Inhibitor development in non-severe haemophilia across Europe.

PubMed

Fischer, Kathelijn; Iorio, Alfonso; Lassila, Riitta; Peyvandi, Flora; Calizzani, Gabriele; Gatt, Alex; Lambert, Thierry; Windyga, Jerzy; Gilman, Estelle A; Hollingsworth, R; Makris, Michael

2015-10-01

Evidence about inhibitor formation in non-severe haemophilia and the potential role for clotting factor concentrate type is scant. It was the aim of this study to report inhibitor development in non-severe haemophilia patients enrolled in the European Haemophilia Safety Surveillance (EUHASS) study. Inhibitors are reported quarterly and total treated patients annually. Incidence rates and 95% confidence intervals (95% CI) were calculated according to diagnosis and concentrate used. Between 1-10-2008 and 31-12-2012, 68 centres reported on 7,969 patients with non-severe haemophilia A and 1,863 patients with non-severe haemophilia B. For haemophilia A, 37 inhibitors occurred in 8,622 treatment years, resulting in an inhibitor rate of 0.43/100 treatment years (95% CI 0.30-0.59). Inhibitors occurred at a median age of 35 years, after a median of 38 exposure days (EDs; P25-P75: 20-80); with 72% occurring within the first 50 EDs. In haemophilia B, one inhibitor was detected in 2,149 treatment years, resulting in an inhibitor rate of 0.05/100 years (95% CI 0.001-0.26). This inhibitor developed at the age of six years, after six EDs. The rate of inhibitors appeared similar across recombinant and plasma derived factor VIII (FVIII) concentrates. Rates for individual concentrates could not be calculated at this stage due to low number of events. In conclusion, inhibitors in non-severe haemophilia occur three times more frequently than in previously treated patients with severe haemophilia at a rate of 0.43/100 patient years (haemophilia A) and 0.05/100 years (haemophilia B). Although the majority of inhibitors developed in the first 50 EDs, inhibitor development continued with increasing exposure to FVIII.

What should men living with severe haemophilia need to know? The perspectives of Canadian haemophilia health care providers.

PubMed

Lane, S; Arnold, E; Webert, K E; Chan, A; Walker, I; Heddle, N M

2013-07-01

Haemophilia is a complex disease to manage. Home-based management of haemophilia has placed greater responsibility for disease management on individuals with haemophilia, heightening the individual's need for knowledge, particularly among individuals with severe haemophilia. The aim of this study was to identify and understand the knowledge needs and gaps of Canadian men with severe haemophilia from the perspectives of health care providers. A qualitative approach was undertaken. Data were collected using semi-structured focus groups and interviews with health care providers from Haemophilia Treatment Centres (HTCs) across Canada; data were analysed using thematic analysis. Three focus groups and two interviews were conducted; 13 individuals participated in this study. Health care providers identified the following areas of knowledge required by men with severe haemophilia: disease pathology, causes and consequences of bleeds, bleed prevention, recognition, treatment, how and when to access support, activity selection and risk reduction, benefits of exercise, genetic inheritance patterns, impact on career selection, travel and ageing. Knowledge gaps and challenges to knowledge provision were highlighted. In addition, providers emphasized the influences of timing, rapport and context on readiness to receive and assimilate information and recommended tailoring education to the individual and creating a developmental curriculum and knowledge assessment tool. Provision and uptake of disease knowledge is essential to patient self-management. To effectively receive, retain and assimilate information, individuals with severe haemophilia require the right information, from the right source, at the right time. Education should be tailored to the needs of the individual, provided throughout the lifespan. © 2013 John Wiley & Sons Ltd.

Haemophilia A: patients' knowledge level of treatment and sources of treatment-related information.

PubMed

Miller, K L; Guelcher, C; Taylor, A

2009-01-01

There are minimal or no data regarding the extent of patient and/or parent/legal guardian/caregiver knowledge about haemophilia A and its treatment, their sources for this information, or their preferred methods of communication. A pilot study using a survey instrument developed by haemophilia nurse coordinators was conducted at a national meeting to obtain information on these topics. A total of 187 surveys were completed. More than 80% of respondents reported high and high-medium knowledge levels about how haemophilia A is inherited, types of bleeding, identifying and treating bleeding emergencies, prophylaxis and on-demand treatment, travel and vacation planning and guidelines for exercise and sports activities. However, a lower proportion of respondents (<65%) reported high and high-medium knowledge levels for drug-related topics. The majority of respondents (>55%) consistently ranked healthcare providers as the most useful source of information for most topics related to haemophilia A. This pilot survey of well-informed respondents identified deficits in knowledge regarding factor concentrates for the treatment of haemophilia A and highlights the need for healthcare providers to provide more information about factor concentrates, insurance coverage for treatments, and community and educational resources. Additional study is necessary to determine the extent of knowledge deficits and how best to address them in the haemophilia A population as a whole. Other areas of study needed are whether information deficits and delivery of information vary by age or by other factors.

Evidence for and cost-effectiveness of physiotherapy in haemophilia: a Dutch perspective.

PubMed

de Kleijn, P; Mauser-Bunschoten, E P; Fischer, K; Smit, C; Holtslag, H; Veenhof, C

2016-11-01

Musculoskeletal impact of haemophilia justifies physiotherapy throughout life. Recently the Dutch Health Care Institute constrained their 'list of chronic conditions', and withdrew financial coverage of physiotherapy for elderly persons with haemophilia (PWH). This decision was based on lack of scientific evidence and not being in accordance with 'state of science and practice'. In general, evidence regarding physiotherapy is limited, and especially in rare diseases like haemophilia. 'Evidence based medicine' classifies and recommends evidence based on meta-analyses, systematic reviews and randomized controlled trials, but also means integrating evidence with individual clinical expertise. For the evaluation of physiotherapy - usually individualized treatment - case studies, observational studies and Case Based Reasoning may be more beneficial. Overall annual treatment costs for haemophilia care in the Netherlands are estimated over 100 million Euros, of which 95% is covered by clotting factor concentrates. The cost for physiotherapy assessments in all seven Dutch HTCs (seven centres for adult PWH and seven centres for children) is limited at approximately 500 000 Euros annually. Costs of the actual physiotherapy sessions, carried out in our Dutch first-line care system, will also not exceed 500 000 Euros. Thus, implementation of physiotherapy in haemophilia care the Netherlands in a most optimal way would cost less than 1% of the total budget. The present paper describes the role of physiotherapy in haemophilia care including available evidence and providing suggestions regarding generation of evidence. Establishing the effectiveness and cost-effectiveness of physiotherapy in haemophilia care is a major topic for the next decennium. © 2016 John Wiley & Sons Ltd.

Pharmacokinetics, phenotype and product choice in haemophilia B: how to strike a balance?

PubMed

Berntorp, E; Dolan, G; Hermans, C; Laffan, M; Santagostino, E; Tiede, A

2014-11-01

At the 7th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) held in Brussels, Belgium, in February 2014, Pfizer sponsored a satellite symposium entitled: "Pharmacokinetics, phenotype and product choice in haemophilia B: How to strike a balance?" Co-chaired by Cedric Hermans (Cliniques Universitaires Saint Luc, Brussels, Belgium) and Mike Laffan (Imperial College, London, UK), the symposium provided an opportunity to debate whether pharmacokinetic (PK) parameters are good surrogates for clinical efficacy for haemophilia B in clinical practice, consider the perceptions and evidence of disease severity, and examine how these considerations can inform approaches to balancing the potential risks and benefits of the currently available treatment options for haemophilia B. PK parameters are routinely measured in clinical practice and are a requirement of regulatory bodies to demonstrate the clinical efficacy of products; however, the relationship between measured PK parameters and clinical efficacy is yet to be determined, an issue that was debated by Gerry Dolan (University Hospital, Queen's Medical Centre, Nottingham, UK) and Erik Berntorp (Lund University, Malmö Centre for Thrombosis and Haemostasis, Malmö, Sweden). Elena Santagostino (Universita degli Studi di Milano, Milano, Italy) reviewed how differing perceptions on the severity of haemophilia B compared with haemophilia A may have an impact on clinical decision-making. Finally, Andreas Tiede (Hannover Medical School, Hannover, Germany), examined the considerations for balancing the potential risks and benefits of the currently available treatment options for haemophilia B. Although the pathophysiology of haemophilia B has been widely studied and is largely understood, continued investigation and discussion around the optimal management course and appropriate therapeutic choice is warranted. © 2014 John Wiley & Sons Ltd.

Gene therapy for haemophilia.

PubMed

Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Neely, Jessica A; Kalipatnapu, Sasank

2014-11-14

Haemophilia is a genetic disorder which is characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 06 November 2014. Eligible trials included randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the effects of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

AHEAD. Advate in HaEmophilia A outcome Database.

PubMed

Oldenburg, J; Kurnik, K; Huth-Kühne, A; Zimmermann, R; Abraham, I; Klamroth, R

2010-11-01

The clinical picture of haemophilia A patients is often characterised by recurrent bleedings, in particular joint bleeds. Thus far, long-term data on the outcome of haemophilia A patients are scarce as regards the development of target joints, joint replacement, lost days from school or work due to bleedings, and the quality of life, as most previous studies were limited to the aspects of safety and efficacy. The Baxter-initiated AHEAD (Advate in HaEmophilia A outcome Database) study is a multi-centre, prospective, non-interventional observational study of haemophilia A patients. All patients with a residual FVIII activity of £5% who are being treated with ADVATE are eligible. There are no limitations in terms of patient age or treatment regimen. AHEAD is scientifically supported by a renowned interdisciplinary steering board and is intended to yield data on 500 patients in up to 30 haemophilia centres, collected during a period of four years. The large patient population has been chosen in order to ensure a valid database. The objective of the study is to record haemophilia-related arthropathies, which will be defined based on imaging techniques (e. g. MRI, X-ray, ultrasound) and the judgment of the attending physician. In addition, extensive data will be collected on joint replacement surgeries, pseudotumour development, bleeding-related pain, quality of life (age-related questionnaires: Haem-A-QoL, Haemo-QoL, SF10, SF12v2), risk factors (diabetes mellitus, arterial hypertension, nicotine abuse), blood group, gene mutation, physical activity, and on the efficacy and safety of Advate. The patient data will be entered into an electronic CRF system at the centres. Plausibility checks during data entry, regular monitoring visits, and the option of auditing all serve to ensure a high data quality for AHEAD. The first patient was enrolled in the study in early June 2010; recruitment is planned to continue until the end of 2011. The Ethics Committee of the University

Gene therapy for haemophilia.

PubMed

Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Reiss, Ulrike M

2016-12-20

Haemophilia is a genetic disorder characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. This is an update of a published Cochrane Review. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 18 August 2016. Eligible trials include randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation for individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the safety and efficacy of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

Current options and new developments in the treatment of haemophilia.

PubMed

Wong, Trisha; Recht, Michael

2011-02-12

Haemophilia A and B are X-linked bleeding disorders due to the inherited deficiency of factor VIII or factor IX, respectively. Of the approximately 1 per 5000-10000 male births affected by haemophilia, 80% are deficient in factor VIII and 20% are deficient in factor IX. Haemophilia is characterized by spontaneous and provoked joint, muscle, gastrointestinal and CNS bleeding leading to major morbidity and even mortality if left untreated or under-treated. The evolution of haemophilia management has been marked by tragedy and triumph over recent decades. Clotting factors and replacement strategies continue to evolve for patients without inhibitors. For patients with an inhibitor, factor replacement for acute bleeding episodes and immune tolerance, immune modulation and extracorporeal methods for inhibitor reduction are the cornerstone of care. In addition, adjuvant therapies such as desmopressin, antifibrinolytics and topical agents also contribute to improved outcomes for patients with and without inhibitors. The future direction of haemophilia care is promising with new longer-acting clotting factors and genetic therapies, including gene transfer and premature termination codon suppressors. With these current and future treatment modalities, the morbidity and mortality rates in patients with haemophilia certainly will continue to improve.

The evolution of comprehensive haemophilia care in the United States: perspectives from the frontline.

PubMed

Aledort, L M

2016-09-01

The establishment of dedicated comprehensive treatment centres more than a half century ago transformed the management of haemophilia in the United States. Formerly, a disease associated with crippling disability and premature death, today, persons with haemophilia who are treated appropriately from infancy and do not develop inhibitors can expect a normal life expectancy and relatively few bleeding episodes. The evolution of the comprehensive haemophilia care, while chastened by the viral epidemics of the 1980s, has been marked by ongoing advances, including prophylaxis, immune tolerance induction, new drugs and gene therapy research. Current challenges include sustaining the comprehensive care model despite decreased funding and expanding the delivery and affordability of comprehensive haemophilia care. © 2016 John Wiley & Sons Ltd.

Implementing haemophilia care in Senegal, West Africa.

PubMed

Diop, S; Seck, M; Sy-Bah, D; Faye, B F; Sow-Ndoye, A; Gueye, Y B; Senghor, A B; Sall-Fall, A; Toure-Fall, A O; Dièye, T N; Thiam, D; Diakhate, L

2014-01-01

Despite significant progres on haemophilia care in developed world, this disease remains unknown in many sub-Saharan African countries. The objectives of this article were to report Senegalese experience on the management of haemophilia care through 18 years of follow-up. This cohort study included 140 patients (127 haemophilia A, 13 haemophilia B), followed in Dakar's haemophilia treatment centre from 1995 to 2012. Our study reported a prevalence of 2.3/100,000 male births, accounting for 11.6% of what is expected in Senegal. From the period 1995-2003 to 2004-2012, significant progress was seen including 67.9% increase in new patient's identification, 11.3 years reduction in mean age at diagnosis (from 15.5 to 4.2 years), lower mortality rate (from 15.3% to 6.8%) and age at death evolved from 6.5 to 23.3 years. Of the 50 haemophilia A patients who were tested for inhibitor presence, 10 were positive (eight severe and two moderate) that is prevalence of 20%. All patients were low responders since inhibitor titre was between 1.5 and 3.8 BU. Disabilities were seen in 36.5% of patients above 20 years old who had musculoskeletal sequels and 39% had no scholar or professional activities in our setting. Implementing haemophilia care in sub-Saharan Africa is a great challenge as this disease is not yet counted in national health problems in many countries. Lessons learned from this study show a significant improvement in diagnosis and prognosis parameters. This emphasizes the needs to set up such follow-up initiatives and to enhance medical and lay cooperation for better results. © 2013 John Wiley & Sons Ltd.

Haemophilia utilization group study - Part Va (HUGS Va): design, methods and baseline data.

PubMed

Zhou, Z-Y; Wu, J; Baker, J; Curtis, R; Forsberg, A; Huszti, H; Koerper, M; Lou, M; Miller, R; Parish, K; Riske, B; Shapiro, A; Ullman, M; Johnson, K

2011-09-01

To describe the study design, procedures and baseline characteristics of the Haemophilia Utilization Group Study - Part Va (HUGS Va), a US multi-center observational study evaluating the cost of care and burden of illness in persons with factor VIII deficiency. Patients with factor VIII level ≤ 30%, age 2-64 years, receiving treatment at one of six federally supported haemophilia treatment centres (HTCs) were enrolled in the study. Participants completed an initial interview including questions on socio-demographical characteristics, health insurance status, co-morbidities, access to care, haemophilia treatment regimen, factor utilization, self-reported joint pain and motion limitation and health-related quality of life. A periodic follow-up survey collected data regarding time lost from usual activities, disability days, health care utilization and outcomes of care. HTC clinicians documented participants' baseline clinical characteristics and pharmacy dispensing records for 2 years. Between July 2005 and July 2007, 329 participants were enrolled. Average age was 9.7 years for children and 33.5 years for adults; two-thirds had severe haemophilia. The distributions of age, marital status, education level and barriers to haemophilia care were relatively consistent across haemophilic severity categories. Differences were found in participants' employment status, insurance status and income. Overall, children with haemophilia had quality of life scores comparable to healthy counterparts. Adults had significantly lower physical functioning than the general US population. As one of the largest economic studies of haemophilia care, HUGS Va will provide detailed information regarding the burden of illness and health care utilization in the US haemophilia A population. © 2011 Blackwell Publishing Ltd.

Haemophilia in Poland.

PubMed

Windyga, J; Lopaciuk, S; Stefanska, E; Juszynski, A; Wozniak, D; Strzelecki, O; Szczepanik, A B

2006-01-01

The primary aim of this study was to analyse the data on 2269 haemophilic patients in the Polish National Register of Inherited Bleeding Disorders -- 1953 haemophilia A patients and 316 haemophilia B patients. Haemophilia A occurred in 1512 families, haemophilia B in 240 families. In the majority of haemophilia A and B cases severe haemophilia prevailed (59.7% and 56.6% respectively). In about 50% of haemophilic patients, no family history of bleeding diathesis was reported. For haemophilia A patients the mean age was 30.9 years and for haemophilia B patients, 29.2 years. Prevalence of haemophilia in Poland is approximately 1:12 300 inhabitants (1:5600 males). The second aim was to describe the orthopaedic status of severe haemophilia patients and to relate this status to the type of replacement therapy they received prior to the study. Ninety-two severe haemophilia patients (median age 26.0 years) were enrolled in the study. Right and left knee, elbow and ankle joints were evaluated clinically using the Gilbert scale. X-ray examinations were evaluated according to the Pettersson scale. Knee joints proved to be most affected. Eighty-four patients (91.3%) reported pain. Only one scored 0 on the Gilbert scale, another on the Pettersson scale. Thirty-seven per cent of patients used orthopaedic equipment, either occasionally or constantly. Twenty-five per cent had a history of orthopaedic surgery. Thirty-eight per cent were unemployed with some form of social subvention. On-demand treatment was applied. None of the patients received primary prophylaxis. The mean consumption of clotting factor concentrates was 68 054 IU per patient during the 12 months prior to the current study. These results indicate that in Poland all severe haemophilia patients above 20 years are affected by haemophilic arthropathy.

The Genetics of bleeding disorders: a report on the UK Haemophilia Centre Doctors' Organisation annual scientific symposium, 10th October 2003.

PubMed

Nicolle, A L; Talks, K L; Hanley, J

2004-07-01

The UK Haemophilia Centre Doctors' Organisation (UKHCDO) held its annual scientific symposium in October 2003, at the International Centre for Life, Newcastle-upon-Tyne. The educational day covered a range of topics relating to the genetics of bleeding disorders, including advances in genetics and gene therapy, antenatal diagnosis and counselling. We present the proceedings from the educational day.

Principles of haemophilia care: The Asia-Pacific perspective.

PubMed

Dunkley, S; Lam, J C M; John, M J; Wong, R S M; Tran, H; Yang, R; Nair, S C; Shima, M; Street, A; Srivastava, A

2018-02-21

Optimal haemophilia care is best established and implemented through a well-coordinated plan guided by clearly defined principles and priorities. A document which enunciates those details is therefore important. A successful example of this approach is the definition of principles of haemophilia care (PHC) outlined by the European Association for Haemophilia and Associated Disorders (EAHAD) and also the World Federation of Hemophilia. A similar document applicable to the Asia-Pacific region must take into account not only the highly varied healthcare systems but also the tremendous socio-economic and cultural diversities which impact provision of such care. The Asia-Pacific Haemophilia Working Group (APHWG), representing the countries in this region, has prepared this perspective of the PHC. While endorsing the overall framework outlined by EAHAD, this APHWG document emphasizes regional priorities on education and training of healthcare personnel in the diagnosis and management of hereditary bleeding disorders. Central coordinating agencies with wide stakeholder input, networks of haemophilia treatment centres and national registries as well as robust processes for procurement and distribution of safe and effective clotting factor concentrates (CFCs), implementation of prophylaxis programmes and management of patients with inhibitors should also be developed. The implementation of these strategies should lead to establishment of good comprehensive care programmes. This document should also be an advocacy tool to lobby for improved care for people with haemophilia (PWH) in the region. We urge national healthcare policy makers to consider these principles and initiate strong and decisive action to reach these goals. © 2018 John Wiley & Sons Ltd.

Intra-patient variability of thromboelastographic parameters following in vivo and ex vivo administration of recombinant activated factor VII in haemophilia patients. A multi-centre, randomised trial.

PubMed

Kenet, G; Stenmo, C B; Blemings, A; Wegert, W; Goudemand, J; Krause, M; Schramm, W; Kirchmaier, C; Martinowitz, U

2010-02-01

Thromboelastography methods have been used to predict or monitor treatment of haemophilia patients with recombinant activated factor VII (rFVIIa). However, neither of the two thromboelastographic methods (ROTEM and TEG) has as yet been validated. This multi-centre, randomised trial compared both methods in terms of intra- and inter- patient variability following in vivo and ex vivo rFVIIa administration to haemophilia A and B patients with and without inhibitors. Patients ((3)16 years old) received the same intravenous rFVIIa dose (45, 90 or 180 microg/kg) twice, 1-12 weeks apart. Blood samples were collected pre-dose and 15, 60, 120 and 240 minutes post-dose for ROTEM and TEG analysis. Pre-dose samples were also spiked ex vivo with rFVIIa (0.6, 1.2 or 2.4 microg/ml), to correspond to the three in vivo doses. Twenty-six haemophilia A and four haemophilia B patients were enrolled. A significant treatment effect was observed with in vivo rFVIIa (p<0.05) with more pronounced effects in inhibitor (n=14) versus non-inhibitor (n=16) patients. There was a strong positive correlation between ROTEM and TEG parameters. Intra- and inter-patient variation was large for all thromboelastography parameters at all time points and rFVIIa doses. Intra-patient variation was generally lower for non-inhibitor than inhibitor patients, and lower following ex vivo spiking versus in vivo rFVIIa administration. In conclusion, there was a clear effect of rFVIIa on all thromboelastography parameters, but the large intra- and inter-patient variability following in vivo rFVIIa administration renders the use of our method unsuitable for dose-response prediction for haemophilia patients in the clinical setting.

Adult males with haemophilia have a different macrovascular and microvascular endothelial function profile compared with healthy controls.

PubMed

Sun, H; Yang, M; Fung, M; Chan, S; Jawi, M; Anderson, T; Poon, M-C; Jackson, S

2017-09-01

Endothelial function has been identified as an independent predictor of cardiovascular risk in the general population. It is unclear if the haemophilia population has a different endothelial function profile compared to the healthy population. This prospective study aims to assess if there is a difference in endothelial function between haemophilia patients and healthy controls, and the impact of endothelial function on vascular outcomes in the haemophilia population. Baseline cardiovascular risk factors and endothelial function were presented. Adult males with haemophilia A or B recruited from the British Columbia and Southern Alberta haemophilia treatment centres were matched to healthy male controls by age and cardiovascular risk factors. Macrovascular endothelial function was assessed by brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD), and microvascular endothelial function was assessed by hyperaemic velocity time integral (VTI). Multivariable linear regression was used to assess the association between haemophilia and endothelial function. A total of 81 patients with haemophilia and 243 controls were included. Patients with haemophilia had a similar FMD and NMD compared to controls, although haemophilia was associated with higher FMD on multivariable analysis. Haemophilia was associated with significantly lower VTI on univariate and multivariable analyses, regardless of haemophilia type and severity. Adult males with haemophilia appear to have lower microvascular endothelial function compared to healthy controls. Future studies to assess the impact of endothelial dysfunction on cardiovascular events in the haemophilia population are needed. © 2017 John Wiley & Sons Ltd.

Unravelling adherence to prophylaxis in haemophilia: a patients' perspective.

PubMed

Schrijvers, L H; Kars, M C; Beijlevelt-van der Zande, M; Peters, M; Schuurmans, M J; Fischer, K

2015-09-01

Given the lifelong therapy in haemophilia patients, insight in non-adherence behaviour from a patient perspective is important to understand patients' difficulties with the following treatment recommendations. The aim of this study was to clarify the process underlying adherence (behaviour) to prophylactic treatment, from a patients' perspective. To develop a grounded theory, a qualitative study using individual in-depth interviews was performed to understand experiences, perceptions and beliefs concerning adherence to prophylaxis. From two Dutch treatment centres, 21 adults with haemophilia using prophylaxis were interviewed. Patients were asked how they experience their task to administer prophylaxis and how they adhere to this. The interviews were transcribed, coded and analysed in an iterative process, leading to the development of the grounded theory. Adherence was determined by the position of prophylaxis in life. The position of prophylaxis was determined by the perception of prophylaxis and the ability to exert prophylaxis. Patients' perception was influenced by two main factors: acceptance of haemophilia and feeling/fearing symptoms. The ability to exert prophylaxis was influenced by understanding haemophilia and prophylaxis and planning/infusion skills. The combination of different perceptions and skills led to four main positions of prophylaxis in life: (i) prophylaxis integrated in life, (ii) prophylaxis according to doctors' advice, struggling with irregular situations, (iii) prophylaxis is too much to handle, (iv) prophylaxis is a confrontation with illness. The adherence level gradually decreased from position 1 to 4. This information can be used to design tailored interventions to promote adherence. © 2015 John Wiley & Sons Ltd.

Health technology assessment and haemophilia.

PubMed

Farrugia, A; O'Mahony, B; Cassar, J

2012-03-01

Although the funding of rare diseases such as haemophilia in developing countries remains a low priority, pressures on the funding of haemophilia treatment are also emerging in developed economies affected by the global economic downturn and the other demands on health care budgets. This is leading advisory bodies and payers alike to explore the tools of Health Technology Assessment (HTAs) in deriving recommendations for reimbursement policies. In particular, the use of cost utility analysis (CUA) in deriving costs per quality adjusted life year (QALY) for different interventions is being used to rank interventions in order of priorities relative to a threshold cost per QALY. In these exercises, rare chronic disorders such as haemophilia emerge as particularly unattractive propositions for reimbursement, as the accepted methodology of deriving a CUA. For e.g. the use of prophylaxis in haemophilia leads to a range of costs/QALY which exceed the willingness to pay thresholds of most payers. In this commentary, we review the principles utilized in a recent systematic review of the use of haemophilia products carried out in Sweden as part of an HTA. We suggest that ranking haemophilia related interventions with the standard interventions of therapeutics and public health in CUA comparisons is inappropriate. Given that haemophilia treatment is a form of blood replacement therapy, we propose that such comparisons should be made with the interventions of mainstream blood transfusion. We suggest that unequivocally effective treatments such as haemophilia therapies should be assessed differently from mainstream interventions, that new methodologies are required for these kinds of diseases and that evidence of a societal willingness to support people with rare disorders needs to be recognized when reimbursement policies are developed. © 2012 Blackwell Publishing Ltd.

Haemophilia Experiences, Results and Opportunities (HERO) Study: influence of haemophilia on interpersonal relationships as reported by adults with haemophilia and parents of children with haemophilia.

PubMed

Cassis, F R M Y; Buzzi, A; Forsyth, A; Gregory, M; Nugent, D; Garrido, C; Pilgaard, T; Cooper, D L; Iorio, A

2014-07-01

Evidence delineating the effects of haemophilia on interpersonal relationships is sparse and largely outdated, failing to reflect the impact of current treatment strategies. HERO (Haemophilia Experiences, Results and Opportunities) was commenced to garner a more comprehensive understanding of psychosocial issues facing persons with haemophilia (PWH). This article describes the findings of the quantitative HERO survey relating to the influence of haemophilia on interpersonal relationships of adult PWH, and parents/caregivers of children with haemophilia. Separate questionnaires were completed by adult PWH and parents of minor children from 10 countries, including satisfaction with support from partners, family, friends and other social contacts; disclosure of haemophilia and carrier status and family dynamics. A total of 675 PWH and 561 parents completed the survey. Over half of PWH (57%) and parents (84%) were married. Most PWH were satisfied with support from partners (94%), family (90%) and friends (85%), with lower percentages reported among those with inhibitors. Most parents were likewise satisfied with support from partners (88%) and family (83%). Whereas PWH were reticent to disclose their diagnosis beyond family and friends, parents were more likely to share their son's diagnosis, and most were satisfied with the support from their son's peers (74%), teachers (83%) and other adults in supervisory roles (85%). PWH and parents surveyed were satisfied overall with the support they received from partners, family, friends and social contacts. Relationships are affected by haemophilia in various ways, and particularly affected in terms of disease burden, age and social life. © 2014 John Wiley & Sons Ltd.

Impact of health instructions on improving knowledge and practices of haemophilia A adolescents: a single centre experience.

PubMed

El Dakhakhny, A M; Hesham, M A; Hassan, T H; El Awady, S; Hanfy, M M

2014-07-01

Nowadays, health education has been elevated to a higher standing in healthcare systems in managing chronic illness; yet, this approach has not received sufficient support in developing countries as these societies still tend to the traditional stage of 'treatment after disease'. Adolescence is a critical period and voyage into adulthood can be more challenging for haemophilia teens. For teens with haemophilia, learning to care for their own disorder is a giant step forward in asserting their independence and preparation for adult life. We aimed to determine impact of health instructions on improving knowledge and practices of haemophilia A adolescents. An interventional study was conducted on 50 haemophilia A adolescents at outpatient clinic of Pediatric Hematology Unit of Zagazig University Hospitals. Three tools were used. The first was a structured interview sheet to evaluate patients' knowledge. The second was a clinical checklist to evaluate patients' practices. The third was health instructions program. Tools were developed by the researchers based on a thorough review of related literature and a full understanding of the needs of haemophilic adolescents. Evaluation of health instructions success was based on comparing scores of tool I and tool II before health instructions (pretest) and after health instructions immediately (posttest) and after 2 months (follow-up test). There was a significant improvement in knowledge and practices of haemophilia A adolescents in posttest and follow-up test compared to pretest. Health instructions have an impact on improving knowledge and practices of haemophilia A adolescents. © 2014 John Wiley & Sons Ltd.

Surgery and survival in birth cohorts with severe haemophilia and differences in access to replacement therapy: The Malmö experience.

PubMed

Osooli, M; Steen Carlsson, K; Astermark, J; Berntorp, E

2017-09-01

Persons with severe haemophilia require lifelong replacement therapy, prophylaxis, to prevent bleeding. Data describing long-term outcomes of prophylactic treatment are scarce. The aim of this study was to investigate joint surgery and survival among persons with severe haemophilia with special attention to access to prophylaxis in the early years of life. Eligible participants had severe haemophilia A or B and were treated at the Malmö centre from the 1960s onward. Time from birth until joint surgery was analysed for participants negative for factor inhibitor and alive in 2000. We compared survival among the entire cohort with severe haemophilia treated at the Malmö centre with the general male population of Sweden and a sample of persons with severe haemophilia from the United Kingdom (UK). Overall, 167 participants were included, 106 (63.5%) of whom had complete data on joint surgery. Among those born before 1970, 1970-1979 and ≥1980 approximately 37%, 21% and 0% had their first joint surgery by age 30, respectively. There were no second joint surgeries reported in cohorts born ≥1970. Persons with severe haemophilia and negative for HIV treated in Malmö have attained approximately similar survival to that of the general male population in Sweden and live slightly longer than persons with severe haemophilia from the UK. Prophylaxis in Sweden, although costly, has markedly improved survival and joint outcomes for persons with severe haemophilia. This study highlights the importance of early start of replacement therapy to prevent or postpone serious joint damage. © 2017 John Wiley & Sons Ltd.

Ten-year experience of recombinant activated factor VII use in surgical patients with congenital haemophilia with inhibitors or acquired haemophilia in Japan.

PubMed

Takedani, H; Shima, M; Horikoshi, Y; Koyama, T; Fukutake, K; Kuwahara, M; Ishiguro, N

2015-05-01

Patients with congenital haemophilia with inhibitors or acquired haemophilia are at risk of bleeding complications during surgery. In these patients, replacement therapy for the missing coagulation factor is ineffective, and a bypassing agent such as recombinant activated factor VII (rFVIIa) is required to manage bleeding. To evaluate the safety and haemostatic efficacy of rFVIIa treatment in Japanese patients with congenital haemophilia with inhibitors to FVIII/FIX or acquired haemophilia undergoing surgery. Postmarketing surveillance data from May 2000 to March 2010 were analysed to assess the haemostatic efficacy of 38 procedures in 22 patients with congenital haemophilia A, 13 procedures in seven patients with congenital haemophilia B, and five procedures in five patients with acquired haemophilia. Postoperative bleeding control was judged to be effective (bleeding was stopped completely or reduced considerably) for 34/38 procedures (89%) in patients with congenital haemophilia A, 10/13 procedures (77%) in patients with congenital haemophilia B, and 4/5 procedures (80%) in patients with acquired haemophilia. Tranexamic acid was used concomitantly for 36/56 procedures (64%). Safety was analysed for 66 procedures in 37 patients. Adverse effects potentially related to rFVIIa treatment included mild superficial thrombophlebitis, mild decrease in platelet count, and mild elevation of the serum alanine transaminase level in one patient each. All adverse effects resolved without treatment. Administration of rFVIIa provided adequate haemostasis without serious adverse effects in the majority of cases. The efficacy and safety data in Japanese patients were similar to previously published data from other countries. © 2014 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Management of haemophilia in the developing world.

PubMed

Srivastava, A; Chuansumrit, A; Chandy, M; Duraiswamy, G; Karagus, C

1998-07-01

The problems with management of haemophilia in developing countries are poor awareness, inadequate diagnostic facilities and scarce factor concentrates for therapy. The priorities in establishing services for haemophilia include training care providers, setting up care centres, initiating a registry, educating affected people and their families about the condition, providing low-cost factor concentrates, improving social awareness and developing a comprehensive care team. A coagulation laboratory capable of reliably performing clotting times with correction studies using normal pooled, FVIII and FIX deficient patient plasma and factor assay is most essential for diagnosis. More advanced centralized laboratories are also needed. Molecular biology techniques for mutation detection and gene tracking should be established in each country for accurate carrier detection and antenatal diagnosis. Different models of haemophilia care exists. In India, there is no support from the government. Services, including import of factor concentrates, are organized by the Haemophilia Federation of India, with support from other institutions. Haemophilia is managed with minimal replacement therapy (about 2000 i.u./PWH/year). In Malaysia, where the system is fully supported by the government, facilities are available at all public hospitals and moderate levels of factor concentrates are available 'on-demand' (about 11,000 i.u./PWH/year) at the hospitals. Haemophilia care in South Africa is provided through major public hospitals. Intermediate purity factor concentrates are locally produced (about 12,000 i.u./PWH/year) at low cost. The combined experience in the developing world in providing haemophilia services should be used to define standards for care and set achievable goals.

Perioperative management of haemophilia B: A critical appraisal of the evidence and current practices.

PubMed

Neufeld, E J; Solimeno, L; Quon, D; Walsh, C; Seremetis, S; Cooper, D; Iyer, N N; Hoxer, C S; Giangrande, P

2017-11-01

While there is substantial literature addressing the principles of general management of haemophilia, literature on perioperative management of haemostasis is scarce. The aim of this study was to better understand perioperative management among congenital haemophilia B patients (without inhibitors) and to gain insights into real-world surgical practices. A systematic literature review, with an emphasis on haemophilia B, was conducted using EMBASE ® , Medline ® and the Cochrane Library. Studies from 1974 to June 2015 were accessed, and 132 studies were eligible for the full-study review. An international expert panel with five haematologists and one surgeon reviewed the resulting literature and provided further insights. The literature review revealed that documented experience in the perioperative management of bleeding risk in haemophilia B patients is relatively scarce. Therefore, the review was amended to provide a comprehensive overview of the perioperative management for haemophilia A and B patients; the expert panel applied a particular focus to haemophilia B. Several gaps were identified in the literature including the lack of consensus on defining surgery in terms of bleeding risk, optimal factor levels during surgery and lack of robust evidence on surgical outcomes. The ensuing discussions with the expert panel provided validation of some of the results from the systematic literature review and proposed future directions for perioperative management. Suggestions included collaboration with haemophilia treatment centres (HTCs) to collect real-world data on perioperative management, establishing the need for optimal factor level monitoring practice, and the appropriate adoption of extended half-life products in clinical settings. © 2017 John Wiley & Sons Ltd.

Comparing the burden of illness of haemophilia between resource-constrained and unconstrained countries: the São Paulo-Toronto Hemophilia Study.

PubMed

Carneiro, J D A; Blanchette, V; Ozelo, M C; Antunes, S V; Villaca, P R; Young, N L; Castro, D; Brandão, L R; Carcao, M; Abad, A; Feldman, B M

2017-09-01

Although the regular replacement of clotting factor concentrates (prophylaxis) has been well established as the standard of care for severe haemophilia, the high cost of factor concentrates has limited access to prophylaxis in countries with under-developed or developing economies. We studied the health gap that could be addressed by providing unlimited access to clotting factor concentrates with implementation of long-term prophylaxis initiated from an early age in life. We performed a cross-sectional study of a random, representative sample of boys with moderate and severe haemophilia at three haemophilia treatment centres in Sao Paulo, Brazil, and one centre in Toronto, Canada. Canadian subjects were more often treated with prophylaxis, and began treatment at an earlier age. Fewer Canadian subjects had bleeds within the preceding 6 months (19 vs. 34, P = 0.003). Canadian subjects had lower (better) Pettersson radiographic scores (1.5 vs. 6.0, P = 0.0016), lower (better) Hemophilia Joint Health Scores (5.5 vs. 10.5, P = 0.0038), higher (better) Activity Scale for Kids scores (96.6 vs. 92.0, P = 0.033), more time spent in vigorous activity, and higher (better) social participation scores. Our findings suggest that increasing access to clotting factor concentrates for young boys with severe haemophilia is a global imperative. © 2017 John Wiley & Sons Ltd.

Bone health in persons with haemophilia.

