prior episodes were imputed when unknown and stratified according to whether the subject had been at risk of presenting the event before t = 0. A frailty term was also used. Two formulations were used for this “Specific Hazard Frailty Model Imputed” based on the “counting process” and “gap time.” Performance was then examined in different scenarios through a comprehensive simulation study. Results The proposed method performed well even when the percentage of subjects at risk before follow-up was very high. Biases were often below 10% and coverages were around 95%, being somewhat conservative. The gap time approach performed better with constant baseline hazards, whereas the counting process performed better with non-constant baseline hazards. Conclusions The use of common baseline methods is not advised when knowledge of prior episodes experienced by a participant is lacking. The approach in this study performed acceptably in most scenarios in which it was evaluated and should be considered an alternative in this context. It has been made freely available to interested researchers as R package miRecSurv.

scholarly journals Association of lung clearance index with survival in individuals with cystic fibrosis

2021 ◽  
pp. 2100432
Author(s):  
Johanna Manuela Kurz ◽  
Kathryn Angela Ramsey ◽  
Romy Rodriguez ◽  
Ben Spycher ◽  
Reta Fischer Biner ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Sensitivity Analyses ◽  
Event Analysis ◽  
Z Score ◽  
Lung Clearance ◽  
Risk Of Death ◽  
Ventilation Inhomogeneity ◽  
Hazard Ratios ◽  
Lung Clearance Index ◽  
The Mean

BackgroundThe lung clearance index (LCI) assesses global ventilation inhomogeneity and is a sensitive biomarker of airway function in cystic fibrosis (CF) lung disease.ObjectivesWe examined the association of LCI with the risk of death or lung transplantation (LTX) in individuals with CF.MethodsWe performed a retrospective analysis in a cohort of individuals with CF aged≥5 years with LCI and FEV1 measurements performed between 1980 and 2006. The outcome was time until death or LTX. We used the earliest available LCI and FEV1 values in a Cox proportional hazard regression adjusted for demographic and clinical variables. For sensitivity analyses, we used the mean of the first three LCI and FEV1 measurements, stratified the cohort based on age, and investigated individuals with normal FEV1.ResultsIn total, 237 individuals with CF with a mean (range) age of 13.9 (5.6–41.0) years were included. The time-to-event analysis accrued 3813 person-years and 94 (40%) individuals died or received LTX. Crude hazard ratios [95% CI] were 1.04 [1.01–1.06] per one z-score increase in LCI and 1.25 [1.11–1.41] per one z-score decrease in FEV1. After adjusting LCI and FEV1 mutually in addition to sex, age, BMI and the number of hospitalisations, hazard ratios were 1.04 [1.01–1.07] for LCI, and 1.12 [0.95–1.33] for FEV1. Sensitivity analyses yielded similar results and using the mean LCI strengthened the associations.ConclusionsIncreased ventilation inhomogeneity is associated with greater risk of death or LTX. Our data support LCI as novel surrogate of survival in individuals with CF.

scholarly journals Clinical correlates of the restless legs syndrome

2012 ◽  
Vol 70 (7) ◽  
pp. 529-531 ◽  
Author(s):  
Luis Fabiano Marin ◽  
Andre Carvalho Felicio ◽  
William Adolfo Santos ◽  
Lucila Bizari Prado ◽  
Gilmar Fernandes Prado
Keyword(s):  
Restless Legs Syndrome ◽  
Treatment Options ◽  
Disease Onset ◽  
Epidemiological Studies ◽  
Deficiency Anemia ◽  
Clinical Correlates ◽  
Restless Legs ◽  
Male Sex ◽  
Stage Renal Disease ◽  
End Stage

OBJECTIVE: To determine the clinical correlates of the restless legs syndrome (RLS) in a Brazilian sleep disorders center. METHODS: We retrospectively studied 118 patients with RLS from January, 2004, to December, 2010. The analyzed variables were: age at disease onset, gender, race, years of school instruction, primary and secondary RLS, and treatment options. RESULTS: Among the studied patients, 83.9% were women with a female/male sex ratio of 5:1. Mean age of the patients at symptom onset ± standard deviation was 41.7±17.9 years-old. The primary RLS was found in 85% of patients. The other 15% remainders consisted of secondary forms, and they were associated with neuropathy, iron deficiency anemia, end-stage renal disease, or Parkinson's disease. Drug therapy for RLS was introduced in 67% of patients. CONCLUSIONS: Most patients presented primary RLS with an early disease onset. Further epidemiological studies are welcomed to provide better information on secondary RLS in Brazil.

scholarly journals A Greater Flavonoid Intake Is Associated with Lower Total and Cause-Specific Mortality: A Meta-Analysis of Cohort Studies

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2350
Author(s):  
Mohsen Mazidi ◽  
Niki Katsiki ◽  
Maciej Banach
Keyword(s):  
Cohort Studies ◽  
Mortality Risk ◽  
Meta Analysis ◽  
Final Analysis ◽  
Epidemiological Studies ◽  
Protective Role ◽  
Sensitivity Analyses ◽  
Mortality Data ◽  
Specific Mortality ◽  
Flavonoid Intake

