Coordinating physiotherapy care for persons with haemophilia

Introduction: Physiotherapy is highly recommended for persons with haemophilia (PWH), to regain functioning after bleeding and to maintain functioning when dealing with haemophilic arthropathy. However, many PWH live too far from their Haemophilia Comprehensive Care Centre (HCCC) to receive regular treatment at their HCCC. Physiotherapists in primary care may have limited experience with a rare disease like haemophilia. Aim: To explore experiences of stakeholders with primary care physiotherapy for PWH and develop recommendations to optimize physiotherapy care coordination. Methods: A RAND approach was used, consisting of a Delphi procedure with e-mailed questionnaires and a consensus meeting. Included stakeholders were PWH, physiotherapists from HCCC's and primary care physiotherapists. HCCC physiotherapists approached patients from their centre and primary care physiotherapists from their network to fill in the questionnaires. Purposive sampling was used to select participants from the survey sample for the consensus meeting. Results: Ninety-six primary care physiotherapists, 54 PWH and eight HCCC physiotherapists completed the questionnaire. Subsequently, four PWH, three primary care physiotherapists and four HCCC physiotherapists participated in the consensus meeting. The questionnaires yielded 33 recommendations, merged into a final list of 20 recommendations based on the consensus meeting. The final rank-order consists of 13 recommendations prioritized by at least one stakeholder. Conclusion: Commitment to a formal network is considered not feasible for a rare disease like haemophilia. Development of a practice guideline, easy-accessible information and contact details, two-way and open communication between HCCC and primary care and criteria to refer back to the HCCC are recommended

COVID-19-associated coagulopathy and antithrombotic agents—lessons after 1 year

COVID-19 is associated with a high incidence of thrombotic complications, which can be explained by the complex and unique interplay between coronaviruses and endothelial cells, the local and systemic inflammatory response, and the coagulation system. Empirically, an intensified dose of thrombosis prophylaxis is being used in patients admitted to hospital with COVID-19 and several guidelines on this topic have been published, although the insufficiency of high quality and direct evidence has led to weak recommendations. In this Viewpoint we summarise the pathophysiology of COVID-19 coagulopathy in the context of patients who are ambulant, admitted to hospital, and critically ill or non-critically ill, and those post-discharge from hospital. We also review data from randomised controlled trials in the past year of antithrombotic therapy in patients who are critically ill. These data provide the first high-quality evidence on optimal use of antithrombotic therapy in patients with COVID-19. Pharmacological thromboprophylaxis is not routinely recommended for patients who are ambulant and post-discharge. A first ever trial in non-critically ill patients who were admitted to hospital has shown that a therapeutic dose of low-molecular-weight heparin might improve clinical outcomes in this population. In critically ill patients, this same treatment does not improve outcomes and prophylactic dose anticoagulant thromboprophylaxis is recommended. In the upcoming months we expect numerous data from the ongoing antithrombotic COVID-19 studies to guide clinicians at different stages of the disease.http://www.thelancet.com/haematologyam2022Medical Oncolog

Functional decline in persons with haemophilia and factors associated with deterioration

INTRODUCTION: The World Haemophilia Federation advises regular musculoskeletal assessment covering all International Classification of Functioning and Health (ICF) domains, including limitations in activities and participation in persons with haemophilia (PWH). This enables clinicians to detect changes early and enable adjustments in personalized healthcare when needed. However, data on the course of physical functioning and occurrence of decline is lacking. The aim of this study is to describe changes in perceived limitations in activities of PWH and to identify factors associated with a change. METHODS: Data were collected from medical health records of regular check-up visits of adults with moderate and severe haemophilia in two time periods. Perceived limitations in activities was measured with the Haemophilia Activities List (HAL). Association between variables (e.g., age, body mass index, bleeding rate and synovitis) and change in perceived limitations was assessed using a generalized linear model. RESULTS: A total of 104 PWH were included. At T0, the median HAL sum score was 79.5 (IQR 62.1-93.6) and at T1 the median HAL sum score was 74.2 (IQR 57.5-88.3). A functional decline was found in 35.6% of PWH, 55.8% remained stable and 8.7% improved. Among other variables, a BMI > 30 kg/m 2 appeared to be an important factor that negatively influenced the change in perceived functioning in adult PWH. With the included factors we could only explain a small part of this decline (R 2 adj : .12). CONCLUSION: The majority of PWH remained stable in their perceived functional ability over mid-long term (median 3.5 years). However, about a third showed a clinical relevant decline in their functional ability

Reduced cardiovascular morbidity in patients with hemophilia:results of a 5-year multinational prospective study