PubMed

Kempton, C L; Antoniucci, D M; Rodriguez-Merchan, E C

2015-09-01

As the population of patients with haemophilia (PWH) ages, healthcare providers are required to direct greater attention to age-related co-morbidities. Low bone mineral density (BMD) is one such co-morbidity where the incidence not only increases with age, but also occurs with greater frequency in PWH. To review risk factors for low BMD, and strategies to promote bone health and identify patients who would benefit from screening for osteoporosis and subsequent treatment. A narrative review of the literature was performed in MEDLINE with keywords haemophilia, bone density, osteoporosis and fracture. Reference lists of retrieved articles were also reviewed. Low BMD occurs more commonly in PWH than the general population and is most likely the result of a combination of risk factors.  Steps to promote bone health include preventing haemarthrosis, encouraging regular exercise, adequate vitamin D and calcium intake, and avoiding tobacco and excessive alcohol intake. Adults 50 years of age and older with haemophilia and those younger than 50 years with a fragility fracture or increased fracture risk based on FRAX (The Fracture Risk Assessment Tool), regardless of haemophilia severity, should be screened for low BMD using dual x-ray absorptiometry (DXA). Once osteoporosis is diagnosed based on DXA, fracture risk should guide treatment. Currently, treatment is similar to those without haemophilia and most commonly includes bisphosphonates. Haemophilia care providers should promote adequate bone formation during childhood and reduce bone loss during adulthood as well as identify patients with low BMD that would benefit from therapy. © 2015 John Wiley & Sons Ltd.

Relationship between haemophilia and social status.

PubMed

Holstein, Katharina; Eifrig, Barbara; Langer, Florian

2014-11-01

The impact of haemophilia and its treatment on social status has not been well studied, although research into the quality of life of patients with haemophilia has shed some light on aspects of social and role functioning. Studies conducted before the advent of safe and effective coagulation factor replacement therapy suggest that the haemophilia population was predominantly of low socioeconomic status with many social disadvantages, including high rates of disability and unemployment and low rates of marriage. Since the availability of purified factor VIII concentrates that could be used in a home-care setting and as prophylaxis, most research suggests that social status and well-being amongst children, adolescents, and adults with haemophilia is not compromised, and is comparable to that of the general population. Children and adolescents with haemophilia do not generally feel disadvantaged, although haemophilia-related issues at school and amongst peer groups do arise. Recent studies in adults show higher than average rates of marriage and cohabitation and the attainment of a generally good educational status, but, as in the past, employment rates remain comparatively lower. Social status amongst the elderly with haemophilia who may have developed severe disability as a result of their condition is poorly defined and has never been formally studied. Additional research is recommended. © 2013.

Learning about Haemophilia

PubMed Central

Kendrick, Carol

1986-01-01

In order to learn about Haemophilia from the point of view of the sufferers, I interviewed six severely affected haemophiliacs, discussing with them their past experience, current status and treatment. I found them to be an optimistic and independent group who, despite their memories of a painful childhood and their current disablement, contrived to live in the present with gusto and vigour. They were very knowledgeable about Haemophilia and were happy to teach me, thus providing me with a valuable body of knowledge and ideas on the subject. PMID:3567678

A tortuous route to a capable fatherhood: the experience of being a father to a child with severe haemophilia.

PubMed

Myrin Westesson, L; Sparud-Lundin, C; Wallengren, C; Baghaei, F

2015-11-01

Haemophilia is a chronic illness that affects the whole family as the child's reactions to the illness occur in interaction with the parents. Limited research has been conducted on how fathers of children with haemophilia experience their life situation. The aim of this study was to describe the lived experience of being a father to a child with severe haemophilia. Individual, qualitative interviews were conducted with 14 fathers of 17 children with severe Haemophilia A. Data were analysed by means of a phenomenological hermeneutic method, including naïve reading, structural analysis and comprehensive interpretation. The results revealed that the fathers gradually grew into fatherhood through a process that can be explained in the metaphor, 'A tortuous road to a capable fatherhood'. The fathers experienced sorrow, powerlessness, concern and loss of a regular fatherhood after the child's diagnosis. The loss of an envisaged fatherhood emerged as the greatest sorrow of being a father to a child with haemophilia. When home treatment with factor concentrates functioned without the involvement of Health Care Personal (HCP), the fathers' sense of insufficiency decreased. A sense of being a capable father was associated with a sense of independence and control of one's life situation. Support from the Haemophilia Treatment Centre (HTC) in the learning process is essential for both parents of a child with severe haemophilia. Awareness of the fathers' struggle to feel capable is also vital while supporting the family in the first years after diagnosis. © 2015 John Wiley & Sons Ltd.

Understanding stakeholder important outcomes and perceptions of equity, acceptability and feasibility of a care model for haemophilia management in the US: a qualitative study.

PubMed

Lane, S J; Sholapur, N S; Yeung, C H T; Iorio, A; Heddle, N M; Sholzberg, M; Pai, M

2016-07-01

Care for persons with haemophilia (PWH) is most commonly delivered through the integrated care model used by Hemophilia Treatment Centers (HTCs). Although this model is widely accepted as the gold standard for the management of haemophilia; there is little evidence comparing different care models. We performed a qualitative study to gain insight into issues related to outcomes, acceptability, equity and feasibility of different care models operating in the US. We used a qualitative descriptive approach with semi-structured interviews. Purposive sampling was used to recruit individuals with experience providing or receiving care for haemophilia in the US through either an integrated care centre, a specialty pharmacy or homecare company, or by a specialist in a non-specialized centre. Persons with haemophilia, parents of PWH aged ≤18, healthcare providers, insurance company representatives and policy developers were invited to participate. Twenty-nine interviews were conducted with participants representing 18 US states. Participants in the study sample had experience receiving or providing care predominantly within an HTC setting. Integrated care at HTCs was highly acceptable to participants, who appreciated the value of specialized, expert care in a multidisciplinary team setting. Equity and feasibility issues were primarily related to health insurance and funding limitations. Additional research is required to document the impact of care on health and psychosocial outcomes and identify effective ways to facilitate equitable access to haemophilia treatment and care. © 2016 John Wiley & Sons Ltd.

The demographics, treatment characteristics and quality of life of adult people with haemophilia in China - results from the HERO study.

PubMed

Sun, J; Zhao, Y; Yang, R; Guan, T; Iorio, A

2017-01-01

Haemophilia management in China needs to be further developed. To further improve the quality of life (QoL) of people with haemophilia (PWH) in China, it is important to investigate the peculiarities of China as compared to other countries. The primary objective of the Haemophilia Experiences, Results and Opportunities (HERO) project was to quantify the impact of key psychosocial factors affecting PWH. This article presents the demographics, treatment characteristics, and QoL of adult PWH in China as compared with the results of the other nine countries participating in the HERO study. This was a web- (except in Algeria) and questionnaire-based survey conducted in 10 countries. A total of 110 adult PWH from China and 565 from other countries completed the questionnaire. Compared with other countries, respondents in China reported: lower rate of employment (45.6% vs. 63.1%); lower percentages of being treated by prophylaxis (4.1% vs. 36.8%), being treated always at home (27.8% vs. 54.3%) and following treatment recommendation as instructed (6.2% vs. 40.5%); greater difficulty in obtaining replacement factor products (97.3% vs. 29.6%) and visiting their treatment centre (60.9% vs. 26.4%); more annual bleeds requiring treatment (mean: 29.4/year vs. 15.4/year); lower mean self-evaluated disease control score (5.5 vs. 7.7), EQ-5D index (0.71 vs. 0.75) and visual analogue scale (7.1 vs. 7.5) scores. Employed PWH in China had a better self-reported generic QoL than those unemployed. The study suggests that there is a major need for further improvement of both medical care and ongoing psychosocial support for PWH in China. © 2016 John Wiley & Sons Ltd.

Health economics of treating haemophilia A with inhibitors.

PubMed

Knight, C

2005-11-01

Haemophilia is a rare, inherited blood disorder in which blood clotting is impaired such that patients suffer from excessive internal and external bleeding. At present there is no cure for haemophilia A and patients require expensive, life-long treatment involving clotting factor replacement therapy. Treatment costs are perceived to be higher for patients who have developed inhibitory antibodies to factor VIII, the standard therapy for haemophilia A. However, initial cost analyses suggest that clotting factor therapy with alternative haemostatic agents, such as recombinant activated factor VII or activated prothrombin complex concentrate, is no more expensive for the majority of haemophilia A patients with inhibitors than for those without inhibitors. With the availability of effective alternative haemostatic agents, orthopaedic surgery for haemophilia A patients with inhibitors is now a clinical option, and initial cost analyses suggest this may be a cost-effective treatment strategy for patients with inhibitors whose quality of life (QoL) is severely impaired by joint arthropathy. In an era of finite healthcare resourcing it is important to determine whether new treatments justify higher unit costs compared with standard therapies and whether such higher costs are justified from an individual perspective in terms of improved QoL, and from a societal perspective in terms of improved productivity and reduced overall healthcare costs. This paper examines current data on the health economics of treating haemophilia A patients with inhibitors, focusing on the overall costs of clotting factor replacement therapy and the cost consequences of joint replacement.

Self-management and skills acquisition in boys with haemophilia.

PubMed

Khair, Kate; Meerabeau, Liz; Gibson, Faith

2015-10-01

There is an increasing prevalence of children/young people with long-term conditions (LTC) in the UK due to improvements in health-care management and delivery. These children are often involved, from an early age, in their own care and management; yet, there are little data to support how or when they develop the necessary skills and knowledge to become competent at this care. This study aimed to understand self-management of haemophilia, from a child's perspective, in the 21st century in the UK where intensive prophylactic therapy is given from early childhood. A qualitative study using grounded theory to evaluate life-experiences of children and young people with haemophilia. Thirty boys aged 4-16 with severe haemophilia treated at a single paediatric haemophilia care centre were interviewed at home or in a focus group. Multimethod qualitative research including age-appropriate research tools (draw and write, photo-elicitation and interviews) to facilitate data collection from children. Boys develop self-management skills over time. They learn from health-care professionals, their parents and other family members with haemophilia. Self-management skills (bleed recognition, self-infusion, self and medicines management, pain and risk management and conceptualizing preventative therapy) are developed through experiential learning and individualized education, and not through formalized expert patient programmes. The boys in this study have benefited from early prophylactic factor replacement therapy. They develop skills in haemophilia and self-management at a relatively young age and are experts in their own haemophilia care. © 2013 John Wiley & Sons Ltd.

Ethical issues in haemophilia.

PubMed

DiMichele, D; Chuansumrit, A; London, A J; Thompson, A R; Cooper, C G; Killian, R M; Ross, L F; Lillicrap, D; Kimmelman, J

2006-07-01

Ethical issues surrounding both the lack of global access to care as well as the implementation of advancing technologies, continue to challenge the international haemophilia community. Haemophilia is not given the priority it deserves in most developing countries. Given the heavy burdens of sickness and disease and severe resource constraints, it may not be possible to provide effective treatment to all who suffer from the various 'orphan' diseases. Nevertheless, through joint efforts, some package of effective interventions can be deployed for a significant number of those who are afflicted with 'orphan' diseases. With cost-effective utilization of limited resources, a national standard of care is possible and affordable. Gene-based diagnosis carries attendant ethical concerns whether for clinical testing or for research purposes, even as the list of its potential benefits to the haemophilia community grows rapidly. As large-scale genetic sequencing becomes quicker and cheaper, moving from the research to the clinic, we will face decisions about the implementation of prenatal, neonatal and other screening programs. Such debates will require input from not just the health care professionals but from all stakeholders in the haemophilia community. Finally, long-term therapeutic success gene transfer in small and large animal models raises the question of when and in which patient population the novel therapeutic approach should first be studied in humans with haemophilia. Although gene therapy represents a worthy goal, the central question for the haemophilia community should be whether it wishes to volunteer itself as a model for a much broader set of innovations.

Achievements, challenges and unmet needs for haemophilia patients with inhibitors

PubMed Central

DARGAUD, Y.; PAVLOVA, A.; LACROIX-DESMAZES, S.; FISCHER, K.; SOUCIE, M.; CLAEYSSENS, S.; SCOTT, D.W.; d’OIRON, R.; LAVIGNE-LISSALDE, G.; KENET, G.; ETTINGSHAUSEN, C. ESCURIOLA; BOREL-DERLON, A.; LAMBERT, T.; PASTA, G.; NÉGRIER, C.

2016-01-01

Summary Over the past 20 years, there have been many advances in haemophilia treatment that have allowed patients to take greater control of their disease. However, the development of factor VIII (FVIII) inhibitors is the greatest complication of the disease and a challenge in the treatment of haemophilia making management of bleeding episodes difficult and surgical procedures very challenging. A meeting to discuss the unmet needs of haemophilia patients with inhibitors was held in Paris on 20 November 2014. Topics discussed were genetic and non-genetic risk factors for the development of inhibitors, immunological aspects of inhibitor development, FVIII products and inhibitor development, generation and functional properties of engineered antigen-specific T regulatory cells, suppression of immune responses to FVIII, prophylaxis in haemophilia patients with inhibitors, epitope mapping of FVIII inhibitors, current controversies in immune tolerance induction therapy, surgery in haemophilia patients with inhibitors and future perspectives for the treatment of haemophilia patients with inhibitors. A summary of the key points discussed is presented in this paper. PMID:26728503

Functional limitations in Romanian children with haemophilia: further testing of psychometric properties of the Paediatric Haemophilia Activities List.

PubMed

Groen, W; van der Net, J; Lacatusu, A M; Serban, M; Helders, P J M; Fischer, K

2013-05-01

Children with haemophilia often experience limitations in activities of daily life. Recently the Paediatric Haemophilia Activities List (PedHAL) has been developed and tested in Dutch children with intensive replacement therapy. The psychometric properties of the PedHAL in children not receiving intensive replacement therapy are not known. The objective was to gain further insight into the psychometric properties of the PedHAL and to study the functional health status of Romanian children and adolescents with haemophilia. Children attending to the rehabilitation centre of Buzias in Romania were sampled consecutively. Construct validity of the PedHAL was evaluated by concurrent testing with objective and subjective measures of physical function and functional ability. Reproducibility was tested by a 3-day test-retest by intraclass correlation coefficient (ICC) and limits of agreement (LOA). Responsiveness to rehabilitation was assessed by Haemophilia Joint Health Score (HJHS) and PedHAL. Twenty-nine children with severe (n = 25) or moderate (n = 4) haemophilia participated. Mean age was 13.2 years (SD 4.0). Median score of the PedHAL was 83.5 (IQR 47.9-90.5). The PedHAL correlated moderately with HJHS (rho = -0.59), Functional Independence Score in& Haemophilia (rho = 0.65) and Child Health Questionnaire-physical function (rho = 0.40) and not with Child Health Questionnaire-mental health, Child Health Questionnaire-behaviour and 6MWT. Test-retest reliability was good (ICC = 0.95). LOA was 17.4 points for the sum score. HJHS scores improved slightly after rehabilitation, whereas PedHAL scores did not change. In general, construct validity and test-retest reliability were good, test-retest agreement showed some variability. Therefore, currently the PedHAL may be more appropriate for research purposes than for individual patient monitoring in clinical practice. © 2013 Blackwell Publishing Ltd.

Joint health and functional ability in children with haemophilia who receive intensive replacement therapy.

PubMed

Groen, W; van der Net, J; Bos, K; Abad, A; Bergstrom, B-M; Blanchette, V S; Feldman, B M; Funk, S; Helders, P; Hilliard, P; Manco-Johnson, M; Petrini, P; Zourikian, N; Fischer, K

2011-09-01

Joint physical examination is an important outcome in haemophilia; however its relationship with functional ability is not well established in children with intensive replacement therapy. Boys aged 4-16 years were recruited from two European and three North American treatment centres. Joint physical structure and function was measured with the Haemophilia Joint Health Score (HJHS) while functional ability was measured with the revised Childhood Health Assessment Questionnaire (CHAQ₃₈. Two haemophilia-specific domains were created by selecting items of the CHAQ₃₈ that cover haemophilia-specific problems. Associations between CHAQ, HJHS, cumulative number of haemarthroses and age were assessed. A total of 226 subjects - mean 10.8 years old (SD 3.8) - participated; the majority (68%) had severe haemophilia. Most severe patients (91%) were on prophylactic treatment. Lifetime number of haemarthroses [median=5; interquartile range (IQR)=1-12] and total HJHS (median = 5; IQR=1-12) correlated strongly (ρ = 0.51). Total HJHS did not correlate with age and only weakly (ρ=-0.19) with functional ability scores (median=0; IQR=-0.06-0). Overall, haemarthroses were reported most frequently in the ankles. Detailed analysis of ankle joint health scores revealed moderate associations (ρ=0.3-0.5) of strength, gait and atrophy with lower extremity tasks (e.g. stair climbing). In this population, HJHS summating six joints did not perform as well as individual joint scores, however, certain elements of ankle impairment, specifically muscle strength, atrophy and gait associated significantly with functional loss in lower extremity activities. Mild abnormalities in ankle assessment by HJHS may lead to functional loss. Therefore, ankle joints may warrant special attention in the follow up of these children. © 2011 Blackwell Publishing Ltd.

Quality of life in haemophilia A: Hemophilia Utilization Group Study Va (HUGS-Va).

PubMed

Poon, J-L; Zhou, Z-Y; Doctor, J N; Wu, J; Ullman, M M; Ross, C; Riske, B; Parish, K L; Lou, M; Koerper, M A; Gwadry-Sridhar, F; Forsberg, A D; Curtis, R G; Johnson, K A

2012-09-01

This study describes health-related quality of life (HRQoL) of persons with haemophilia A in the United States (US) and determines associations between self-reported joint pain, motion limitation and clinically evaluated joint range of motion (ROM), and between HRQoL and ROM. As part of a 2-year cohort study, we collected baseline HRQoL using the SF-12 (adults) and PedsQL (children), along with self-ratings of joint pain and motion limitation, in persons with factor VIII deficiency recruited from six Haemophilia Treatment Centres (HTCs) in geographically diverse regions of the US. Clinically measured joint ROM measurements were collected from medical charts of a subset of participants. Adults (N = 156, mean age: 33.5 ± 12.6 years) had mean physical and mental component scores of 43.4 ± 10.7 and 50.9 ± 10.1, respectively. Children (N = 164, mean age: 9.7 ± 4.5 years) had mean total PedsQL, physical functioning, and psychosocial health scores of 85.9 ± 13.8, 89.5 ± 15.2, and 84.1 ± 15.3, respectively. Persons with more severe haemophilia and higher self-reported joint pain and motion limitation had poorer scores, particularly in the physical aspects of HRQoL. In adults, significant correlations (P < 0.01) were found between ROM measures and both self-reported measures. Except among those with severe disease, children and adults with haemophilia have HRQoL scores comparable with those of the healthy US population. The physical aspects of HRQoL in both adults and children with haemophilia A in the US decrease with increasing severity of illness. However, scores for mental aspects of HRQoL do not differ between severity groups. These findings are comparable with those from studies in European and Canadian haemophilia populations. © 2012 Blackwell Publishing Ltd.

The economics of inpatient on-demand treatment for haemophilia with high-responding inhibitors: a US retrospective data analysis.

PubMed

Pokras, S M; Petrilla, A A; Weatherall, J; Lee, W C

2012-03-01

Inpatient costs comprise >50% of annual healthcare costs for haemophilia patients with inhibitors but no reports exist on inpatient resource use and costs at a US national level. To quantify inpatient resource use and costs for on-demand treatment of bleeds of US haemophilia patients with inhibitors and compare costs and treatment duration between Factor VIII bypassing agents (BAs). Stays with haemophilia A from 2003-2008 were identified from inpatient billing records. Presence of inhibitors was inferred through use of BA; recombinant activated Factor VII and plasma-derived activated prothrombin complex concentrate. Duration and number of infusions of BA, length of stay, use of opioid-containing analgesics and costs were assessed and compared. Among 1322 stays mean BA treatment duration was 4.6 days with 4.9 infusions, 6.1 nights spent in hospital, and 58% administered opioid-containing analgesics. In unadjusted analyses there were significant differences in the above mentioned outcomes by BA use, reflecting underlying differences between the two patient populations. Average inpatient costs were $82,911. In adjusted analyses, African-American race, greater disease severity, hospital region outside the southern US and older age (cost model only) were significant predictors of longer BA treatment duration and higher costs. The economic burden of inpatient on-demand treatment of haemophilia with inhibitors is substantial and is associated with lengthy stays, high costs and inadequate pain relief. Availability of more effective BAs could reduce the need for re-treatment, reducing treatment costs and other medical costs, while improving health related quality of life. © 2011 Blackwell Publishing Ltd.

Treatment for preventing bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgery.

PubMed

Coppola, Antonio; Windyga, Jerzy; Tufano, Antonella; Yeung, Cindy; Di Minno, Matteo Nicola Dario

2015-02-09

In people with haemophilia or other congenital bleeding disorders undergoing surgical interventions, haemostatic treatment is needed in order to correct the underlying coagulation abnormalities and minimise the bleeding risk. This treatment varies according to the specific haemostatic defect, its severity and the type of surgical procedure. The aim of treatment is to ensure adequate haemostatic coverage for as long as the bleeding risk persists and until wound healing is complete. To assess the effectiveness and safety of different haemostatic regimens (type, dose and duration, modality of administration and target haemostatic levels) administered in people with haemophilia or other congenital bleeding disorders for preventing bleeding complications during and after surgical procedures. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of the last search: 20 November 2014. Randomised and quasi-randomised controlled trials comparing any hemostatic treatment regimen to no treatment or to another active regimen in children and adults with haemophilia or other congenital bleeding disorders undergoing any surgical intervention. Two authors independently assessed trials (eligibility and risks of bias) and extracted data. Meta-analyses were performed on available and relevant data. Of the 16 identified trials, four (112 participants) were eligible for inclusion.Two trials evaluated 59 people with haemophilia A and B undergoing 63 dental extractions. Trials compared the use of a different type (tranexamic acid or epsilon-aminocaproic acid) and regimen of antifibrinolytic agents as haemostatic support to the initial replacement treatment. Neither trial specifically addressed mortality (one of this review's primary outcomes); however, in the frame

Benefits of prophylaxis versus on-demand treatment in adolescents and adults with severe haemophilia A: the POTTER study.

PubMed

Tagliaferri, Annarita; Feola, Giulio; Molinari, Angelo Claudio; Santoro, Cristina; Rivolta, Gianna Franca; Cultrera, Dorina Bianca; Gagliano, Fabio; Zanon, Ezio; Mancuso, Maria Elisa; Valdré, Lelia; Mameli, Luciana; Amoresano, Susanna; Mathew, Prasad; Coppola, Antonio

2015-07-01

Rigorous evidence is lacking on long-term outcomes of factor VIII (FVIII) prophylaxis initiated in adolescent or adult patients with severe haemophilia A. The prospective, open-label Prophylaxis versus On-demand Therapy Through Economic Report (POTTER) study (ClinicalTrials.gov NCT01159587) compared long-term late secondary prophylaxis (recombinant FVIII-FS 20-30 IU/kg thrice weekly) with on-demand treatment in patients aged 12 to 55 years with severe haemophilia A. The annual number of joint bleeding episodes (primary endpoint), total bleeding episodes, orthopaedic and radiologic (Pettersson) scores, health-related quality of life (HRQoL), pharmacoeconomic impact, and safety were evaluated over a > 5-year period (2004-2010). Fifty-eight patients were enrolled at 11 centres in Italy; 53 (27 prophylaxis, 26 on demand) were evaluated and stratified into 2 age subgroups (12-25 and 26-55 years). Patients receiving prophylaxis experienced a significantly lower number of joint bleeding episodes vs the on-demand group (annualised bleeding rate, 1.97 vs 16.80 and 2.46 vs 16.71 in younger and older patients, respectively; p=0.0043). Results were similar for total bleeding episodes. Prophylaxis was associated with significantly fewer target joints (p< 0.001), better orthopaedic (p=0.0019) and Pettersson (p=0.0177) scores, better HRQoL, and fewer days of everyday activities lost (p< 0.0001) but required significantly higher FVIII product consumption. The POTTER study is the first prospective, controlled trial documenting long-term benefits of late secondary prophylaxis in adolescents and adults with severe haemophilia A. The benefits of reduced bleeding frequency, improved joint status, and HRQoL may offset the higher FVIII consumption and costs.

Haemophilia care in Europe - A survey of 37 countries.

PubMed

Mahony, B O; Savini, L; Hara, J O; Bok, A

2017-07-01

The European Haemophilia Consortium (EHC) is an international non-profit organization representing 45 national patients' organizations in Europe. Every 3 years, the EHC circulates a survey to its national member organizations to assess the state of haemophilia care. The purpose of this exercise is to ascertain information about the organization of haemophilia care and treatment availability at national levels. Furthermore, the survey provides a basis from which the EHC are able to monitor the unmet need and stability of care/treatment access in the individual member countries. Surveys are distributed to EHC member organizations in English and Russian. Patient organizations are encouraged to share the survey with local clinicians to ensure accuracy of responses. The data collected are in part consistent to provide a longitudinal overview for treatment access, but topical items are included such as ageing. Subsequently, completed surveys are transposed into a database for analysis and reporting. Thirty-seven responses were received from the 45 countries approached, representing an 82% response rate from members. Findings suggest increased access to treatment and some improvement in certain areas of care. However, access to treatment has declined or remained largely unchanged in some countries. The survey has been a successful exercise in enabling a greater understanding of the current Haemophilia care landscape across Europe. However, there remain unmet needs in various aspects of patient care, and specific examples include psychosocial care and general preparedness for an ageing haemophilia population. © 2017 John Wiley & Sons Ltd.

Physical and mental quality of life in adult patients with haemophilia in Belgium: the impact of financial issues.

PubMed

Carvalhosa, A M; Henrard, S; Lambert, C; Hermans, C

2014-07-01

In Belgium, where haemophilia affects approximately 1:7000 people (2011), data on patients' quality of life (QoL) is scarce. This project aims to assess physical and mental QoL (P-QoL and M-QoL) simultaneously, and to analyse the influence of different variables on these two aspects of QoL. After Ethics Committee approval, we contacted 84 adult haemophilia A (HA) and haemophilia B (HB) patients, without current inhibitors, on replacement therapy (on-demand or secondary prophylaxis), regularly followed up at our comprehensive treatment centre. Seventy-one (n = 59 HA, n = 12 HB) replied to our questionnaire, which included the SF36v2 QoL assessment forms. We analysed two groups of variables: one including variables previously associated with decreased QoL, and another including variables with unclear impact on QoL (e.g., patients' understanding of haemophilia-related issues, economical concerns). In our population (mean ± SD age: 45.2 ± 14.7 years old), P-QoL appeared more reduced than M-QoL. P-QoL was strongly influenced by the number of arthropathies while M-QoL was primarily affected by patients' concern of personal costs due to haemophilia. Among this latter group, having knowledge of insurance coverage had a positive impact on M-QoL. Scores did not depend on haemophilia type. QoL was impaired in our haemophilia patients. A simultaneous assessment of P-QoL and M-QoL confirmed the benefit of primary prophylaxis in P-QoL, while originally pointing out the major burden of patients' concerns and poor understanding of haemophilia-related economical issues on their M-QoL. This might become a particularly challenging issue in times of financial crisis. © 2013 John Wiley & Sons Ltd.

A study of prospective surveillance for inhibitors among persons with haemophilia in the United States.

PubMed

Soucie, J M; Miller, C H; Kelly, F M; Payne, A B; Creary, M; Bockenstedt, P L; Kempton, C L; Manco-Johnson, M J; Neff, A T

2014-03-01

Inhibitors are a rare but serious complication of treatment of patients with haemophilia. Phase III clinical trials enrol too few patients to adequately assess new product inhibitor risk. This project explores the feasibility of using a public health surveillance system to conduct national surveillance for inhibitors. Staff at 17 U.S. haemophilia treatment centres (HTC) enrolled patients with haemophilia A and B into this prospective study. HTC staff provided detailed historic data on product use and inhibitors at baseline, and postenrolment patients provided monthly detailed infusion logs. A central laboratory performed inhibitor tests on blood specimens that were collected at baseline, annually, prior to any planned product switch or when clinically indicated. The central laboratory also performed genotyping of all enrolled patients. From January 2006 through June 2012, 1163 patients were enrolled and followed up for 3329 person-years. A total of 3048 inhibitor tests were performed and 23 new factor VIII inhibitors were identified, 61% of which were not clinically apparent. Infusion logs were submitted for 113,205 exposure days. Genotyping revealed 431 distinct mutations causing haemophilia, 151 of which had not previously been reported elsewhere in the world. This study provided critical information about the practical issues that must be addressed to successfully implement national inhibitor surveillance. Centralized testing with routine monitoring and confirmation of locally identified inhibitors will provide valid and representative data with which to evaluate inhibitor incidence and prevalence, monitor trends in occurrence rates and identify potential inhibitor outbreaks associated with products. © 2013 John Wiley & Sons Ltd.

The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

PubMed

Castro, Hector E; Briceño, María Fernanda; Casas, Claudia P; Rueda, Juan David

2014-03-01

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease".

Falling and fall risk factors in adults with haemophilia: an exploratory study.

PubMed

Sammels, M; Vandesande, J; Vlaeyen, E; Peerlinck, K; Milisen, K

2014-11-01

Falls are a particular risk in persons with haemophilia (PWH) because of damaged joints, high risk of bleeding, possible impact on the musculoskeletal system and functioning and costs associated with treatment for these fall-related injuries. In addition, fall risk increases with age and PWH are increasingly entering the over 65 age group. The aim of this study was to determine the occurrence of falls during the past year and to explore which fall risk factors are present in community-dwelling PWH. Dutch speaking community-dwelling adults were included from the age of 40 years with severe or moderate haemophilia A or B, independent in their mobility and registered at the University Hospitals Leuven. They were asked to come to the haemophilia centre; otherwise a telephone survey was conducted. Demographic and social variables, medical variables, fall evaluation and clinical variables were queried. From the 89 PWH, 74 (83.1%) participated in the study. Twenty-four (32.4%) fell in the past year, and 10 of them (41.7%) more than once with an average of four falls. Living conditions, physical activity, avoidance of winter sports due to fear of falling, orthopaedic status, urinary incontinence and mobility impairments are potential fall risk factors in adult PWH. This exploratory study indicates that PWH are attentive to falling since they are at higher risk for falls and because of the serious consequences it might have. Screening and fall prevention should be stimulated in the daily practice of haemophilia care. © 2014 John Wiley & Sons Ltd.

Psychosocial care for children with haemophilia and their parents in the Netherlands.

PubMed

Limperg, P F; Haverman, L; Beijlevelt, M; van der Pot, M; Zaal, G; de Boer, W A; Fijnvandraat, K; Peters, M; Grootenhuis, M A

2017-05-01

Children growing up with haemophilia are at greater risk for psychosocial problems than their healthy peers. Providing psychosocial care to children with haemophilia and their families is indispensable, since psychosocial factors can have a significant impact on health and health-related quality of life (HRQOL). Our aim was to give a description of psychosocial care provided by the multidisciplinary team of the Hemophilia Comprehensive Care Centre (HCCC) at the Emma Children's Hospital in Amsterdam, the Netherlands. With this overview, other caregivers and hospitals can benefit in organizing their psychosocial care for children with haemophilia. The focus of the psychosocial care provided by the multidisciplinary team is on preventing psychosocial problems and medical-related stress, and supporting and equipping the child with haemophilia and its parents with as many skills as possible to lead an independent life with a high HRQOL. Core elements of the psychosocial care are therefore monitoring and screening of HRQOL (e.g. in daily clinical practice via www.hetklikt.nu), psychoeducation (haemophilia camp, haemophilia school, disease-specific activities, meetings for girls, parent meetings), practical help (Emma at Work, an employment agency for adolescents and young adults; Educational Facility and school visits), psychosocial interventions (the On Track group intervention and the Haemophilia Coping and Perception Test) and individual care (psychological counselling and referrals). By providing this overview of psychosocial support offered and by sharing this knowledge, psychosocial care can become more structured and consistent between HCCCs around the world. Potentially, processes and outcomes of care can be improved. © 2017 John Wiley & Sons Ltd.

Neonatal circumcision in severe haemophilia: a survey of paediatric haematologists at United States Hemophilia Treatment Centers.

PubMed

Kearney, S; Sharathkumar, A; Rodriguez, V; Chitlur, M; Valentino, L; Boggio, L; Gill, J

2015-01-01

Neonatal circumcision in patients with severe haemophilia has not been well studied. We performed a survey of paediatric haematologists from Hemophilia Treatment Centers (HTC) across the United States to better understand the attitudes toward and management of neonatal circumcision in haemophilia patients. Response rate to our survey was 40% (n = 64/159). Thirty-eight percent of respondents (n = 24) said that they would allow this procedure in the newborn period but in many cases this was against medical advice. The most reported concern regarding neonatal circumcision in haemophilia patients was the risk of development of an inhibitor (n = 25; 39%) followed by the concern for bleeding (n = 22; 34%) and issues related to vascular access in the neonate (n = 11; 17%). All respondents recommended at least one preprocedure dose of factor replacement. Twenty-two percent (n = 14) of respondents did not use more than one dose of factor replacement but 32% (n = 21) used 1-2 postoperative doses. The remainder of paediatric haematologists surveyed recommended between 3-5 (16%; n = 10) and 6-10 (3%, n = 2) additional days postoperatively. There was wide variation in both techniques of circumcision as well as adjuvant haemostatic agents used. Only 22% of respondents said that they had an established protocol for management of circumcision in the newborn haemophilia patient. These survey results highlight the need for evidence-based guidelines regarding the optimal management of circumcision in neonates with severe haemophilia. © 2014 John Wiley & Sons Ltd.

Perceived competence in children and adolescents with haemophilia: an explorative study.

PubMed

Hegeman, A K; Van Genderen, F R; Meijer, S; Van Den Briel, M M; Tamminga, R Y J; Van Weert, E

2011-01-01

With the introduction of prophylaxis, restricting children with haemophilia to participate in physical activities was no longer necessary. Subsequently, many studies report on improved physical functioning in children and adolescents with haemophilia. However, little is known about psychological aspects such as perceived competence and impact of disease. Therefore, the aims of this study were to explore: (i) perceived competence, (ii) perceived impact of illness, and (iii) analyse associations between perceived competence and demographic factors, disease-related factors and joint status in young haemophiliacs in the Netherlands. Fifty-four children (age 8-12 years) and 72 adolescents (12-18 years) with haemophilia participated in this cross-sectional, multi-centre, explorative study. Measurements included perceived competence (Self Perception Profile for Children/Adolescents; range 6-24/5-20), impact of disease (Revised Perception Illness Experience; range 1-5), demographic factors, disease-related factors, joint status and functional status. Mean (SD) scores for perceived competence in the children ranged from 17.3 (±4.0) to 19.6 (±4.0), and for adolescents from 13.3 (±2.4) to 15.7 (±2.8) points. In general, scores were comparable with those of healthy peers, but children with haemophilia had a lower global self-worth score and competence in close friendship was lower for adolescents when compared with those of healthy peers. Mean (SD) scores for impact of disease ranged from 1.2 (±0.4) to 2.3 (±0.8) in children and from 1.3 (±0.4) to 2.0 (±0.8) in adolescents. Severe haemophilia, prophylactic medication, high impact of disease and a shorter walking distance showed a weak to moderate association with perceived competence. Children and adolescents with haemophilia in general have a perceived competence that is nearly comparable with that of healthy peers, with the exception of a lower global self-worth in children and a lower competence for close friendship

Severe and moderate haemophilia A and B in US females.

PubMed

Di Michele, D M; Gibb, C; Lefkowitz, J M; Ni, Q; Gerber, L M; Ganguly, A

2014-03-01

Haemophilia A and B are rare X-lined hemorrhagic disorders that typically affect men. Women are usually asymptomatic carriers, but may be symptomatic and, rarely, also express severe (factor VIII (FVIII) or factor IX (FIX) <0.01 U mL(-1)) or moderately severe (FVIII/FIX 0.01-0.05 U mL(-1)) phenotypes. However, data on clinical manifestations, genotype and the psychosocial ramifications of illness in severely affected females remain anecdotal. A national multi-centre retrospective study was conducted to collect a comprehensive data set on affected US girls and women, and to compare clinical observations to previously published information on haemophilic males of comparable severity and mildly affected haemophilic females. Twenty-two severe/moderate haemophilia A/B subjects were characterized with respect to clinical manifestations and disease complications; genetic determinants of phenotypic severity; and health-related quality of life (HR-QoL). Clinical data were compared as previously indicated. Female patients were older than male patients at diagnosis, but similarly experienced joint haemorrhage, disease- and treatment-related complications and access to treatment. Gynaecological and obstetrical bleeding was unexpectedly infrequent. F8 or F9 mutations, accompanied by extremely skewed X-chromosome inactivation pattern (XIP), were primary determinants of severity. HR-QoL was diminished by arthropathy and viral infection. Using systematic case verification of participants in a national surveillance registry, this study elucidated the genetics, clinical phenotype and quality of life issues in female patients with severe/moderate haemophilia. An ongoing international case-controlled study will further evaluate these observations. Novel mechanistic questions are raised about the relationship between XIP and both age and tissue-specific FVIII and FIX expression. © 2014 John Wiley & Sons Ltd.

Is on-demand treatment effective in patients with severe haemophilia?

PubMed

Aznar, J A; Marco, A; Jiménez-Yuste, V; Fernández-Fontecha, E; Pérez, R; Soto, I; Parra, R; Moreno, M; Mingot, M E; Moret, A

2012-09-01

On-demand therapy enables stopping haemorrhages rapidly, reducing joint pain and restoring joint mobility, but does not prevent the beginning and subsequent development of haemophilic arthropathy. The main objective of this study was to identify the clinical and orthopaedic status of severe haemophilic patients with bleeding phenotype receiving on-demand treatment in Spain. We conducted an epidemiological, observational, retrospective study, recruiting 167 patients from 36 centres (92% of them with haemophilia A), median age at enrolment of 35 years. Forty per cent of the patients received a combination of on-demand and short-term prophylaxis regimen; the rest was under on-demand treatment. One hundred and forty-five patients (87%) reported at least one bleeding episode and 22 (13%) of the biologically severe patients had no bleeding phenotype. Seventy-one per cent of the studied population presented established haemophilic arthropathy, reaching 80% if we exclude patients without bleeding phenotype. Forty-three per cent of these patients had one or two joints affected, 28% of them had three or four affected joints, 20% reported five or six affected joints and 9% more than six injured joints. An increase in established haemophilic arthropathy with age was observed. Forty-six patients underwent orthopaedic surgery at least once. These data show that on-demand therapy is not effective in preventing the development of haemophilic arthropathy in severe haemophilic population with bleeding phenotype. Therefore, we suggest that the optimal treatment in these patients should be based on prophylaxis. We recommend analysing the reasons for ending prophylaxis, in case its reinstatement should be necessary. © 2012 Blackwell Publishing Ltd.

