Development of a new wheelchair for wheelchair basketball players in the Netherlands

AbstractThe aim of the development of a new basketball wheelchair was to reduce the weight of the frame, to develop a program to fit anthropometric measurements to design a custom made wheelchair and to develop high-end wheels to increase propulsion efficiency by reducing rolling resistance. The redesigning process resulted in a frame which is 30% lighter than current aluminium wheelchair frames, a program that links anthropometric data to a CAD model of wheelchairs and a new wheel. Several tests were performed to evaluate the new wheelchair. The tests showed promising results with respect to improving both technical performance combined with the athlete's performance

Peri-operative desmopressin combined with pharmacokinetic-guided factor VIII concentrate in non-severe haemophilia A patients

Introduction: Non-severe haemophilia A patient can be treated with desmopressin or factor VIII (FVIII) concentrate. Combining both may reduce factor consumption, but its feasibility and safety has never been investigated. Aim: We assessed the feasibility and safety of combination treatment in nonsevere haemophilia A patients. Methods: Non-severe, desmopressin responsive, haemophilia A patients were included in one of two studies investigating peri-operative combination treatment. In the single-arm DAVID study intravenous desmopressin (0.3 μg/kg) once-a-day was, after sampling, immediately followed by PK-guided FVIII concentrate, for maximally three consecutive days. The Little DAVID study was a randomized trial in patients undergoing a minor medical procedure, whom received either PK-guided combination treatment (intervention arm) or PK-guided FVIII concentrate only (standard arm) up to 2 days. Dose predictions were considered accurate if the absolute difference between predicted and measured FVIII:C was ≤0.2 IU/mL. Results: In total 32 patients (33 procedures) were included. In the DAVID study (n = 21), of the FVIII:C trough levels 73.7% (14/19) were predicted accurately on day 1 (D1), 76.5% (13/17) on D2. On D0, 61.9% (13/21) of peak FVIII:C levels predictions were accurate. In the Little DAVID study (n = 12), on D0 83.3% (5/6) FVIII:C peak levels for both study arms were predicted accurately. Combination treatment reduced preoperative FVIII concentrate use by 47% versus FVIII monotherapy. Desmopressin side effects were mild and transient. Two bleeds occurred, both despite FVIII:C &gt; 1.00 IU/mL. Conclusion: Peri-operative combination treatment with desmopressin and PK-guided FVIII concentrate dosing in nonsevere haemophilia A is feasible, safe and reduces FVIII consumption.</p

Apixaban versus no anticoagulation after anticoagulation-associated intracerebral haemorrhage in patients with atrial fibrillation in the Netherlands (APACHE-AF):a randomised, open-label, phase 2 trial

Background In patients with atrial fibrillation who survive an anticoagulation-associated intracerebral haemorrhage, a decision must be made as to whether restarting or permanently avoiding anticoagulation is the best long-term strategy to prevent recurrent stroke and other vascular events. In APACHE-AF, we aimed to estimate the rates of non-fatal stroke or vascular death in such patients when treated with apixaban compared with when anticoagulation was avoided, to inform the design of a larger trial. Methods APACHE-AF was a prospective, randomised, open-label, phase 2 trial with masked endpoint assessment, done at 16 hospitals in the Netherlands. Patients who survived intracerebral haemorrhage while treated with anticoagulation for atrial fibrillation were eligible for inclusion 7-90 days after the haemorrhage. Participants also had a CHA2DS2-VASc score of at least 2 and a score on the modified Rankin scale (mRS) of 4 or less. Participants were randomly assigned (1:1) to receive oral apixaban (5 mg twice daily or a reduced dose of 2.5 mg twice daily) or to avoid anticoagulation (oral antiplatelet agents could be prescribed at the discretion of the treating physician) by a central computerised randomisation system, stratified by the intention to start or withhold antiplatelet therapy in participants randomised to avoiding anticoagulation, and minimised for age and intracerebral haemorrhage location. The primary outcome was a composite of non-fatal stroke or vascular death, whichever came first, during a minimum follow-up of 6 months, analysed using Cox proportional hazards modelling in the intention-to-treat population. APACHE-AF is registered with ClinicalTrials.gov (NCT02565693) and the Netherlands Trial Register (NL4395), and the trial is closed to enrolment at all participating sites. Findings Between Jan 15, 2015, and July 6, 2020, we recruited 101 patients (median age 78 years [IQR 73-83]; 55 [54%] were men and 46 [46%] were women; 100 [99%] were White and one [1%] was Black) a median of 46 days (IQR 21-74) after intracerebral haemorrhage. 50 were assigned to apixaban and 51 to avoid anticoagulation (of whom 26 [51%] started antiplatelet therapy). None were lost to follow-up. Over a median follow-up of 1.9 years (IQR 1.0-3.1; 222 person-years), non-fatal stroke or vascular death occurred in 13 (26%) participants allocated to apixaban (annual event rate 12.6% [95% CI 6.7-21.5]) and in 12 (24%) allocated to avoid anticoagulation (11.9% [95% CI 6.2-20.8]; adjusted hazard ratio 1.05 [95% CI 0.48-2.31]; p=0.90). Serious adverse events that were not outcome events occurred in 29 (58%) of 50 participants assigned to apixaban and 29 (57%) of 51 assigned to avoid anticoagulation. Interpretation Patients with atrial fibrillation who had an intracerebral haemorrhage while taking anticoagulants have a high subsequent annual risk of non-fatal stroke or vascular death, whether allocated to apixaban or to avoid anticoagulation. Our data underline the need for randomised controlled trials large enough to allow identification of subgroups in whom restarting anticoagulation might be either beneficial or hazardous. Copyright (C) 2021 Elsevier Ltd. All rights reserved