Introduction: The links between flavonoid intake and mortality were previously evaluated in epidemiological studies. The aim of the present study was to perform a systematic review and meta-analysis of cohort studies evaluating the link of flavonoid consumption with total and cause-specific mortality. Methods: Prospective cohort studies reporting flavonoid intake and mortality data published up to 30th April 2019 (without language restriction) were searched using PubMed, Scopus and EMBASE database. Generic inverse variance methods and random effects models were used to synthesize pooled and quantitative data. Sensitivity analysis was also performed by a leave-one-out method. Results: Overall, 16 articles met the inclusion criteria (nine studies were performed in Europe, five in the USA, one in Asia and one in Oceania); a total of 462,194 participants (all adults aged >19 years) with 23,473 mortality cases were included in the final analysis. The duration of follow-up ranged from 4.8 to 28 years. Most of the studies assessed flavonoid intake using food frequency questionnaires, whereas four studies used interviews and 1 study used 4-day food records. The meta-analysis showed that flavonoid consumption was inversely and significantly associated with total (relative risk (RR): 0.87, 95% confidence interval (CI) = 0.77–0.99) and cardiovascular disease mortality risk (RR: 0.85, 95%CI = 0.75–0.97), but not cancer (0.86, 95%CI = 0.65–1.14) mortality risk. These findings remained robust in sensitivity analyses. Conclusions: The present findings highlight the potential protective role of flavonoids against total and cause-specific mortality. These results support the recommendations for flavonoid-rich foods intake to prevent chronic diseases.

Natalizumab (Tysabri®) - Re-defining Efficacy in Multiple Sclerosis - Data from Clinical Trials to Post-marketing Experience

2009 ◽  
Vol 4 (2) ◽  
pp. 58
Author(s):  
David Bates ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Disease Progression ◽  
Large Scale ◽  
Rare Event ◽  
Management Plan ◽  
Social Consequences ◽  
Substantial Impact ◽  
Natalizumab Treatment ◽  
Post Marketing

Multiple sclerosis (MS) is a chronic, disabling condition with severe clinical and social consequences. Current first-line disease-modifying treatments have limited efficacy and do not halt long-term disease progression in the majority of patients. Natalizumab (Tysabri®) is the only monoclonal antibody licensed for use in relapsing–remitting MS (RRMS). It is regarded by many neurologists as the most effective MS drug on the market today, and has the potential to re-define successful MS therapy. Its efficacy has been demonstrated both in large-scale clinical trials and in post-marketing settings. Beneficial effects include reduction of relapse rates and disease progression and magnetic resonance imaging (MRI) measures of disease activity. Natalizumab treatment has a substantial impact on patient quality of life. Moreover, patients have shown significant improvement following natalizumab treatment, making continuing clinical remission a realistic goal in MS for the first time. However, the benefits of natalizumab must be balanced against risk. Progressive multifocal leukoencephalopathy (PML) is a rare event associated with natalizumab treatment that may be minimised with a risk management plan to educate physicians on patient selection and management.

scholarly journals Anatomical and clinical predictors of valve dysfunction and aortic dilation in bicuspid aortic valve disease

Heart ◽  
2017 ◽  
Vol 104 (7) ◽  
pp. 566-573 ◽  
Author(s):  
Arturo Evangelista ◽  
Pastora Gallego ◽  
Francisco Calvo-Iglesias ◽  
Javier Bermejo ◽  
Juan Robledo-Carmona ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Regurgitation ◽  
Bicuspid Aortic Valve ◽  
Aortic Root ◽  
Ascending Aorta ◽  
Clinical Predictors ◽  
Valve Dysfunction ◽  
Tertiary Hospitals ◽  
Male Sex

ObjectiveBicuspid aortic valve (BAV) is associated with early valvular dysfunction and proximal aorta dilation with high heterogeneity. This study aimed to assess the determinants of these complications.MethodsEight hundred and fifty-two consecutive adults diagnosed of BAV referred from cardiac outpatient clinics to eight echocardiographic laboratories of tertiary hospitals were prospectively recruited. Exclusion criteria were aortic coarctation, other congenital disorders or intervention. BAV morphotype, significant valve dysfunction and aorta dilation (≥2 Z-score) at sinuses and ascending aorta were established.ResultsThree BAV morphotypes were identified: right–left coronary cusp fusion (RL) in 72.9%, right–non-coronary (RN) in 24.1% and left–non-coronary (LN) in 3.0%. BAV without raphe was observed in 18.3%. Multivariate analysis showed aortic regurgitation (23%) to be related to male sex (OR: 2.80, p<0.0001) and valve prolapse (OR: 5.16, p<0.0001), and aortic stenosis (22%) to BAV-RN (OR: 2.09, p<0.001), the presence of raphe (OR: 2.75, p<0.001), age (OR: 1.03; p<0.001), dyslipidaemia (OR: 1.77, p<0.01) and smoking (OR: 1.63, p<0.05). Ascending aorta was dilated in 76% without differences among morphotypes and associated with significant valvular dysfunction. By contrast, aortic root was dilated in 34% and related to male sex and aortic regurgitation but was less frequent in aortic stenosis and BAV-RN.ConclusionsNormofunctional valves are more prevalent in BAV without raphe. Aortic stenosis is more frequent in BAV-RN and associated with some cardiovascular risk factors, whereas aortic regurgitation (AR) is associated with male sex and sigmoid prolapse. Although ascending aorta is the most commonly dilated segment, aortic root dilation is present in one-third of patients and associated with AR. Remarkably, BAV-RL increases the risk for dilation of the proximal aorta, whereas BAV-RN spares this area.

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