A synopsis of current haemophilia care in Hong Kong.

PubMed

Au, W Y; Lee, Vincent; Kho, Bonnie; Ling, Alvin S C; Chan, Desmond; Chan, Eric Y T; Chan, Godfrey C F; Cheung, Winnie W W; Lau, C W; Lee, C Y; Li, Rever C H; Li, C K; Lin, S Y; Mak, Vivien; Sun, Lina; Wong, Kris H F; Wong, Raymond; Yau, Jeffrey; Yuen, H L

2011-06-01

To provide a synopsis of current haemophilia care in Hong Kong. Retrospective survey. All haematology units of the Hospital Authority in Hong Kong. All patients with haemophilia A and haemophilia B. To date, there were 222 mild-to-severe haemophilia patients (192 type A, 30 type B) under regular public care in Hong Kong (43% were considered severe, 33% moderate, and 24% mild), which gave a crude prevalence of 6.8/100 000 male inhabitants. A total of 12.8 million units of Factor VIII and 3 million units of Factor IX were prescribed annually. This amounts to 1.83 units of FVIII per capita of the population, which is comparable to that of other developed countries. Leading causes of mortality were human immunodeficiency virus-related complications (10 cases) and cerebral bleeding (2 cases). The life expectancy of patients with severe haemophilia in Hong Kong is improving; currently the oldest patient is 60 years old. Such improved survival may be due to enhanced factor availability, prompt treatment of bleeding episodes at home, safer factor products, and better antiviral treatment. Primary prophylaxis is the accepted standard of care for severe and moderate cases, and "Factor First" has become hospital policy. However, 12 patients continue to present treatment challenges, due to the documented presence of factor inhibitors. In all, 28, 100, and 14 cases respectively were positive for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus; the youngest patients with the corresponding infections being 28, 13, and 22 years old. Comprehensive care with dedicated physiotherapy, surgical support, and radionucleotide synovectomy may reduce morbidity further. A multidisciplinary approach can further improve the future care for haemophilia patients in Hong Kong.

Similar bleeding phenotype in young children with haemophilia A or B: a cohort study.

PubMed

Clausen, N; Petrini, P; Claeyssens-Donadel, S; Gouw, S C; Liesner, R

2014-11-01

The bleeding phenotype has been suggested to differ between haemophilia A and B. More knowledge on the bleeding phenotype at initiation of treatment is important to optimize patient care. The aim of this study was to investigate the severity of the bleeding phenotype and the variation in bleeding in children with severe or moderate haemophilia A and B. Consecutive, previously untreated patients with severe or moderate haemophilia A and B (factor VIII or IX activity <0.01 or 0.01-0.05 IU mL(-1) respectively) born between January 1st 2000 and January 1st 2010 were included. Primary outcome was severity of bleeding tendency. Secondary outcome was variation in bleeding pattern. A total of 582 patients with severe haemophilia A and 76 with severe haemophilia B did not differ in age at first exposure to clotting factor (0.81 vs. 0.88 years, P = 0.20), age at first bleed (0.82 vs. 0.88 years, P = 0.36), and age at first joint bleed (1.18 vs. 1.20 years, P = 0.59). Patients with moderate haemophilia were older compared to patients with severe haemophilia. In patients with moderate haemophilia there were no clear differences between haemophilia A and B. Severity and variation in bleeding phenotype are similar during the early stage of treatment in patients with severe and moderate haemophilia A and B respectively. The findings imply that children with haemophilia B should be observed and treated as vigilantly as those with haemophilia A. © 2014 John Wiley & Sons Ltd.

The impact of the economic downturn and health care reform on treatment decisions for haemophilia A: patient, caregiver and health care provider perspectives.

PubMed

Tarantino, M D; Ye, X; Bergstrom, F; Skorija, K; Luo, M P

2013-01-01

Little is known about the impact of the recent US economic downturn and health care reform on patient, caregiver and health care provider (HCP) decision-making for haemophilia A. To explore the impact of the recent economic downturn and perceived impact of health care reform on haemophilia A treatment decisions from patient, caregiver and HCP perspectives. Patients/caregivers and HCPs completed a self-administered survey in 2011. Survey participants were asked about demographics, the impact of the recent economic downturn and health care reform provisions on their treatment decisions. Seventy three of the 134 (54%) patients/caregivers and 39 of 48 (81%) HCPs indicated that the economic downturn negatively impacted haemophilia care. Seventy of the 73 negatively impacted patients made financially related treatment modifications, including delaying/cancelling routine health care visit, skipping doses and/or skipping filling prescription. Treatment modifications made by HCPs included delaying elective surgery, switching from higher to lower priced product, switching from recombinant to plasma-derived products and delaying prophylaxis. Health care reform was generally perceived as positive. Due to the elimination of lifetime caps, 30 of 134 patients (22%) and 28 of 48 HCPs (58%) indicated that they will make treatment modifications by initiating prophylaxis or scheduling routine appointment/surgery sooner. Both patients/caregivers and HCPs reported that the economic downturn had a negative impact on haemophilia A treatment. Suboptimal treatment modifications were made due to the economic downturn. Health care reform, especially the elimination of lifetime caps, was perceived as positive for haemophilia A treatment and as a potential avenue for contributing to more optimal treatment behaviours. © 2012 Blackwell Publishing Ltd.

Haemophilia care in India: innovations and integrations by various chapters of Haemophilia Federation of India (HFI).

PubMed

Ghosh, K; Shetty, S; Sahu, D

2010-01-01

Care of persons with haemophilia (PWH) in western countries is the responsibility of the government of those countries with or without funding from health insurers. Haemophilia societies in western countries work as pressure groups to ensure better care, and they disseminate information on the disease and some of the societies even support medical research for haemophilia care. In India, Haemophilia Federation of India (HFI) was established in 1982 with few haemophilia families and sympathizers of their cause; subsequently more than 65 chapters involving more than 12 500 PWH came up under HFI. HFI and its constituent chapters are unique in the world in the sense that they are not only trying to involve state and federal government to take responsibility for delivering haemophilia care, but they are also using various innovative and integrative techniques to deliver haemophilia care to PWH themselves, till the time federal and state governments of the country make suitable arrangement for their care. In this study, several of these approaches are discussed with the understanding that 80% of worlds' haemophilia population needs similar help, and the national haemophilia organizations (NMO) of various developing countries will find some of the approaches useful and adaptable to their own circumstances.

Real-world resource use and costs of haemophilia A-related bleeding.

PubMed

Shrestha, A; Eldar-Lissai, A; Hou, N; Lakdawalla, D N; Batt, K

2017-07-01

Prophylaxis treatment is recommended for haemophilia patients, but associated real-world economic costs and potential cost-savings associated with improved disease management are not fully known. This study aimed to assess haemophilia A-related resource use and cost by treatment type (prophylaxis versus non-prophylaxis) and any associated cost-savings. Truven MarketScan Commercial claims data (2004-2012) were used to identify haemophilia A-related healthcare utilization, healthcare costs and patterns of prophylaxis and non-prophylaxis treatment among 6- to 64-year-old males. We estimated bleeding-related resource utilization and costs in three age groups (6-18, 19-44, 45-64) by treatment types and assessed the extent to which early initiation of prophylactic treatment can mitigate them. T-tests and ordinary least squares regressions were used to compare unadjusted and demographics-adjusted cost estimates. Among children, overall haemophilia- and bleeding-related non-pharmacy costs were substantially lower for patients receiving prophylaxis (haemophilia-related: $15,864 vs. $53,408; P < 0.001; bleeding-related: $696 vs. $2013, respectively; P = 0.04). Among younger adults (19-44), haemophilia-related non-pharmacy costs were lower for patients receiving prophylaxis ($22,028 vs. $56,311, respectively; P = 0.001). Among children, these savings fully offset the incremental pharmacy cost due to prophylaxis. Among younger adults, the savings offset approximately 34% of the incremental pharmacy cost. No differences were found for older adults (45-64). These results suggest that initiating prophylaxis earlier in life may reduce the healthcare costs of bleeding events and their long-term complications. Future studies should strive to collect more detailed information on disease severity and treatment protocols to improve estimates of disease burden. © 2017 John Wiley & Sons Ltd.

Co-morbidities and bleeding in elderly patients with haemophilia-A survey of the German, Austrian and Swiss Society of Thrombosis and Haemostasis Research (GTH).

PubMed

Miesbach, W; Reitter-Pfoertner, S-E; Klamroth, R; Langer, F; Wolf, H-H; Tiede, A; Siegmund, B; Scholz, U; Müller, P R; Eichler, H; Pabinger, I

2017-09-01

Nowadays patients with haemophilia survive longer due to improvements in haemophilia care. It has been hypothesized that the bleeding type and frequency may vary with age and are influenced by co-morbidities and co-medication in elderly patients. To investigate a large group of patients older than 60 years of age with haemophilia concerning haemophilia treatment, bleeding pattern changes, co-morbidities, co-medication, bleeding sites and patient mortality. A retrospective multi-centre data collection study was initiated on behalf of the German, Austrian and Swiss Society of Thrombosis and Haemostasis Research (GTH). Parameters of interest were investigated over the 5 years prior to study entry. A total of 185 haemophilia patients (mean age, 69.0±7.0 years, 29% with severe haemophilia) were included in the study. Regular prophylaxis was performed in 30% of the patients with severe haemophilia. In total, the annual bleeding rate was 2.49 and in patients with severe haemophilia 5.61, mostly caused by joint bleeds. Hypertension was the most common co-morbidity, but it occurred significantly less frequently than in an age-matched general population older than 70 years; 12% of the patients suffered from ischaemic heart disease, and 13% of the patients received anticoagulant or antiplatelet therapy. Within the observation period, 17% of the patients with severe haemophilia developed a higher frequency of bleeding symptoms, which was significantly associated with the use of antiplatelet or anticoagulant drugs. The most common co-morbidity of the patient population was hypertension, a considerable part had ischemic heart disease and antiplatelet or anticoagulant drugs. © 2017 John Wiley & Sons Ltd.

Disability in Indian patients with haemophilia.

PubMed

Kar, A; Mirkazemi, R; Singh, P; Potnis-Lele, M; Lohade, S; Lalwani, A; Saha, A S

2007-07-01

Chronic shortage of clotting factor concentrates, exorbitant treatment costs and the poor economic status of patients makes disability an inevitable consequence of haemophilia in India. The prevalence and risk factors for disability were studied in 148 patients with severe haemophilia A registered at five haemophilia clinics in the country. Disability was measured using a scoring method that used a compilation of functional ability, mobility and range-of-motion scores for each patient. Patients ranged in age from 5 to 55 years. Only nine of 148 patients were free of disability. The proportion of disability free patients in the 5-12, 13-24 and 25+ age groups were 14.3%, 4.4% and 0% respectively. The risk factors significantly associated with disability were patients age, socio-economic status, number of persons in the family, family history of haemophilia, frequency of physiotherapy exercises, home use of coagulation factor concentrate and type of blood product(s) used, that is clotting factor concentrate or cryoprecipitate. The study highlights the need to provide coagulation factor concentrates in sufficient amounts to prevent disability, the beneficial role of physiotherapy exercises and the advantage of older patients as peer educators for younger patients. The most important utility of the data is to demonstrate the widespread prevalence of disability amongst patients, its social costs in terms of incomplete education and unemployment, which justifies the need to include haemophilia as one of the conditions under the Disability Act of India.

A European curriculum for nurses working in haemophilia.

PubMed

Harrington, C; Bedford, M; Andritschke, K; Barrie, A; Elfvinge, P; Grønhaug, S; Mueller-Kagi, E; Leenders, B; Schrijvers, L H

2016-01-01

Currently, there is no consensus on education required to develop haemophilia nursing. The aim was to develop a curriculum for haemophilia nurses that could be used as a resource in Europe. This could form a basis for continuous professional development and used in the preparation of specialized educational programmes. The EAHAD nurses working group set out to describe the skills and knowledge needed for a nurse to work in this specialty. This was considered at two levels: basic requirements and at a more advanced level. The working group acted as a focus group for this project drawing on existing specialist training, national role definitions, competencies and results of the EAHAD Nurses survey (2012). A template was populated with the knowledge base and the skills required. Themes were analysed and information generated organized into domains: content of curriculum; learning outcomes, defined in terms of knowledge, skills, behaviour and attitudes; and suggestions for teaching methods. For curriculum content the following domains were identified: Applied biological science; treatment and management of haemophilia and associated disorders; genetic practice; care management of affected carriers and women; the impact of living with bleeding disorders; evidence base and applied research in haemophilia practice; and, the specialist role of the haemophilia nurse. Examples are given for teaching and learning process. This curriculum is intended for use as a strategic resource to outline education for the haemophilia nurse and contribute to the standardization and benchmarking of haemophilia nursing care and thus to improvement in the quality of patient care. © 2015 John Wiley & Sons Ltd.

[Haemophilia A and B in dogs].

PubMed

Mischke, R

2012-01-01

Based on own clinical experiences and the literature, this review article elaborates on aspects of aetiology, pathogenesis, clinical signs, diagnosis and therapy of haemophilia A and B in dogs. When compared to humans, dogs reveal more severe haemorrhagic symptoms at a defined residual factor activity (e.g. subcutaneous, intramuscular, and intraarticular haemorrhages after inappropriate trauma resulting in lameness and paralysis, excessive haemorrhage during second dentition, venal puncture, and surgery). Fortunately, genetic tests are now commercially available in Germany for selected breeds (haemophilia B in Rhodesian Ridgebacks; haemophilia A in Havaneses), which complement the conventional individual factor activity measurements and facilitate the detection of female carrier dogs. Treatment of bleeding crises is still mainly based on substitution therapy with fresh or fresh frozen plasma in addition to local haemostatic measures. In contrast, expectations regarding the timely clinical availability of gene therapy (particularly in humans) have not yet been fulfilled.

The impact of sport on health status, psychological well-being and physical performance of adults with haemophilia.

PubMed

von Mackensen, S; Harrington, C; Tuddenham, E; Littley, A; Will, A; Fareh, M; Hay, C R M; Khair, K

2016-07-01

There is increasing recognition that sport is important for individuals with haemophilia; however, there remains a paucity of data of the importance of this in adults, many of whom already have joint pathology related to childhood bleeds and treatment access. This multicentre, cross-sectional study presents the impact of sport on health-related quality of life (HRQoL), physical performance and clinical outcomes in adults with haemophilia. Fifty adults aged 35.12±14.7 with mild (n = 12), moderate (n = 10), or severe (n = 28) haemophilia A (70%) or B (30%) from four haemophilia centres across the United Kingdom participated in the study. A total of 64% were overweight/obese according to their BMI; median orthopaedic joint scores using the WFH Orthopaedic Joint Score (OJS) were 6 (range 0-48). On a VAS pain scale (range of 0-10), patients reported mean score of 5.66 ± 2.4. 36% of participants reported not doing any sport, mainly due to their physical condition. However, 64% of participants reported undertaking sporting activity including contact sports, mostly twice per week in average 4 h week(-1) . Participating in sport did not have a statistically significant impact on HRQoL; except in the domain 'sport and leisure' of the Haem-A-QoL. Patients doing more sport reported significantly better HRQoL than those doing less sport (P < 0.005). Those doing sport for more than 4 h week(-1) had a significantly better physical performance than patients doing less sport (assessed with Hep-Test-Q). Encouraging physical activity and sport in older patients with haemophilia may have a direct impact on their HRQoL; thus, education about sport activity should be incorporated into routine haemophilia care. © 2016 John Wiley & Sons Ltd.

Epidemiology & social costs of haemophilia in India

PubMed Central

Kar, Anita; Phadnis, Supriya; Dharmarajan, Sumedha; Nakade, Juhi

2014-01-01

India lacks a national policy on the prevention and control of genetic disorders. Although the haemoglobinopathies have received some attention, there are scarce data on the epidemiology of other genetic disorders in India. Haemophilia, an inherited single gene disorder with an incidence of 1 per 10,000 births, manifests as spontaneous or trauma-induced haemorrhagic episodes in patients, progressing to chronic disability and premature mortality in untreated patients or patients with sub-optimal treatment. Although the genetic basis of this disorder has been well studied in India, data on the number of patients, trends of the disorder in India, social costs of the condition and opportunities and competencies for offering genetic counselling through a public health programme have not been reported. This review article summarizes the available Indian data, which show that the country harbours the second highest number of global patients with haemophilia A. The reported number of patients with haemophilia A is 11,586 while the estimated prevalence could be around 50,000 patients. This review also identifies the need to immediately initiate a national programme for haemophilia, with components of prevention, care for patients, surveillance and education and support for families. PMID:25222774

Epidemiology & social costs of haemophilia in India.

PubMed

Kar, Anita; Phadnis, Supriya; Dharmarajan, Sumedha; Nakade, Juhi

2014-07-01

India lacks a national policy on the prevention and control of genetic disorders. Although the haemoglobinopathies have received some attention, there are scarce data on the epidemiology of other genetic disorders in India. Haemophilia, an inherited single gene disorder with an incidence of 1 per 10,000 births, manifests as spontaneous or trauma-induced haemorrhagic episodes in patients, progressing to chronic disability and premature mortality in untreated patients or patients with sub-optimal treatment. Although the genetic basis of this disorder has been well studied in India, data on the number of patients, trends of the disorder in India, social costs of the condition and opportunities and competencies for offering genetic counselling through a public health programme have not been reported. This review article summarizes the available Indian data, which show that the country harbours the second highest number of global patients with haemophilia A. The reported number of patients with haemophilia A is 11,586 while the estimated prevalence could be around 50,000 patients. This review also identifies the need to immediately initiate a national programme for haemophilia, with components of prevention, care for patients, surveillance and education and support for families.

Quality of life, psychosocial strains and coping in parents of children with haemophilia.

PubMed

Wiedebusch, S; Pollmann, H; Siegmund, B; Muthny, F A

2008-09-01

Quality of life in parents of children suffering from haemophilia may be diminished by the illness burden experienced in daily life and by non-adaptive ways of coping. The aim of this study was to examine the relation between parents' quality of life, their perceived psychosocial strains and ways of coping, and to compare parents' outcome to other paediatric illness groups (juvenile idiopathic arthritis, type 1 diabetes). In a cross-sectional study, parents completed a questionnaire concerning quality of life, psychosocial strains, coping strategies and needs as well as sociodemographic and illness parameters. Study participants were recruited in an ambulant haemophilia centre. A total of 55 parents (32 mothers, 23 fathers; age = 39.6; SD = 8.6) of children suffering from haemophilia (age = 11.0; SD = 6.4) took part in the study. Comparison groups were parents of children with juvenile idiopathic arthritis (n = 161) and parents of children with type 1 diabetes (n = 69). Compared to parents from other paediatric illness groups, the parents of children with haemophilia experience less impact on their quality of life and lower psychosocial strains. Quality of life was predicted by the coping strategy 'improving marital relationship' (beta = 0.48) and by emotional strains and worries concerning future (beta = -0.43; explained variance 49%). Parents reported a pronounced need for further information on the comprehensive management of haemophilia. In the psychosocial care of families with a child suffering from -haemophilia, reducing psychosocial strains and strengthening adaptive coping strategies may be a preventive intervention for improving parents' quality of life.

[Haemophilia--then and now].

PubMed

Nilsson, I M

1994-01-01

Haemophilia is a bleeding disorder which has always attracted wide interest both among physicians and the laity--uncontrollable haemorrhage, blood that fails to coagulate and heredity with only males affected. The disease is probably best known to the public through its appearance in European royal families and in the Russian Imperial family. The oldest known description of haemophilia is to be found in the Talmud, the collection of ancient Judaic books from the early centuries of our era. The first clinical account of haemophilia was published by the American, Otto, in 1803. He described the disease as an inheritable bleeding disorder occurring only in males, and transmitted by female carriers who are not themselves affected. The disease manifests itself in early childhood, joint bleedings being its most characteristic feature. Otto called the male patients "bleeders". The term, haemophilia, originated with a German, Friedrich Hopff (1828), who coined the name "haemorrhaphilia" which was later abbreviated to haemophilia. ... As to future prospects, it is hoped that it will soon be possible to cure the disease by means of gene therapy, and to this end promising experimental work is already in progress.

Musculoskeletal evaluation in severe haemophilia A patients from Latin America

PubMed Central

Ozelo, M C; Villaça, P R; Pérez-Bianco, R; Candela, M; Garcia-Chavez, J; Moreno-Rodriguez, B; Rodrigues, M B; Rodriguez-Grecco, I; Solano, M H; Chumpitaz, G; Morales-Gana, M M; Ruiz-Sáez, A

2013-01-01

Summary There is a paucity of literature on haemophilia treatment in Latin American countries, a region characterized by rapidly improving systems of care, but with substantial disparities in treatment between countries. The aim of this study was to evaluate the musculoskeletal status of haemophilia patients from Latin America and to examine the relationship between musculoskeletal status and treatment practices across countries. The Committee of Latin America on the Therapeutics of Inhibitor Groups conducted a survey of its member country representatives on key aspects of haemophilia treatment in 10 countries. Musculoskeletal status of patients was obtained during routine comprehensive evaluations between March 2009 and March 2011. Eligible patients had severe haemophilia A (factor VIII <1%) without inhibitors (<0.6 BU mL−1) and were ≥5 years of age. Musculoskeletal status was compared between three groups of countries, based primarily on differences in the availability of long-term prophylaxis. Overall, 143 patients (5–66 years of age) were enrolled from nine countries. In countries where long-term prophylaxis had been available for at least 10 years (Group A), patients aged 5–10 years had significantly better mean World Federation of Hemophilia clinical scores, fewer target joints and fewer affected joints than patients from countries where long-term prophylaxis has been available for about 5 years (Group B) or was not available (Group C). In Latin America, the musculoskeletal status of patients with severe haemophilia without inhibitors has improved significantly in association with the provision of long-term prophylaxis. As more countries in Latin America institute this practice, further improvements are anticipated. PMID:24354487

Efficacy, safety and tolerability of recombinant factor VIII (REFACTO) in patients with haemophilia A: interim data from a postmarketing surveillance study in Germany and Austria.

PubMed

Pollmann, H; Externest, D; Ganser, A; Eifrig, B; Kreuz, W; Lenk, H; Pabinger, I; Schramm, W; Schwarz, T F; Zimmermann, R; Zavazava, N; Oldenburg, J; Klamroth, R

2007-03-01

An open-label, multicentre, postmarketing surveillance study conducted in Germany and Austria with recombinant factor VIII (REFACTO) has enrolled 217 patients (mean age 26.3 years) from 38 haemophilia centres during the first 4.8 years. Most patients (188/217; 86.6%) had severe to moderately severe haemophilia A, of whom 153 completed sufficient diary information for the main efficacy analysis. These 153 patients experienced a median of 6.6 (interquartile range 1.4-18.6) bleeding episodes per year. Patients treated with prophylaxis experienced a median of 4.4 (1.1-9.3) bleeds per year, while patients treated on-demand experienced a median of 22.8 (11.3-29.0) bleeds per year. Overall, most physicians (41/43 [95.3%]) were 'very satisfied' or 'satisfied' with the efficacy of REFACTO in the treatment of bleeding episodes. A total of 137 non-serious adverse events have been reported in 52/217 patients (24.0%) to date. In addition, 129 serious adverse events in 87 patients (40%) were reported, including 41 cases of 'less than expected therapeutic effect' (LETE). Of these, 39 LETE cases were reported in one centre; however, patients in this centre experienced considerably fewer bleeding episodes per year than patients outside this centre. Overall, six patients (2.8%) have developed de novo inhibitors, three of which were considered high titre. Four of these patients were at high risk (0-50 exposure days [ED]) of inhibitor formation, one was at intermediate risk (51-100 ED) and one was at low risk (>100 ED). These results emphasize the benefit of postmarketing surveillance and, overall, this study confirms the efficacy, safety and tolerability of REFACTO in the treatment of patients with haemophilia A.

Health promotion for young patients with haemophilia. Counselling, adjuvant exercise therapy and school sports.

PubMed

Sondermann, Judith; Herbsleb, Marco; Stanek, Frank-Detlef; Gabriel, Holger; Kentouche, Karim

2017-05-10

The haemophilia treatment centre of the Clinic for Children and Youth Medicine in Jena extends medical care by health-promotion measures, namely: health counselling, adjuvant exercise therapy and school sports. In addition to the regular medical checks at the treatment centre patients are examined regarding physical fitness, joint situation, quality of life in general and disease-specific manner, as well as psycho-social and nutritional behaviour. Findings and medical results of the examinations are integrated into an individual advice on therapy, school sports, and health recommendations. This aimed at strengthening health-related resources and minimizing potential injuries. First long-term evaluation shows an increase of activity behaviour and physical fitness without increasing bleeding rate and maintained joint function. Combining functional prevention diagnostics and individual health counselling shows signs of improved patient's health knowledge, self-competence and physical fitness.

Methods for detection of haemophilia carriers: a Memorandum*

PubMed Central

1977-01-01

This Memorandum discusses the problems and techniques involved in the detection of carriers of haemophilia A (blood coagulation factor VIII deficiency) and haemophilia B (factor IX deficiency), particularly with a view to its application to genetic counselling. Apart from the personal suffering caused by haemophilia, the proper treatment of haemophiliacs places a great strain on the blood transfusion services, and it is therefore important that potential carriers should have precise information about the consequences of their having children. The Memorandum classifies the types of carrier and describes the laboratory methods used for the assessment of coagulant activity and antigen concentration in blood. Particular emphasis is laid on the establishment of international, national, and laboratory (working) standards for factors VIII and IX and their calibration in international units (IU). This is followed by a detailed account of the statistical analysis of pedigree and laboratory data, which leads to an assessment of the likelihood that a particular person will transmit the haemophilia gene to her children. Finally, the problems and responsibilities involved in genetic counselling are considered. PMID:304395

The experience of being a female carrier of haemophilia and the mother of a haemophilic child.

PubMed

Myrin-Westesson, L; Baghaei, F; Friberg, F

2013-03-01

Limited research has been conducted on how the female carrier experiences her life with a haemophilic child, and earlier studies are mostly questionnaire-based. No previous qualitative study on the female carrier's situation has been conducted in Sweden. The aim of the study was to describe the lived experience of being a carrier of severe or moderate haemophilia and of being the mother of a haemophilic child. The study was conducted via qualitative interviews and analysed by means of a phenomenological hermeneutic method; a total of 13 haemophilia carriers were interviewed in 2010. Being a carrier of haemophilia and having a haemophilic child was life changing. The women moved from a state of sad, guilty chaos to reconciling themselves with the new situation. Our analysis revealed three acts in which phenomena appeared: the time after diagnosis, the turning point and reconciliation with a changing life. Emerging as crucial to the process of reconciliation with a changing life was a sense of being fully informed and supported. The Haemophilia Treatment Centre (HTC) should create an environment that encourages learning, and the team should invite and encourage the woman's partner to be actively involved in the child's care. Moreover, the results indicate that it would be beneficial to invite female carriers to receive patient education at the HTC before they plan to start a family. During this visit, the woman may gain a greater understanding of her carriership to prepare her for future decisions concerning prenatal diagnosis, for example. © 2012 Blackwell Publishing Ltd.

Parents of children with haemophilia at an early age: assessment of perceived stress and family functioning.

PubMed

Torres-Ortuño, A; Cuesta-Barriuso, R; Nieto-Munuera, J

2014-11-01

Haemophilia is a chronic disease that requires a multidisciplinary approach for proper management and control of its clinical manifestations. The perception and management of parents of children with haemophilia can be affected by stressful situations as a result of treatment or disease progression. The aim of this study was to evaluate the perception of stress and family functioning in parents of children with haemophilia 1-7 years. This is an observational clinical study involving 49 parents of children with haemophilia 1-7 years who attended the VIII Workshop for Parents of Children with haemophilia, organized by the Spanish Federation of Hemophilia in La Charca, Murcia (Spain). After obtaining parental consent, the questionnaires was applied to them, FACES III (family functioning) and Pediatric Inventory for Parents (perceived stress), and a record of data on the clinical characteristics and treatment. Significant differences in the perception of stressors by gender of parents were found. A family history of haemophilia, the use of port-a-cath, inhibitor development and gender of the parents were the descriptive variables most correlated with dependents variables. These variables, together with the type of haemophilia affect significantly in the parental stress and family functioning. Parents have difficulty adjusting to disease management, perceiving many stressors. Gender and family history, can hinder the proper compliance with treatments, reducing its effectiveness. © 2014 John Wiley & Sons Ltd.

Haemophilia at various stages of life: design of new therapeutic strategies through an interactive course - the Kogeniale project

PubMed Central

Santagostino, Elena; Messina, Maria; Tagliaferri, Annarita; Iorio, Alfonso; Morfini, Massimo

2013-01-01

Background High-quality evidence is lacking in several areas of haemophilia treatment, in part because little time is allocated to the treatment and care of haemophilia in university education in Italy. Physicians caring for patients with haemophilia must, therefore, rely on their information on background pathophysiology and more experienced colleagues. This makes diagnostic and therapeutic choices difficult, especially when the patient has concomitant disorders or psychological issues. Material and methods This article describes a course to educate young physicians who were already engaged in the management of haemophilia on the emerging and unmet issues of haemophilia care and to implement existing guidelines. Physicians (n=53) already caring for patients with haemophilia in their haematology, internal medicine, or paediatric practices in Italy attended the course. Problem-solving group activity and open discussion were the methods chosen to formulate consensus statements. During the specifically designed interactive course, three clinical cases were simulated: a young child with congenital dislocation of the hip, an adolescent refusing prophylactic treatment, and an elderly man with cardiovascular disorders. The physicians were asked questions during the course and, through a Wi-Fi console, were able to answer and discuss each case interactively. Results Following discussion of each case, agreement was reached regarding general statements on the management of patients with severe haemophilia A in the three different age ranges considered. Discussion This project helped to outline useful decision-making tools for handling diagnostic and treatment issues in the field of haemophilia. PMID:23399360

Orthopaedic co-morbidities in the elderly haemophilia population: a review.

PubMed

Stephensen, D; Rodriguez-Merchan, E C

2013-03-01

Due to improvements in the treatment and medical care of haemophilia, the life expectancy of individuals with haemophilia has approached that of the general population. To review the main co-morbidities of the musculoskeletal system in elderly persons with haemophilia, we have performed a review of the literature on the musculoskeletal problems of elderly haemophiliacs. Chronic arthropathy is the main co-morbidity in the ageing person with haemophilia. Age-related orthopaedic co-morbidities include degenerative joint changes, osteoporosis, muscle atrophy or sarcopenia, muscle weakness and disturbance of gait and balance. Increased pain, muscle weakness and atrophy along with an increased risk of falling are key features of advanced haemophilic arthropathy and ageing. An ageing haemophilia population in which arthropathy continues to be the primary co-morbidity is a current challenge for those responsible for their care. Exercise programmes undertaken two to three times per week for at least 12 weeks seem most effective in reducing the impact of age-related changes on the musculoskeletal system. Establishing effective exercise programmes and strategies to identify individuals who would benefit from early surgical intervention together with presurgical physiotherapy prehabilitation is a priority for future research. © 2012 Blackwell Publishing Ltd.

Towards personalizing haemophilia care: using the Haemophilia Severity Score to assess 178 patients in a single institution.

PubMed

Vyas, S; Enockson, C; Hernandez, L; Valentino, L A

2014-01-01

The phenotypic variability in haemophilia is well documented; however, the biological basis beyond factor VIII and IX activities to explain the differing clinical pictures of the disease remains unclear. It has therefore been of interest to explore other modulators of the disease's variability. Furthermore, a scoring system that reflects the multiple facets of haemophilia symptoms would be useful to compare patients via a comprehensive assessment tool. To this end, Schulman et al., created a measure known as the Haemophilia Severity Score (HSS) as one way to compare phenotypic severity. The aim of this study was to document the differing symptomatology of haemophilia patients using the HSS. Clinical data for 178 haemophilia patients without inhibitors were reviewed and annual incidence of haemarthrosis, orthopaedic joint scores and annual factor usage calculated. Each parameter was then entered into the formula to create the HSS for haemophilia A and B patients with mild, moderate and severe factor deficiencies. Variability in the HSS for patients with the same baseline level of factor was observed for all three deficiency levels and both haemophilia types. In addition, we found that moderate and severe haemophilic B patients tended to have more morbidity based on the above calculations than the haemophilic A counterparts. The HSS is a comprehensive tool that allows for easy numerical comparison of haemophilic patients and elucidates the variable clinical presentation of the disease. The HSS could be used to stratify patients via other possible modulators of haemophilia and discover other aetiologies of the disease. © 2013 John Wiley & Sons Ltd.

The impact of sport on children with haemophilia.

PubMed

Khair, K; Littley, A; Will, A; von Mackensen, S

2012-11-01

Sport is nowadays perceived as beneficial for children with haemophilia, as good muscle strength supports joints and may reduce bleed frequency; by contrast psychological benefits are less known. This study introduces the impact of sport on health-related quality of life (HRQoL) and physical performance in children with haemophilia. A cross-sectional, multi-site, study of boys aged 6-17 years with haemophilia A or B of any severity, current or past inhibitor, which assessed physical performance, sporting activity and HRQoL using age appropriate questionnaires including KINDL, Haemo-QoL and HEP-Test-Q. Eighty-four haemophilic boys (23 mild, 19 moderate, 42 severe) with a mean age of 11.52 years (SD = 3.4) were enrolled from two haemophilia centres in the United Kingdom. 28.4% were overweight/obese according to their BMI/age and had a good orthopaedic status (M = 1.55, SD = 3.3). Boys watching < 1-2 h of TV/PC/day had fewer days lost (M = 3, SD = 3.2) than those with a more sedentary lifestyle (M = 9.40, SD = 7.1) (P < 0.032). 90.5% participated in regular sporting activity; 79.9% at least twice a week. HRQoL in children was generally good, with highest impairments in boys aged 8-12 years. Boys aged 8-16 years reported good physical performance (M = 80.0, SD = 16.0) with highest impairments in the dimensions 'endurance' and 'mobility'. Boys doing sport had a significant better physical performance and HRQoL than boys not doing sport. Sedentary life styles had a negative impact on the subjective physical performance and number of days lost of children. Encouraging haemophilic boys to participate in sport will have a direct impact on their overall HRQoL. © 2012 Blackwell Publishing Ltd.

Partnering to change the world for people with haemophilia: 7th Haemophilia Global Summit, Madrid, Spain 22-24 September 2016.

PubMed

Dolan, Gerry

2017-10-01

The 7th Haemophilia Global Summit was held in Madrid, Spain, in September 2016. With a programme designed, for the 6th consecutive year, by a Scientific Steering Committee of haemophilia experts, the aim of the summit was to share optimal management strategies for haemophilia at all life stages and to provide an opportunity for specialists from across the haemophilia multidisciplinary care team to engage in discussion and debate with leading international experts on current and future areas of research. Topics covered ranged from the optimisation of haemophilia management, emerging issues in clinical care, practical approaches and future perspectives, in addition to patient engagement and empowerment in modern haemophilia care. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A comparison of traditional vs. Canadian tailored prophylaxis dosing of prophylactic factor infusions in children with haemophilia A and B in a single hemophilia treatment center.

PubMed

Dodd, C; Watts, R G

2012-07-01

Prophylactic infusion of clotting factor concentrates is a developing standard of care for individuals with haemophilia. The ideal schedule and techniques of prophylactic infusions remain incompletely defined. Our aim was to determine the optimal techniques and schedules for factor prophylaxis in paediatric patients. A retrospective electronic medical record review of all children treated with prophylactic factor infusions in a single Haemophilia Treatment Center was conducted. Comparison of traditional vs. Canadian dosing regimens and primary vs. secondary prophylaxis was made. Failure of prophylaxis was defined as the first serious bleed. A total of 58 children were identified for review. Five cases were excluded (four due to high titre inhibitors and one due to repeated non-compliance), thus there were 53 total cases: 46 with severe haemophilia, 2 with moderate haemophilia, 5 with mild haemophilia, 44 with haemophilia A and 9 with haemophilia B; 32 Traditional dosing and 21 Canadian dosing regimens. Patients on primary prophylaxis had a decreased failure rate (25%) compared to children treated with secondary prophylaxis (67%) regardless of technique of prophylaxis. When compared to a 'Traditional' factor prophylaxis schedule, the 'Canadian' tailored prophylaxis protocol was comparable with the exception of a decreased use of implanted venous devices in the 'Canadian' group. Ongoing bleeding (primarily joint bleeds) occurs with all prophylactic regimens. The lowest incidence of treatment failure was noted in children who began primary prophylaxis at a young age and before initial joint bleeds. Primary prophylaxis is superior to secondary prophylaxis regardless of dosing regimen. Traditional and Canadian dosing regimens were equivalent in outcome when measured over several years of follow-up. © 2012 Blackwell Publishing Ltd.

[Development and evaluation of a dance-based exercise therapy for patients with haemophilia].