Diagnostic yield and accuracy of CT angiography, MR angiography, and digital subtraction angiography for detection of macrovascular causes of intracerebral haemorrhage: Prospective, multicentre cohort study

Study question What are the diagnostic yield and accuracy of early computed tomography (CT) angiography followed by magnetic resonance imaging/angiography (MRI/MRA) and digital subtraction angiography (DSA) in patients with non-traumatic intracerebral haemorrhage? Methods This prospective diagnostic study enrolled 298 adults (18-70 years) treated in 22 hospitals in the Netherlands over six years. CT angiography was performed within seven days of haemorrhage. If the result was negative, MRI/MRA was performed four to eight weeks later. DSA was performed when the CT angiography or MRI/MRA results were inconclusive or negative. The main outcome was a macrovascular cause, including arteriovenous malformation, aneurysm, dural arteriovenous fistula, and cavernoma. Three blinded neuroradiologists independently evaluated the images for macrovascular causes of haemorrhage. The reference standard was the best available evidence from all findings during one year's follow-up. Study answer and limitations A macrovascular cause was identified in 69 patients (23%). 291 patients (98%) underwent CT angiography; 214 with a negative result underwent additional MRI/MRA and 97 with a negative result for both CT angiography and MRI/MRA underwent DSA. Early CT angiography detected 51 macrovascular causes (yield 17%, 95% confidence interval 13% to 22%). CT angiography with MRI/MRA identified two additional macrovascular causes (18%, 14% to 23%) and these modalities combined with DSA another 15 (23%, 18% to 28%). This last extensive strategy failed to detect a cavernoma, which was identified on MRI during follow-up (reference strategy). The positive predictive value of CT angiography was 72% (60% to 82%), of additional MRI/MRA was 35% (14% to 62%), and of additional DSA was 100% (75% to 100%). None of the patients experienced complications with CT angiography or MRI/MRA; 0.6% of patients who underwent DSA experienced p

Peri-operative desmopressin combined with pharmacokinetic-guided factor VIII concentrate in non-severe haemophilia A patients

Introduction: Non-severe haemophilia A patient can be treated with desmopressin or factor VIII (FVIII) concentrate. Combining both may reduce factor consumption, but its feasibility and safety has never been investigated. Aim: We assessed the feasibility and safety of combination treatment in nonsevere haemophilia A patients. Methods: Non-severe, desmopressin responsive, haemophilia A patients were included in one of two studies investigating peri-operative combination treatment. In the single-arm DAVID study intravenous desmopressin (0.3 μg/kg) once-a-day was, after sampling, immediately followed by PK-guided FVIII concentrate, for maximally three consecutive days. The Little DAVID study was a randomized trial in patients undergoing a minor medical procedure, whom received either PK-guided combination treatment (intervention arm) or PK-guided FVIII concentrate only (standard arm) up to 2 days. Dose predictions were considered accurate if the absolute difference between predicted and measured FVIII:C was ≤0.2 IU/mL. Results: In total 32 patients (33 procedures) were included. In the DAVID study (n = 21), of the FVIII:C trough levels 73.7% (14/19) were predicted accurately on day 1 (D1), 76.5% (13/17) on D2. On D0, 61.9% (13/21) of peak FVIII:C levels predictions were accurate. In the Little DAVID study (n = 12), on D0 83.3% (5/6) FVIII:C peak levels for both study arms were predicted accurately. Combination treatment reduced preoperative FVIII concentrate use by 47% versus FVIII monotherapy. Desmopressin side effects were mild and transient. Two bleeds occurred, both despite FVIII:C > 1.00 IU/mL. Conclusion: Peri-operative combination treatment with desmopressin and PK-guided FVIII concentrate dosing in nonsevere haemophilia A is feasible, safe and reduces FVIII consumption

