Lifetime vigorous but not light-to-moderate habitual physical activity impacts favorably on carotid stiffness in young adults the Amsterdam growth and health longitudinal study

Higher levels of habitual physical activity favorably impact on arterial stiffness. It is not clear, however, whether lifetime habitual physical activities of different intensities carry the same protective effect and to what extent any such effect is mediated by other biological cardiovascular risk factors. We, therefore, examined longitudinal data on habitual physical activity and cardiovascular risk factors (8 repeated measures between the ages of 13 and 36 years) in 373 subjects in whom stiffness estimates of the carotid artery were assessed at age 36 years using noninvasive ultrasonography. The time spent in habitual physical activities (in minutes per week) throughout the longitudinal period was compared between subjects across tertiles of the following stiffness estimates: β-stiffness index, distensibility and compliance coefficients, and the Young's elastic modulus. After adjustments for sex, body height, and other lifestyle variables, subjects in the highest tertile of the β-stiffness index (ie, with stiffer arteries) had spent, on average, throughout the longitudinal period, less time in vigorous (-26.5 [95% CI:-45.9 to-7.1]) but less so in light-to-moderate habitual physical activities (-11.2 [95% CI:-53.5 to 31.1]) as compared with subjects in the lowest tertile. The difference in time spent in vigorous activities was greatly attenuated when further adjusted for blood lipids, cardiorespiratory fitness, fat distribution, resting heart rate, and mean arterial pressure (to-11.2 [95% CI:-29.4 to 7.0]). Similar results were found for the other stiffness estimates. Promoting vigorous intensity physical activities among the healthy young may, therefore, prevent arterial stiffness and related cardiovascular sequelae later in life, partly through its favorable impact on other biological cardiovascular risk factors

Exploring co-dispensed drug use in patients on sevelamer or polystyrene sulfonate to identify potential novel binding interactions:a cross sectional in silico study: Potential novel binding interactions with resins

Background Sevelamer and polystyrene sulfonate are used for treating hyperphosphatemia and hyperkalaemia in chronic kidney disease patients. Because of their binding properties, these resins potentially bind other drugs in the gastrointestinal tract, thereby decreasing their bioavailability and clinical effectiveness. Aim The aim of this study was to explore co-dispensed drug use in patients on sevelamer or polystyrene sulfonate to identify potential novel binding interactions. Method In this in silico study, the 100 drugs most frequently co-dispensed with sevelamer/polystyrene sulfonate in the period 2000-2018 were extracted from the University Groningen IADB.nl database. Drugs dispensed to  2.0 were identified as potential interacting drug. For polystyrene sulfonate, drugs with a pKa (base) > 1.5 were identified as potential interacting drug. Results Of the top 100 drugs most frequently co-dispensed with sevelamer/polystyrene sulfonate, 22 and 27 potentially clinically relevant new interacting drugs were identified for sevelamer and polystyrene sulfonate respectively. Conclusion Several potentially relevant novel binding interactions for sevelamer and polystyrene sulfonate were identified based on dispensing data and assessment of chemical properties for which further interaction research is warranted

PERFECTRA:A pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs

Objective To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting. Methods Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) &lt;2.6, changes in PROMs and radiographic progression. Results A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP &lt;2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients. Conclusion Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.</p

PERFECTRA:A pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs

Objective To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting. Methods Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) &lt;2.6, changes in PROMs and radiographic progression. Results A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP &lt;2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients. Conclusion Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.</p

PERFECTRA:A pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs

Objective To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting. Methods Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) &lt;2.6, changes in PROMs and radiographic progression. Results A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP &lt;2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients. Conclusion Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.</p

Monitoring recently acquired HIV infections in Amsterdam, The Netherlands:The attribution of test locations

Background:  Surveillance of recent HIV infections (RHI) using an avidity assay has been implemented at Dutch sexual health centres (SHC) since 2014, but data on RHI diagnosed at other test locations is lacking. Setting:  Implementation of the avidity assay in HIV treatment clinics for the purpose of studying RHI among HIV patients tested at different test locations. Methods: We retrospectively tested leftover specimens from newly diagnosed HIV patients in care in 2013–2015 in Amsterdam. Avidity Index (AI) values ≤0.80 indicated recent infection (acquired ≤6 months prior to diagnosis), and AI > 0.80 indicated established infection (acquired >6 months prior to diagnosis). An algorithm for RHI was applied to correct for false recency. Recency based on this algorithm was compared with recency based on epidemiological data only. Multivariable logistic regression analysis was used to identify factors associated with RHI among men who have sex with men (MSM).Results: We tested 447 specimens with avidity; 72% from MSM. Proportions of RHI were 20% among MSM and 10% among heterosexuals. SHC showed highest proportions of RHI (27%), followed by GPs (15%), hospitals (5%), and other/unknown locations (11%) (p < 0.001). Test location was the only factor associated with RHI among MSM. A higher proportion of RHI was found based on epidemiological data compared to avidity testing combined with the RHI algorithm. Conclusion:  SHC identify more RHI infections compared to other test locations, as they serve high-risk populations and offer frequent HIV testing. Using avidity-testing for surveillance purposes may help targeting prevention programs, but the assay lacks robustness and its added value may decline with improved, repeat HIV testing and data collection