PubMed

Czepa, D; van Ravenstein, S; Stäuber, F; Hilberg, T

2013-01-01

So far, the use of methods derived from creative arts has not been considered in the haemophilia treatment. The AIM was to investigate the expectations for a dance-based exercise therapy for patients with haemophilia and the extent of its acceptance. The one-hour dance-based exercise therapy was offered to 30 haemophilia patients (HI30) (49 ± 11, 30-67 years). For the evaluation of expectations, questionnaires were created and filled out by participants before and after the intervention. Additionally, 19 haemophilia patients (HF) and 20 controls without haemophilia (KF) who did not participate in the intervention were also questioned. The RESULTS show that haemophilia patients have more experience in dance than controls (HI30:62%, HF:74%, KF:45%). In contrast, the proportion of those who are currently dancing is higher in controls without haemophilia (HI30: 17%, HF: 10%, KF:26%). The termination of dance activity in patients with haemophilia who were part of the intervention was mainly due to pain (HI30: 40%, HF: 29%, KF: 0%), whereby controls without intervention terminated the dance activity mainly due to lack of time (HI30: 30%, HF: 57%, KF: 56%). Ultimately, 24 out of 30 patients with haemophilia (HI24) completed the intervention. All HI24 met their expectations. 38% felt limited by haemophilia while carrying out the exercises. The majority of the participants were able to follow the exercises well (96%) and were did not overstrain physically (92%) nor mentally (87%), also 79% did not have pain. 23 of HI24 (96%) can envision a continuation of the dance-based exercise therapy. The experience with the dance-based exercise therapy was predominantly positive. It represents an alternative sports therapy programme for patients with haemophilia. Further studies are needed in order to make statements concerning the long-term use of such training.

Health status and health-related quality of life of children with haemophilia from six West European countries.

PubMed

Gringeri, A; von Mackensen, S; Auerswald, G; Bullinger, M; Perez Garrido, R; Kellermann, E; Khair, K; Lenk, H; Vicariot, M; Villar, A; Wermes, C

2004-03-01

A multicentre, international, cross-sectional study was carried out in the frame of field testing of the first haemophilia-specific quality-of-life (QoL) questionnaire (Haemo-QoL). The aim of this paper is to describe health status and health care and their impact on QoL in haemophilic children in Western Europe. Children aged 4-16 years with severe haemophilia without inhibitors were enrolled by 20 centres in France, Germany, Italy, the Netherlands, Spain and the United Kingdom. Clinical information was collected by the physicians with a medical documentation form. Health-related QoL (HRQoL) of children was assessed with Haemo-QoL, available for three age groups. Clinical data were available in 318 patients, 85.5% with haemophilia A. The mean age at first bleeding was 11 months, at first joint bleed 25 months. Functional joint impairments were found in 11.3%. Prophylaxis treatment was given to 66.7% of children in whom breakthrough bleeds occurred 0.4 times a month compared to 1.1 bleeds in children receiving on-demand treatment. A significantly higher factor consumption was found only in the two younger age groups of prophylaxis patients compared to on-demand patients. HRQoL was satisfactory in this cohort: young children were impaired mainly in the dimension 'family' and 'treatment', whereas older children had higher impairments in the so-called 'social' dimensions, such as 'perceived support' and 'friends'. Health care of children in Western Europe is progressively improving with a large diffusion of home treatment and prophylaxis. This provides a high level of health status and HRQoL, being better in haemophilic adolescents on prophylaxis.

Choosing outcome assessment tools in haemophilia care and research: a multidisciplinary perspective.

PubMed

Fischer, K; Poonnoose, P; Dunn, A L; Babyn, P; Manco-Johnson, M J; David, J A; van der Net, J; Feldman, B; Berger, K; Carcao, M; de Kleijn, P; Silva, M; Hilliard, P; Doria, A; Srivastava, A; Blanchette, V

2017-01-01

The implementation of early long-term, regular clotting factor concentrate (CFC) replacement therapy ('prophylaxis') has made it possible to offer boys with haemophilia a near normal life. Many different regimens have reported favourable results, but the optimum treatment regimens have not been established and the cost of prophylaxis is very high. Both for optimizing treatment and reimbursement issues, there is a need to provide objective evidence of both short- and long-term results and benefits of prophylactic regimens. This report presents a critical review of outcome measures for use in the assessment of musculoskeletal health in persons with haemophilia according to the International Classification of Functioning, Disability and Health (ICF). This framework considers structural and functional changes, activities and participation in a context of both personal and environmental factors. Results were generated by a combination of a critical review of available literature plus expert opinion derived from a two day consensus conference between 48 health care experts from different disciplines involved in haemophilia assessment and care. Outcome tools used in haemophilia were reviewed for reliability and validity in different patient groups and for resources required. Recommendations for choice of outcome tools were made according to the ICF domains, economic setting, and reason for use (clinical or research). The next step will be to identify a 'core' set of outcome measures for use in clinical care or studies evaluating treatment. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Prospects for research in haemophilia with real-world data-An analysis of German registry and secondary data.

PubMed

Schopohl, D; Bidlingmaier, C; Herzig, D; Klamroth, R; Kurnik, K; Rublee, D; Schramm, W; Schwarzkopf, L; Berger, K

2018-02-28

Open questions in haemophilia, such as effectiveness of innovative therapies, clinical and patient-reported outcomes (PROs), epidemiology and cost, await answers. The aim was to identify data attributes required and investigate the availability, appropriateness and accessibility of real-world data (RWD) from German registries and secondary databases to answer the aforementioned questions. Systematic searches were conducted in BIOSIS, EMBASE and MEDLINE to identify non-commercial secondary healthcare databases and registries of patients with haemophilia (PWH). Inclusion of German patients, type of patients, data elements-stratified by use in epidemiology, safety, outcomes and health economics research-and accessibility were investigated by desk research. Screening of 676 hits, identification of four registries [national PWH (DHR), national/international paediatric (GEPARD, PEDNET), international safety monitoring (EUHASS)] and seven national secondary databases. Access was limited to participants in three registries and to employees in one secondary database. One registry asks for PROs. Limitations of secondary databases originate from the ICD-coding system (missing: severity of haemophilia, presence of inhibitory antibodies), data protection laws and need to monitor reliability. Rigorous observational analysis of German haemophilia RWD shows that there is potential to supplement current knowledge and begin to address selected policy goals. To improve the value of existing RWD, the following efforts are proposed: ethical, legal and methodological discussions on data linkage across different sources, formulation of transparent governance rules for data access, redefinition of the ICD-coding, standardized collection of outcome data and implementation of incentives for treatment centres to improve data collection. © 2018 John Wiley & Sons Ltd.

Exploring internet needs and use among adolescents with haemophilia: a website development project.

PubMed

Sterling, L; Nyhof-Young, J; Blanchette, V S; Breakey, V R

2012-03-01

Youth frequently access health information online, yet little is known about internet use among adolescents with haemophilia (AWH). A youth-centred, age-appropriate online programme is being developed to address the heightened educational needs of AWH as they transit from paediatric to adult care. To describe internet needs and use among AWH treated at the Hospital for Sick Children and determine the features that would make the website useable and desirable for this population. Semi-structured interviews addressed participants' internet use and thoughts about a website for AWH. The interviews were audio-recorded and transcribed verbatim. Three independent reviewers coded the data to determine descriptive categories and grouped them into themes. Eleven of 12 subjects approached consented to interviews. Data saturation was achieved. Most participants had used the internet to find haemophilia information, although none could recall specific websites they had visited for information. Some felt more comfortable using the internet than asking health care providers. Others liked the 24/7 availability of the internet if questions arose. Overall, they felt a website for AWH would help them to learn about haemophilia and explain it to others. Online social networking with an older peer mentor with haemophilia, as well as with others of their age was cited as a potentially valuable source of support. AWH are interested in a haemophilia website and have identified a variety of features which they believe may help to support them during transition to adult care and beyond. Website development is ongoing. © 2011 Blackwell Publishing Ltd.

Oral health status in children and adolescents with haemophilia.

PubMed

Othman, N A A; Sockalingam, S N M P; Mahyuddin, A

2015-09-01

This case-controlled study aimed to evaluate the existing oral health status in children and adolescents with haemophilia. A total of 50 haemophilia patients and 50 matched controls aged seven to 16 years were recruited into the study. Clinical examination was carried out to determine dental caries experience, oral hygiene status and gingival condition in these two groups. Information regarding previous dental history, oral hygiene practices and dietary habits were also obtained. No significant difference was found in mean caries experience in primary and secondary dentitions (P = 0.86 and 0.32) and in Simplified Oral Hygiene Index (OHI-S, P = 0.20) between both groups. However, a significantly higher proportion of haemophilia patients (24%) had better oral hygiene status as compared to the controls (2%, P = 0.004). Furthermore, there was a significant difference in Modified Gingival Index (MGI, P = 0.02) between the two groups with the study group having less gingival inflammation. A total of 88% (n = 44) of the haemophilia patients were registered and received dental treatment in specialist dental clinics. More than half (56%, n = 28) had frequent dental visits and only one-third of the haemophilia patients had history of hospitalization due to oral problems. There was no significant difference in oral hygiene practices and dietary habits between both groups. In general, haemophilia children and adolescents in this study had similar caries experience, a significantly better oral hygiene status and gingival health as compared to healthy controls. The main reason for this is the multidisciplinary approach implemented by medical health-care professionals as primary care provider and the dental team. © 2015 John Wiley & Sons Ltd.

The effects of joint disease, inhibitors and other complications on health-related quality of life among males with severe haemophilia A in the United States.

PubMed

Soucie, J M; Grosse, S D; Siddiqi, A-E-A; Byams, V; Thierry, J; Zack, M M; Shapiro, A; Duncan, N

2017-07-01

Health-related quality of life (HRQoL) is reduced among persons with haemophilia. Little is known about how HRQoL varies with complications of haemophilia such as inhibitors and joint disease. Estimates of preference-based HRQoL measures are needed to model the cost-effectiveness of prevention strategies. We examined the characteristics of a national sample of persons with severe haemophilia A for associations with two preference-based measures of HRQoL. We analysed utility weights converted from EuroQol 5 Dimensions (EQ-5D) and the Short Form 6 Dimensions (SF-6D) scores from 1859 males aged ≥14 years with severe haemophilia A treated at 135 US haemophilia treatment centres in 2005-2011. Bivariate and regression analyses examined age-group-specific associations of HRQoL with inhibitor status, overweight/obesity, number of bleeds, viral infections, indicators of liver and joint disease, and severe bleeding at the time of the first HRQoL measurement. Overall mean HRQoL utility weight values were 0.71 using the SF-6D and 0.78 using the EQ-5D. All studied patient characteristics except for overweight/obesity were significantly associated with HRQoL in bivariate analyses. In a multivariate analysis, only joint disease was significantly associated with utility weights from both HRQoL measures and across all age groups. After adjustment for joint disease and other variables, the presence of an inhibitor was not significantly associated with HRQoL scores from either of the standardized assessment tools. Clinically significant complications of haemophilia, especially joint disease, are strongly associated with HRQoL and should be accounted for in studies of preference-based health utilities for people with haemophilia. © 2017 John Wiley & Sons Ltd.

Participation in sports by Dutch persons with haemophilia.

PubMed

Heijnen, L; Mauser-Bunschoten, E P; Roosendaal, G

2000-09-01

Patients with haemophilia are now widely advised to participate in sports. However, no extensive data are available about their actual participation. A self-administered questionnaire was used to investigate sports participation by persons with haemophilia in the Netherlands. All 293 questionnaires that were distributed have been returned; 217 were from people with severe haemophilia A or B (this is 40% of the severely affected Dutch population with haemophilia). Of this group, 155 (71%) participate in one or more sports: 66 swim, 36 cycle, 21 play tennis, 18 do fitness exercises, 16 ice skate, 10 ski and 10 play table tennis; in total 44 different sports are mentioned. Of a group of 16 persons with haemophilia who are unable to run, 10 (63%) participate in sport and of a group of 91 who can only run sometimes, 64 (70%) engage in sports. This shows that there are ample opportunities for persons with haemophilia to participate in sports, even if they are unable to run. Severely affected persons with haemophilia are as active as the general Dutch population; in fact, a higher proportion swims and/or cycles. In conclusion, sports participation in the Netherlands by persons with haemophilia is in accordance with World Federation of Hemophilia directives.

Establishing a harmonized haemophilia registry for countries with developing health care systems.

PubMed

Alzoebie, A; Belhani, M; Eshghi, P; Kupesiz, A O; Ozelo, M; Pompa, M T; Potgieter, J; Smith, M

2013-09-01

Over recent decades tremendous progress has been made in diagnosing and treating haemophilia and, in resource-rich countries, life expectancy of people with haemophilia (PWH) is now close to that of a healthy person. However, an estimated 70% of PWH are not diagnosed or are undertreated; the majority of whom live in countries with developing health care systems. In these countries, designated registries for people with haemophilia are often limited and comprehensive information on the natural history of the disease and treatment outcomes is lacking. Taken together, this means that planning efforts for future treatment and care of affected individuals is constrained in countries where it is most needed. Establishment of standardized national registries in these countries would be a step towards obtaining reliable sociodemographic and clinical data for an entire country. A series of consensus meetings with experts from widely differing countries with different health care systems took place to discuss concerns specific to countries with developing health care systems. As a result of these discussions, recommendations are made on parameters to include when establishing and harmonizing national registries. Such recommendations should enable countries with developing health care systems to establish standardized national haemophilia registries. Although not a primary objective, the recommendations should also help standardized data collation on an international level, enabling treatment and health care trends to be monitored across groups of countries and providing data for advocacy purposes. Greater standardization of data collation should have implications for optimizing resources for haemophilia care both nationally and internationally. © 2013 John Wiley & Sons Ltd.

Achievements, challenges and unmet needs for haemophilia patients with inhibitors: Report from a symposium in Paris, France on 20 November 2014.

PubMed

Dargaud, Y; Pavlova, A; Lacroix-Desmazes, S; Fischer, K; Soucie, M; Claeyssens, S; Scott, D W; d'Oiron, R; Lavigne-Lissalde, G; Kenet, G; Escuriola Ettingshausen, C; Borel-Derlon, A; Lambert, T; Pasta, G; Négrier, C

2016-01-01

Over the past 20 years, there have been many advances in haemophilia treatment that have allowed patients to take greater control of their disease. However, the development of factor VIII (FVIII) inhibitors is the greatest complication of the disease and a challenge in the treatment of haemophilia making management of bleeding episodes difficult and surgical procedures very challenging. A meeting to discuss the unmet needs of haemophilia patients with inhibitors was held in Paris on 20 November 2014. Topics discussed were genetic and non-genetic risk factors for the development of inhibitors, immunological aspects of inhibitor development, FVIII products and inhibitor development, generation and functional properties of engineered antigen-specific T regulatory cells, suppression of immune responses to FVIII, prophylaxis in haemophilia patients with inhibitors, epitope mapping of FVIII inhibitors, current controversies in immune tolerance induction therapy, surgery in haemophilia patients with inhibitors and future perspectives for the treatment of haemophilia patients with inhibitors. A summary of the key points discussed is presented in this paper. © 2016 John Wiley & Sons Ltd.

The current status of prophylactic replacement therapy in children and adults with haemophilia.

PubMed

Ljung, Rolf; Gretenkort Andersson, Nadine

2015-06-01

Initiating prophylactic treatment at an early age is considered to be the optimal form of therapy for a child with haemophilia A or B. The pioneering long term experiences of prophylactic treatment from Sweden and The Netherlands demonstrated the benefit of prophylaxis in retrospective and observational studies. Decades later, these benefits were confirmed in a randomized controlled study in USA. We review the current status of prophylactic replacement therapy of haemophilia in children, adolescents, adults and the elderly. Prophylaxis should begin at an early age and there are arguments for continuing it into adulthood. The dose of prophylaxis is dependent on the goal of treatment, economic resources and venous access and should be tailored individually. Starting the first exposures to clotting factor concentrates as prophylactic treatment, instead of on-demand in response to a bleed, may decrease the frequency of inhibitors in patients with haemophilia A. Novel longer-acting products are being introduced that could be helpful for patients with difficult venous access and enable higher trough levels. © 2015 John Wiley & Sons Ltd.

The role of rehabilitation and sports in haemophilia patients with inhibitors.

PubMed

Heijnen, L

2008-11-01

Treatment of haemophilia patients with inhibitors against factor VIII/IX (FVIII/IX) is still challenging and recurrent haemarthroses cause arthropathy with associated restrictions on participation in physical activities and sports. Rehabilitation is a multidisciplinary approach which includes physiotherapy, occupational therapy, psychology, social work and technical applications like prostheses, orthoses (splints and braces), shoe adaptations, walking aids and adaptations in the house and work situation, but also education. The theoretical principles and practical advice regarding rehabilitation and physiotherapy for both children and adults with haemophilia without inhibitors are highly applicable for patients with inhibitors. Hydrotherapy is useful in the treatment of painful or stiff joints and/or muscles after an acute haemarthrosis, muscle bleeds and chronic arthropathy. In addition, it is of use in cases of chronic synovitis and to start mobilization after long periods of bed rest or during the weaning of a splint. In cases of bleeding and arthropathy, adequate treatment of pain is very important, as are functional exercises. Everyone should be physically active for 30-60 min day(-1). Participation in sports is recommended for people with haemophilia, the best sport being swimming. Children should participate in sports appropriate to their size and physical characteristics.

Health economics in haemophilia: a review from the clinician's perspective.

PubMed

Escobar, M A

2010-05-01

Health economic evaluations provide valuable information for healthcare providers, facilitating the treatment decision-making process in a climate where demand for healthcare exceeds the supply. Although an uncommon disease, haemophilia is a life-long condition that places a considerable burden on patients, healthcare systems and society. This burden is particularly large for patients with haemophilia with inhibitors, who can develop serious bleeding complications unresponsive to standard factor replacement therapies. Hence, bleeding episodes in these patients are treated with bypassing agents such as recombinant activated FVII (rFVIIa) and plasma-derived activated prothrombin complex concentrates (pd-APCC). With the efficacy of these agents now well established, a number of health economic studies have been conducted to compare their cost-effectiveness for the on-demand treatment of bleeding episodes in haemophiliacs with inhibitors. In a cost-utility analysis, which assesses the effects of treatment on quality of life (QoL) and quantity of life, the incremental cost per quality-adjusted life-year (QALY) gained (US $44,834) indicated that rFVIIa was cost-effective. Similarly, eight of 11 other economic modelling evaluations found that rFVIIa was more cost-effective than pd-APCC in the on-demand treatment of bleeding episodes. These findings indicate that treating patients with haemophilia promptly and with the most effective therapy available may result in cost savings.

Physician preferences for medication attributes for the prophylactic treatment of patients with severe haemophilia A with inhibitors to factor VIII.

PubMed

Gelhorn, H; Merikle, E; Krishnan, S; Nemes, L; Leissinger, C; Valentino, L

2013-01-01

Prophylaxis may be beneficial for patients with severe haemophilia A who have developed inhibitors to factor VIII. The aim of this study was to determine physicians' preferences for medication attributes in the prophylactic treatment of this patient population. Haematologists from Europe (EU) and the United States (US) participated in a discrete choice exercise to explore their preferences for medication attributes (efficacy, cost, scientific evidence, dosing frequency and administration time) associated with prophylaxis for severe haemophilia A in patients with inhibitors to factor VIII. Physicians' preferences for medication attributes were assessed through completion of 25 trade-off tasks that included a choice between two hypothetical medications each comprised of one randomized level of each medication attribute. Participants also completed a sociodemographic questionnaire. Data were analysed using a random effects logit model. Participants (N = 36: US = 19; EU = 17) were 80.6% men, had a mean of 19.8 years (SD ± 8.1) [range 6-35] of practice experience. The physicians treated an average of 5.7 (± 5.5) patients with severe haemophilia A and inhibitors per month and reported treating 36.2% of these patients prophylactically. The most important medication attributes for prophylactic treatment were efficacy [Relative Importance (RI) = 35.0%] and scientific evidence (RI = 34.1%), whereas treatment cost (12.0%), dosing frequency (10.8%) and administration time (8.2%) were less important. Results were similar across the EU and US. Efficacy and scientific evidence are the primary considerations for physicians' choice of prophylactic medications for use in this patient population. © 2012 Blackwell Publishing Ltd.

Physician trust and depression influence adherence to factor replacement: a single-centre cross-sectional study.

PubMed

Tran, D Q; Barry, V; Antun, A; Ribeiro, M; Stein, S; Kempton, C L

2017-01-01

Poor adherence to factor replacement therapy among patients with haemophilia can lead to joint bleeding and eventual disability. The aim of this study was to determine patient-related characteristics associated with adherence to factor replacement in adults with haemophilia. Adults with haemophilia were recruited to participate in this cross-sectional study. Adherence was measured using either the Validated Hemophilia Regimen Treatment Adherence Scale (VERITAS)-Pro or the VERITAS-PRN questionnaire. Simple and multiple regression analyses that controlled for confounding were performed to determine the association between patient-related characteristics and adherence to factor replacement therapy. Of the 99 subjects enrolled, all were men; 91% had haemophilia A and 78% had severe disease. Age ranged from 18 to 62 years. Most (95%) had functional health literacy; but only 23% were numerate. Mean adherence scores were 45.6 (SD 18) and 51.0 (SD 15) for those on a prophylactic and those on an episodic regimen, respectively, with a lower score indicating better adherence. On multivariable analysis, being on any chronic medication, longer duration followed at our haemophilia treatment centre, higher physician trust and better quality of life were associated with higher adherence. A history of depression was associated with lower adherence. Two potentially modifiable characteristics, physician trust and depression, were identified as motivator and barrier to adherence to factor replacement therapy. Promoting a high level of trust between the patient and the healthcare team as well as identifying and treating depression may impact adherence to factor replacement therapy and accordingly reduce joint destruction. © 2016 John Wiley & Sons Ltd.

Estimating unknown parameters in haemophilia using expert judgement elicitation.

PubMed

Fischer, K; Lewandowski, D; Janssen, M P

2013-09-01

The increasing attention to healthcare costs and treatment efficiency has led to an increasing demand for quantitative data concerning patient and treatment characteristics in haemophilia. However, most of these data are difficult to obtain. The aim of this study was to use expert judgement elicitation (EJE) to estimate currently unavailable key parameters for treatment models in severe haemophilia A. Using a formal expert elicitation procedure, 19 international experts provided information on (i) natural bleeding frequency according to age and onset of bleeding, (ii) treatment of bleeds, (iii) time needed to control bleeding after starting secondary prophylaxis, (iv) dose requirements for secondary prophylaxis according to onset of bleeding, and (v) life-expectancy. For each parameter experts provided their quantitative estimates (median, P10, P90), which were combined using a graphical method. In addition, information was obtained concerning key decision parameters of haemophilia treatment. There was most agreement between experts regarding bleeding frequencies for patients treated on demand with an average onset of joint bleeding (1.7 years): median 12 joint bleeds per year (95% confidence interval 0.9-36) for patients ≤ 18, and 11 (0.8-61) for adult patients. Less agreement was observed concerning estimated effective dose for secondary prophylaxis in adults: median 2000 IU every other day The majority (63%) of experts expected that a single minor joint bleed could cause irreversible damage, and would accept up to three minor joint bleeds or one trauma related joint bleed annually on prophylaxis. Expert judgement elicitation allowed structured capturing of quantitative expert estimates. It generated novel data to be used in computer modelling, clinical care, and trial design. © 2013 John Wiley & Sons Ltd.

Evaluation of the utility of the ISTH-BAT in haemophilia carriers: a multinational study.

PubMed

James, P D; Mahlangu, J; Bidlingmaier, C; Mingot-Castellano, M E; Chitlur, M; Fogarty, P F; Cuker, A; Mancuso, M E; Holme, P A; Grabell, J; Satkunam, N; Hopman, W M; Mathew, P

2016-11-01

There has been increasing recognition in recent years that female carriers of haemophilia manifest abnormal bleeding; however, data on the use of bleeding assessment tools in this population are lacking. Our objective was to validate the ISTH-BAT in haemophilia carriers to describe bleeding symptoms and allow for comparisons with factor levels and other patient groups. This was a prospective, observational, cross-sectional study performed by members of Global Emerging HEmostasis Panel (GEHEP). Unselected consecutive haemophilia carriers were recruited and a CRF and the ISTH-BAT were completed by study personnel. A total of 168 haemophilia carriers were enrolled: 155 haemophilia A and 13 haemophilia B. The mean age was 40 years (range: 20-82). Carriers had higher mean bleeding scores (BS) compared with age-matched controls (n = 46; 5.7 vs. 1.43; P < 0.0001) and Type 3 VWD OC (n = 32; 3.0; P = 0.009), but lower BS compared with women with Type 1 VWD (n = 83; 8.7; P < 0.0001). Fifteen carriers reported haemarthrosis, and of those six had normal FVIII/FIX levels. There was a significant but weak negative correlation between BS and factor level (Spearman's r 2  = -0.36, P < 0.001). Our results show that haemophilia carriers experience abnormal bleeding, including haemarthrosis. Overall, BS in women with Type 1 VWD > haemophilia carriers > Type 3 VWD OC > controls. Understanding the performance of the ISTH-BAT in this population is a critical step in future research aimed at investigating the underlying pathophysiology of abnormal bleeding, with the ultimate goal of optimizing treatment. © 2016 John Wiley & Sons Ltd.

[Food consumption and dietary behaviour in haemophilia patients before and after a nutrition consultation].

PubMed

Czepa, D; Hilberg, W; Poschmann, J; Straaten, S; Hilberg, T

2014-01-01

In over two-thirds of deaths, nutrition is a determining factor. Nutritional condition and dietary recommandations are unspecified in the haemophilia treatment. Aim of this study was to examine the food consumption and dietary behaviour in affected patients before and after a nutrition consultation. Data were assessed via questionnaires and compared between 38 patients with haemophilia (PwH) and 20 controls without haemophilia. Furthermore, in a randomised controlled trial 11 patients with haemophilia (PwH-I) took part in an adapted nutrition consultation and were supervised over six months as opposed to 12 patients with haemophilia (PwH-O) without intervention. PwH were compared to controls more pleased with their weight (53 vs. 40%), used more nutrition consultations in the past (53 vs. 15%) and consumed more dairy products (40 vs. 15%) and fruits (45 vs. 30%). After nutrition consultation PwH-I were better informed about their own blood values than PwH-O. The nutrition rated high in both groups, but PwH-I were more mindful of the feeling of satiety (9 vs. 36%) compared to PwH-O (33 vs. 17%). Moreover, PwH-I ate less under stress and/or out of boredom, showed a higher satisfaction regarding their weight and increased the liquid intake (55 vs. 73%), which remained unchanged in PwH-O with 42%. Compared to PwH-O, PwH-I ate more roughage, low-fat food, fish and fruits, therefore consuming less coffee/tea. Food consumption and dietary behaviour are similar between patients with haemophilia and controls without haemophilia. A nutrition consultation affected the food consumption and dietary behaviour in patients with haemophilia positively and can consequently contribute to preservation of health and prevention of nutritional diseases.

Patient-reported outcomes of 182 adults with severe haemophilia in Germany comparing prophylactic vs. on-demand replacement therapy.

PubMed

Mondorf, W; Kalnins, W; Klamroth, R

2013-07-01

Clotting factor replacement therapy has a major impact on the quality of life in patients with haemophilia. To analyse and compare the outcomes of on-demand and prophylactic treatment regimens in child- and adulthood, a self-evaluation questionnaire was sent to 182 patients over 30 years of age with severe haemophilia A or B. Analysis of the questionnaire results revealed that most study participants had been treated on-demand in childhood, but that the majority of these patients subsequently switched to prophylaxis. However, of those patients who began with prophylaxis as children, the vast majority maintained prophylactic treatment as adults. Inhibitor development was reported significantly more frequently by patients who started with on-demand treatment than by those who started with prophylaxis. In the year prior to completing the questionnaire, adults with severe haemophilia who received prophylactic treatment reported a significantly lower incidence of bleeding as a result of more frequent factor consumption. These results are in close accordance with published prospective data. Although nearly all patients with severe haemophilia had joint pain due to bleeding, those who had always had prophylactic treatment reported superior outcomes in terms of the need for joint replacement, walking speed and distance, participation in school sports and further education. These data clearly underline the superiority of prophylactic treatment for the majority of individuals with severe haemophilia. The worst outcomes were found in those treated on-demand in childhood who later switched to prophylaxis. In contrast to most studies which have compared treatment regimens on the basis of data from healthcare professionals, this study reflects treatment outcomes from the patient's perspective. © 2013 John Wiley & Sons Ltd.

Fitness and quality of life in children with haemophilia.

PubMed

Broderick, C R; Herbert, R D; Latimer, J; Curtin, J A

2010-01-01

Prior to the introduction of prophylactic clotting factor, children with haemophilia were discouraged from physical activity due to the risk of bleeds. Reports of children with haemophilia having lower levels of fitness and strength than their healthy peers were therefore well accepted. This study aimed to establish whether these deficits continued, and specifically, whether Australian boys with haemophilia and von Willebrand disorder had lower strength and aerobic capacity than their peers, despite widespread use of prophylaxis. Forty-four boys aged 6.1-17.0 years (mean 10.9, SD 3.2) with haemophilia A and B and von Willebrand disorder participated in the study. Fitness, strength and body mass index (BMI) measures were compared with age- and gender-matched data from a representative cohort of school children. Quality of Life was measured using the Haemo-QoL to obtain baseline measures in an Australian population. There were no statistically significant or clinically important differences in aerobic fitness or BMI between the boys with haemophilia and controls in any age category. Boys with haemophilia in Years 4, 6 and 10 had greater strength than their peers. Australian boys with bleeding disorders do not have impaired aerobic capacity or strength compared with their peers. Quality of life in Australian boys with haemophilia is comparable to their European counterparts.

Lonoctocog Alfa: A Review in Haemophilia A.

PubMed

Al-Salama, Zaina T; Scott, Lesley J

2017-10-01

Lonoctocog alfa (rVIII-SingleChain; Afstyla ® ) is a novel single-chain recombinant factor VIII (FVIII) molecule, with a truncated B-domain and the heavy and light chains covalently linked to form a stable and homogenous drug that binds with high affinity to von Willebrand factor (VWF). Intravenous lonoctocog alfa is approved for the prophylaxis and treatment of bleeding in patients with haemophilia A in several countries worldwide. In two pivotal, multicentre trials, lonoctocog alfa was effective in the treatment of bleeding episodes and as prophylaxis, including for perioperative management in adults, adolescents and children. In terms of haemostatic efficacy in controlling bleeding episodes, overall treatment and investigator-assessed success rates were high across all age groups, with the majority of these bleeds controlled with a single injection of lonoctocog alfa. Low median spontaneous, overall and traumatic annualized bleeding rates were evident with prophylactic lonoctocog alfa regimens in both trials. Lonoctocog alfa was generally well-tolerated, with very low rates of injection-site reactions. No previously treated patient experienced an anaphylactic reaction or developed an inhibitor. In conclusion, lonoctocog alfa is an effective and generally well-tolerated alternative to conventional FVIII products for the treatment and prophylaxis of bleeding, including in the surgical setting, in adults, adolescents and children with haemophilia A.

Health care resource utilization and cost of care for haemophilia A and B patients in Iran.

PubMed

Gharibnaseri, Zahra; Davari, Majid; Cheraghali, Abdolmajid; Eshghi, Peyman; Ravanbod, Roya; Espandar, Ramin; Hantooshzadeh, Razieh

2016-02-01

Despite the fact that the total therapeutic expenditure of haemophilia is paid by the national health system in Iran, a limited number of research has been performed to evaluate the economic burden of haemophilia. It is even more important when considering the fact that "prophylaxis" has never been used as the main treatment protocol in haemophiliacs in the country, causing high arthropathy rates. The aim of this study is to evaluate the cost drivers in the treatment of haemophilia A and B patients in Iran. The national registry database of Ministry of Health (MoH) was queried to identify total number of individuals characteristics diagnosed with Factor VIII and IX deficiency. The service package defined by the department for special diseases was used as the reference for the type and frequency of health care utilization in haemophiliacs in Iran. The direct medical costs including prescription, medical intervention, inpatient, outpatient and diagnostics services and arthroplasty were considered. The prices were extracted from Iranian medical tariff book 2014-15. Medication cost was obtained from the Iranian Food and Drug Organization. Among 8,337 patients registered with bleeding disorders, 3,948 and 848 were identified with haemophilia A and B respectively, of whom 856 (18%) patients had inhibitor at any time in the past. In the two groups, 2,328 (59%) and 452 (53%) patients suffered from severe, 686 (17%) and 186 (22%) from moderate and 902 (23%) and 185 (22%) from mild type of haemophilia. The average annual health care cost for every patient was USD 15,130, mostly allocated to medication USD 10,180 (67%), followed by therapeutic services USD 4,775 (32%) while diagnostic services stood third USD 177 (1%). There is an urgent need for developing clinical practice guidelines for treatment protocols, procedures and supportive care in haemophilia management in Iran. Copyright © 2016 Elsevier Ltd. All rights reserved.

Measurement properties of the Haem-A-QoL in haemophilia clinical trials.

PubMed

von Mackensen, S; Eldar-Lissai, A; Auguste, P; Krishnan, S; von Maltzahn, R; Yu, R; Wyrwich, K W

2017-05-01

Patients with haemophilia on long-acting prophylactic treatment may experience an improvement in health-related quality of life (HRQoL) through reductions in breakthrough bleeds and associated complications, including long-term joint damage, compared with episodic treatment. This analysis examined clinical trial data to understand the psychometric characteristics (reliability, validity and sensitivity to change over time) of the Haem-A-QoL Questionnaire in adult males with haemophilia. Two recent, multinational, Phase 3 clinical trials of new, long-acting factor concentrates (A-LONG: rFVIIIFc; B-LONG: rFIXFc) assessed HRQoL in adolescent and adult males with severe haemophilia A or B respectively. The adults' baseline assessments, via the 46-item Haem-A-QoL Questionnaire, and change over time at the 6-month assessment were used in the psychometric analyses. Internal consistency reliability was adequate (Cronbach's alpha > 0.70) for nine of the 10 Haem-A-QoL domains and for 'Total Score' in both trials at baseline (A-LONG, n = 133; B-LONG, n = 73). At baseline, several Haem-A-QoL domains and 'Total Score' demonstrated known-groups and convergent validity when compared with other trial measures, including the EQ-5D (items and total scores) and joint impairment. Change score correlations (baseline to 28 weeks) between the EQ-5D and the Haem-A-QoL 'Total Score', and 'Physical Health' and 'Feelings' domains were moderate in magnitude (│r│ ≥ 0.33; P < 0.03), demonstrating sensitivity to change for these outcome measures in A-LONG. These psychometric analyses provide evidence of the reliability, validity and ability to detect change of the Haem-A-QoL to assess the HRQoL of adult males with severe haemophilia A and B in longitudinal clinical trials. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Psychosocial correlates of physical activity in adolescents with haemophilia.

PubMed

Buxbaum, N P; Ponce, M; Saidi, P; Michaels, L A

2010-07-01

Boys with haemophilia are now encouraged to exercise and take part in physical activities, but actual measures of time spent in active participation is lacking. The aim of this study was to obtain an objective measure of daily physical activity in boys with haemophilia as compared with healthy controls. The study also aimed to ascertain the social and cognitive factors associated with exercise in this population. Seventeen patients (aged 11-18 years) with haemophilia were studied and compared with 44 healthy controls (aged 10-16.5 years). Physical activity was measured by accelerometry. Psychosocial correlates were assessed using validated questionnaires. Measured physical activity levels in subjects with haemophilia were slightly higher than for the control group. Both groups spent 70% of the day inactive, with similar proportions of time in moderate and vigorous activity. Subjects with haemophilia had a favourable self-image and similar levels of anxiety as peers without a bleeding disorder. Self-efficacy scores were lower than for controls suggesting increased sensitivity to barriers and lack of acceptance of alternatives. Health beliefs did not influence physical activity, but a negative correlation of time spent in high or vigorous activity with scores for support-seeking was observed. The data demonstrate that in the appropriate social environment and with medical support, patients with haemophilia may be as physically active as their peers without a bleeding disorder. Further investigation into the psychosocial barriers of physical activity in patients with haemophilia is needed to more effectively encourage healthy behaviours.

Measuring activities and participation in persons with haemophilia: A systematic review of commonly used instruments.

PubMed

Timmer, M A; Gouw, S C; Feldman, B M; Zwagemaker, A; de Kleijn, P; Pisters, M F; Schutgens, R E G; Blanchette, V; Srivastava, A; David, J A; Fischer, K; van der Net, J

2018-03-01

Monitoring clinical outcome in persons with haemophilia (PWH) is essential in order to provide optimal treatment for individual patients and compare effectiveness of treatment strategies. Experience with measurement of activities and participation in haemophilia is limited and consensus on preferred tools is lacking. The aim of this study was to give a comprehensive overview of the measurement properties of a selection of commonly used tools developed to assess activities and participation in PWH. Electronic databases were searched for articles that reported on reliability, validity or responsiveness of predetermined measurement tools (5 self-reported and 4 performance based measurement tools). Methodological quality of the studies was assessed according to the COSMIN checklist. Best evidence synthesis was used to summarize evidence on the measurement properties. The search resulted in 3453 unique hits. Forty-two articles were included. The self-reported Haemophilia Acitivity List (HAL), Pediatric HAL (PedHAL) and the performance based Functional Independence Score in Haemophilia (FISH) were studied most extensively. Methodological quality of the studies was limited. Measurement error, cross-cultural validity and responsiveness have been insufficiently evaluated. Albeit based on limited evidence, the measurement properties of the PedHAL, HAL and FISH are currently considered most satisfactory. Further research needs to focus on measurement error, responsiveness, interpretability and cross-cultural validity of the self-reported tools and validity of performance based tools which are able to assess limitations in sports and leisure activities. © 2018 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Enhancing lifestyle for individuals with haemophilia through physical activity and exercise: the role of physiotherapy.

