Key issues in inhibitor management in patients with haemophilia.
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ABSTRACT:
SUBMITTER: Gomez K
PROVIDER: S-EPMC3934290 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The standard therapy for patients with haemophilia is prophylactic treatment with replacement factor VIII (FVIII) or factor IX (FIX). Patients who develop inhibitors against FVIII/FIX face an increased risk of bleeding, and the likelihood of early development of progressive arthropathy, alongside higher treatment-related costs. Bypassing agents can be used to prevent and control bleeding, as well as the recently licensed prophylaxis, emicizumab, but their efficacy is less predictable than that of factor replacement therapy. Antibody eradication, by way of immune tolerance induction (ITI), is still the preferred management strategy for treating patients with inhibitors. This approach is successful in most patients, but some are difficult to tolerise and/or are unresponsive to ITI, and they represent the most complicated patients to treat. However, there are limited clinical data and guidelines available to help guide physicians in formulating the next treatment steps in these patients. This review summarises currently available treatment options for patients with inhibitors, focussing on ITI regimens and those ITI strategies that may be used in difficult-to-treat patients. Some alternative, non-ITI approaches for inhibitor management, are also proposed.
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Project description:IntroductionThe Haemophilia Experiences, Results and Opportunities (HERO) Study identified sexual health as an important psychosocial issue affecting people with haemophilia (PWH) worldwide. However, sexual health is inadequately addressed at haemophilia treatment centres (HTCs), because PWH and healthcare professionals (HCPs) experience barriers to broaching the subject. There is a clear need for HCP training to support communication in this area and improve comprehensive care.AimThe Sexual Health: Strategies for Effective Communication pilot programme was trialled in Canada to assess HCP readiness and ability to discuss sexual health issues with PWH and test communication tools to facilitate these conversations.MethodsThe pilot programme consisted of two 3-h sessions attended by seven HCPs from Calgary's Alberta Children's and Foothills Hospitals. The sessions included lectures and case scenarios and explained the check-in-affirm-clarify-answer and head-heart-body tools designed by the Centre for Sexuality to aid communication. The pilot was evaluated through discussions and an online questionnaire.ResultsThe pilot was well received by all HCP participants. Questionnaire data showed improvements in participants' knowledge, skills and comfort level in conducting sexual health discussions. Greatest improvements were noted in knowledge (100% 'good' or 'excellent' after the pilot, compared with 29% beforehand). Importantly, 86% felt that the material presented would be applicable in clinical practice.ConclusionThe Canadian pilot demonstrated the effectiveness of the proposed educational programme. The underlying principles could be adapted to similar programmes for other HTCs to facilitate sexual health discussions.
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Project description:IntroductionInhibitor development affects about 30% of patients with severe haemophilia A (HA) and results from different environmental and genetic risk factors. Previously, we identified the missense variant rs3754689 in the LCT gene linked with this predisposition. Since rs3754689 variant is benign and is located in a conserved haplotype region, we hypothesized that the association signal captured by this variant is located in coinherited, neighbouring genes.AimTo identify novel genetic risk factors associated with inhibitor development in coding regions of R3HDM1, UBXN4, CXCR4, MCM6, DARS and miR128-1 genes.MethodsTargeted sequencing was performed in 246 severe HA patients (72 with and 174 without inhibitor): 181 previously and 65 newly enrolled.ResultsForty-one common and 152 rare variants passed the quality control. Logistic regression analysis of common variants identified rs3754689 and four additional variants (.011 < P < .047; FDR ranging .2-.38). Logistic regression analysis performed only in the 220 Italian patients showed similar results (.004 < P < .05; FDR ranging .12-.22). Three of these variants (rs3213892 and rs3816155 in the LCT intron 13 and rs961360 in the R3HDM1 intron10-exon11 junction) may affect the expression of UBXN4 and R3HDM1, respectively. Rare variants did not show association with inhibitor development. Identified variants were not replicated in the multi-ethnic SIPPET cohort of 230 severe HA patients.ConclusionDue to the limited sample size that may be responsible of the high FDR values, we could not confirm with certainty the analysed association. Further evaluation of the expression levels of analysed genes will confirm or not their role in inhibitor development.
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Project description:BackgroundThe health risks associated with poor medication practices in the home suggest that patients would benefit from home-based medication reviews that could detect and resolve these issues. However, remuneration for home visits often excludes ambulatory, nonhomebound patients. A subset of these patients have issues that cannot be adequately identified and resolved during the course of a typical pharmacy-based medication review.PurposeThis study aims to characterize the prevalence and nature of "hidden in the home" medication management issues in nonhomebound patients.MethodsPharmacists facilitated subject enrollment among patients at 6 community pharmacies in Toronto over a 15-month period, from January 2016 to March 2017. Patients taking 5 or more chronic medications who were ambulatory (able to visit the pharmacy) and scored 3 points or higher on a prescreening questionnaire were invited to participate. Visits included a standard medication review, the identification of drug therapy problems and an assessment of the patient's medication and organization/storage practices, followed by a medication cabinet cleanup.ResultsOne hundred patients were recruited, with a mean age of 76.9 years and taking on average 10 chronic medications. Pharmacists identified a total of 275 drug therapy problems (2.75 per patient). The most common issues reported additional therapy required (23.6%), nonadherence (23.3%) and adverse drug reactions (17.8%). For those patients 65 years or older (87%), 32% were found to be using at least 1 medication on the Beers Criteria list, while 6% were using 3 or more. Sulfonylureas, non-steroidal anti-inflammatory drugs and short-acting benzodiazepines were the most commonly implicated drugs. Medications were removed from the homes of 67% of the patients, with expiry of medication being the most common reason for removal (54.2%). The mean duration of a home visit was 49.5 minutes.ConclusionPharmacist-directed home medication reviews offer an effective mechanism to address the pharmacotherapy issues of patients taking multiple medications. These findings highlight the frequency of medication management issues in this group and suggest that home medication reviews could serve to minimize inappropriate use of medication and maximize health care cost savings in this unique patient population. Can Pharm J (Ott) 2019;152:xx-xx.
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Project description:Haemophilia care is commonly provided via multidisciplinary specialized management. To date, there has been no systematic assessment of the impact of haemophilia care delivery models on patient-important outcomes.To conduct a systematic review of published studies assessing the effects of the integrated care model for persons with haemophilia (PWH).We searched MEDLINE, EMBASE and CINAHL up to April 22, 2015, contacted experts in the field, and reviewed reference lists.Randomized and non-randomized studies of PWH or carriers, focusing mainly on the assessment of care models on delivery.Two investigators independently screened title, abstract, and full text of retrieved articles for inclusion. Risk of bias and overall quality of evidence was assessed using Cochrane's ACROBAT-NRSI tool and GRADE respectively. Relative risks, mean differences, proportions, and means and their variability were calculated as appropriate.27 non-randomized studies were included: eight comparative and 19 non-comparative studies. We found low- to very low-quality evidence that in comparison to other models of care, integrated care may reduce mortality, hospitalizations and emergency room visits, may lead to fewer missed days of school and work, and may increase knowledge seeking.Our comprehensive review found low- to very low-quality evidence from a limited number of non-randomized studies assessing the impact of haemophilia care models on some patient-important outcomes. While the available evidence suggests that adoption of the integrated care model may provide benefit to PWH, further high-quality research in the field is needed.
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