Heavy menstrual bleeding on direct factor Xa inhibitors: Rationale and design of the MEDEA study

Background: In premenopausal women, treatment with direct oral factor Xa inhibitors is associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists (VKA). Treatment with the direct oral thrombin inhibitor dabigatran appears to be associated with a reduced risk of HMB compared with VKA. These findings come from small observational studies or post hoc analyses of trials in which HMB was not a primary outcome. Use of tranexamic acid during the menstrual period may be effective in patients with HMB, but prospective data regarding efficacy and safety in patients on anticoagulant treatment are lacking. Rationale and Design: A direct comparison of a factor Xa inhibitor and a thrombin inhibitor with HMB as primary outcome, as well as an evaluation of the effects of adding tranexamic acid in women with anticoagulant-associated HMB is highly relevant for clinical practice. The MEDEA study is a randomized, open-label, pragmatic clinical trial to evaluate management strategies in premenopausal women with HMB associated with factor Xa inhibitor therapy. Outcomes: Women using factor Xa inhibitors with proven HMB, as assessed by a pictorial blood loss assessment chart (PBAC) score of >150, will be randomized to one of three study arms: (i) switch to dabigatran; (ii) continue factor Xa inhibitor with addition of tranexamic acid during the menstrual period; or (iii) continue factor Xa inhibitor without intervention. The primary outcome is the difference in PBAC score before and after randomization. Here, we present the rationale and highlight several unique features in the design of the study

Association Between Income and Risk of Out-of-Hospital Cardiac Arrest: A Retrospective Cohort Study

BACKGROUND: Previous studies have observed a higher out-of-hospital cardiac arrest (OHCA) risk among lower socioeconomic groups. However, due to the cross-sectional and ecological designs used in these studies, the magnitude of these inequalities is uncertain. This study is the first to assess the individual-level association between income and OHCA using a large-scale longitudinal study. METHODS: This retrospective cohort study followed 1 688 285 adults aged 25 and above, living in the catchment area of an OHCA registry in a Dutch province. OHCA cases (n=5493) were linked to demographic and income registries. Cox proportional hazard models were conducted to determine hazard ratios of OHCA for household and personal income quintiles, stratified by sex and age. RESULTS: The total incidence of OHCA per 100 000 person years was 30.9 in women and 87.1 in men. A higher OHCA risk was observed with lower household and personal income. Compared with the highest household income quintile, the adjusted hazard ratios from the second highest to the lowest household income quintiles ranged from 1.24 (CI=1.01-1.51) to 1.75 (CI=1.46-2.10) in women and from 0.95 (CI=0.68-1.34) to 2.30 (CI=1.74-3.05) in men. For personal income, this ranged from 0.95 (CI=0.68-1.34) to 2.30 (CI=1.74-3.05) in women and between 1.28 (CI=1.16-1.42) and 1.68 (CI=1.48-1.89) in men. Comparable household and personal income gradients were found across age groups except in the highest (>84 years) age group. For example, household income in women aged 65 to 74 ranged from 1.25 (CI=1.02-1.52) to 1.65 (CI=1.36-2.00). Sensitivity analyses assessing the prevalence of comorbidities at baseline and different lengths of follow-up yielded similar estimates. CONCLUSIONS: This study provides new evidence for a substantial increase in OHCA risk with lower income in different age and sex groups. Low-income groups are likely to be a suitable target for intervention strategies to reduce OHCA risk

Socioeconomic differences in sympathovagal balance: The healthy life in an urban setting study