PubMed

Wittmeier, K; Mulder, K

2007-09-01

For individuals with haemophilia, the benefits of many forms of physical activity outweigh their risks. Although activities with significant trauma risk should be avoided, persons who have haemophilia can participate in, enjoy and even excel in a variety of physical activities and sports. Both the National Hemophilia Foundation and the World Foundation of Hemophilia have produced documents to guide individuals with haemophilia and their healthcare professionals, coaches and parents in developing physical activity programmes and participation in sports. Physical activity guidelines for promoting health benefits exist worldwide and can be incorporated into individualized exercise programmes to ensure that a person with haemophilia is not only choosing appropriate activities, but also improving overall health and preparing the body to manage haemophilia better. Physiotherapy treatment is paramount in helping individuals prevent, manage and optimally recover from bleeds. Furthermore, the physical therapist, along with the haemophilia care team, can assist in preparing an individual to begin or progress to a physical activity programme that enhances fitness level, body composition and overall well-being. This article presents the unique role of the physiotherapist in facilitating safe participation in quality physical activity in the context of risks, benefits and activity recommendations. Participation in physical activity from an early age is ideal to facilitate the development of body awareness and capability and to foster the adoption of a physically active lifestyle; however, it is never too late to start. Consistent participation in quality physical activity beginning at any age is central to managing haemophilia and, equally important, to achieving overall health and well-being.

An institutional pilot study to investigate physical activity patterns in boys with haemophilia.

PubMed

Bouskill, V; Hilliard, P; Stephens, S; Zhang, C; Whitney, K; Carcao, M

2016-09-01

Haemophilia is a bleeding disorder characterized by musculoskeletal bleeding. Trauma-induced bleeding into joints and muscles may be associated with participation in physical activities. Recognizing this, persons with haemophilia may limit physical activities to avoid bleeding. The characterization of physical activity profiles (type, intensity, frequency and duration) in children with differing severities of haemophilia has not been well documented. This is required to better understand the relationship between physical activity and bleeding in children with haemophilia. This study was a prospective, cross-sectional, observational study to compare the quantity, type and intensity of physical activity as measured by accelerometry in boys with different haemophilia severities. Subjects wore an accelerometer daily for 1 week and completed validated self-report PedHAL and 3DPAR questionnaires. Accelerometer activity levels were classified as sedentary, light, moderate or vigorous. A total of 66 males were enrolled, 24 had mild/moderate and 42 had severe haemophilia. Subjects average age was 11.52 years (±3.99) and their average BMI was 20.74 kg m(2) (±5.68). Boys with severe haemophilia reported significantly more time per day spent in sedentary activities compared to those with mild/moderate haemophilia. Furthermore, the amount of time engaged in sedentary activities increased with age in those boys with severe haemophilia, whereas the opposite was true in those with mild/moderate haemophilia. We speculate that prophylaxis in children with severe haemophilia permitted them to engage in similar amounts of moderate to vigorous physical activity (MVPA) as children with mild/moderate haemophilia. Increasing sedentary time in the severe cohort with age may be attributed to increasing arthropathy among other psychosocial factors. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

The impact of a haemophilia education intervention on the knowledge and health related quality of life of parents of Indian children with haemophilia.

PubMed

Phadnis, S; Kar, A

2017-01-01

The impact of haemophilia education on the quality of life of parents of children with haemophilia from low income settings has not been studied. The purpose of this study was to determine the impact of an education intervention on health related quality of life (HRQOL) of parents of children with haemophilia, parent's knowledge about haemophilia and its management, and to determine whether education about haemophilia can positively impact these outcomes. One hundred thirty-three parents from across Maharashtra state, India were provided information about haemophilia, care of child and self-care. The impact of the intervention was measured as changes occurring from baseline to 6 months and 1 year after intervention. Knowledge and practice of management of bleeding was measured using pretested structured questionnaires. HRQOL was measured using a validated Peds Quality of Life ™ Family Impact Module (PedsQL ™ FIM) tool. There was improvement in knowledge scores immediately after intervention, which remained significantly higher than baseline 1 year after intervention. HRQOL showed significant improvement at 6 months but reduced to baseline levels 1 year after intervention. There were statistically significant changes in terms of practice of management of bleeding episodes at 6 months and 1 year after intervention. Education about haemophilia resulted in improvement of knowledge, and practice of management of bleeding which was retained till a year after the intervention. However, a long-term effect on the HRQOL of parents could not be observed after administration of a single education intervention. © 2016 John Wiley & Sons Ltd.

Haemophilia A carriers experience reduced health-related quality of life.

PubMed

Gilbert, L; Paroskie, A; Gailani, D; Debaun, M R; Sidonio, R F

2015-11-01

Haemophilia A is an X-linked recessive bleeding disorder that primarily affects males. Emerging data support evidence for increased bleeding in female haemophilia A carriers despite factor VIII activity within the normal range. Data regarding the effect of increased bleeding on health-related quality of life (HR-QOL) in haemophilia A carriers is sparse. We tested the hypothesis that haemophilia A carriers have reduced HR-QOL related to bleeding symptoms. We conducted a cross-sectional study at Vanderbilt University. Case subjects were obligate or genetically verified haemophilia A carriers age 18-60 years. Control subjects were mothers of children with cancer who receive care at the Vanderbilt paediatric haematology-oncology clinic. Trained interviewers administered the Rand 36-Item Health Survey 1.0, a validated questionnaire evaluating eight health concepts that may affect HR-QOL, to each study participant. Mann-Whitney U-tests were used to compare median scores for the eight health domains between the case and control groups. Forty-two haemophilia A carriers and 36 control subjects were included in analyses. Haemophilia A carriers had significantly lower median scores for the domains of 'Pain' (73.75 vs. 90; P = 0.02) and 'General health' (75 vs. 85; P = 0.01) compared to control subjects. Haemophilia A carriers in our study demonstrated significantly lower median scores on the Rand 36-item Health Survey 1.0 in the domains of 'Pain' and 'General Health' compared to women in the control group. Our findings highlight the need for further investigation of the effect of bleeding on HR-QOL in this population. © 2015 John Wiley & Sons Ltd.

Habitual physical activity in Dutch children and adolescents with haemophilia.

PubMed

Groen, W G; Takken, T; van der Net, J; Helders, P J M; Fischer, K

2011-09-01

For patients with haemophilia, a physically active lifestyle is important to maintain musculoskeletal health and to prevent chronic diseases, such as cardiovascular disease. Therefore, we studied physical activity levels, in Dutch children and adolescents with haemophilia as well as its association with aerobic fitness and joint health. Forty-seven boys with haemophilia (aged 8-18) participated. Physical activity was measured using the Modifiable Activity Questionnaire (MAQ) and was compared with the general population. Aerobic fitness was determined using peak oxygen uptake (VO(₂peak)). Joint health was measured using the Haemophilia Joint Health Score (HJHS). Associations between physical activity, joint health and aerobic fitness were evaluated by correlation analysis. Subjects were 12.5 (SD 2.9) years old, had a Body Mass Index (BMI) of 19.5 (SD 3.1; z-score 0.5) and a median HJHS score of 0 (range 0-6). Cycling, physical education and swimming were most frequently reported (86%, 69% and 50% respectively). Children with severe haemophilia participated significantly less in competitive soccer and more in swimming than children with non-severe haemophilia. Physical activity levels were similar across haemophilia severities and comparable to the general population. VO(₂peak) kg⁻¹ was slightly lower than healthy boys (42.9 ± 8.6 vs. 46.9 ± 1.9 mL kg⁻¹ min⁻¹; P = 0.03). Joint health, aerobic fitness and physical activity showed no correlation. Dutch children with haemophilia engaged in a wide range of activities of different intensities and showed comparable levels of physical activity to the general population. Aerobic fitness was well preserved and showed no associations with physical activity levels or joint health. © 2011 Blackwell Publishing Ltd.

Organized sports participation and the association with injury in paediatric patients with haemophilia.

PubMed

McGee, S; Raffini, L; Witmer, C

2015-07-01

With the wide availability of factor and the routine use of prophylaxis boys with haemophilia are now able to participate in regular physical activity, including organized sports. Current guidelines vary regarding specific recommendations for sports participation and concerns remain regarding safety. To determine if participation in organized sports is associated with an increased risk for injury in paediatric subjects with haemophilia. Retrospective single-centre cohort study from January 1, 2008 to December 31, 2010 in male subjects ages 10-18 years with a factor VIII (FVIII) or FIX level <40%. The number of injuries per subject and participation in organized sports was recorded. 48 male subjects with a mean age of 14.3 ± 2.6 years (range: 10-18.8) were included; 64.6% (31/48) FVIII deficiency, 54.2% (26/48) severe haemophilia, 18.8% (9/48) moderate and 27.1% (13/48) mild. The majority [62.5% (30/48)] of subjects participated in at least one season of organized sport. There were 77 injuries in 36/48 (75%) subjects. The mean number of injuries per subject was 1.6 ± 1.5. There was no statistical difference in the mean number of injuries (P = 0.44) or target joint formation (P = 0.52) between the subjects who participated in organized sports compared to those who did not. In this study, participation in organized sports by boys with haemophilia, ages 10-18 years, is common and not associated with an increased number of injuries or the development of a target joint. As injuries occurred equally in both groups, concerted efforts should be directed at reducing injuries in all patients. © 2015 John Wiley & Sons Ltd.

Use of the dual force system to correct chronic knee deformities due to severe haemophilia.

PubMed

Kale, J S; Ghosh, K; Mohanty, D; Pathare, A V; Jijina, F

2000-05-01

In this study, the use of the dual force system to correct recent or relatively longstanding knee deformities in ten patients is described. (Nine of the patients had severe haemophilia and one had severe von Willebrand's disease.) The mean duration of deformity in these patients was 10 months. The mean range of movement at the affected knee joints increased from 50 degrees at pre-intervention to 110 degrees following 6 weeks of application of the dual force system. In nine of ten patients (90%) the residual flexion deformity ranged from 0 degrees to 10 degrees. The dual force system offers an easily affordable and effective means of correcting a flexion deformity of the knee joint in severely affected haemophilia and allied disorders. More extensive use of this technique in different centres is required to determine its place in the day-to-day management of such patients.

Prioritisation in haemophilia A: a qualitative study of stakeholder attitudes and preferences.

PubMed

Dörries, A; Ude-Koeller, S; Wermes, C; Eisert, R; Ganser, A

2012-04-01

To learn more about prioritisation in the health care system, we performed an exploratory qualitative study on haemophilia A. The aim was to generate haemophilia disease-specific criteria and to learn more about reasoning in the decision-making process. The 40 participants (patients, relatives, physicians, nurses) were asked in semi-structured interviews about their experiences regarding the German health care system in general and the management of haemophilia A. The 4 stakeholder groups agreed that treatment in haemophilia A was very good; there were complaints about increased bureaucracy. Arguments originated in personal past experiences (patients, relatives) and in the professional background (healthcare professionals). Decision-making criteria ranking high were the maintenance of mobility, social responsibility and the prospect of a long working life span. Criteria with lower ranking were a high social professional status and age. There was ambivalence as to whether savings in the healthcare system in general were necessary or inacceptable. Prophylactic factor administration was rejected when high-risk sports were practiced regularly. Decision-making among actual individuals was rejected as 'immoral'. Patient representatives should be included in the political decision-making process. In conclusion, solidarity in the German health insurance is a highly esteemed principle, but was not well comprehended. The findings demonstrate the variety of individual attitudes with strong context affinity to the disease and the background of the stakeholder groups. The challenge will be to find ways of prioritising in an accountable and transparent way to maintain an excellent health care service for the individual haemophilia patient while also serving the public good. © Georg Thieme Verlag KG Stuttgart · New York.

Recommendations for postmarketing surveillance studies in haemophilia and other bleeding disorders.

PubMed

Lassila, R; Rothschild, C; De Moerloose, P; Richards, M; Perez, R; Gajek, H

2005-07-01

Prospective surveillance studies to monitor drug safety in the postapproval period are rarely employed systematically, although they are of greatest value for caregivers, drug users and regulatory authorities. Safety issues have affected not only conventional pharmaceuticals, but also especially coagulation factors in haemophilia treatment. The reputation of postmarketing surveillance (PMS) studies has been questionable, mainly due to their misuse to solicit prescriptions. Other weaknesses include inappropriate design, lack of standardized observation, limited follow-up periods, absence of rigour in identifying potential adverse drug effects, and infrequent publication. Although well-designed clinical trials represent the gold standard for generating sound clinical evidence, a number of aspects would make PMS studies valuable, if properly conducted. One of their main advantages is broader inclusion, and absence of an 'experimental' design. Lack of proper guidelines, and standardization may constitute a reason for the generally low quality of PMS studies. This paper proposes guidelines for haemophilia-specific PMS studies, in order to improve the acceptance of a basically valuable tool. In the absence of consistent regulatory guidance it will be especially important that the design and supervision of PMS studies involves physicians from the beginning. This will not only make such studies more scientifically relevant, but also help to implement them into daily clinical practice. Specifically in haemophilia, PMS studies may provide valuable data on clinical outcomes, or Quality of Life, which is of great importance when considering adequate standards of care in haemophilia patients.

Physical activity levels and participation in sport in Irish people with haemophilia.

PubMed

Sherlock, E; O'Donnell, J S; White, B; Blake, C

2010-01-01

Physical activity and sport are associated with a range of health and social benefits. The aim of this study was to assess the level of sports participation and physical activity of Irish people with haemophilia (PWH). A questionnaire was administered to Irish PWH attending the National Centre for Hereditary Coagulation Disorders over a 3-month period. This included the International Physical Activity Questionnaire (IPAQ) and the Haemophilia Activities List (HAL). Comparisons with EU average data from European Physical Activity Surveillance System for physical activity scores (IPAQ) were made using independent t-tests and percentage variance. Relationships between age, functional limitation (based on HAL) and IPAQ scores were tested with Pearson's correlation. Sixty-one questionnaires were completed, representing 12% of the Irish haemophilia population. Age ranged from 16 to 63; all levels of severity were included. Forty-six percent of Irish PWH achieved a high level of physical activity, but overall physical activity [total metabolic equivalents of task (MET) min] in the group was only 66% of the EU average. Elderly patients and those with more functional limitations (with lower HAL scores) were significantly less active. Sports participation levels were in line with other PWH at 66%. Although 55% reported bleeds resulting from sport and 31% reported having had a significant injury attributable to sport, overall sport was viewed in a positive light. Irish PWH are physically active and play a wide range of sports. Further efforts are needed to achieve optimal safety and to ensure that maximum benefit is gained.

Incidence and risk factors for inhibitor development in previously untreated severe haemophilia A patients born between 2005 and 2010.

PubMed

Vézina, C; Carcao, M; Infante-Rivard, C; Lillicrap, D; Stain, A M; Paradis, E; Teitel, J; Rivard, G E

2014-11-01

The objective of this study was to evaluate the inhibitor development (ID) in previously untreated patients (PUPs) with severe haemophilia A (FVIII ≤ 0.01 IU mL(-1) ). All Canadian Haemophilia Treatment Centres completed a questionnaire on patients born between September 2005 and August 2010 and followed for up to 7 years. Eligible patients had at least 20 exposure days (ED) or had developed an inhibitor. The odds ratio (OR) and 95% confidence intervals (95% CI) for risk factors to develop an inhibitor were estimated using unconditional logistic regression. A total of 99 haemophilia A PUPs were studied. Thirty-four (34%) developed an inhibitor (24/34 of high titre). Inhibitors developed in 25/63 (40%) patients with a high-risk mutation. ID was most frequent in Aboriginals (86%). Dose intensity (IU kg(-1)  day(-1) X number of ED) at first exposure to factor VIII (FVIII) was associated with a crude OR increase of 1.10 (95% CI: 0.99-1.23) with each increase of 100 dose-intensity units. Haemarthrosis and intracranial bleeding as the indication for first exposure to FVIII concentrate were associated with a crude OR for ID of 7.63 (95% CI: 2.14-27.17) and 5.08 (95% CI: 1.11-23.31) respectively. ID according to FVIII concentrate used was: Advate (®) 18/50 (36%), Kogenate FS(®) or Helixate FS(®) 15/36 (42%), Wilate(®) 0/11 and Xyntha(®) 1/2. In multivariate analysis, Aboriginal ethnicity (OR = 11.69; 95% CI: 1.11-122.86) and haemarthrosis (OR = 4.49; 95% CI: 1.08-18.61) were statistically significant. The cumulative incidence of ID in severe haemophilia A PUPs was 34% and varied according to ethnicity, type of bleeding at first ED, type of FVIII product and dose intensity at first exposure. © 2014 John Wiley & Sons Ltd.

Exercise for haemophilia.

PubMed

Strike, Karen; Mulder, Kathy; Michael, Rojer

2016-12-19

Haemophilia is a bleeding disorder associated with haemorrhaging into joints and muscles. Exercise is often used to aid recovery after bleeds, and to improve joint function in the presence of arthropathy. Our objective was to systematically review the available evidence on the safety and effectiveness of exercise for people with haemophilia. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register and electronic databases PubMed, OVID-Embase, and CINAHL. We hand searched abstracts from congresses of the World Federation of Hemophilia and the European Hematology Association, trial registries and the reference lists of relevant articles.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 14 December 2016. Randomized or quasi-randomized controlled studies comparing any exercise intervention considered relevant in haemophilia management including supervised, unsupervised, aquatic, strengthening, aerobic or cardiovascular, stretching, proprioceptive and balance training exercise programs in males of any age with haemophilia A or B of any severity (those with co-morbidities were not excluded). Two authors reviewed the identified abstracts to determine their eligibility. For studies meeting the inclusion criteria, full articles were obtained. The two authors extracted data and assessed the risk of bias. Any disagreements were resolved by discussion. The authors contacted study investigators to obtain any missing data. Eight studies were included, which represented 233 males with all severities of haemophilia A and B, ranging in age from eight years to 49 years. Study duration ranged from four to 12 weeks. Exercise interventions varied greatly and included resistance exercises, isometric exercises, bicycle ergometry, treadmill walking and hydrotherapy; therefore, comparison between studies was difficult.None of the studies measured or reported adverse effects from

Protein A sepharose immunoadsorption: immunological and haemostatic effects in two cases of acquired haemophilia.

PubMed

Guillet, B; Kriaa, F; Huysse, M G; Proulle, V; George, C; Tchernia, G; D'Oiron, R; Laurian, Y; Charpentier, B; Lambert, T; Dreyfus, M

2001-09-01

Acquired haemophilia is a life-threatening disorder caused by circulating auto-antibodies that inhibit factor VIII coagulant activity (FBIII:C). Immunoadsorption on protein A sepharose (IA-PA) was performed in two bleeding patients with acquired haemophilia: we observed a dramatic and quick decrease in the anti-FVIII:C inhibitor titre leading to a normal, albeit transient, haemostatic status. In one case, IA-PA was the only procedure which succeeded in stopping massive haemorrhage. In the second case, IA-PA reinforced the haemostatic effect of recombinant activated factor VII by increasing the endogenous plasma factor VIII level. The efficacy of IA-PA was sustained with immunosuppressive treatment introduced, respectively, 10 and 15 d before the IA-PA procedures. Our experience with IA-PA suggests that this extracorporeal anti-FVIII:C removal procedure is a valuable therapeutic tool for acquired haemophilia and can alleviate life-threatening haemorrhages.

Recombinant activated factor VII in the treatment of bleeds and for the prevention of surgery-related bleeding in congenital haemophilia with inhibitors.

PubMed

Santagostino, Elena; Escobar, Miguel; Ozelo, Margareth; Solimeno, Luigi; Arkhammar, Per; Lee, Hye Youn; Rosu, Gabriela; Giangrande, Paul

2015-06-01

The availability of recombinant activated factor VII (rFVIIa, eptacog alfa activated) has greatly advanced the care of patients with haemophilia A or B who have developed inhibitors against the infused replacement factor. Recombinant FVIIa is licensed for the on-demand treatment of bleeding episodes and the prevention of bleeding in surgery or invasive procedures in patients with congenital haemophilia with inhibitors. This article attempts to review in detail the extensive evidence of rFVIIa in congenital haemophilia patients with inhibitors. Patients with acute bleeding episodes are best treated on demand at home, to achieve the short- and long-term benefits of rapid bleed control. Key prospective studies have shown that rFVIIa achieves consistently high efficacy rates in the management of acute (including joint) bleeds in inhibitor patients in the home treatment setting. Substantial post-approval data from key registries also support the on-demand efficacy profile of rFVIIa established by the prospective clinical trials. The availability of rFVIIa has allowed major surgery to become a reality for inhibitor patients. Studies in key surgery, including orthopaedic procedures, have found that rFVIIa provides consistently high efficacy rates. Importantly, the wealth of data does not raise any unexpected safety concerns surrounding rFVIIa use; this is likely because rFVIIa is a recombinant product with a localised mechanism of action at the site of vascular injury. In summary, rFVIIa is established as an effective and well-tolerated first-line treatment for on-demand bleeding control and bleed prevention during minor and major (including elective orthopaedic) surgery in inhibitor patients. Use of rFVIIa has been a major step towards narrowing the gap in outcomes between inhibitor patients and non-inhibitor patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

The relationship between target joints and direct resource use in severe haemophilia.

PubMed

O'Hara, Jamie; Walsh, Shaun; Camp, Charlotte; Mazza, Giuseppe; Carroll, Liz; Hoxer, Christina; Wilkinson, Lars

2018-01-16

Target joints are a common complication of severe haemophilia. While factor replacement therapy constitutes the majority of costs in haemophilia, the relationship between target joints and non drug-related direct costs (NDDCs) has not been studied. Data on haemophilia patients without inhibitors was drawn from the 'Cost of Haemophilia across Europe - a Socioeconomic Survey' (CHESS) study, a cost assessment in severe haemophilia A and B across five European countries (France, Germany, Italy, Spain, and the United Kingdom) in which 139 haemophilia specialists provided demographic and clinical information for 1285 adult patients. NDDCs were calculated using publicly available cost data, including 12-month ambulatory and secondary care activity: haematologist and other specialist consultant consultations, medical tests and examinations, bleed-related hospital admissions, and payments to professional care providers. A generalized linear model was developed to investigate the relationship between NDDCs and target joints (areas of chronic synovitis), adjusted for patient covariates. Five hundred and thirteen patients (42% of the sample) had no diagnosed target joints; a total of 1376 target joints (range 1-10) were recorded in the remaining 714 patients. Mean adjusted NDDCs for persons with no target joints were EUR 3134 (standard error (SE) EUR 158); for persons with one or more target joints, mean adjusted NDDCs were EUR 3913 (SE EUR 157; average mean effect EUR 779; p < 0.001). Our analysis suggests that the presence of one or more target joints has a significant impact on NDDCs for patients with severe haemophilia, ceteris paribus. Prevention and management of target joints should be an important consideration of managing haemophilia patients.

Cost of care of haemophilia with inhibitors.

PubMed

Di Minno, M N D; Di Minno, G; Di Capua, M; Cerbone, A M; Coppola, A

2010-01-01

In Western countries, the treatment of patients with inhibitors is presently the most challenging and serious issue in haemophilia management, direct costs of clotting factor concentrates accounting for >98% of the highest economic burden absorbed for the healthcare of patients in this setting. Being designed to address questions of resource allocation and effectiveness, decision models are the golden standard to reliably assess the overall economic implications of haemophilia with inhibitors in terms of mortality, bleeding-related morbidity, and severity of arthropathy. However, presently, most data analyses stem from retrospective short-term evaluations, that only allow for the analysis of direct health costs. In the setting of chronic diseases, the cost-utility analysis, that takes into account the beneficial effects of a given treatment/healthcare intervention in terms of health-related quality of life, is likely to be the most appropriate approach. To calculate net benefits, the quality adjusted life year, that significantly reflects such health gain, has to be compared with specific economic impacts. Differences in data sources, in medical practice and/or in healthcare systems and costs, imply that most current pharmacoeconomic analyses are confined to a narrow healthcare payer perspective. Long-term/lifetime prospective or observational studies, devoted to a careful definition of when to start a treatment; of regimens (dose and type of product) to employ, and of inhibitor population (children/adults, low-responding/high responding inhibitors) to study, are thus urgently needed to allow for newer insights, based on reliable data sources into resource allocation, effectiveness and cost-utility analysis in the treatment of haemophiliacs with inhibitors.

Comparative burden of arthropathy in mild haemophilia: a register-based study in Sweden.

PubMed

Osooli, M; Lövdahl, S; Steen Carlsson, K; Knobe, K; Baghaei, F; Holmström, M; Astermark, J; Berntorp, E

2017-03-01

Mild haemophilia is a congenital bleeding disorder affecting males. The burden of arthropathy in mild haemophilia has not been comprehensively described. The aim of this study was to compare the incidence, age at diagnosis and surgery for arthropathy and related hospitalizations between people with mild haemophilia and the general population in Sweden. This was a register-based cohort study. Eligible participants were those with mild haemophilia born between 1941 and 2008 and a randomly selected, birthdate and sex-matched comparison group from the general population. Follow-up was from birth (or earliest 1984) until death, emigration or end of the study in 2008. Data on arthropathy were obtained from a national patient register. Negative binomial and competing risk regression and Kaplan-Meier estimate curves were used in the analysis. Overall, 315 people with haemophilia and 1529 people in the comparison group were included. Participants with haemophilia born between 1984 and 2008 had a ninefold (95% CI: 3.3-27.2) and 16-fold (95% CI: 6.7-36.5) increased incidence of arthropathy-related hospital admission and arthropathy diagnosis respectively. None in this cohort underwent surgery. Among participants with haemophilia born prior to 1984, the rates of arthropathy diagnosis and surgery of the index joints (knee, elbow, ankle) were increased twofold (95% CI: 1.0-3.2) and fivefold (95% CI: 1.7-17.8) respectively. Our data suggested a higher burden of arthropathy among individuals with mild haemophilia compared to the general population. Further research should investigate the need for targeted joint screening programmes among individuals with mild haemophilia. © 2017 John Wiley & Sons Ltd.

The impact of severe haemophilia and the presence of target joints on health-related quality-of-life.

PubMed

O'Hara, Jamie; Walsh, Shaun; Camp, Charlotte; Mazza, Giuseppe; Carroll, Liz; Hoxer, Christina; Wilkinson, Lars

2018-05-02

Joint damage remains a major complication associated with haemophilia and is widely accepted as one of the most debilitating symptoms for persons with severe haemophilia. The aim of this study is to describe how complications of haemophilia such as target joints influence health-related quality of life (HRQOL). Data on hemophilia patients without inhibitors were drawn from the 'Cost of Haemophilia across Europe - a Socioeconomic Survey' (CHESS) study, a cost-of-illness assessment in severe haemophilia A and B across five European countries (France, Germany, Italy, Spain, and the UK). Physicians provided clinical and sociodemographic information for 1285 adult patients, 551 of whom completed corresponding questionnaires, including EQ-5D. A generalised linear model was developed to investigate the relationship between EQ-5D index score and target joint status (defined in the CHESS study as areas of chronic synovitis), adjusted for patient covariates including socio-demographic characteristics and comorbidities. Five hundred and fifteen patients (42% of the sample) provided an EQ-5D response; a total of 692 target joints were recorded across the sample. Mean EQ-5D index score for patients with no target joints was 0.875 (standard deviation [SD] 0.179); for patients with one or more target joints, mean index score was 0.731 (SD 0.285). Compared to having no target joints, having one or more target joints was associated with lower index scores (average marginal effect (AME) -0.120; SD 0.0262; p < 0.000). This study found that the presence of chronic synovitis has a significant negative impact on HRQOL for adults with severe haemophilia. Prevention, early diagnosis and treatment of target joints should be an important consideration for clinicians and patients when managing haemophilia.

The association between health utility and joint status among people with severe haemophilia A: findings from the KAPPA register.

PubMed

Osooli, M; Steen Carlsson, K; Baghaei, F; Holmström, M; Rauchensteiner, S; Holme, P A; Hvitfeldt, L; Astermark, J; Berntorp, E

2017-05-01

People with severe haemophilia A have reportedly impaired health related quality of life (utility) mainly due to recurrent bleeding, arthropathy and treatment burden. To estimate utilities and evaluate their potential correlates - most importantly the joint status - among people with severe haemophilia A. In this cross-sectional study, eligible participants had severe haemophilia A, were aged ≥15, negative for factor VIII inhibitor and included in the KAPPA register of Denmark, Norway and Sweden. Data on demographics, treatment history, haemophilia joint health score, and EQ-5D utility were obtained from the register. We used box plots to present utilities and joint status and ordinary least squares regression to evaluate correlates of utilities. Participants were consecutively enrolled in the KAPPA register between April 2013 and June 2016. Overall, 173 participants with median age of 34 (interquartile range: 25-45) were included. Twelve (6.9%) participants were on episodic treatment while 161 (93.1%) were treated using prophylaxis. Concomitant diseases and positive inhibitor history were reported for 73 (43.2%) and 21 (12.1%) participants, respectively. The highest median utility (1.0) was observed among those aged <29 on prophylaxis and those aged 30-44 who had started prophylaxis by age 3. In the multi-variable regression, joint scores of 16-25 (Coef. -0.18, 95% CI: -0.30, -0.06), 26-35 (Coef. -0.21, 95% CI: -0.36, -0.06) and >35 (Coef. -0.37, 95% CI: -0.52, -0.23) were associated with lower utilities. Moderate to severe joint manifestations are associated with reduced utilities among persons with severe haemophilia A. © 2017 John Wiley & Sons Ltd.

Modification of family size in families reporting history of haemophilia from Maharashtra, India.

PubMed

Potnis-Lele, Mugdha; Kar, Anita

2003-04-01

In India, genetic counselling services are largely unavailable. The question of whether awareness of the hereditary nature of the disorder leads to modified family size in affected families remains unanswered. The objective of this study was to determine whether family history of haemophilia resulted in modification of family size in families reporting haemophilia in the State of Maharashtra, India. The study was a retrospective cohort analysis from pedigrees collected from an earlier survey on haemophilia in Maharashtra. Pedigree data were manually defined into families with or without experience of haemophilia. Family size was defined as the number of live births per woman as documented in the pedigree. The data were analysed using Microsoft Excel package (version 2000) and SPSS package (version 10). Family size of obligate carriers who were daughters of patients was significantly less than the family size of obligate carriers who reported haemophilia in a brother or maternal relative (z = 7.14, P < 0.001). As compared with parents from an older generation, a significant reduction in the number of children born to younger families with haemophilia was observed, irrespective of family history of the condition. In families with history of haemophilia, there was no significant reduction in the number of families with more than one affected son in between two generations of parents (chi(2) = 1.43). The results revealed a reduction in size of families with haemophilia over a generation, which possibly reflected the reducing fertility trends observed in the Indian population. Reduction in the number of children born to women with a haemophilic father suggested a comprehension of father to daughter transmission of haemophilia. This was not true when relatives other than the father were affected. The lack of significant reduction in the number of families with history of haemophilia of having more than one affected son may suggest a compensatory response to the high

Prompt immune tolerance induction at inhibitor diagnosis regardless of titre may increase overall success in haemophilia A complicated by inhibitors: experience of two U.S. centres.

PubMed

Nakar, C; Manco-Johnson, M J; Lail, A; Donfield, S; Maahs, J; Chong, Y; Blades, T; Shapiro, A

2015-05-01

Current guidelines recommend delaying the start of immune tolerance induction (ITI) until the inhibitor titre is <10 Bethesda units (BU) to improve success. This study was conducted to evaluate ITI outcome relative to time to start ITI from inhibitor detection irrespective of inhibitor titre. Data were retrospectively collected from two U.S. haemophilia treatment centres (HTCs) on subjects with severe/moderate factor VIII (FVIII) deficiency with inhibitors who underwent ITI. Outcomes were defined pragmatically: success--negative inhibitor titre and ability to use FVIII concentrate for treatment/bleed prevention; partial success--inhibitor titre 1 to <5 BU with ability to use FVIII concentrate for treatment of bleeding; failure--ITI ongoing >3 years without achieving success/partial success, or ITI discontinuation. Fifty-eight subjects were included; 32 of 39 (82%) with high-responding inhibitor (HRI) achieved success, 7 failed. HRI subjects were subdivided based on ITI start time: 23/39 subjects started within 1 month of detection and 22/23 (96%) achieved success. Of these 23, 13 started ITI with an inhibitor titre ≥10 BU; all were successes. Eleven of 39 HRI subjects had an interval >6 months until ITI start; 7 (64%) achieved success. Time from inhibitor detection to ITI start may play a critical role in outcome. A titre ≥10 BU at ITI start did not influence outcome in subjects when ITI was initiated within 1 month of detection. Prompt ITI should be considered a viable therapeutic option in newly identified patients with inhibitors regardless of current inhibitor titre. © 2014 John Wiley & Sons Ltd.

The social burden and quality of life of patients with haemophilia in Italy

PubMed Central

Kodra, Yllka; Cavazza, Marianna; Schieppati, Arrigo; De Santis, Marta; Armeni, Patrizio; Arcieri, Romano; Calizzani, Gabriele; Fattore, Giovanni; Manzoli, Lamberto; Mantovani, Lorenzo; Taruscio, Domenica

2014-01-01

Background In Italy, the project on the social burden and quality of life (QoL) of patients with haemophilia investigates costs from a society perspective and provides an overview of their quality of life. Moreover, as life expectancy increased in recent years along with new treatment strategies implemented in the last decades, it analyses trends of costs other than drugs simulating impacts during patient whole life. Material and methods We ran a web-based cross-sectional survey supported by the Italian Federation of Haemophilia Societies in recruiting patients with haemophilia and their caregivers. We developed a questionnaire to collect information on demographic characteristics, healthcare and social services consumption, formal and informal care utilisation, productivity loss and quality of life. In particular, quality of life was assessed through the EuroQoL tool. Last, we applied the illness cost method from a society perspective. Results On average, quality of life is worse in adult patients compared to child and caregivers: more than 75% of adult patients declare physical problems, 43% of adult patients and 54% of their parents have anxiety problems. Assuming a society perspective, the estimated mean annual total cost per patient in 2012 is 117,732 €. Drugs represent 92% of total costs. Focusing on costs other than drugs, each additional point of EuroQoL tool implies a costs’ reduction of 279 €. The impact of age varies across age groups: each added year implies a total decrease of costs up to 46.6 years old. Afterwards, every additional year increases costs. Discussion Quality of life of patients with haemophilia and their caregivers improved and it influences positively on consumed resources and on their contribution to the social-economic system. Costs other than drugs for patients with haemophilia follow the same trends of general population. PMID:24922297

Pharmacokinetics, safety and efficacy of a recombinant factor IX product, trenonacog alfa in previously treated haemophilia B patients.

PubMed

Collins, P W; Quon, D V K; Makris, M; Chowdary, P; Kempton, C L; Apte, S J; Ramanan, M V; Hay, C R M; Drobic, B; Hua, Y; Babinchak, T J; Gomperts, E D

2018-01-01

Trenonacog alfa (IB1001) is a recombinant factor IX (rFIX) manufactured in Chinese hamster ovary (CHO) cells. IB1001 was evaluated in a multicentre clinical trial with haemophilia B patients. The aim was to establish IB1001 pharmacokinetic non-inferiority to comparator rFIX, safety and efficacy in previously treated patients (PTPs) with haemophilia B. Subjects were severe or moderately severe haemophilia B adult and adolescent PTPs with no history of FIX inhibitors. IB1001 PK non-inferiority to comparator rFIX was demonstrated through ratio of AUC 0-∞ in 32 subjects. IB1001 was well tolerated in all 76 treated subjects; the most common adverse drug reaction was headache (2.6% of subjects) and there were no reports of FIX inhibitors. Transient non-inhibitory binding FIX antibodies and anti-CHO cell protein antibodies developed in 21% and 29% of subjects respectively; no safety concerns were associated with development of these antibodies. Prophylaxis (mean duration ± SD: 17.9 ± 9.6 months, mean dose: 55.5 ± 12.9 IU/kg, median 1.0 infusion per week) was effective in preventing bleeds (median annual bleed rate: 1.52, interquartile range: 0.0-3.46). One or two IB1001 infusions resolved 84% of the bleeds, while for 84% of treatments haemostatic efficacy of IB1001 was rated excellent or good. IB1001 haemostatic efficacy for all 19 major surgeries was rated adequate or better than adequate. IB1001 is safe and efficacious for treatment of bleeds, routine prophylaxis and perioperative management in haemophilia B patients. © 2017 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Impact of severe haemophilia A on patients' health status: results from the guardian(™) 1 clinical trial of turoctocog alfa (NovoEight(®) ).

PubMed

Ozelo, M; Chowdary, P; Regnault, A; Busk, A K

2015-07-01

Haemophilia and its treatment interfere with patients' life and may affect adherence to treatment. This study explored the impact of severe haemophilia A on patients' health status, especially in young adults (YA), using data from guardian(™) 1, a multinational, open-label, non-controlled phase 3 trial investigating safety and efficacy of turoctocog alfa (NovoEight(®) ) in previously treated patients aged 12 years and older with severe haemophilia A (FVIII ≤ 1%). Health status was assessed using the EuroQoL-5 dimensions (EQ-5D-3L), covering 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), and a visual analogue scale (VAS) measuring self-rated overall health status. EQ-5D was administered pretreatment (screening/baseline) and posttreatment (end-of-trial). Baseline responses to the EQ-5D dimensions and VAS were described overall and by age and compared to reference values from UK general population. Guardian(™) 1 included 150 patients (16 adolescents, 83 YA aged 16-29 and 51 adults aged 30+). All five dimensions of patients' health status were impacted at baseline. The percentage of haemophilia patients reporting problems was consistently significantly greater than age-matched general population reference values. Likewise, for all age groups mean baseline EQ-5D VAS score was significantly lower for haemophilia patients (YA: 78.0) than for the general population (YA aged 18-29: 87.3). The health status of patients with severe haemophilia A entering guardian(™) 1 was markedly poorer than that of the general population, particularly regarding mobility and pain. YA patients reported better health status than older patients, but considerably lower than that of the general YA population. © 2015 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Von Willebrand factor-containing factor VIII concentrates and inhibitors in haemophilia A. A critical literature review.