Hemophilia is a congenital bleeding disorder caused by low levels of clotting factor VIII or IX. The life expectancy of people with hemophilia (PWH) has increased with the availability of clotting factor concentrates. At the same time, the incidence of cardiovascular disease (CVD) has increased; in retrospective studies, there are conflicting data regarding if, despite this increase, the incidence is still lower than in the general population. We prospectively compared the incidence of CVD in PWH vs the predicted incidence. This prospective, multicenter, observational study included adult PWH (aged &gt;30 years) from The Netherlands and United Kingdom. They were followed up for a 5-year period, and CVD incidence was compared with a predicted event rate based on the QRISK2-2011 CVD risk model. The primary end point was the observed fatal and nonfatal CVD incidence after 5 years compared with the estimated events and in relation to severity of hemophilia. The study included 709 patients, of whom 687 (96.9%) completed 5 years' follow-up or reached an end point. For 108 patients, the QRISK score could not be calculated at inclusion. For the remaining 579, fewer CVD events were observed than predicted: 9 vs 24 (relative risk, 0.38; 95% confidence interval, 0.18-0.80; P 5 .01), corresponding with an absolute risk reduction of 2.4%. Severe hemophilia treated on demand had the highest risk reduction. There was no statistically significant relation between severity of hemophilia and incidence of CVD. In hemophilia, a lower-than-predicted CVD incidence was found, supporting the theory that hemophilia protects against CVD. The study is registered at www.clinicaltrials.gov as #NCT01303900.</p

Diagnostic accuracy of point-of-care testing for acute coronary syndromes, heart failure and thromboembolic events in primary care: a cluster-randomised controlled trial

Background: Evidence of the clinical benefit of 3-in-1 point-of-care testing (POCT) for cardiac troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP) and D-dimer in cardiovascular risk stratification at primary care level for diagnosing acute coronary syndromes (ACS), heart failure (HF) and thromboembolic events (TE) is very limited. The aim of this study is to analyse the diagnostic accuracy of POCT in primary care. Methods: Prospective multicentre controlled trial cluster-randomised to POCT-assisted diagnosis and conventional diagnosis (controls). Men and women presenting in 68 primary care practices in Zurich County (Switzerland) with chest pain or symptoms of dyspnoea or TE were consecutively included after baseline consultation and working diagnosis. A follow-up visit including confirmed diagnosis was performed to determine the accuracy of the working diagnosis, and comparison of working diagnosis accuracy between the two groups. Results: The 218 POCT patients and 151 conventional diagnosis controls were mostly similar in characteristics, symptoms and pre-existing diagnoses, but differed in working diagnosis frequencies. However, the follow-up visit showed no statistical intergroup difference in confirmed diagnosis frequencies. Working diagnoses overall were significantly more correct in the POCT group (75.7% vs 59.6%, p = 0.002), as were the working diagnoses of ACS/HF/TE (69.8% vs 45.2%, p = 0.002). All three biomarker tests showed good sensitivity and specificity. Conclusion: POCT confers substantial benefit in primary care by correctly diagnosing significantly more patients

Biochemical marker research in hemophilic arthropathy: A systematic review

Hemophilic arthropathy (HA) causes major morbidity. Breakthrough therapies reduce the bleeding frequency tremendously, but well-defined joint outcome assessments with a focus on early changes and subclinical damage are lacking. Biomarkers reflecting joint tissue turnover/inflammation might be useful to predict invalidating arthropathy. This systematic review summarized and categorized publications on blood/urinary biomarkers in HA to provide leads for implementation. A PubMed/EMBASE search was performed on September 9, 2019. All publications were assessed and allocated to one or several BIPED-categories, based on the utility of biomarkers. Of the initial 1307 publications found, 27 were eligible for inclusion. The majority (81%, n = 32/42) was cross-sectional in design, including relatively small numbers of patients (median 44, interquartile range 35-78). Fourteen percent (n = 6/42) investigated dynamic changes around a bleeding or treatment. Only two studies investigated the prognostic value of biomarkers. Most promising biomarkers were serum Coll2-1, COL-18N, COMP, C1,2C, C2M, CS846, MIF, plasma sVCAM-1 and urinary CTX-II. Comparing performances and pooling data was not possible due to heterogeneity. Currently, biomarker research in HA is still in an explorative stage and not yet sufficient for translation into daily practice. Clearly, larger homogeneous longitudinal studies in well-defined populations should be performed for further development

The fear for adverse bleeding and cardiovascular events in hemophilia patients using (non-)selective non-steroidal anti-inflammatory drugs: A systematic review reporting on safety

(Non-)selective non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for musculoskeletal related pain. These cheap and easily accessible drugs may be of great value for hemophilia patients in developing countries and countries with a high rate of opioid poisoning, but also in developed countries due to potential joint protective effects. However, fear for adverse bleeding and cardiovascular events during the use of these drugs restrains prescription within this population. To give a complete overview of all publications reporting on safety, a systematic search till March 2021 was performed. All studies were reviewed and critically appraised and this resulted in 19 studies eligible for inclusion. Most studies with (non-)selective NSAIDs showed no evident risk for relevant adverse bleeding or cardiovascular events. However, some studies had a high risk of bias and studies reporting on cardiovascular events were limited. Future studies with longitudinal follow-up in well-defined large patient populations, including older patients, focusing on both adverse bleeding and cardiovascular events are required to confirm the alleged safe use