Denktank Overlijdensschade: nieuwe richting benadering en berekening overlijdensschade

De denktank overlijdensschade is ontstaan, omdat de rekenmethodiek voor overlijdensschade niet uit te leggen is aan nabestaanden en geen recht doet aan de maatschappelijke ontwikkelingen. Diverse professionals besloten niet langer slechts te ageren tegen de bestaande situatie, maar er werkelijk wat aan te doen. Dit heeft geresulteerd in een conceptnotitie ‘Nieuwe richting benadering en berekening overlijdensschade’. In dit artikel wordt deze notitie kort besproken

Improving the evaluation of worldwide biomedical research output: classification method and standardised bibliometric indicators by disease

Merit, Expertise and Measuremen

Comparative effectiveness of improvement in pain and physical function for baricitinib versus adalimumab, tocilizumab, and tofacitinib monotherapies in rheumatoid arthritis patients who are naïve to treatment with biologic or conventional synthetic disease-modifying antirheumatic drugs: a matching-adjusted indirect comparison

Objective To compare improvement in pain and physical function for patients treated with baricitinib, adalimumab, tocilizumab and tofacitinib monotherapy from randomised, methotrexate (MTX)-controlled trials in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)/biologic (bDMARD)-naïve RA patients using matching-adjusted indirect comparisons (MAICs). Methods Data were from Phase III trials on patients receiving monotherapy baricitinib, tocilizumab, adalimumab, tofacitinib or MTX. Pain was assessed using a visual analogue scale (0–100 mm) and physical function using the Health Assessment Questionnaire-Disability Index (HAQ-DI). An MAIC based on treatment-arm matching, an MAIC with study-level matching and Bucher’s method without matching compared change in outcomes between therapies. Matching variables included age, gender, baseline disease activity and baseline value of outcome measure. Results With all methods, greater improvements were observed in pain and HAQ-DI at 6 months for baricitinib compared with adalimumab and tocilizumab (p<0.05). Differences in treatment effects (TEs) favouring baricitinib for pain VAS for treatment-arm matching, study-level matching and Bucher’s method, respectively, were −12, −12 and −12 for baricitinib versus adalimumab and −7, −7 and −9 for baricitinib versus tocilizumab; the difference in TEs for HAQ-DI was −0.28, −0.28 and −0.30 for adalimumab and −0.23, −0.23 and −0.26 for tocilizumab. For baricitinib versus tofacitinib, no statistically significant differences for pain improvement were observed except with one of the three methods (Bucher method) and none for HAQ-DI. Conclusions Results suggest greater pain reduction and improved physical function for baricitinib monotherapy compared with tocilizumab and adalimumab monotherapy. No statistically significant differences in pain reduction and improved physical function were observed between baricitinib and tofacitinib with the MAIC analyses

Notitie Denktank Overlijdensschade. Nieuwe richting benadering en berekening overlijdensschade

In 2009 is een werkgroep onder de naam Denktank Overlijdensschade gestart met het bestuderen van een ander, aan de huidige tijd aangepast model voor de berekening van overlijdensschade. Doelstelling was te komen tot een, ook voor nabestaanden, transparantie systematiek welke recht doet aan de vorderingsgerechtigdheid van de nabestaanden. In 2014 heeft de Denktank Overlijdensschade haar werkzaamheden voltooid met het opleveren van een nieuwe rekenmethodiek. In deze Notitie wordt beschreven hoe de Denktank tot deze nieuwe benadering van het berekenen van overlijdensschade is gekomen, welke onderzoeken daaraan ten grondslag liggen en wat de uiteindelijke rekenregel is, die nu voorgesteld wordt. Kern van de nieuwe methodiek is het uitgangspunt dat het gezin als economische eenheid wordt beschouwd, voor én na het overlijden