PubMed

Franchini, Massimo; Lippi, Giuseppe

2010-11-01

The development of inhibitors that neutralise the function of factor VIII (FVIII) is currently not only the most challenging complication associated with the treatment of haemophilia A but it also increases the disease-related morbidity as bleeding episodes do not respond to standard therapy. The main short-term goal of the treatment of inhibitor patients is to control bleeding episodes while the long-term one is to permanently eradicate the inhibitor by immune tolerance induction, particularly in the case of high-titer antibodies. Due to some in vitro studies and clinical observations, some investigators have suggested that FVIII concentrates containing von Willebrand factor (VWF) may be less immunogenic than high-purity or recombinant FVIII products. It has also been suggested that success rates for immune tolerance induction are higher when plasma-derived FVIII products are used. The currently available data from laboratory and clinical studies on the role of VWF in inhibitor development and eradication in haemophilia A is critically analysed in this review. As a result, we have not found definitive evidence supporting a role for product type on inhibitor incidence and inhibitor eradication in haemophilia A patients.

Results from a large multinational clinical trial (guardian™1) using prophylactic treatment with turoctocog alfa in adolescent and adult patients with severe haemophilia A: safety and efficacy.

PubMed

Lentz, S R; Misgav, M; Ozelo, M; Salek, S Z; Veljkovic, D; Recht, M; Cerqueira, M; Tiede, A; Brand, B; Mancuso, M E; Seremetis, S; Lindblom, A; Martinowitz, U

2013-09-01

Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prophylaxis and treatment of bleeding episodes in patients with severe haemophilia A. This multinational, open-label, non-controlled trial investigated the safety and efficacy of turoctocog alfa, a new rFVIII product. The primary objective was to evaluate safety. A total of 150 patients (24 adolescents and 126 adults) with severe haemophilia A (FVIII activity ≤ 1%), with at least 150 exposure days (EDs) to any FVIII product and no history of inhibitors were enrolled, and 146 patients (97%) completed the trial. All patients received prophylaxis with turoctocog alfa for approximately 6 months and had a mean of 85 EDs during the trial. None of the patients developed FVIII inhibitors, there were no indications of early FVIII inhibitor development and no safety concerns were identified. A total of 225 adverse events were reported in 100 (67%) patients, with the most common being events associated with dosing procedures, headaches, and nasopharyngitis. A total of 499 bleeding episodes were reported during the trial, the majority (89%) were controlled with 1-2 infusions of turoctocog alfa. Based on patient reports, the success rate (defined as 'excellent' or 'good' haemostatic response) for treatment of bleeding episodes was 81%. The overall median annualized bleeding rate was 3.7 (interquartile range: 8.7) bleeds/patient/year. In conclusion, turoctocog alfa provides a new, safe and effective alternative for prophylaxis and treatment of bleeding episodes in patients with haemophilia A. © 2013 John Wiley & Sons Ltd.

Falling and fall risk in adult patients with severe haemophilia.

PubMed

Rehm, Hanna; Schmolders, Jan; Koob, Sebastian; Bornemann, Rahel; Goldmann, Georg; Oldenburg, Johannes; Pennekamp, Peter; Strauss, Andreas C

2017-05-10

The objective of this study was to define fall rates and to identify possible fall risk factors in adult patients with severe haemophilia. 147 patients with severe haemophilia A and B were evaluated using a standardized test battery consisting of demographic, medical and clinical variables and fall evaluation. 41 (27.9 %) patients reported a fall in the past 12 months, 22 (53.7 %) of them more than once. Young age, subjective gait insecurity and a higher number of artificial joints seem to be risk factors for falling. Falls seem to be a common phenomenon in patients with severe haemophilia. Fall risk screening and fall prevention should be implemented into daily practice.

TRUST trial: BAY 86-6150 use in haemophilia with inhibitors and assessment for immunogenicity.

PubMed

Mahlangu, J; Paz, P; Hardtke, M; Aswad, F; Schroeder, J

2016-11-01

The most serious and challenging complication of haemophilia treatment is development of inhibitors to replacement factors VIII or IX. Innovative therapies currently being explored for patients with haemophilia and inhibitors include BAY 86-6150, a modified recombinant activated factor VII (FVIIa). Immunogenicity remains a substantial barrier in this endeavour. To present safety and efficacy results of the BAY 86-6150 study in patients with inhibitors and report detailed analysis of epitope mapping in a patient who developed anti-BAY 86-6150 antibodies. Patients aged 12-62 years with moderate or severe haemophilia A or B were eligible for the phase 3 TRUST trial if they had a history of high-titre inhibitors. Four escalating doses of BAY 86-6150 (6.5, 20, 50, 90 μg kg -1 ) were planned with ≥10 patients per dose level. Bleeding episodes were treated with BAY 86-6150. Development of anti-BAY 86-6150 antibodies was considered a serious adverse event. TRUST was discontinued after one patient in the 6.5-μg kg -1 cohort developed anti-BAY 86-6150 neutralizing antibodies following three exposures. The anti-BAY 86-6150 antibodies cross-reacted with and neutralized wild-type FVIIa (WT-FVIIa). Post hoc epitope mapping using peripheral blood mononuclear cells from the responding patient found that none of the 14 peptides unique to BAY 86-6150 were recognized by the patient's T cells, but strong responses were detected against 2 WT-FVIIa peptides. In the single patient with haemophilia A who developed anti-BAY 86-6150 antibodies, results of T-cell epitope mapping indicated BAY 86-6150 was no more immunogenic than WT-FVIIa. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Developing education tailored to clinical roles: genetics education for haemophilia nurses.

PubMed

Burke, Sarah; Barker, Colin; Marshall, Dianne

2012-01-01

Genetics is an important component of the clinical work of haemophilia nurses, but little was known about the genetic education needs of haemophilia nurses. To develop, deliver and evaluate genetic education for haemophilia nurses, based on clinical roles. Perceived relevance of genetics to haemophilia nursing practice was explored using electronic voting (response rate 75%, 58/77). A follow-on questionnaire to a volunteer sample of participants explored educational preferences (response rate 41%, 17/41). Results informed development of a two-hour genetics workshop session, evaluated by questionnaire (response rate 67%, 47/70). Genetic competences were considered relevant to the clinical practice of haemophilia nurses, and learning needs were identified. Preference was expressed for education focused on practical skills. During the subsequent workshop, participant confidence ratings significantly increased in the four areas addressed. Planned changes to clinical care and training were reported. Within new areas of advanced nursing practice, learning needs can be addressed by: identifying relevant clinical activities and associated learning needs; creating a strategy and resources using preferred forms of delivery; implementing the strategy; and evaluating its effect. This will enable development of education that addresses the real needs of practising nurses, grounded in their daily clinical practice. Copyright © 2011 Elsevier Ltd. All rights reserved.

BAY 81-8973 safety and efficacy for prophylaxis and treatment of bleeds in previously treated children with severe haemophilia A: results of the LEOPOLD Kids Trial.

PubMed

Ljung, R; Kenet, G; Mancuso, M E; Kaleva, V; Rusen, L; Tseneklidou-Stoeter, D; Michaels, L A; Shah, A; Hong, W; Maas Enriquez, M

2016-05-01

BAY 81-8973, a full-length, unmodified, recombinant factor VIII (FVIII) in development for treatment of haemophilia A, has the same primary amino acid sequence as Bayer's sucrose-formulated recombinant FVIII but is produced with more advanced manufacturing technologies. To demonstrate safety and efficacy of BAY 81-8973 for prophylaxis and treatment of bleeds in previously treated children. In this phase III, multicentre, open-label, nonrandomized study, boys aged ≤12 years with severe haemophilia A and ≥50 exposure days (EDs) to FVIII products received prophylaxis with BAY 81-8973 25-50 IU kg(-1) ≥2 times weekly for ≥50 EDs. The efficacy endpoint was annualized number of total bleeds. Adverse events (AEs) and immunogenicity were assessed. Fifty-one patients were treated (age: <6 years, n = 25; 6-<12 years, n = 26) with a 2× per week (43%) or >2× per week (57%) regimen at study start. Median [quartile 1; quartile 3 (Q1; Q3)] annualized number of bleeds for the combined age groups was 1.90 (0; 6.02) for total bleeds, 0 (0; 2.01) for joint bleeds and 0 (0; 0) for spontaneous bleeds. Median (Q1; Q3) annualized number of total bleeds within 48 h of previous prophylaxis infusion was 1.88 (0; 3.97) for children aged <6 years and 0 (0; 1.96) for children aged 6-<12 years. No drug-related serious AEs or inhibitors were reported. Prophylaxis with BAY 81-8973 using individualized prophylaxis regimens of 2× per week, 3× per week and every-other-day infusions was efficacious in prevention and treatment of bleeds in children with severe haemophilia A. Treatment with BAY 81-8973 was well tolerated. © 2015 John Wiley & Sons Ltd.

The cost of severe haemophilia in Europe: the CHESS study.

PubMed

O'Hara, Jamie; Hughes, David; Camp, Charlotte; Burke, Tom; Carroll, Liz; Diego, Daniel-Anibal Garcia

2017-05-31

Severe haemophilia is associated with major psychological and economic burden for patients, caregivers, and the wider health care system. This burden has been quantified and documented for a number of European countries in recent years. However, few studies have taken a standardised methodology across multiple countries simultaneously, and sought to amalgamate all three levels of burden for severe disease. The overall aim of the 'Cost of Haemophilia in Europe: a Socioeconomic Survey' (CHESS) study was to capture the annualised economic and psychosocial burden of severe haemophilia in five European countries. A cross-section of haemophilia specialists (surveyed between January and April 2015) provided demographic and clinical information and 12-month ambulatory and secondary care activity for patients via an online survey. In turn, patients provided corresponding direct and indirect non-medical cost information, including work loss and out-of-pocket expenses, as well as information on quality of life and adherence. The direct and indirect costs for the patient sample were calculated and extrapolated to population level. Clinical reports for a total of 1,285 patients were received. Five hundred and fifty-two patients (43% of the sample) provided information on indirect costs and health-related quality of life via the PSC. The total annual cost of severe haemophilia across the five countries for 2014 was estimated at EUR 1.4 billion, or just under EUR 200,000 per patient. The highest per-patient costs were in Germany (mean EUR 319,024) and the lowest were in the United Kingdom (mean EUR 129,365), with a study average of EUR 199,541. As expected, consumption of clotting factor replacement therapy represented the vast majority of costs (up to 99%). Indirect costs are driven by patient and caregiver work loss. The results of the CHESS study reflect previous research findings suggesting that costs of factor replacement therapy account for the vast majority of the cost

Cost-effectiveness of recombinant activated factor VII vs. plasma-derived activated prothrombin complex concentrate in the treatment of mild-to-moderate bleeding episodes in patients with severe haemophilia A and inhibitors in Spain.

PubMed

Jimenez-Yuste, V; Núñez, R; Romero, J A; Montoro, B; Espinós, B

2013-11-01

Several analyses have shown that recombinant activated factor VII (rFVIIa) is a cost-effective intervention compared with plasma-derived activated prothrombin complex concentrate (pd-aPCC) for the on-demand treatment of mild-to-moderate bleeds in haemophilia patients with inhibitors. The aim of the study was to assess the cost-effectiveness of rFVIIa vs. pd-aPCC in the treatment of bleeding episodes in severe haemophilia A patients with inhibitors in Spain. A decision analytic model was designed to evaluate the costs and clinical outcomes of using rFVIIa or pd-aPCC to treat mild-to-moderate joint bleeds in children (≤14 years old) and adults with inhibitors. Data were obtained from a published meta-analysis and a panel of haemophilia experts. The analysis was conducted from the perspective of the Spanish National Healthcare System. One-way sensitivity analyses were performed to assess the impact of model assumptions on study results. In the Treur meta-analysis, rFVIIa resulted in cumulative joint bleed resolution of 88% and 95% after 24 and 36 h, respectively, compared with 62% and 76%, respectively, with pd-aPCC (Treur et al. Haemophilia 2009; 15: 420-36). Here, the mean cost per bleed was estimated at €8473 and €15 579 in children and adults treated with rFVIIa, vs. €8627 and €15 677 in children and adults treated with pd-aPCC. rFVIIa treatment was found to be the dominating option (cheaper and more effective). The one-way sensitivity analysis also confirmed that rFVIIa was less costly than pd-aPCC. The model suggests that rFVIIa is a cost-effective option compared with pd-aPCC for the treatment of mild-to-moderate bleeding episodes in a Spanish setting. © 2013 John Wiley & Sons Ltd.

Haemophilia and exercise.

PubMed

Souza, J C; Simoes, H G; Campbell, C S G; Pontes, F L; Boullosa, D A; Prestes, J

2012-02-01

One of the most important objectives of intervention programs for persons with haemophilia (PWH) is to improve their quality of life. Regular physical activity has been recommended as an adjunct to conventional treatment, with positive results in the prevention of joint problems and bleeding, in addition to the improvement in cardiovascular function, muscle strength, and body composition. The objective of the present review was to present the benefits of aerobic and resistance training programs in PWH, as well to discuss the best exercise dose-response in the different levels of disease severity. We considered randomized controlled trials, study cases and literature reviews from MEDLINE and Highwire databases. After a detailed analysis of the studies involving exercise for PWH, it can be concluded that this intervention elicits some benefits for physical fitness and blood coagulation mechanisms, suggesting the application of physical training as a non pharmacological treatment in association with conventional treatment. Adequate and periodized resistance training considering the disease severity, accompanied by physical education professionals could improve muscle strength, balance and proprioception. In addition, aerobic training could reduce the risks of obesity and several metabolic and cardiovascular diseases. Exercise can improve several outcomes of quality in PWH. © Georg Thieme Verlag KG Stuttgart · New York.

Concizumab, an anti-tissue factor pathway inhibitor antibody, induces increased thrombin generation in plasma from haemophilia patients and healthy subjects measured by the thrombin generation assay.

PubMed

Waters, E K; Sigh, J; Friedrich, U; Hilden, I; Sørensen, B B

2017-09-01

Concizumab, a humanized monoclonal antibody against tissue factor pathway inhibitor (TFPI), is being developed as a subcutaneously (s.c.) administered treatment for haemophilia. It demonstrated a concentration-dependent procoagulant effect in functional TFPI assays; however, global haemostatic assays, such as the thrombin generation assay (TGA), offer a more complete picture of coagulation. We investigated how concizumab affects thrombin generation following ex vivo spiking in plasma from haemophilia patients using the TGA, and if the assay can detect the effect of multiple s.c. concizumab doses in healthy subjects. For the ex vivo spiking study, platelet-poor plasma (PPP) from 18 patients with severe haemophilia was spiked with 0.001-500 nm concizumab. For the multiple-dosing study, four healthy males received concizumab 250 μg kg -1 s.c. every other day for eight doses; blood was collected before and after dosing and processed into PPP. In both studies, thrombin generation was measured using a Calibrated Automated Thrombogram ® system with 1 pm tissue factor. In spiked samples from haemophilia patients, peak thrombin and endogenous thrombin potential (ETP) increased concentration dependently, reaching near-normal levels at concizumab concentrations >10 nm. Repeated s.c. doses of concizumab in healthy subjects increased both peak thrombin and ETP; these effects were sustained throughout the dosing interval. Thrombin generation assay demonstrated increased thrombin generation with concizumab after ex vivo spiking of haemophilia plasma and multiple s.c. doses in healthy subjects, supporting both the utility of the TGA in evaluating concizumab treatment and the potential of s.c. concizumab as a novel haemophilia therapy. © 2017 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A.

PubMed

Du, Lily M; Nurden, Paquita; Nurden, Alan T; Nichols, Timothy C; Bellinger, Dwight A; Jensen, Eric S; Haberichter, Sandra L; Merricks, Elizabeth; Raymer, Robin A; Fang, Juan; Koukouritaki, Sevasti B; Jacobi, Paula M; Hawkins, Troy B; Cornetta, Kenneth; Shi, Qizhen; Wilcox, David A

2013-01-01

It is essential to improve therapies for controlling excessive bleeding in patients with haemorrhagic disorders. As activated blood platelets mediate the primary response to vascular injury, we hypothesize that storage of coagulation Factor VIII within platelets may provide a locally inducible treatment to maintain haemostasis for haemophilia A. Here we show that haematopoietic stem cell gene therapy can prevent the occurrence of severe bleeding episodes in dogs with haemophilia A for at least 2.5 years after transplantation. We employ a clinically relevant strategy based on a lentiviral vector encoding the ITGA2B gene promoter, which drives platelet-specific expression of human FVIII permitting storage and release of FVIII from activated platelets. One animal receives a hybrid molecule of FVIII fused to the von Willebrand Factor propeptide-D2 domain that traffics FVIII more effectively into α-granules. The absence of inhibitory antibodies to platelet-derived FVIII indicates that this approach may have benefit in patients who reject FVIII replacement therapies. Thus, platelet FVIII may provide effective long-term control of bleeding in patients with haemophilia A.

Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A

PubMed Central

Du, Lily M.; Nurden, Paquita; Nurden, Alan T.; Nichols, Timothy C.; Bellinger, Dwight A.; Jensen, Eric S.; Haberichter, Sandra L.; Merricks, Elizabeth; Raymer, Robin A.; Fang, Juan; Koukouritaki, Sevasti B.; Jacobi, Paula M.; Hawkins, Troy B.; Cornetta, Kenneth; Shi, Qizhen; Wilcox, David A.

2013-01-01

It is essential to improve therapies for controlling excessive bleeding in patients with haemorrhagic disorders. As activated blood platelets mediate the primary response to vascular injury, we hypothesize that storage of coagulation Factor VIII within platelets may provide a locally inducible treatment to maintain haemostasis for haemophilia A. Here we show that haematopoietic stem cell gene therapy can prevent the occurrence of severe bleeding episodes in dogs with haemophilia A for at least 2.5 years after transplantation. We employ a clinically relevant strategy based on a lentiviral vector encoding the ITGA2B gene promoter, which drives platelet-specific expression of human FVIII permitting storage and release of FVIII from activated platelets. One animal receives a hybrid molecule of FVIII fused to the von Willebrand Factor propeptide-D2 domain that traffics FVIII more effectively into α-granules. The absence of inhibitory antibodies to platelet-derived FVIII indicates that this approach may have benefit in patients who reject FVIII replacement therapies. Thus, platelet FVIII may provide effective long-term control of bleeding in patients with haemophilia A. PMID:24253479

First analysis of 10-year trends in national factor concentrates usage in haemophilia: data from CHARMS, the Canadian Hemophilia Assessment and Resource Management System.

PubMed

Traore, A N; Chan, A K C; Webert, K E; Heddle, N; Ritchie, B; St-Louis, J; Teitel, J; Lillicrap, D; Iorio, A; Walker, I

2014-07-01

The Canadian Hemophilia Assessment and Resource Management System (CHARMS) tracks factor concentrates (FC) from the sole suppliers, Canadian Blood Services (CBS) and Hema-Quebec (HQ), to hospitals and to patients' homes. Patients FC infusion data are entered into CHARMS at Canadian Hemophilia Treatment Centres (HTCs) then exported to the national database (CentrePoint). From 2000 to 2009, 2260 registered haemophilia A or B patients received FVIII (1,009,097,765 IU) and FIX (272,406,859 IU). Over 91% of FVIII and over 84% of FIX was infused at home. Utilization of FVIII progressively increased; this was accounted for by an increase in the number of patients treated (r = 0.97; P < 0.001), there being a linear relationship between the increase in utilization and the increase in number of patients treated (P < 0.001). There was also a correlation with the annual amount used per patient (r = 0.95; P < 0.001). Utilization of FIX did not increase over time. The highest proportional utilization of both FVIII and FIX was for prophylaxis, and this proportion progressively increased being, in year 10 (2009), 77% and 66% for FVIII and FIX respectively. The proportion used for bleeding remained steady; in year 10 that proportion was 14% for FVIII and 26% for FIX, the use per patient for bleeding decreasing. The HTC-based CHARMS tracking system is essential, in Canada, for analysing indications for infusion, for predicting utilization and planning for future needs. © 2014 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

NHF-McMaster Guideline on Care Models for Haemophilia Management.

PubMed

Pai, M; Key, N S; Skinner, M; Curtis, R; Feinstein, M; Kessler, C; Lane, S J; Makris, M; Riker, E; Santesso, N; Soucie, J M; Yeung, C H T; Iorio, A; Schünemann, H J

2016-07-01

This guideline was developed to identify evidence-based best practices in haemophilia care delivery, and discuss the range of care providers and services that are most important to optimize outcomes for persons with haemophilia (PWH) across the United States. The guideline was developed following specific methods described in detail in this supplement and based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation approach). Direct evidence from published literature and the haemophilia community, as well as indirect evidence from other chronic diseases, were reviewed, synthesized and applied to create evidence-based recommendations. The Guideline panel suggests that the integrated care model be used over non-integrated care models for PWH (conditional recommendation, moderate certainty in the evidence). For PWH with inhibitors and those at high risk for inhibitor development, the same recommendation was graded as strong, with moderate certainty in the evidence. The panel suggests that a haematologist, a specialized haemophilia nurse, a physical therapist, a social worker and round-the-clock access to a specialized coagulation laboratory be part of the integrated care team, over an integrated care team that does not include all of these components (conditional recommendation, very low certainty in the evidence). Based on available evidence, the integrated model of care in its current structure, is suggested for optimal care of PWH. There is a need for further appropriately designed studies that address unanswered questions about specific outcomes and the optimal structure of the integrated care delivery model in haemophilia. © 2016 John Wiley & Sons Ltd.

Facilitating the implementation of pharmacokinetic-guided dosing of prophylaxis in haemophilia care by discrete choice experiment.

PubMed

Lock, J; de Bekker-Grob, E W; Urhan, G; Peters, M; Meijer, K; Brons, P; van der Meer, F J M; Driessens, M H E; Collins, P W; Fijnvandraat, K; Leebeek, F W G; Cnossen, M H

2016-01-01

Patients', parents' and providers' preferences with regard to medical innovations may have a major impact on their implementation. To evaluate barriers and facilitators for individualized pharmacokinetic (PK)-guided dosing of prophylaxis in haemophilia patients, parents of young patients, and treating professionals by discrete choice experiment (DCE) questionnaire. The study population consisted of patients with haemophilia currently or previously on prophylactic treatment with factor concentrate (n = 114), parents of patients aged 12-18 years (n = 19) and haemophilia professionals (n = 91). DCE data analysis was performed, taking preference heterogeneity into account. Overall, patients and parents, and especially professionals were inclined to opt for PK-guided dosing of prophylaxis. In addition, if bleeding was consequently reduced, more frequent infusions were acceptable. However, daily dosing remained an important barrier for all involved. 'Reduction of costs for society' was a facilitator for implementation in all groups. To achieve implementation of individualized PK-guided dosing of prophylaxis in haemophilia, reduction of bleeding risk and reduction of costs for society should be actively discussed as they are motivating for implementation; daily dosing is still reported to be a barrier for all groups. The knowledge of these preferences will enlarge support for this innovation, and aid in the drafting of implementable guidelines and information brochures for patients, parents and professionals. © 2015 John Wiley & Sons Ltd.

Global measurement of coagulation in plasma from normal and haemophilia dogs using a novel modified thrombin generation test – Demonstrated in vitro and ex vivo

PubMed Central

Madsen, Daniel Elenius; Nichols, Timothy C.; Merricks, Elizabeth P.; Waters, Emily K.; Wiinberg, Bo

2017-01-01

Introduction Canine models of severe haemophilia resemble their human equivalents both regarding clinical bleeding phenotype and response to treatment. Therefore pre-clinical studies in haemophilia dogs have allowed researchers to make valuable translational predictions regarding the potency and efficacy of new anti-haemophilia drugs (AHDs) in humans. To refine in vivo experiments and reduce number of animals, such translational studies are ideally preceded by in vitro prediction of compound efficacy using a plasma based global coagulation method. One such widely used method is the thrombin generation test (TGT). Unfortunately, commercially available TGTs are incapable of distinguishing between normal and haemophilia canine plasma, and therefore in vitro prediction using TGT has so far not been possible in canine plasma material. Aim Establish a modified TGT capable of: 1) distinguishing between normal and haemophilia canine plasma, 2) monitoring correlation between canine plasma levels of coagulation factor VIII (FVIII) and IX (FIX) and thrombin generation, 3) assessing for agreement between compound activity and thrombin generation in ex vivo samples. Methods A modified TGT assay was established where coagulation was triggered using a commercially available activated partial thromboplastin time reagent. Results With the modified TGT a significant difference was observed in thrombin generation between normal and haemophilia canine plasma. A dose dependent thrombin generation was observed when assessing haemophilia A and B plasma spiked with dilution series of FVIII and FIX, respectively. Correlation between FVIII activity and thrombin generation was observed when analyzing samples from haemophilia A dogs dosed with canine FVIII. Limit of detection was 0.1% (v/v) FVIII or FIX. Conclusion A novel modified TGT suitable for monitoring and prediction of replacement therapy efficacy in plasma from haemophilia A and B dogs was established. PMID:28384182

Tailoring treatment of haemophilia B: accounting for the distribution and clearance of standard and extended half-life FIX concentrates.

PubMed

Iorio, Alfonso; Fischer, Kathelijn; Blanchette, Victor; Rangarajan, Savita; Young, Guy; Morfini, Massimo

2017-06-02

The prophylactic administration of factor IX (FIX) is considered the most effective treatment for haemophilia B. The inter-individual variability and complexity of the pharmacokinetics (PK) of FIX, and the rarity of the disease have hampered identification of an optimal treatment regimens. The recent introduction of extended half-life recombinant FIX molecules (EHL-rFIX), has prompted a thorough reassessment of the clinical efficacy, PK and pharmacodynamics of plasma-derived and recombinant FIX. First, using longer sampling times and multi-compartmental PK models has led to more precise (and favourable) PK for FIX than was appreciated in the past. Second, investigating the distribution of FIX in the body beyond the vascular space (which is implied by its complex kinetics) has opened a new research field on the role for extravascular FIX. Third, measuring plasma levels of EHL-rFIX has shown that different aPTT reagents have different accuracy in measuring different FIX molecules. How will this new knowledge reflect on clinical practice? Clinical decision making in haemophilia B requires some caution and expertise. First, comparisons between different FIX molecules must be assessed taking into consideration the comparability of the populations studied and the PK models used. Second, individual PK estimates must rely on multi-compartmental models, and would benefit from adopting a population PK approach. Optimal sampling times need to be adapted to the prolonged half-life of the new EHL FIX products. Finally, costs considerations may apply, which is beyond the scope of this manuscript but might be deeply connected with the PK considerations discussed in this communication.

Effectiveness of the Medtep Hemophilia online platform for adherence to prophylactic treatment in haemophilia patients: Results from a 1-year observational study.

PubMed

Cuesta-Barriuso, R; López-Pina, J A; Nieto-Munuera, J; Sagarra-Valls, G; Panisello-Royo, J M; Torres-Ortuño, A

2018-03-01

Medtep Hemophilia platform is an online tool that allows patients with congenital coagulopathies to keep track of their daily condition-related events with the objective of ensuring successful adherence to therapy. To assess the effectiveness of Medtep Hemophilia in improving adherence to prophylactic treatment in haemophilia A and B patients in a 1-year prospective observational study, as well as its impact on the patient's disease status. Patients (>13 years old) received support material to familiarize themselves with Medtep Hemophilia. Adherence to treatment, quality of life (QoL) and illness perception were assessed. Values at baseline, 1, 6 and 12 months, and changes from baseline value were analysed. The Hemophilia Joint Health Score (HJHS) test was applied at baseline and study completion. Forty-six patients were enrolled (43 evaluable). After 1 year, 56.4% patients showed continued use of the platform (100% compliance) whereas 25.6% were inactive. Treatment adherence increased both significantly (P < .001) and progressively during the study. Similarly, improved QoL and illness perception were observed with respect to baseline in most of the questionnaire components (P < .05 after 12 months). A patient's age had no influence on the results, whereas compliant patients (>80% of platform use) tended to score better than noncompliant. The HJHS test values remained similar during the study. The Medtep Hemophilia online platform helped the studied patients with haemophilia to improve their adherence to prophylactic treatment, while increasing their QoL and illness perception, as well as joint arthropathies stabilization. © 2018 John Wiley & Sons Ltd.

Programmed Sports Therapy (PST) in People with Haemophilia (PwH) "Sports Therapy Model for Rare Diseases".

PubMed

Hilberg, Thomas

2018-03-05

Sports and exercise therapy becomes more and more integrated in the treatment plan of different diseases. Although the benefits of this therapy are of high quality evidence, e.g. in cardiovascular diseases, no concepts of sports therapy are available as a treatment option for rare diseases.During the last eighteen years, we analyzed the situation as well as necessity, and developed a model, contents and the concept of the "Programmed Sports Therapy (PST)" for the treatment of PwH (people with haemophilia) as our model of rare disease. Many studies have shown that motoric skills are depressed in PwH, and that this gap to healthy people increases during age. The only way to reduce this progression is an appropriate therapy, adapted to the necessities of PwH. In haemophilia, in particular, physio- and sports therapy treatments should go hand in hand, the first in the acute phase after bleeding, the second later, after the acute phase has finished. One model, which considers all the different challenges, can be the cogwheel model presented here. Since haemophilia is a rare disease, new training concepts are necessary because classical group therapies are often impossible. PST based on the combination of sports therapy camps together with a supervised autonomous home training helps to directly bring the training to the trainee, in order to enhance key competences and improve the individual situation in PwH, and perhaps in patients with other rare diseases.The experience and scientific data substantiate the success of "Programmed Sports Therapy (PST)" and even this can be a model for other rare diseases.

Haemophilia and joint disease: pathophysiology, evaluation, and management

PubMed Central

Knobe, Karin; Berntorp, Erik

2011-01-01

In patients with haemophilia, regular replacement therapy with clotting factor concentrates (prophylaxis) is effective in preventing recurrent bleeding episodes into joints and muscles. However, despite this success, intra-articular and intramuscular bleeding is still a major clinical manifestation of the disease. Bleeding most commonly occurs in the knees, elbows, and ankles, and is often evident from early childhood. The pathogenesis of haemophilic arthropathy is multifactorial, with changes occurring in the synovium, bone, cartilage, and blood vessels. Recurrent joint bleeding causes synovial proliferation and inflammation (haemophilic synovitis) that contribute to end-stage degeneration (haemophilic arthropathy); with pain and limitation of motion severely affecting patients’ quality of life. If joint bleeding is not treated adequately, it tends to recur, resulting in a vicious cycle that must be broken to prevent the development of chronic synovitis and degenerative arthritis. Effective prevention and management of haemophilic arthropathy includes the use of early, aggressive prophylaxis with factor replacement therapies, as well as elective procedures, including restorative physical therapy, analgesia, aspiration, synovectomy, and orthopaedic surgery. Optimal treatment of patients with haemophilia requires a multidisciplinary team comprising a haematologist, physiotherapist, orthopaedic practitioner, rehabilitation physician, occupational therapist, psychologist, social workers, and nurses. Journal of Comorbidity 2011;1:51–59 PMID:29090136

Patterns of physical activity in children with haemophilia.

PubMed

Broderick, C R; Herbert, R D; Latimer, J; van Doorn, N

2013-01-01

The current widespread use of prophylaxis in developed countries has enabled greater participation in physical activity. However, there are no data available on leisure-time physical activity in Australian children with haemophilia. The data reported here were obtained from a case-crossover study nested in a prospective cohort study of 104 boys with moderate and severe haemophilia followed for one year. Each child's physical activity was assessed using a modifiable physical activity questionnaire (Kriska's MAQ) administered at baseline, and a one-week prospective activity diary at a randomly determined time. Children were aged 4-18 years. The median time spent in sport or leisure-time physical activity in the preceding year was 7.9 h/week (IQR 4.6 to 12.9). The median time spent in vigorous physical activity was 3.8 h/week (IQR 1.6 to 6.4) and in moderate and vigorous physical activity 6.4 h/week (IQR 3.7 to 10.0). The median small-screen time was 2.5 h/day (IQR 0.5 to 2.5). Forty-five per cent of all children and 61% of children over the age of 10 years played at least one competitive sport. Averaged across one week, 43% of all children met the Australian government physical activity guidelines for children and 36% met the guidelines for small-screen time. This study provides the first data regarding leisure-time physical activity in children with haemophilia living in Australia. The majority of Australian children with haemophilia are not meeting the national physical activity and small-screen time guidelines. © 2012 Blackwell Publishing Ltd.

Recombinant factor VIIa (eptacog alfa): a pharmacoeconomic review of its use in haemophilia in patients with inhibitors to clotting factors VIII or IX.

PubMed

Lyseng-Williamson, Katherine A; Plosker, Greg L

2007-01-01

Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor VII or eptacog alfa) is indicated as an intravenous haemostatic agent in haemophilia patients with inhibitors to clotting factors VIII or IX. In noncomparative trials in haemophilia patients with inhibitors, on-demand home treatment with recombinant factor VIIa was effective in controlling episodes of mild to moderate bleeding and well tolerated, with early treatment being associated with a greater rate of success and the need for fewer doses than delayed treatment. Prophylactic treatment with recombinant factor VIIa was also effective in maintaining haemostasis in patients with this indication undergoing surgery. Relative to prior treatment with plasma-derived agents, treatment with recombinant factor VIIa was associated with improvements in health-related quality of life in a cost-utility study in haemophilia patients with inhibitors in Australia. In well designed decision-model cost analyses conducted from a healthcare payer perspective in several countries, on-demand treatment with recombinant factor VIIa to control mild to moderate bleeding episodes in this patient population was predicted to be cost saving or cost neutral relative to on-demand treatment with intravenous activated prothrombin complex concentrate (aPCC). Although the acquisition cost of recombinant factor VIIa was greater than that of aPCC in some studies, the greater initial efficacy of recombinant factor VIIa than aPCC resulted in lower predicted total medical costs. Results were generally robust to plausible changes in key parameters. Orthopaedic surgery with recombinant factor VIIa to maintain haemostasis in haemophilia patients with inhibitors was generally predicted to be cost saving, relative to not having surgery, over the medium to long term in modelled cost analyses from a healthcare payer perspective in the UK and US. The initial cost of surgery was high, but the difference in costs between patients

Pain and pain management in haemophilia

PubMed Central

Auerswald, Günter; Dolan, Gerry; Duffy, Anne; Hermans, Cedric; Jiménez-Yuste, Victor; Ljung, Rolf; Morfini, Massimo; Lambert, Thierry; Šalek, Silva Zupančić

2016-01-01

Joint pain is common in haemophilia and may be acute or chronic. Effective pain management in haemophilia is essential to reduce the burden that pain imposes on patients. However, the choice of appropriate pain-relieving measures is challenging, as there is a complex interplay of factors affecting pain perception. This can manifest as differences in patients’ experiences and response to pain, which require an individualized approach to pain management. Prophylaxis with factor replacement reduces the likelihood of bleeds and bleed-related pain, whereas on-demand therapy ensures rapid bleed resolution and pain relief. Although use of replacement or bypassing therapy is often the first intervention for pain, additional pain relief strategies may be required. There is an array of analgesic options, but consideration should be paid to the adverse effects of each class. Nevertheless, a combination of medications that act at different points in the pain pathway may be beneficial. Nonpharmacological measures may also help patients and include active coping strategies; rest, ice, compression, and elevation; complementary therapies; and physiotherapy. Joint aspiration may also reduce acute joint pain, and joint steroid injections may alleviate chronic pain. In the longer term, increasing use of prophylaxis or performing surgery may be necessary to reduce the burden of pain caused by the degenerative effects of repeated bleeds. Whichever treatment option is chosen, it is important to monitor pain and adjust patient management accordingly. Beyond specific pain management approaches, ongoing collaboration between multidisciplinary teams, which should include physiotherapists and pain specialists, may improve outcomes for patients. PMID:27439216

The role of ultrasonography in the diagnosis of the musculo-skeletal problems of haemophilia.

PubMed

Querol, F; Rodriguez-Merchan, E C

2012-05-01

Recurrent haemarthrosis is the final cause of haemophilic arthrosic disease in haemophilia patients. Therefore, it is essential to diagnose it early, both clinically and by imaging. In addition, haemophilia patients experience chronic synovitis, joint degeneration, muscle haematoma and pseudotumours. The objective of this article is to highlight the value of ultrasounds in the diagnosis and control of the evolution of musculo-skeletal problems in haemophilia patients. To this end, we have performed a literature search in the PubMed, Web of Science(®) (WOS) and SciVerse bases, using the following keywords: hemophilia or haemophilia and ultrasonography (US), ultrasound, echography and sonography. The search was limited to studies published in English between the years 1991 and 2011, finding a total of 221 references. After reviewing the title or abstract for evidence of the use of US for the diagnosis of musculo-skeletal lesions in haemophilia, we selected 24 of these references. We added data collected from our experience to the most important data found in the references. Our main conclusion is that US is highly valuable for the diagnosis of musculo-skeletal diseases in haemophilia. It is a fast, effective, safe, available, comparative, real-time technique that can help us confirm the clinical examination. It is particularly important in acute haemarthrosis, as it can be used to objectively identify the presence of blood in the joints, measure its size, pinpoint its location, assess its evolution and confirm its complete disappearance. © 2011 Blackwell Publishing Ltd.

Goal Attainment Scaling for haemophilia (GAS-Hēm): testing the feasibility of a new patient-centric outcome measure in people with haemophilia.