Host model uncertainties in aerosol radiative forcing estimates: results from the AeroCom Prescribed intercomparison study

Simulated multi-model “diversity” in aerosol direct radiative forcing estimates is often perceived as a measure of aerosol uncertainty. However, current models used for aerosol radiative forcing calculations vary considerably in model components relevant for forcing calculations and the associated “host-model uncertainties” are generally convoluted with the actual aerosol uncertainty. In this AeroCom Prescribed intercomparison study we systematically isolate and quantify host model uncertainties on aerosol forcing experiments through prescription of identical aerosol radiative properties in twelve participating models. Even with prescribed aerosol radiative properties, simulated clear-sky and all-sky aerosol radiative forcings show significant diversity. For a purely scattering case with globally constant optical depth of 0.2, the global-mean all-sky top-of-atmosphere radiative forcing is −4.47Wm−2 and the inter-model standard deviation is 0.55Wm−2, corresponding to a relative standard deviation of 12 %. For a case with partially absorbing aerosol with an aerosol optical depth of 0.2 and single scattering albedo of 0.8, the forcing changes to 1.04Wm−2, and the standard deviation increases to 1.01W−2, corresponding to a significant relative standard deviation of 97 %. However, the top-of-atmosphere forcing variability owing to absorption (subtracting the scattering case from the case with scattering and absorption) is low, with absolute (relative) standard deviations of 0.45Wm−2 (8 %) clear-sky and 0.62Wm−2 (11 %) all-sky. Scaling the forcing standard deviation for a purely scattering case to match the sulfate radiative forcing in the Aero- Com Direct Effect experiment demonstrates that host model uncertainties could explain about 36% of the overall sulfate forcing diversity of 0.11Wm−2 in the AeroCom Direct Radiative Effect experiment

Proof of concept and feasibility of a blended physiotherapy intervention for persons with haemophilic arthropathy

BACKGROUND: Regular physiotherapy with a physiotherapist experienced in the field is not feasible for many patients with haemophilia. We, therefore, developed a blended physiotherapy intervention for persons with haemophilic arthropathy (HA) (e-Exercise HA), integrating face-to-face physiotherapy with a smartphone application. AIM: The aim of the study was to determine proof of concept of e- Exercise HA and to evaluate feasibility. METHODS: Proof of concept was evaluated by a single-case multiple baseline design. Physical activity (PA) was measured with an accelerometer during a baseline, intervention and post-intervention phase and analysed using visual inspection and a single case randomisation test. Changes in limitations in activities (Haemophilia Activities List [HAL]) and a General Perceived Effect (GPE) were evaluated between baseline (T0), post-intervention (T1) and 3 months post-intervention (T2) using Wilcoxson signed rank test. Feasibility was evaluated by the number of adverse events, attended sessions and open-ended questions. RESULTS: Nine patients with HA (90% severe, median age 57.5 (quartiles 50.5-63.3) and median HJHS 32 (quartiles 22-36)) were included. PA increased in two patients. HAL increased mean 15 (SD 9) points (p = .001) at T1, and decrease to mean +8 points (SD 7) (p = .012) at T2 compared to T0. At T1 and T2 8/9 participants scored a GPE > 3. Median 5 (range 4-7) face-to-face sessions were attended and a median 8 out of 12 information modules were viewed. No intervention-related bleeds were reported. CONCLUSION: A blended physiotherapy intervention is feasible for persons with HA and the first indication of the effectiveness of the intervention in decreasing limitations in activities was observed

Towards Personalized Treatment in Haemophilia: The Role of Genetic Factors in Iron and Heme Control to Identify Patients at Risk for Haemophilic Arthropathy

The treatment landscape for haemophilia is changing rapidly, creating opportunities for personalized treatment. As major morbidity is still caused by haemophilic arthropathy, understanding the factors affecting joint damage and joint damage progression might lead to more individualized treatment regimens. We investigated the association of HFE mutations or HMOX1 polymorphisms affecting iron/heme handling with radiographic joint damage in 252 haemophilia patients (severe and moderate). Although iron levels and transferrin saturation were significantly increased in the 95 patients with an HFE mutation, neither carrying this mutation nor the HMOX1 polymorphism was associated with radiographic joint damage, and the same was true after adjustment for well-known factors associated with arthropathy. In conclusion, this study does not support the hypothesis that HFE mutations or HMOX1 polymorphisms can be used to predict the development of haemophilic arthropathy