Objective: Alterations in sympathovagal balance are associated with cardiovascular disease. If sympathovagal balance differs across socioeconomic groups, it may reflect a mechanism through which disparities in cardiovascular disease occur. We therefore assessed the association between education and occupation with measures of sympathovagal balance in a large multiethnic sample. Methods: We included cross-sectional data of 10,202 South Asian Surinamese, African Surinamese, Ghanaian, Turkish, Moroccan, and Dutch-origin participants from the Healthy Life in an Urban Setting study. Sympathovagal balance was measured by baroreflex sensitivity (BRS) and the standard deviation of the interbeat interval, calculated fromchanges in blood pressure and interbeat intervals, from5-minute recordings.We calculated geometric means and estimated the relative index of inequality, using age- and ethnicity-adjusted linear regression, to quantify the association between education and occupation and sympathovagal balance. In addition, we assessed whether the association was consistent across ethnic groups. Results: The geometric means of BRS ranged from 8.16 ms/mm Hg (confidence interval [CI] = 7.91-8.43 ms/mm Hg) in low-educated to 14.00 ms/mm Hg (CI = 13.53-14.48 ms/mm Hg) in highly educated women, and from 8.32 ms/mm Hg (CI, 7.97-8.69 ms/mm Hg) in low-educated to 12.25 ms/mm Hg (CI = 11.86-12.66 ms/mm Hg) in highly educated men. High education and occupation were statistically significantly associated with higher BRS and standard deviation of the interbeat interval. Compared with the participants of Dutch origin, a pattern of weaker associations was found in the Surinamese and Ghanaian ethnic groups, but not the Turkish and Moroccan groups. Conclusions: There is a clear socioeconomic gradient in measures of sympathovagal balance, indicating that sympathovagal balance may play a role in socioeconomic disparities in cardiovascular morbidity and mortality

Is the Association Between Education and Sympathovagal Balance Mediated by Chronic Stressors?

Background: This study investigated whether raised chronic stress in low education groups contributes to education differences in cardiovascular disease by altering sympathovagal balance. Methods: This study included cross-sectional data of 10,202 participants from the multi-ethnic, population-based HELIUS-study. Sympathovagal balance was measured by baroreflex sensitivity (BRS), the standard deviation of the inter-beat interval (SDNN) and the root mean square of successive differences between normal heartbeats (RMSSD). The associations between chronic stressors (work, home, psychiatric, financial, negative life events, lack of job control and perceived discrimination) in a variety of domains and BRS, SDNN and RMSSD were assessed using linear regression, adjusted for age, ethnicity, waist-to-hip ratio and pack-years smoked. Mediation analysis was used to assess the contribution of chronic stress to the association between education and sympathovagal balance. Results: Modest but significant associations were observed between financial stress and BRS and SDNN in women, but not in RMSSD nor for any outcome measure in men. Women with the highest category of financial stress had 0.55% lower BRS (ms/mmHg; β = -0.055; CI = -0.098, -0.011) and 0.61% lower SDNN (ms; β = -0.061; CI = -0.099, -0.024) than those in the lowest category. Financial stress in women contributed 7.1% to the association between education and BRS, and 13.8% to the association between education and SDNN. Conclusion: No evidence was found for the hypothesized pathway in which sympathovagal balance is altered by chronic stress, except for a small contribution of financial stress in women

Socioeconomic Differences in Sympathovagal Balance: The Healthy Life in an Urban Setting Study

OBJECTIVE: Alterations in sympathovagal balance are associated with cardiovascular disease. If sympathovagal balance differs across socioeconomic groups, it may reflect a mechanism through which disparities in cardiovascular disease occur. We therefore assessed the association between education and occupation with measures of sympathovagal balance in a large multiethnic sample. METHODS: We included cross-sectional data of 10,202 South Asian Surinamese, African Surinamese, Ghanaian, Turkish, Moroccan, and Dutch-origin participants from the Healthy Life in an Urban Setting study. Sympathovagal balance was measured by baroreflex sensitivity (BRS) and the standard deviation of the interbeat interval, calculated from changes in blood pressure and interbeat intervals, from 5-minute recordings. We calculated geometric means and estimated the relative index of inequality, using age- and ethnicity-adjusted linear regression, to quantify the association between education and occupation and sympathovagal balance. In addition, we assessed whether the association was consistent across ethnic groups. RESULTS: The geometric means of BRS ranged from 8.16 ms/mm Hg (confidence interval [CI] = 7.91-8.43 ms/mm Hg) in low-educated to 14.00 ms/mm Hg (CI = 13.53-14.48 ms/mm Hg) in highly educated women, and from 8.32 ms/mm Hg (CI, 7.97-8.69 ms/mm Hg) in low-educated to 12.25 ms/mm Hg (CI = 11.86-12.66 ms/mm Hg) in highly educated men. High education and occupation were statistically significantly associated with higher BRS and standard deviation of the interbeat interval. Compared with the participants of Dutch origin, a pattern of weaker associations was found in the Surinamese and Ghanaian ethnic groups, but not the Turkish and Moroccan groups. CONCLUSIONS: There is a clear socioeconomic gradient in measures of sympathovagal balance, indicating that sympathovagal balance may play a role in socioeconomic disparities in cardiovascular morbidity and mortality