PubMed

Roberts, J C; Lattimore, S; Recht, M; Jackson, S; Gue, D; Squire, S; Robinson, K S; Price, V; Denne, M; Richardson, S; Rockwood, K

2018-04-06

To address the need for a patient-reported outcome that can measure clinically and personally meaningful change in people with haemophilia (PwH) on prophylaxis, an approach based on Goal Attainment Scaling (GAS) was developed: the GAS-Hēm. To establish real-world feasibility of GAS-Hēm in PwH. Patients aged 5-65 years were enroled from four North American centres for a 12-week study. The primary outcome was the proportion of participants who completed GAS-Hēm interviews at baseline, 6 and 12 weeks. GAS-Hēm scores were obtained by subject- and clinician-rated goal attainment at Weeks 6 and 12, and compared with quality of life (QoL) measures and annualized bleed rate (ABR) for construct validity. Goals were evaluated qualitatively for content validity. Responsiveness was calculated using standardized response means (SRM). Forty-two participants set 63 goals. Participants preferred to define (37/63) their own goals or further individualize (23/63) from the GAS-Hēm menu. Thirty of the 37 self-defined goals were matched to goals on the GAS-Hēm menu. The most common goal areas were: weight, exercise and nutrition (n = 17); leisure activities (n = 8); and joint problems (n = 7). Both participant- and clinician-rated GAS-Hēm scores at 6 weeks (n = 40) and 12 weeks (n = 41) demonstrated satisfactory goal attainment (SRM [subject-rated] at 12 weeks for adult and paediatric groups was 1.25 and 1.16, respectively). Correlations of GAS-Hēm scores with QoL measures and ABR were uniformly small. GAS-Hēm was feasible and tapped constructs not captured by ABR or QoL measures. © 2018 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Long-term safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in subjects with haemophilia A.

PubMed

Nolan, B; Mahlangu, J; Perry, D; Young, G; Liesner, R; Konkle, B; Rangarajan, S; Brown, S; Hanabusa, H; Pasi, K J; Pabinger, I; Jackson, S; Cristiano, L M; Li, X; Pierce, G F; Allen, G

2016-01-01

The safety, efficacy and prolonged half-life of recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously treated patients with severe haemophilia A was demonstrated in the phase 3 A-LONG and Kids A-LONG studies. Here, we report interim safety and efficacy data from the rFVIIIFc extension study, ASPIRE (ClinicalTrials.gov #NCT01454739). Eligible subjects could enrol in ASPIRE upon completing A-LONG or Kids A-LONG. There were four treatment groups: individualized prophylaxis; weekly prophylaxis; modified prophylaxis (for subjects in whom optimal treatment could not be achieved with individualized or weekly prophylaxis); and episodic treatment. The primary endpoint was development of inhibitors. A total of 150 A-LONG subjects and 61 Kids A-LONG subjects enrolled in ASPIRE. As of the interim data cut (6 January 2014), the median time on study was 80.9 (A-LONG) and 23.9 (Kids A-LONG) weeks. The majority of subjects (A-LONG, 92.0%; Kids A-LONG, 57.4%) had ≥100 cumulative rFVIIIFc exposure days. No inhibitors were observed. Adverse events were generally consistent with those expected in the general haemophilia A population. Median annualized bleeding rates (ABRs) were low with individualized [A-LONG: 0.66; Kids A-LONG: 0.00 (<6 years old), 1.54 (6 to <12 years old)], weekly (A-LONG: 2.03) and modified (A-LONG: 1.97) prophylaxis. There was no change in prophylactic infusion frequency or total weekly prophylactic dose in the majority of subjects from A-LONG and Kids A-LONG. Interim data from ASPIRE confirm the long-term safety of rFVIIIFc and the maintenance of a low ABR with extended-interval prophylactic dosing in patients with severe haemophilia A. © 2015 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Grandpaternal mosaicism in a family with isolated haemophilia A.

PubMed

Casey, G J; Rodgers, S E; Hall, J R; Rudzki, Z; Lloyd, J V

1999-12-01

About one third of cases of haemophilia A have no family history of the disorder, and 20% are thought to be due to a new mutation. In the family reported here, a 3 bp deletion was detected in DNA from the proband at the 3' end of exon 15. Direct sequencing of genomic DNA prepared from blood and buccal cells of the grandfather revealed both normal and mutant sequences, suggesting that he is a mosaic for this mutation. This highlights the usefulness of mutation detection, both for accurate genetic counselling and to determine the origin of new mutations of haemophilia.

Comparison of physical activity and sedentary behaviours between young haemophilia A patients and healthy adolescents.

PubMed

González, L M; Peiró-Velert, C; Devís-Devís, J; Valencia-Peris, A; Pérez-Gimeno, E; Pérez-Alenda, S; Querol, F

2011-07-01

In recent studies, adolescent haemophilia A patients and healthy adolescents have been encouraged to participate in physical activity (PA) based on its many established health benefits. However, none of the studies to date has used objective measures of PA and sedentary behaviour. The aims of the current study included: (i) to determine the amount and intensity of habitual PA among haemophilia A and healthy adolescents, and in haemophilia A patients with and without bleeding episodes in the previous year, and (ii) to identify the type and determine the time spent in sedentary activities in which both groups participate to obtain a broadened view of their daily activities. A total of 41 adolescent haemophiliacs and 25 healthy adolescents, between the ages of 8 and 18 years, participated in this cross-sectional study. A triaxial accelerometer was used to measure PA and the Adolescent Sedentary Activity Questionnaire to assess sedentary behaviours among members of both groups. Adolescent haemophilia A patients showed a higher daily mean time engaged in light, moderate and moderate-to-vigorous PAs relative to their healthy counterparts (P < 0.001). Patients who had experienced bleeding episodes during the previous year also spent more time participating in vigorous PAs than healthy adolescents (P = 0.002). With regard to sedentary behaviours, healthy adolescents spent more time listening to music than haemophilia A adolescents (P = 0.003), whereas haemophilia A adolescents spent more time watching TV (P < 0.001) and playing videogames (P = 0.003) than healthy counterparts. Findings suggest that increased participation in moderate intensity PAs and reduced sedentary behaviours should be recommended among adolescents with haemophilia A. © 2011 Blackwell Publishing Ltd.

The optimal mode of delivery for the haemophilia carrier expecting an affected infant is vaginal delivery.

PubMed

Ljung, R

2010-05-01

The optimal mode of delivery of a haemophilia carrier expecting a child is still a matter of uncertainty and debate. The aim of this commentary/review is to suggest that normal vaginal delivery should be the recommended mode of delivery for the majority of carriers, based on review of studies on obstetric aspects of haemophilia. About 2.0-4.0% of all haemophilia boys born in countries with a good standard of health care will suffer from ICH during the neonatal period. This is an average figure including all modes of delivery and regardless of whether the carrier status of the mother or the haemophilia status of the foetus was known or not at the time of delivery. On the basis of current literature, one may conclude that the risk of serious bleeding in the neonate affected with haemophilia is small in conjunction with normal vaginal delivery. It should be possible to further reduce the low frequency of complications if appropriate precautions are taken when planning the delivery in pregnant woman with known carrier status, if the sex of the foetus is known and, even more, when the haemophilia status of the foetus is known. Instrumental delivery such as use of vacuum extraction and foetal scalp monitors must be avoided at delivery of carriers.

Prevalence and impact of obesity in people with haemophilia: Review of literature and expert discussion around implementing weight management guidelines.

PubMed

Kahan, S; Cuker, A; Kushner, R F; Maahs, J; Recht, M; Wadden, T; Willis, T; Majumdar, S; Ungar, D; Cooper, D

2017-11-01

Obesity affects more than 35% of Americans, increasing the risk of more than 200 comorbid conditions, impaired quality of life and premature mortality. This review aimed to summarize literature published over the past 15 years regarding the prevalence and impact of obesity in people with haemophilia (PWH) and to discuss implementing general guidelines for weight management in the context of the haemophilia comprehensive care team. Although few studies have assessed the effects of obesity on haemophilia-specific outcomes, existing evidence indicates an important impact of weight status on lower extremity joint range of motion and functional disability, with potentially important effects on overall quality of life. Data regarding bleeding tendency in PWH with coexisting obesity are largely inconclusive; however, some individuals may experience reduced joint bleeds following moderate weight loss. Additionally, conventional weight-based dosing of factor replacement therapy leads to increased treatment costs for PWH with obesity or overweight, suggesting pharmacoeconomic benefits of weight loss. Evidence-based recommendations for weight loss include behavioural strategies to reduce caloric intake and increase physical activity, pharmacotherapy and surgical therapy in appropriate patients. Unique considerations in PWH include bleed-related risks with physical activity; thus, healthcare professionals should advise patients on types and intensities of, and approaches to, physical activity, how to adjust treatment to accommodate exercise and how to manage potential activity-related bleeding. Increasing awareness of these issues may improve identification of PWH with coexisting obesity and referral to appropriate specialists, with potentially wide-ranging benefits in overall health and well-being. © 2017 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Relationship between physical function and biomechanical gait patterns in boys with haemophilia.

PubMed

Stephensen, D; Taylor, S; Bladen, M; Drechsler, W I

2016-11-01

The World Federation of Haemophilia recommends joint and muscle health is evaluated using X-ray and magnetic resonance imaging, together with clinical examination scores. To date, inclusion of performance-based functional activities to monitor children with the condition has received little attention. To evaluate test-retest repeatability of physical function tests and quantify relationships between physical function, lower limb muscle strength and gait patterns in young boys with haemophilia. Timed 6-minute walk, timed up and down stairs, timed single leg stance, muscle strength of the knee extensors, ankle dorsi and plantar flexors, together with joint biomechanics during level walking were collected from 21 boys aged 6-12 years with severe haemophilia. Measures of physical function and recording of muscle strength with a hand-held myometer were repeatable (ICC > 0.78). Distances walked in six minutes, time taken to go up and down a flight of stairs and lower limb muscle strength correlated closely with ankle range of motion, together with peak knee flexion and ankle dorsi and plantarflexion moments during walking (P < 0.05). Alterations in gait patterns of boys with haemophilia appear to be associated with changes in performance of physical function and performance seems to depend on their muscle strength. Timed 6-minute walk test, timed up and down steps test and muscle strength of the knee extensors showed the strongest correlation with biomechanical joint function, and hence might serve as a basis for the clinical monitoring of physical function outcomes in children with haemophilia. © 2016 John Wiley & Sons Ltd.

Factor for felons: how can we provide haemophilia care to the incarcerated?

PubMed

Lambing, A; Kachalsky, E; Mueller, L M; Kuriakose, P

2015-11-01

In 2011, 6.98-million offenders were documented in the adult correctional system, with state operating costs designated 12% towards medical care ($11.97 day per inmate) for the general population. Common co-existing health problems identified are: arthritis (13%), hypertension (11%), asthma (10%) and heart problems (6%). Less than 5% of inmates have health issues related to cancer, diabetes, liver or renal problems and communicable diseases. The leading cause of death is suicide (33.2%), followed by heart disease (26.1%). Despite these statistics quality is lacking. Given these statistics, one would expect that a small proportion of patients from Hemophilia Treatment Center (HTC) will spend some time within the justice system. Currently there are no data addressing haemophilia care needs while incarcerated. This article will review the current health care issues in the adult correctional system. Additionally, six case reports of incarcerated haemophiliacs will be highlighted exploring the successes and challenges with maintaining haemophilia care addressing the priority of meeting the haemophilia care needs verses the penal system regulations. It can be expected that at some point, the HTC will experience a patient incarcerated for some period of time. The HTC will continue to advocate for their patient within this system, despite the many challenges faced. Despite the challenges outlined, ongoing communication and education with the correctional system, education of the medical personnel and prison personnel remains the priority as we advocate for our patients. Continued strategies in these areas are paramount. © 2015 John Wiley & Sons Ltd.

Physical activity in individuals with haemophilia and experience with recombinant factor VIII Fc fusion protein and recombinant factor IX Fc fusion protein for the treatment of active patients: a literature review and case reports.

PubMed

Wang, Michael; Álvarez-Román, María Teresa; Chowdary, Pratima; Quon, Doris V; Schafer, Kim

2016-10-01

The World Federation of Hemophilia and the National Hemophilia Foundation encourage people with haemophilia (PWH) to participate in routine physical activity. The benefits of physical activity for PWH include improvements in joint, bone, and muscle health. Accordingly, a number of studies suggest that levels of physical activity among PWH are similar to those of their healthy peers, especially among individuals who began prophylaxis at an early age (≤3 years). Importantly, several studies found either no increased risk or only a transient increase in risk of bleeding with more intensive physical activity compared with less intensive physical activity. Data on optimal prophylaxis regimens for PWH who participate in physical/sporting activities; however, remain sparse. Long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc) and recombinant factor IX Fc fusion protein (rFIXFc) demonstrated efficacy for the prevention and treatment of bleeding episodes in Phase 3 clinical trials of participants with haemophilia A and B, respectively, with most individuals able to maintain or increase their physical activities. This manuscript reviews the current literature that describes physical activity in PWH. Additionally, case studies are presented to provide supplemental information to clinicians illustrating the use of rFVIIIFc and rFIXFc in physically active patients with haemophilia A and B, respectively. These case reports demonstrate that it is possible for patients to be physically active and maintain good control of their haemophilia with extended interval prophylactic dosing using rFVIIIFc or rFIXFc.

Physical activity in individuals with haemophilia and experience with recombinant factor VIII Fc fusion protein and recombinant factor IX Fc fusion protein for the treatment of active patients: a literature review and case reports

PubMed Central

Wang, Michael; Álvarez-Román, María Teresa; Chowdary, Pratima; Quon, Doris V.; Schafer, Kim

2016-01-01

The World Federation of Hemophilia and the National Hemophilia Foundation encourage people with haemophilia (PWH) to participate in routine physical activity. The benefits of physical activity for PWH include improvements in joint, bone, and muscle health. Accordingly, a number of studies suggest that levels of physical activity among PWH are similar to those of their healthy peers, especially among individuals who began prophylaxis at an early age (≤3 years). Importantly, several studies found either no increased risk or only a transient increase in risk of bleeding with more intensive physical activity compared with less intensive physical activity. Data on optimal prophylaxis regimens for PWH who participate in physical/sporting activities; however, remain sparse. Long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc) and recombinant factor IX Fc fusion protein (rFIXFc) demonstrated efficacy for the prevention and treatment of bleeding episodes in Phase 3 clinical trials of participants with haemophilia A and B, respectively, with most individuals able to maintain or increase their physical activities. This manuscript reviews the current literature that describes physical activity in PWH. Additionally, case studies are presented to provide supplemental information to clinicians illustrating the use of rFVIIIFc and rFIXFc in physically active patients with haemophilia A and B, respectively. These case reports demonstrate that it is possible for patients to be physically active and maintain good control of their haemophilia with extended interval prophylactic dosing using rFVIIIFc or rFIXFc. PMID:27116081

Genetic engineering for haemophilia A.

PubMed

Gan, Shu Uin; Kon, Oi Lian; Calne, Roy Y

2006-10-01

At first sight, haemophilia A would appear to be an ideal candidate for treatment by gene therapy. There is a single gene defect; cells in different parts of the body, but especially the liver, produce Factor VIII, and only 5% of normal levels of Factor VIII are necessary to prevent the serious symptoms of bleeding. This review attempts to outline the status of gene therapy at present and efforts that have been made to overcome the difficulties and remaining problems that require solving. Undoubtedly, success will be achieved, but it is likely that considerably more work will be necessary before experimental models can be introduced into the clinic with any likelihood of success. The most successful results in animals that may have clinical application were from introducing the Factor VIII gene to newborn animals before antibodies are produced, presumably inducing a state of tolerance.

[Detection of factor VIII intron 1 inversion in severe haemophilia A].

PubMed

Liang, Yan; Yan, Zhen-yu; Yan, Mei; Hua, Bao-lai; Xiao, Bai; Zhao, Yong-qiang; Liu, Jing-zhong

2009-06-01

Screening the intron 1 inversion of factor VIII (FVIII) in the population of severe haemophilia A(HA) in China and performing carrier detection and prenatal diagnosis. Using LD-PCR to detect intron 22 inversions and multiple-PCR within two tubes to intron 1 inversions in severe HA patients. Carrier detection and prenatal diagnosis were performed in affected families. Linkage analysis and DNA sequencing were used to verify these tests. One hundred and eighteen patients were seven diagnosed as intron 22 inversions and 7 were intron 1 inversions out of 247 severe HA patients. The prevalence of the intron 1 inversion in Chinese severe haemophilia A patients was 2.8% (7/247). Six women from family A and 2 from family B were diagnosed as carriers. One fetus from family A was affected fetus. Intron 1 inversion could be detected directly by multiple-PCR within two tubes. This method made the strategy more perfective in carrier and prenatal diagnosis of haemophilia A.

Use of the UKHCDO Database for a postmarketing surveillance study of different doses of recombinant factor VIIa in haemophilia.

PubMed

Hay, C R M; Sharpe, T; Dolan, G

2017-05-01

Recombinant factor VIIa (rFVIIa) is recommended in Europe at standard (3 × 90 μg kg -1 ) or high (1 × 270 μg kg -1 ) doses. When granting the license for the high dose, the European Medicines Agency (EMA) requested postmarketing surveillance for thrombosis. This was conducted by the United Kingdom National Haemophilia Database (NHD) on behalf of Novo Nordisk and the EMA. To assess the use and safety of rFVIIa utilizing prospective data collected by the NHD (1 January 2008 to 30 June 2011). Data were obtained from 67 haemophilia A/B patients with inhibitors treated for 1057 bleeds and 31 acquired haemophilia patients treated for 70 bleeds. Initial rFVIIa dose was categorized post hoc as low (<90 μg kg -1 ), intermediate (≥90-<180 μg kg -1 ) or high (≥180-<270 or ≥270 μg kg -1 ). For haemophilia A/B, high and lower initial rFVIIa dose was used for 38.4% and 51.4% of episodes, respectively, while for acquired haemophilia, the values were 11.4% and 77.1% respectively. Median initial doses were higher for haemophilia A/B (146.3 μg kg -1 ) than acquired haemophilia (90.5 μg kg -1 ). A single administration of rFVIIa was the most frequently used regimen for haemophilia A/B, in contrast with standard recommendations and previous reports. For acquired haemophilia, most episodes were treated with multiple doses. No adverse drug reactions or thromboembolic events were reported for any rFVIIa dose. The novel use of a national database for postmarketing surveillance has demonstrated acceptable safety for all recommended doses of rFVIIa. © 2016 John Wiley & Sons Ltd.

Haemophilia & Exercise Project (HEP): subjective and objective physical performance in adult haemophilia patients--results of a cross-sectional study.

PubMed

Czepa, D; Von Mackensen, S; Hilberg, T

2012-01-01

Recurrent musculoskeletal haemorrhages in people with haemophilia (PWH) lead to restrictions in the locomotor system and consequently in physical performance. Patients' perceptions of their health status have gained an important role in the last few years. The assessment of subjective physical performance in PWH is a new approach. This study aimed to compare the subjective physical performance of PWH with healthy controls and to correlate the results with objective data. Subjective physical performance was assessed via the new questionnaire HEP-Test-Q, which consists of 25 items pertaining to four subscales 'mobility', 'strength & coordination', 'endurance' and 'body perception'. HEP-Test-Q subscales were compared with objective data in terms of range of motion, one-leg-stand and 12-minute walk test. Forty-eight patients (44 ± 11 years) with haemophilia A (43 severe, three moderate) or B (two severe) and 43 controls without haemophilia (42 ± 11 years) were enrolled. PWH showed an impaired subjective physical performance in all HEP-Test-Q subscales and in the total score (52 ± 20) compared with controls (77 ± 10; P ≤ 0.001). Correlation analyses for the total score of the HEP-Test-Q and objective data revealed values ranging from r = 0.403 (one-leg-stand) to r = 0.757 (12-minute walk test) (P ≤ 0.001). PWH evaluated their physical performance poorer in comparison with healthy people. As self-assessment did not always correlate highly with objective data, objective examinations of physical performance in PWH should be complemented with subjective perceptions. © 2011 Blackwell Publishing Ltd.

Integrated specialty service readiness in health reform: connections in haemophilia comprehensive care.

PubMed

Pritchard, A M; Page, D

2008-05-01

The World Health Organization (WHO) has identified primary healthcare reform as a global priority whereby innovative practice changes are directed at improving health. This transformation to health reform in haemophilia service requires clarification of comprehensive care to reflect the WHO definition of health and key elements of primary healthcare reform. While comprehensive care supports effective healthcare delivery, comprehensive care must also be regarded beyond immediate patient management to reflect the broader system purpose in the care continuum with institutions, community agencies and government. Furthermore, health reform may be facilitated through integrated service delivery (ISD). ISD in specialty haemophilia care has the potential to reduce repetition of assessments, enhance care plan communication between providers and families, provide 24-h access to care, improve information availability regarding care quality and outcomes, consolidate access for multiple healthcare encounters and facilitate family self-efficacy and autonomy [1]. Three core aspects of ISD have been distinguished: clinical integration, information management and technology and vertical integration in local communities [2]. Selected examples taken from Canadian haemophilia comprehensive care illustrate how practice innovations are bridged with a broader system level approach and may support initiatives in other contexts. These innovations are thought to indicate readiness regarding ISD. Reflecting on the existing capacity of haemophilia comprehensive care teams will assist providers to connect and direct their existing strengths towards ISD and health reform.

Classification and regression tree analysis vs. multivariable linear and logistic regression methods as statistical tools for studying haemophilia.

PubMed

Henrard, S; Speybroeck, N; Hermans, C

2015-11-01

Haemophilia is a rare genetic haemorrhagic disease characterized by partial or complete deficiency of coagulation factor VIII, for haemophilia A, or IX, for haemophilia B. As in any other medical research domain, the field of haemophilia research is increasingly concerned with finding factors associated with binary or continuous outcomes through multivariable models. Traditional models include multiple logistic regressions, for binary outcomes, and multiple linear regressions for continuous outcomes. Yet these regression models are at times difficult to implement, especially for non-statisticians, and can be difficult to interpret. The present paper sought to didactically explain how, why, and when to use classification and regression tree (CART) analysis for haemophilia research. The CART method is non-parametric and non-linear, based on the repeated partitioning of a sample into subgroups based on a certain criterion. Breiman developed this method in 1984. Classification trees (CTs) are used to analyse categorical outcomes and regression trees (RTs) to analyse continuous ones. The CART methodology has become increasingly popular in the medical field, yet only a few examples of studies using this methodology specifically in haemophilia have to date been published. Two examples using CART analysis and previously published in this field are didactically explained in details. There is increasing interest in using CART analysis in the health domain, primarily due to its ease of implementation, use, and interpretation, thus facilitating medical decision-making. This method should be promoted for analysing continuous or categorical outcomes in haemophilia, when applicable. © 2015 John Wiley & Sons Ltd.

Effectiveness of an educational intervention of physiotherapy in parents of children with haemophilia.

PubMed

Cuesta-Barriuso, R; Torres-Ortuño, A; López-García, M; Nieto-Munuera, J

2014-11-01

Haemophilia is a haematological disorder with an orthopaedic outcome. It requires not only medical but rather comprehensive care from infancy. The aim of this study was to assess the effectiveness of an educational intervention of Physiotherapy in parents of children with haemophilia under 4 years old. This is a non-randomized clinical trial, in which 22 parents participated children's with haemophilia under 4 years old. Half of them received an educational intervention of Physiotherapy. At the beginning and end of the study, a psychologist blinded to the assignment of subjects to each of the study groups, assessed the perceived quality of life, anxiety, perceived stress and family functioning of parents. A significant improvement was observed in the variables of perceived stress and family functioning of parents in the experimental group. The realization of an educational intervention in parents of children with haemophilia under 4 years old is effective. It reduces the stressors perceived by the parents and improves family cohesion and adaptability, as a consequence of the disease. It is necessary to carry out studies with follow-up periods to assess the effectiveness of educational programs of Physiotherapy for long term. © 2014 John Wiley & Sons Ltd.

Physical fitness in children with haemophilia and the effect of overweight.

PubMed

Douma-van Riet, D C M; Engelbert, R H H; van Genderen, Frank R; Ter Horst-De Ronde, Manon T M; de Goede-Bolder, Arja; Hartman, Annelies

2009-03-01

Although children with haemophilia are advised to participate in physical activities, their physical fitness has not been studied in a large group. In addition, children with haemophilia may be at increased risk for becoming overweight as a result of inactivity because of joint bleedings or because of overprotection. This study aimed to assess physical fitness (aerobic capacity), joint status, muscle strength, quality of life (QoL), self-reported motor competence and also prevalence of overweight and its association with physical parameters. Weight and height were measured. Skin folds were measured unilaterally at biceps, triceps, subscapular and supra-iliac sites. Aerobic capacity was determined on a cycle ergometer or with a 6-min walk test (6MWT). Muscle strength and active range of motion of elbows, knees and ankle joints were measured. Self-reported motor competence was measured with the 'Competentie BelevingsSchaal voor Kinderen'. Joint pain was scored on a Visual Analogue Scale. The Haemo-QoL Index was used to measure QoL. In 158 Dutch boys with haemophilia, with a mean age of 12.7 years (SD 2.9), normal aerobic capacity and muscle strength were found. Joint pain was reported by 16% of the participants. The prevalence of overweight (16%) was slightly increased when compared with healthy Dutch boys (13.5%). Being overweight had a negative association with the6MWT and QoL. Dutch children with haemophilia have normal aerobic exercise capacity and muscle strength. The majority also has normal joint mobility. Prevalence of overweight is slightly increased.

Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions.

PubMed

van Galen, Karin P M; Engelen, Eveline T; Mauser-Bunschoten, Evelien P; van Es, Robert J J; Schutgens, Roger E G

2015-12-24

Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease. The amount and severity of singular bleedings depend on disease-related factors, such as the severity of the haemophilia, both local and systemic patient factors (such as periodontal inflammation, vasculopathy or platelet dysfunction) and intervention-related factors (such as the type and number of teeth extracted or the dimension of the wound surface). Similar to local haemostatic measures and suturing, antifibrinolytic therapy is a cheap, safe and potentially effective treatment to prevent bleeding complications in individuals with bleeding disorders undergoing oral or dental procedures. However, a systematic review of trials reporting outcomes after oral surgery or a dental procedure in people with an inherited bleeding disorder, with or without, the use of antifibrinolytic agents has not been performed to date. The primary objective was to assess the efficacy of local or systemic use of antifibrinolytic agents to prevent bleeding complications in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures. Secondary objectives were to assess if antifibrinolytic agents can replace or reduce the need for clotting factor concentrate therapy in people with haemophilia or Von Willebrand disease and to further establish the effects of these agents on bleeding in oral or dental procedures for each of these populations. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches of the Cochrane Central Register of Controlled Trials (CENTRAL), of MEDLINE and from handsearching of journals and conference abstract books. We additionally searched the reference lists of relevant articles and reviews. We searched Pub

Outcome measures in European patients with haemophilia: Survey of implementation in routine clinical practice, perception of relevance and recommendations by European treaters in the EHTSB.

PubMed

Hermans, C; Klamroth, R; Richards, M; de Moerloose, P; Garrido, R P

2017-03-01

This study was conducted to evaluate the current implementation of outcome measures in routine clinical haemophilia practice and to explore and appreciate the perception of the relevance of such measures by treaters. A survey was completed by 19 of the 26 physicians involved in the European Haemophilia Therapy Strategy Board (EHTSB). Employing an extensive inventory of outcome measures used in patients with haemophilia, information was collected about the frequency of data collection and the subjective appreciation of their importance during clinic review. The survey revealed that most treaters currently collect data that are mainly related to the haemostatic treatment (consumption of concentrates) and the bleeding symptoms (number and location of bleeds) in a non-uniform and non-standardized way. By contrast, functional, physical and quality of life scorings are rarely used and show considerable heterogeneity between treaters. Also, many disparities emerged between practice and perception, in particular quality of life data that are perceived as being important but for most of the time are not collected. This survey represents, in our view, the first attempt to evaluate the actual utilization of outcome measures in haemophilia care. While the value of outcome measures is appreciated, they are not assessed regularly. Therefore, there is a need to include appropriate performance indicators (outcome measures) of haemophilia care in routine clinical practice. Consensus recommendations to provide a framework for achieving this aim are provided. © 2016 John Wiley & Sons Ltd.

Pheochromocytoma and haemophilia: an unusual combination.

PubMed

Jebasingh, K F; Koshy, T G; Paul, T V; Paul, M J; Abraham, D; Viswabandya, A

2009-02-01

We report pheochromocytoma and haemophilia occurring in a 19-year-old South Indian man. To the best of our knowledge, this case is the first of its kind to be reported in the medical literature. The patient had bilateral adrenal pheochromocytomas with an extradrenal pheochromocytoma on the left side, and was successfully operated on after optimal preoperative blood pressure control and factor VIII support.

Health-related quality of life questionnaires in individuals with haemophilia: a systematic review of their measurement properties.

PubMed

Limperg, P F; Terwee, C B; Young, N L; Price, V E; Gouw, S C; Peters, M; Grootenhuis, M A; Blanchette, V; Haverman, L

2017-07-01

The evaluation of health related quality of life (HRQOL) is essential for a full assessment of the influence of an illness on patients' lives. The aim of this paper is to critically appraise and compare the measurement properties of HRQOL questionnaires studied in haemophilia. Bibliographic databases (Embase, Medline, Cinahl and PsycInfo) were searched for articles evaluating measurement properties of HRQOL questionnaires in haemophilia. Articles were excluded that did not report HRQOL measurement properties, or when <50% of the study population had haemophilia. The methodological quality of the selected studies was evaluated using the COSMIN checklist. The measurement properties of the HRQL questionnaires were rated as 'positive', 'indeterminate' or 'negative', accompanied by levels of evidence. The search resulted in 1597 unique hits, of which 22 studies were included. These articles evaluated three questionnaires for children (CHO-KLAT, Haemo-QoL and one unnamed measure) and five for adults (Hemofilia-QoL, Haemophilia Well-Being Index, HAEMO-QoL-A, Haem-A-QoL, and SF-36). The CHO-KLAT was the paediatric measure that showed the strongest measurement properties in high-quality studies. The Haemophilia Well-Being Index and HAEMO-QoL-A performed best among the adult measures. None of the studies reported measurement error and responsiveness. Our findings suggest that there is no need for new disease-specific HRQOL questionnaires for haemophilia, but rather that additional research is necessary to document the measurement properties of the currently available questionnaires, specifically focusing on the structural validity, measurement error and responsiveness of these questionnaires. © 2017 John Wiley & Sons Ltd.

F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity.

PubMed

Miller, C H; Benson, J; Ellingsen, D; Driggers, J; Payne, A; Kelly, F M; Soucie, J M; Craig Hooper, W

2012-05-01

Both genetic and treatment-related risk factors contribute to the development of inhibitors in haemophilia. An inhibitor surveillance system piloted at 12 US sites has the goal of assessing risk factors through prospective data collection. This report examines the relationship of genotype and race/ethnicity to history of inhibitor in a large cohort of US haemophilia patients. Mutation analysis was performed on 676 haemophilia A (HA) and 153 haemophilia B (HB) patients by sequencing, Multiplex Ligation-dependent Probe Amplification, and PCR for inversions in F8 introns 22 (inv22) and 1 (inv1). Two HB patients with deletions had history of inhibitor. In severe HA, frequency of history of inhibitor was: large deletion 57.1%, splice site 35.7%, inv22 26.8%, nonsense 24.5%, frameshift 12.9%, inv1 11.1% and missense 9.5%. In HA, 19.6% of 321 White non-Hispanics (Whites), 37.1% of 35 Black non-Hispanics (Blacks) and 46.9% of 32 Hispanics had history of inhibitor (P = 0.0003). Mutation types and novel mutation rates were similar across ethnicities. When F8 haplotypes were constructed, Whites and Hispanics showed only H1 and H2. Within H1, history of inhibitor was 12.4% in Whites, 40.0% in Blacks (P = 0.009) and 32.4% in Hispanics (P = 0.002). Inhibitor frequency is confirmed to vary by mutation type and race in a large US population. White patients with history of inhibitor did not exhibit rare F8 haplotypes. F8 gene analysis did not reveal a cause for the higher inhibitor frequencies in Black and Hispanic patients. © 2011 Blackwell Publishing Ltd.

The 'royal disease'--haemophilia A or B? A haematological mystery is finally solved.

PubMed

Lannoy, N; Hermans, C

2010-11-01

  'History can change blood. And blood can change the course of history'. Haemophilia is an illustration of this, as this congenital hereditary coagulation disorder, passed through the majority of royal European families at the beginning of the 20th century by Queen Victoria of England and Empress of the Indies, had indisputable political consequences, which led to one of the most defining moments of contemporary history: the Bolshevik Revolution. Today, none of Queen Victoria's living descendents carry haemophilia. Because of this, the characterization of haemophilia (deficit of either factor VIII or XI) and the identification of the causal mutation are rendered impossible. In 1991, a tomb containing the remains of Czar Nicolas II's entire family was discovered. A second tomb was discovered in 2007, allowing Russian and American scientists to fill in this gap in medical history. Following a scientific approach combining current genetic experimentation tools and the development of biological information technology, researchers were able to identify each body, allowing them to obtain precious genetic material from the young Czar Alexis, who was stricken by the disease, which revealed a causal substitution in the splice acceptor site of exon 4 in the F9 gene. This mutation that is responsible for haemophilia B had traumatized European royal families throughout the 20th century! © 2010 Blackwell Publishing Ltd.

Cost-effectiveness analysis of alternative factor VIII products in treatment of haemophilia A.

PubMed

Hay, J W; Ernst, R L; Kessler, C M

1999-05-01

Manufactured factor VIII (FVIII) concentrates of varying purity are available for managing patients with haemophilia A. This study is a cost-effectiveness analysis of ultra-high purity and recombinant (UHP/R) FVIII products relative to intermediate and very-high purity (IP/VHP) preparations. Because the societal (including research and development) costs of FVIII products are unknown and product prices vary with market conditions, we conducted the analysis with treatment cost as a variable quantity. We estimated the largest price premium that could be paid for a UHP/R concentrate relative to an IP/VHP concentrate such that the UHP/R product is the more cost-effective preparation. In the analysis haemophilic patients were assumed to be seropositive for human immunodeficiency virus, seropositive for hepatitis C (HCV), or at risk for seroconversion of hepatitis A (HAV) or hepatitis B (HBV). The results showed that the maximum cost-effective UHP/R price premium is essentially zero if the patient is only at risk of HAV or HBV infection, positive but small for the base-case HCV+ patient, and positive and large for the base-case HIV+ patient having a short life expectancy. Thus UHP/R preparations are not uniformly more cost-effective than IP/VHP products across the spectrum of haemophilic patients' health problems, and the relative cost-effectiveness of the two classes of prepared FVIII products is sensitive to product prices. The methodology employed here can be used in other circumstances where multiple treatments exist for illnesses for which there are significant multiple comorbidities or health risks.

A prospective study of health-related quality of life of boys with severe haemophilia A in China: comparing on-demand to prophylaxis treatment.

PubMed

Wu, R; Sun, J; Xiao, J; Liu, Y; Xue, F; Wang, H; Tang, L; Zhao, Y; Li, K; Yang, R; Hu, Y; Luke, K-H; Poon, M-C; Blanchette, V S; Usuba, K; Young, N L

2017-05-01

Treatment for boys with haemophilia in China is rapidly improving; however, comprehensive outcomes have not been examined prospectively. The aim of this study was to evaluate the effect of short-term full-dose prophylaxis compared to on-demand treatment, on the Health-Related Quality of Life (HR-QoL) of boys with severe haemophilia A (HA) in China. Boys with severe HA (FVIII<1%) completed 3 months of on-demand treatment and 3 months of full-dose prophylaxis (25 FVIII IU per kg 3x per week). The primary outcomes were child- and parent-reported Canadian Hemophilia Outcomes - Kids Life Assessment Tool (CHO-KLAT) scores. The number and type of bleeds and Activities Scale for Kids (ASK) scores were also recorded. Analyses included 23 boys between 4 and 15.9 years of age. The number of bleeds decreased by 94% on prophylaxis (P < 0.0001, Wilcoxon Signed-Rank test). The mean child-reported CHO-KLAT scores for boys ≥7 years (n = 20) was 61.4 (±10.9) during on-demand treatment and 61.9 (±11.4) following short-term prophylaxis (P = 0.72, paired t-test). The mean parent-reported CHO-KLAT score during the on-demand phase was 54.4 (±10.5) with an increase of 3.8 points (±8.1; P = 0.04, paired t-test) following prophylaxis. Child-reported CHO-KLAT scores were lower in boys with severe HA in China than reported in countries with access to full-dose prophylaxis. Boys reported higher HR-QoL scores than their parents. Small improvements in ASK scores were noted following the prophylaxis phase. These changes were only significant in the parent-reported CHO-KLAT scores. Longer term prospective clinical trials are needed in China to determine the impact of prophylaxis on HR-QoL in boys with severe HA. © 2017 John Wiley & Sons Ltd.

Measuring the quality of haemophilia care across different settings: a set of performance indicators derived from demographics data.

PubMed

Iorio, A; Stonebraker, J S; Brooker, M; Soucie, J M

2017-01-01

Haemophilia is a rare disease for which quality of care varies around the world. We propose data-driven indicators as surrogate measures for the provision of haemophilia care across countries and over time. The guiding criteria for selection of possible indicators were ease of calculation and direct applicability to a wide range of countries with basic data collection capacities. General population epidemiological data and haemophilia A population data from the World Federation of Hemophilia (WFH) Annual Global Survey (AGS) for the years 2013 and 2010 in a sample of 10 countries were used for this pilot exercise. Three indicators were identified: (i) the percentage difference between the observed and the expected haemophilia A incidence, which would be close to null when all of the people with haemophilia A (PWHA) theoretically expected in a country would be known and reported to the AGS; (ii) the percentage of the total number of PWHA with severe disease; and (iii) the ratio of adults to children among PWHA standardized to the ratio of adults to children for males in the general population, which would be close to one if the survival of PWHA is equal to that of the general population. Country-specific values have been calculated for the 10 countries. We have identified and evaluated three promising indicators of quality of care in haemophilia. Further evaluation on a wider set of data from the AGS will be needed to confirm their value and further explore their measurement properties. © 2016 John Wiley & Sons Ltd.

Measuring the quality of haemophilia care across different settings: a set of performance indicators derived from demographics data

PubMed Central

IORIO, A.; STONEBRAKER, J. S.; BROOKER, M.; SOUCIE, J. M.

2017-01-01

Background Haemophilia is a rare disease for which quality of care varies around the world. We propose data-driven indicators as surrogate measures for the provision of haemophilia care across countries and over time. Materials and methods The guiding criteria for selection of possible indicators were ease of calculation and direct applicability to a wide range of countries with basic data collection capacities. General population epidemiological data and haemophilia A population data from the World Federation of Hemophilia (WFH) Annual Global Survey (AGS) for the years 2013 and 2010 in a sample of 10 countries were used for this pilot exercise. Results Three indicators were identified: (i) the percentage difference between the observed and the expected haemophilia A incidence, which would be close to null when all of the people with haemophilia A (PWHA) theoretically expected in a country would be known and reported to the AGS; (ii) the percentage of the total number of PWHA with severe disease; and (iii) the ratio of adults to children among PWHA standardized to the ratio of adults to children for males in the general population, which would be close to one if the survival of PWHA is equal to that of the general population. Country-specific values have been calculated for the 10 countries. Conclusions We have identified and evaluated three promising indicators of quality of care in haemophilia. Further evaluation on a wider set of data from the AGS will be needed to confirm their value and further explore their measurement properties. PMID:27928881

Complex strength performance in patients with haemophilia A. Method development and testing.

PubMed

Runkel, B; Kappelhoff, M; Hilberg, T

2015-01-01

The aim of this study was to develop a complex strength measurement method and to apply this new method for the first time in patients with haemophilia (PwH). 20 PwH with severe haemophilia A and 20 controls were included into the study. All subjects completed ten measurements of maximum isometric strength. Furthermore, the 20 control subjects completed re-test-measurements to evaluate the method. As a result, the method showed a high reliability (ICC 0.764 to 0.934). Between the two groups significant reductions in PwH between -(19-35%) were detected, regarding the relative force of the M. triceps brachii (-19%; p = 0.008), M. biceps brachii (-19%; p = 0.031), M. latissimus dorsi (-17%; p = 0.019), M. biceps femoris right (-20%; p = 0.036) and M. quadriceps femoris (right: -29%; p = 0.004; left: -35%; p = 0.002). No differences were found for M. rectus abdominis and in the hand strength. Thus, there is no general deficit in the muscle strength in PwH. The most obvious deficits exist in the upper and lower extremities and in the back muscles. PwH should carry out complex muscle strength training and integrate it early into a comprehensive treatment concept.

Potential misdiagnosis of von Willebrand disease and haemophilia caused by ineffective mixing of thawed plasma.

PubMed

Favaloro, E J; Oliver, S; Mohammed, S; Ahuja, M; Grzechnik, E; Azimulla, S; McDonald, J; Lima-Oliveira, G; Lippi, G

2017-09-01

von Willebrand disease (VWD) reflects a loss or dysfunction in von Willebrand factor (VWF), while haemophilia represents a loss or dysfunction of clotting factors such as factor VIII (FVIII) or FIX. Their diagnosis requires laboratory testing, with this potentially compromised by preanalytical events, including poor sample quality. This study assessed the effect of inadequate mixing as a potential cause of VWD and haemophilia misdiagnosis. After completion of requested testing, 48 consecutive patient samples comprising separate aliquots from single collections were individually pooled, appropriately mixed, then frozen in separate aliquots, either at -20°C or -80°C for 2-7 days. Each sample set was then thawed and the separate aliquots subjected to separate mixing protocols (several inversions, blood roller, vortex) vs a non-mix sample, and all aliquots then tested for various VWF and factor assays. Non-mixing led to substantial reduction in VWF and factors in about 25% of samples, that in some cases could lead to misdiagnosis of VWD or haemophilia. Interestingly, there were also some differences observed with respect to different mixing protocols. Our study identified ineffective or variable mixing of thawed plasma samples as potential causes of misdiagnosis of VWD or haemophilia. Further education regarding the importance of appropriate mixing appears warranted. © 2017 John Wiley & Sons Ltd.

Comparison of biomechanical gait parameters of young children with haemophilia and those of age-matched peers.

PubMed

Stephensen, D; Drechsler, W; Winter, M; Scott, O

2009-03-01

Quality of life for children with haemophilia has improved since the introduction of prophylaxis. The frequency of joint haemorrhages has reduced, but the consequences of reduced bleeding on the biomechanical parameters of walking are not well understood. This study explored the differences in sagittal plane biomechanics of walking between a control group (Group 1) of normal age-matched children and children with haemophilia (Group 2) with a target ankle joint. A motion capture system and two force platforms were used to collect sagittal plane kinematic, kinetic and temporal-spatial data during walking of 14 age-matched normal children and 14 children with haemophilia aged 7-13 years. Group differences in maximum and minimum flexion/extension angles and moments of the hip, knee and ankle joints, ground reaction forces and temporal-spatial gait cycle parameters were analysed using one-way anova. Significant changes (P < 0.05) in kinematic and kinetic parameters but not temporal-spatial parameters were found in children with haemophilia; greater flexion angles and external moments of force at the knee, greater ankle plantarflexion external moments and lower hip flexion external moments. These results suggest that early biomechanical changes are present in young haemophilic children with a history of a target ankle joint and imply that lower limb joint function is more impaired than current clinical evaluations indicate. Protocols and quantitative data on the biomechanical gait pattern of children with haemophilia reported in this study provide a baseline to evaluate lower limb joint function and clinical progression.

Safety and efficacy of turoctocog alfa (NovoEight®) during surgery in patients with haemophilia A: results from the multinational guardian™ clinical trials.

PubMed

Santagostino, E; Lentz, S R; Misgav, M; Brand, B; Chowdary, P; Savic, A; Kilinc, Y; Amit, Y; Amendola, A; Solimeno, L P; Saugstrup, T; Matytsina, I

2015-01-01

Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prevention and treatment of bleeding episodes in patients with haemophilia A. The present investigations from the multinational, open-label guardian(™) clinical trials assessed the haemostatic response of turoctocog alfa (NovoEight(®)), a rFVIII product, in patients with severe haemophilia A (FVIII ≤ 1%) undergoing surgery. All patients had a minimum of 50 exposure days to any FVIII product prior to surgery and no history of inhibitors. A total of 41 procedures (13 orthopaedic, 19 dental and 9 general) were performed in 33 patients aged 4-59 years. Of the 41 procedures, 15 were major surgeries in 13 patients and 26 were minor surgeries in 21 patients. The success rate for haemostatic response was 100% (success was defined as 'excellent' or 'good' haemostatic outcome). Turoctocog alfa consumption on the day of surgery ranged from 27 to 153 IU kg(-1). The mean daily dose declined over time, while retaining adequate FVIII coverage as measured by trough levels. Overall, no safety issues were identified. No thrombotic events were observed and none of the patients developed FVIII inhibitors. In conclusion, the present results show that turoctocog alfa was effective in controlling blood loss by obtaining a sufficient haemostatic response in patients with severe haemophilia A undergoing surgery. © 2014 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Favourable impact of regular swimming in young people with haemophilia: experience derived from 'Desafio del Caribe' project.

PubMed

Boadas, A; Osorio, M; Gibraltar, A; Rosas, M M; Berges, A; Herrera, E; Gadea, S; Gutiérrez, M Á; Salazar, F; Ruiz-Sáez, A

2015-01-01

Swimming is beneficial for persons with haemophilia (PWH) providing good maintenance of the cardiovascular and musculoskeletal system and improving many psychological characteristics. In the Desafío del Caribe Project, young PWH from Venezuela and Mexico took part in an open water competition in the Gulf of Mexico under a multidisciplinary team supervision. Eight severe haemophilia A, two moderate haemophilia A, one severe haemophilia B and two moderate haemophilia B subjects were included. Haematological, musculoskeletal and psychological evaluations were carried out before and during training for the competition. Training program included physical exercise routines and swimming practices that alternated between pools and open water. Swimmers had coverage with factor concentrates before pool and open water trainings. In physiatric evaluations, the Hemophilia Joint Health Score (HJHS) was used. The objective of the psychology area was to analyse self-esteem, precompetition anxiety, coping mechanisms and relaxation levels. The need of factor prophylaxis before intense trainings was confirmed. In the musculoskeletal system a decrease of elbow pain as well as an increase of muscle strength in the ankles were observed. In the psychological area significant differences between the first and second test in self-esteem levels, cognitive anxiety and group cohesion were found. PWH must be provided with orientation and encouragement to practice swimming regularly. High competition exercise must be supervised by a multidisciplinary team which must evaluate the pros and cons of the activity to make relevant recommendations. © 2014 John Wiley & Sons Ltd.

Protected by nature? Effects of strenuous physical exercise on FVIII activity in moderate and mild haemophilia A patients: a pilot study.

PubMed

Groen, W G; den Uijl, I E M; van der Net, J; Grobbee, D E; de Groot, Ph G; Fischer, K

2013-07-01

Increase of factor VIII activity (FVIII) after physical exercise has been reported in healthy subjects and small-scale studies in patients with coagulopathies. The aim was to study whether moderate and mild haemophilia A patients are able to increase their endogenous FVIII activity levels by physical activity. We studied changes in FVIII activity levels after high-intensity exercise in 15 haemophilia A patients, 20-39 years, eight with moderate, seven with mild haemophilia. Patients cycled until volitional exhaustion, blood samples were drawn before and 10 min after the exercise test. FVIII activity increased 2.5 times (range 1.8-7.0 times), for both severities. Absolute increases were markedly different: median 7 IU dL(-1) (range 3-9 IU dL(-1) ) in patients with moderate, compared to 15 IU dL(-1) (range 6-62 IU dL(-1) ) in mild haemophilia patients. VWF and VWFpp increased independently of severity; median 50% (range 8-123%) and median 165% (range 48-350%), respectively, reflecting acute release of VWF. These observations may be used to promote high-intensity activities before participating in sports for moderate and mild haemophilia A patients, to reduce bleeding risk. Further studies are warranted to fully appreciate the clinical significance of exercise on different levels of intensity in patients with mild and moderate haemophilia A. © 2013 John Wiley & Sons Ltd.

Haemophilia & Exercise Project (HEP): the impact of 1-year sports therapy programme on physical performance in adult haemophilia patients.

PubMed

Czepa, D; von Mackensen, S; Hilberg, T

2013-03-01

Episodes of bleeding in people with haemophilia (PWH) are associated with reduced activity and limitations in physical performance. Within the scope of the 'Haemophilia & Exercise Project' (HEP) PWH were trained in a sports therapy programme. Aim of this study was to investigate subjective and objective physical performance in HEP-participants after 1 year training. Physical performance of 48 adult PWH was compared before and after sports therapy subjectively (HEP-Test-Q) and objectively regarding mobility (range of motion), strength and coordination (one-leg-stand) and endurance (12-min walk test). Sports therapy included an independent home training that had previously been trained in several collective sports camps. Forty-three controls without haemophilia and without training were compared to PWH. Of 48 PWH, 13 performed a regular training (active PWH); 12 HEP-participants were constantly passive (passive PWH). Twenty-three PWH and 24 controls dropped out because of incomplete data. The activity level increased by 100% in active PWH and remained constant in passive PWH, and in controls (P ≤ 0.05). Only mobility of the right knee was significantly improved in active PWH (+5.8 ± 5.3°) compared to passive PWH (-1.3 ± 8.6°). The 12-min walk test proved a longer walking distance for active PWH (+217 ± 199 m) compared to controls (-32 ± 217 m). Active PWH reported a better subjective physical performance in the HEP-Test-Q domains 'strength & coordination', 'endurance' and in the total score (+9.4 ± 13.8) compared to passive PWH (-5.3 ± 13.5) and controls (+3.7 ± 7.5). The 'mobility'-scale and one-leg-stand remained unchanged. Sports therapy increases the activity level and physical performance of PWH, whereby objective effects do not always correspond with subjective assessments. © 2012 Blackwell Publishing Ltd.

Experimental study on the role of intra-articular injection of MSCs on cartilage regeneration in haemophilia.

PubMed

Ravanbod, R; Torkaman, G; Mophid, M; Mohammadali, F

2015-09-01

Mesenchymal stem cells (MSCs) therapy is a field in progress in cartilage repair strategies. We tried to investigate the functional properties of the joint and cartilage in experimental haemarthrosis (EH) after MSCs intra-articular (IA) injection. One millilitre of fresh autologous blood was injected twice a week for three consecutive weeks in three groups including control haemophilia 10 days (n = 8), control haemophilia 38 days (n = 8) and MSCs (n = 8) group. In later, 10 days after the end of IA blood injections, MSCs IA injection was performed. Eight animals received no treatment as the normal control group. Thirty-eight days after the end of IA blood injections, animals were sacrificed. Joint friction and stress-relaxation tests were done, inflammatory cytokines of synovial membrane and scanning electron microscopy of the cartilage assessed. Joint friction decreased in MSCs in comparison to other groups and was significant with normal control group, (P = 0.011). The mechanical properties of cartilage showed no significant differences between groups. Tumour necrosis factor alpha and interleukin 1 beta decreased and IL-4 very slightly increased in MSCs in comparison to the time-matched control group. Scanning electron microscopy enabled acquisition of good structural properties of the surface and layers of the cartilage after MSCs injection. The hole induced in the medial plateau of the tibia bones, after inducing haemarthrosis, were covered with cartilage-like structure. The results showed that MSCs IA injection has some beneficial effects on cartilage structure and function in haemarthrosis model and is promising in patients with haemophilia. © 2015 John Wiley & Sons Ltd.

Understanding the experience of caring for children with haemophilia: cross-sectional study of caregivers in the United States.

PubMed

DeKoven, M; Karkare, S; Kelley, L A; Cooper, D L; Pham, H; Powers, J; Lee, W C; Wisniewski, T

2014-07-01

Congenital haemophilia is an inherited bleeding disorder typically diagnosed at birth or shortly thereafter. Haemophilia imposes a significant burden on patients and their caregivers. The aim of the study was to quantify the overall burden of haemophilia on caregivers in the USA using a novel disease-specific questionnaire and the previously validated CarerQol. Targeted literature review and a previous survey conducted by the authors was used to develop an online questionnaire with six burden domains of interest to caregivers (emotional stress, financial, sacrifice, medical management, child's pain and transportation) and several visual analogue scales (VAS). Content validity of the questionnaire was confirmed by three haemophilia caregivers. The study sample consisted of caregivers of children with haemophilia identified via a previously developed opt-in research database. Descriptive statistics were employed for demographic and clinical characteristics; a generalized linear model (GLM) was used to identify factors influencing caregiver burden. A total of 310 caregivers completed the survey (45.5% response rate). Most of the participating caregivers were mothers of a child with haemophilia (88%), between 35 and 44 years of age (48%), and with a college education or a postgraduate degree (63%). 'Child's pain' was identified as the most burdensome domain to caregivers (median score = 3.50 out of 5), followed by 'emotional stress' (2.67), 'financial' (2.40), 'transportation' (2.33), 'sacrifice' (2.17) and 'medical management' (2.00) domains. Although higher income exhibited a protective effect, episodes of bleeds, current presence of an inhibitor and lower caregiver productivity in the past month negatively affected caregiver burden per GLM results. Training and educational programs should potentially be developed to address caregiver burden. © 2014 John Wiley & Sons Ltd.

How we use recombinant activated Factor VII in patients with haemophilia A or B complicated by inhibitors. Working group of hematology experts from Australia and New Zealand, Melbourne, April 2011.

PubMed

Brown, S A; Barnes, C; Curtin, J; Dunkley, S; Ockelford, P; Phillips, J; Rowell, J; Smith, M; Tran, H

2012-11-01

The management of bleeds in patients with haemophilia A or B complicated by inhibitors is complex. Recombinant activated Factor VII (rFVIIa; NovoSeven RT) is an established therapy in these patients. To develop a consensus-based guide on the practical usage of rFVIIa in haemophilia complicated by inhibitors, nine expert haemophilia specialists from Australia and New Zealand developed practice points on the usage of rFVIIa, based on their experience and supported by published data. Practice points were developed for 13 key topics: control of acute bleeding; prophylaxis; surgical prophylaxis; control of breakthrough bleeding during surgery or treatment of acute bleeds; paediatric use; use in elderly; intracranial haemorrhage; immune tolerance induction; difficult bleeds; clinical monitoring of therapy; laboratory monitoring of therapy; concomitant antifibrinolytic medication; practical dosing. Access to home therapy with rFVIIa is important in allowing patients to administer treatment early in bleed management. In adults, 90-120 μg/kg is the favoured starting dose in most settings. Initial dosing using 90-180 μg/kg is recommended for children due to the effect of age on the pharmacokinetics of rFVIIa. In the management of acute bleeds, 2-hourly dosing is appropriate until bleeding is controlled, with concomitant antifibrinolytic medication unless contraindicated. The practice points provide guidance on the usage of rFVIIa for all clinicians involved in the management of haemophilia complicated by inhibitors. © 2012 The Authors; Internal Medicine Journal © 2012 Royal Australasian College of Physicians.

Fibrin glue for local haemostasis in haemophilia surgery.

PubMed

Rodriguez-Merchan, E Carlos

2017-12-01

Local fibrin glue (FG) appears to be a useful local haemostatic agent for severe haemorrhage in people with haemophilia (PWH) undergoing surgical procedures. To evaluate the role of local FG in PWH. A review of the literature on the topic has been performed. Local FG is not always necessary to achieve haemostasis in all surgical procedures performed in PWH. However, it could be a good adjunct therapy, primarily when a surgical field will bleed more than expected (e.g. patients with inhibitors), and also for circumcisions, dental extractions, and surgical treatment of pseudotumours. Although correct surgical haemostasis can typically be achieved by the infusion of factor concentrate at the adequate dose, my recommendation for surgeons is always to have local FG by their side. Local FG appears to be an effective adjunctive therapy for cases in which bleeding is likely (e.g. patients with inhibitors), and for circumcisions, oral surgery, and treatment of pseudotumours. Through the use of local FG, the doses of factor concentrate necessary to prevent bleeding could be reduced, providing considerable cost savings.

Long-term outcome of total hip arthroplasty in patients with haemophilia.

PubMed

Strauss, A C; Rommelspacher, Y; Nouri, B; Bornemann, R; Wimmer, M D; Oldenburg, J; Pennekamp, P H; Schmolders, J

2017-01-01

Besides the target joints (elbow, knee and ankle), the hip is one of the commonly affected joints in haemophilic arthropathy. Hip arthroplasty is the therapy of choice after failure of conservative treatment. There are only limited data on long-term results after primary total hip arthroplasty (THA). The aim of this retrospective study was to analyse clinical outcome and complication rate after total hip replacement in patients with severe haemophilic arthropathy. Forty-three patients with haemophilia (PWH), one patient with von Willebrand disease and one patient with a Factor-VII-deficiency undergoing 49 total hip arthroplasties, were evaluated in a retrospective study. Harris hip score (HHS), range of motion (ROM), pain status (visual analogue scale, VAS) complication rate and patient satisfaction were assessed at a mean follow-up of 11.5 years (range: 3-32). HSS, ROM and VAS improved significantly combined with high patient satisfaction. In total, three (6.1%) periprosthetic infections and five (10.2%) aseptic implant loosenings occurred after THA leading to revision arthroplasty. In two (4.1%) cases, a pseudotumour and one (2.0%) periarticular ossification had to be resected after THA. Total hip replacement in PWH leads to a significant increase of function, reduction of pain and a high satisfaction. Due to the relatively high complication rate (infections and aseptic loosening) compared to patients without haemophilia, an individual assessment of the risk-benefit ratio from surgical and haemostaseological point of view is needed. © 2016 John Wiley & Sons Ltd.

Improvement in health-related quality of life in patients with haemophilia B treated with nonacog beta pegol, a new extended half-life recombinant FIX product.

PubMed

Chowdary, P; Kearney, S; Regnault, A; Hoxer, C S; Yee, D L

2016-07-01

Health-related quality of life (HRQoL) of individuals with haemophilia has greatly improved with the use of factor replacement and routine prophylaxis. To explore the HRQoL of individuals with haemophilia B treated with nonacog beta pegol, an extended half-life recombinant factor IX, in a single-blind, randomized multinational phase III pivotal trial (paradigm(™) 2) and its open-label extension (paradigm(™) 4). In the pivotal trial, adolescents and adults with haemophilia B were allocated to 28-week on-demand treatment or randomized to 52 weeks of prophylaxis with 10 or 40 IU kg(-1) nonacog beta pegol administered every seven days. In the extension trial, patients could continue on the same treatment or switch to the alternate dosing regimen at any time. HRQoL was assessed with the HAEMO-QOL/HAEM-A-QOL age-specific questionnaires and the EQ-5D. In the pivotal trial, adults receiving 40 IU kg(-1) prophylaxis reported significant improvements in the 'HAEM-A-QOL Total' score (-6.4 ± 8.5, P = 0.017) and in 'Sport' (-15.3 ± 8.5, P = 0.020), 'Feeling' (-15.2 ± 18.3, P = 0.010) and 'Partnership' (-9.6 ± 15.5, P = 0.046) domain scores; no significant improvements were seen in the other arms. At the pivotal trial end, fewer patients reported problems in the EQ-5D 'Mobility' and 'Pain/Discomfort' dimensions, in particular those receiving prophylaxis. In the extension trial, adult patients switching from 10 to 40 IU kg(-1) prophylaxis showed significant improvements in 'HAEM-A-QOL Total' score (-12.5 ± 8.7, P = 0.016) and 'Physical health' domain (-23.1 ± 14.4, P = 0.016). Prophylactic treatment with nonacog beta pegol 40 IU kg(-1) once weekly leads to HRQoL benefits in individuals with haemophilia B; this might be related to fewer bleeding episodes and higher FIX activity levels. © 2016 John Wiley & Sons Ltd.

Susoctocog Alfa: A Review in Acquired Haemophilia A.

PubMed

Burness, Celeste B; Scott, Lesley J

2016-05-01

Intravenous susoctocog alfa (Obizur(®)) is a recombinant, B-domain deleted, porcine sequence antihaemophilic factor VIII (FVIII) product that has recently been approved for the treatment of bleeding episodes in adults with acquired haemophilia A (AHA). Intravenous susoctocog alfa was an effective and generally well tolerated treatment for serious bleeding episodes in adult patients with AHA in a multinational, phase II/III trial (n = 28 evaluable). Patients received an initial dose of susoctocog alfa 200 U/kg, with subsequent dosages based on target FVIII trough levels and clinical assessments. All patients had a positive haemostatic response (based on predefined criteria) of the primary bleed 24 h after the first infusion of susoctocog alfa, with the bleed successfully controlled at the time of final dosing in 86 % of patients. The most frequently reported adverse reaction (incidence >5 %) was the development of inhibitory antibodies against susoctocog alfa (porcine FVIII). Overall, 25 % of antibody naive patients developed anti-susoctocog alfa antibodies during the study. No serious treatment-related adverse events, thrombotic events or allergic reactions were reported during the trial. In conclusion, intravenous susoctocog alfa is a useful addition to the limited treatment options available for the management of acute bleeding episodes in adults with AHA.

Tailored frequency-escalated primary prophylaxis for severe haemophilia A: results of the 16-year Canadian Hemophilia Prophylaxis Study longitudinal cohort.

PubMed

Feldman, Brian M; Rivard, Georges E; Babyn, Paul; Wu, John K M; Steele, MacGregor; Poon, Man-Chiu; Card, Robert T; Israels, Sara J; Laferriere, Nicole; Gill, Kulwant; Chan, Anthony K; Carcao, Manuel; Klaassen, Robert J; Cloutier, Stephanie; Price, Victoria E; Dover, Saunya; Blanchette, Victor S

2018-06-01

Severe haemophilia A has high morbidity, and treatment, while effective, is very expensive. We report the 16-year follow-up of the Canadian Hemophilia Prophylaxis Study, which examined the effectiveness of tailored frequency-escalated primary prophylaxis with a focus on health outcomes within the domains of body structures and functions, and activities and participation (according to the WHO International Classification of Functioning, Disability and Health [WHO-ICF] framework) and a view to reducing consumption of costly clotting factor, which accounts for more than 90% of the cost of care of severe haemophilia. In this longitudinal study, boys with severe haemophilia A from 12 Canadian centres were enrolled at age 1·0-2·5 years. They were treated with standard half-life recombinant factor VIII (SHL-rFVIII), beginning as once-weekly prophylaxis with 50 IU/kg and escalating in frequency (with accompanying dose adjustments) in response to breakthrough bleeding as determined by the protocol. The primary endpoint for this analysis was joint health, as measured by the modified Colorado Child Physical Examination Scores (CCPES) at study end. All analyses were done by intention to treat. The trial is complete, and is registered with ClinicalTrials.gov, number NCT01085344. Between June 26, 1997, and Jan 30, 2007, 56 boys were enrolled. They were followed for a median of 10·2 years (to a maximum of 16·1 years). Median rFVIII usage was about 3600 IU/kg per year. The median end-of-study CCPES physical examination score was 1 (IQR 1-3; range 0-12) for the left ankle and 1 (1-2; 0-12) for the right ankle, with all other joints having a median score of 0. No treatment-related safety events occurred over the duration of the study, including central venous catheter infections. The median annualised index joint bleeding rate was 0·95 per year (IQR 0·44-1·35; range 0·00-13·43), but 17 (30%) patients had protocol-defined unacceptable breakthrough bleeding at some point

The detrimental effects of iron on the joint: a comparison between haemochromatosis and haemophilia.

PubMed

van Vulpen, Lize F D; Roosendaal, Goris; van Asbeck, B Sweder; Mastbergen, Simon C; Lafeber, Floris P J G; Schutgens, Roger E G

2015-08-01

Joint damage due to (recurrent) joint bleeding in haemophilia causes major morbidity. Although the exact pathogenesis has not been fully elucidated, a central role for iron is hypothesised. Likewise, in hereditary haemochromatosis joint destruction is caused by iron overload. A comparison between these types of arthropathy could provide more insight in the influence of iron in inducing joint damage. A literature review was performed to compare both disorders with respect to their clinical and histological characteristics, and preclinical studies on the influence of iron on different joint components were reviewed. Similarities in the features of arthropathy in haemochromatosis and haemophilia are cartilage degeneration, subchondral bone changes with osteophyte and cyst formation, and osteoporosis. In both disorders synovial inflammation and proliferation are seen, although this is much more explicit in haemophilia. Other substantial differences are the age at onset, the occurrence of chondrocalcinosis radiographically and calcium pyrophosphate dihydrate deposition disease in haemochromatosis, and a rapid progression with joint deformity and neovascularisation in haemophilia. Preclinical studies demonstrate detrimental effects of iron to all components of the joint, resulting in synovial inflammation and hyperplasia, chondrocyte death, and impaired osteoblast function. These effects, particularly the synovial changes, are aggravated in the presence of a pro-inflammatory signal, which is prominent in haemophilic arthropathy and minimal in haemochromatosis. Additional research is needed to further specify the role of iron as a specific target in treating these types of arthropathy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Reconstituting factor concentrates: Defining Evidence of Coaching Non-Experts (DEVICE) in haemophilia--a prospective randomized feasibility study.

PubMed

Bidlingmaier, C; Kurnik, K; Hölscher, G; Kappler, M

2007-09-01

The introduction of new needleless devices as demanded by the US Department of Labor Occupational Safety and Health Administration (OSHA) has caused problems with the reconstitution of antihaemophilic factor in emergency situations. Our aim therefore was to evaluate the feasibility of a needleless device for reconstitution of antihaemophilic factor for non-haemophilia experts and to define evidence of the need for coaching these physicians via providing two additional photographs illustrating the two key points of the factor reconstitution process. Twenty-eight physicians of a tertiary care university children's hospital were randomized into two groups, either with no further explanation of the reconstitution device or with two additional photographs, showing the two key steps of the procedure. Reconstitution of dummy-factor concentrate was video-taped and evaluated by a blinded helper. Main outcome measure was the successful reconstitution of dummy-factor concentrate and procedure failure respectively. Of the group without explanation of the reconstitution device, only two of 14 physicians were able to reconstitute the dummy-factor concentrate. Of the group receiving two photographs, nine of 14 completed the task successfully (P = 0.0068). The needleless device is not self explaining to non-haemophilia physicians involved in emergency services. Coaching via short to the point instructions as provided by simple visual educational material therefore is crucial to enable these physicians to resolve the expensive emergency drug quickly and correctly. Companies concerned with the production of any devices to dissolve drugs, especially for treatment of rare diseases as haemophilia, therefore should take measures to simplify therapy.

Physical fitness, functional ability and quality of life in children with severe haemophilia: a pilot study.

PubMed

van der Net, J; Vos, R C; Engelbert, R H H; van den Berg, M H; Helders, P J M; Takken, T

2006-09-01

In the Netherlands comparable levels of sports-participation between persons with haemophilia and healthy controls have been reported. This raises the question if children with haemophilia under the currently available prophylaxis do reach comparable levels of physical fitness and health-related quality of life (HRQoL) as their healthy peers. The aim of this study was to investigate the level of physical fitness, functional ability and quality of life and to determine the feasibility to safely test the exercise capacity of boys with severe haemophilia A. Thirteen subjects participated in this study. Physical fitness was determined using the measurement of maximal oxygen uptake (VO2peak) attained during a graded maximal exercise test to volitional exhaustion. Joint health, physical activity levels and health-related quality of life (Haemo-Qol) were also measured. Mean VO2peak was 1.86+/-0.77 L min-1 (Z-score: -0.39+/-1.61) which was not significantly different from reference values. Relative VO2peak was 47.42+/-8.29 mL min-1 kg-1 (Z-score: -0.52+/-1.43), which did not differ significantly from reference values either. One boy suffered a joint bleeding one day after the test. Haemo-Qol scores in parents and children ranged from 3.2% to 36.7% (100% reflects poor outcome). Relationship between the child or parent reports of Haemo-QoL and both absolute and relative VO2peak ranged from R=0.00 and R=0.4. Exercise testing in children with severe haemophilia A was a safe procedure. Patients with severe haemophilia A with good joint health and no limitations of activities have comparable physical fitness and physical active lifestyle with healthy peers and good HRQoL.

Joint health scores in a haemophilia A cohort from Pakistan with minimal or no access to factor VIII concentrate: correlation with thrombin generation and underlying mutation.

PubMed

Khanum, F; Bowen, D J; Kerr, B C; Collins, P W

2014-05-01

Haemophilia A is associated with recurrent joint bleeding which leads to synovitis and debilitating arthropathy. Coagulation factor VIII level is an important determinant of bleed number and development of arthropathy . The aim of this study was to compare the haemophilia joint health score (HJHS) and Gilbert score with severity, age, thrombin generation (TG) and underlying mutation in a haemophilia A cohort which had minimal access to haemostatic replacement therapy. Ninety-two haemophilia A individuals were recruited from Pakistan. Age, age at first bleed, target joints, haemophilic arthropathy joints, HJHS and Gilbert score were recorded. A strong correlation was found between HJHS and Gilbert score (r = 0.98), both were significantly higher in severe (n = 59) compared with non-severe (n = 29) individuals before the age of 12 years (P ≤ 0.01) but not thereafter. When individuals were divided according to developmental age (<12 years, 12-16 years and >16 years), both HJHS and Gilbert score were significantly lower in the youngest group (P ≤ 0.001), there was no difference between 12-16 years and >16 years. In severe individuals there was no correlation between in vitro TG and joint score, whereas in non-severe individuals there was a weak negative correlation. In the severe group, no significant difference was observed for either joint score according to the underlying mutation type (inversion, missense, nonsense, frameshift). In this cohort of haemophilia A individuals with minimal access to haemostatic treatment, haemophilic arthropathy correlated with severity and age; among severe individuals, joint health scores did not relate to either the underlying mutation or in vitro TG. © 2013 John Wiley & Sons Ltd.

The role of recombinant activated factor VII in the haematological management of elective orthopaedic surgery in haemophilia A patients with inhibitors

PubMed Central

Castaman, Giancarlo

2017-01-01

The clinical profile and expectations of haemophilic patients with inhibitors have changed over the last three decades, mainly because of the prolongation of life-expectancy, often resulting in an increase of the orthopaedic burden. Recombinant activated factor VII (rFVIIa) is the most frequently used bypassing agent in haemophilia patients with inhibitors during elective orthopaedic surgery. For nearly 30 years, rFVIIa has been successfully used to control haemostasis in several major and minor surgical procedures. Clinical trials, case series, reports and surveys were progressively aimed at optimising rFVIIa usage in very demanding conditions managed in highly specialised centres. Recommendations from consensus opinions and guidelines have been provided on the basis of this clinical experience. PMID:28686157

Pharmacokinetic properties of IB1001, an investigational recombinant factor IX, in patients with haemophilia B: repeat pharmacokinetic evaluation and sialylation analysis.

PubMed

Martinowitz, U; Shapiro, A; Quon, D V; Escobar, M; Kempton, C; Collins, P W; Chowdary, P; Makris, M; Mannucci, P M; Morfini, M; Valentino, L A; Gomperts, E; Lee, M

2012-11-01

IB1001 trenacog alfa is an investigational recombinant factor IX (FIX) for the treatment and prevention of bleeding in individuals with haemophilia B. To compare the pharmacokinetics (PK) of IB1001 with nonacog alfa in individuals with haemophilia B and to assess the relationship between sialylation and PK of IB1001 (NCT00768287). A randomized, double-blind, non-inferiority, cross-over study conducted in participants aged ≥ 12 years weighing ≥ 40 kg, with severe or moderately severe haemophilia B (FIX activity ≤ 2 IU dL (-1) ). PK parameters were derived using observed FIX concentration levels and actual PK sampling times, and repeated in a subset of participants who had received IB1001 prophylaxis for 4-18 months. A retrospective analysis was conducted in subgroups according to the sialylation levels of IB1001 (50.8, 57.8-59.0%, or 71.7%). In the 32 adolescent and adult males evaluated, there were no clinically meaningful differences in PK parameters between those receiving IB1001 75 IU kg(-1) or nonacog alfa. The lower limit of the one-sided 95% confidence interval for the ratio of AUC(0-t) and AUC(0-∞) (IB1001/nonacog alfa) was 0.90, establishing non-inferiority. Terminal phase half-lives were similar (29.7 ± 18.2 h for IB1001 and 33.4 ± 21.2 h for nonacog alfa). The PK results were stable for up to 18 months of IB1001 exposure; the impact of sialylation levels was not clinically meaningful. There were no clinically meaningful PK differences between IB1001 and nonacog alfa. IB1001 was well tolerated and without safety concerns. The non-inferiority of IB1001 to nonacog alfa supports IB1001 becoming a useful alternative recombinant agent for the management of haemophilia B. © 2012 Blackwell Publishing Ltd.

Long-term tolerability, immunogenicity and efficacy of Nuwiq® (human-cl rhFVIII) in children with severe haemophilia A.

PubMed

Klukowska, A; Szczepański, T; Vdovin, V; Knaub, S; Bichler, J; Jansen, M; Dzhunova, I; Liesner, R J

2018-03-26

Nuwiq ® (human-cl rhFVIII, simoctocog alfa) is a 4th generation recombinant human FVIII, without chemical modification or fusion with any other protein, produced in a human cell line. This study (GENA-13) was an extension of the GENA-03 study in which previously treated children aged 2-12 years with severe haemophilia A received Nuwiq ® prophylaxis for ≥6 months. GENA-13 examined long-term tolerability, immunogenicity and efficacy of Nuwiq ® prophylaxis in children. Of 59 patients enrolled in GENA-03, 49 continued Nuwiq ® prophylaxis in GENA-13 for a median (range) of 30.0 (9.5-52.0) months. No patient withdrew due to drug-related adverse events or developed inhibitors. Only 2 of 20 518 infusions were associated with possibly related adverse events (dyspnoea, fever). The estimated annualized bleeding rate (ABR) was 0.67 (95% CI: 0.44, 1.02) for spontaneous and 2.88 (95% CI: 1.86, 4.46) for all bleeds. Younger children (2-5 years) had lower ABRs than children aged 6-12 years. Annualized bleeding rates were reduced in GENA-13 vs GENA-03, especially for spontaneous bleeds in younger children (71% reduction; ABR ratio 0.29 [95% CI: 0.11, 0.74]). Nuwiq ® efficacy was rated as excellent/good in the treatment of 83.0% of 305 evaluated breakthrough bleeds. Surgical prophylaxis with Nuwiq ® was rated as excellent for all 17 assessed procedures. Long-term treatment with Nuwiq ® for the prevention of bleeds in children with severe haemophilia A was well tolerated, effective and reduced spontaneous bleeding by up to 70% compared with GENA-03. © 2018 The Authors. Haemophilia published by John Wiley & Sons Ltd.

[Curricula oriented inclusion of children and adolescents with haemophilia in school sports--a new approach within the project "fit for life"].

PubMed

Joeres, J; Seuser, A; Kurme, A; Trunz-Carlisi, E; Ochs, S; Böhm, P

2012-01-01

Inclusive paedagogic thinking and acting is a modern and increasingly important topic in school sports. It will affect teachers as well as parents and students. The new international guidelines and national curricula enable new ways of inclusion especially for students with chronic illnesses like haemophilia. Special help from the sport teachers is of vital importance. In our project "fit for life" where we advice children and young adults with haemophilia to find their appropriate sport, we developed a new approach for an optimised inclusion of children with haemophilia into sport lessons. The whole project is running in corporation with the German Sport Teachers Association/Hessen. We analysed and rated the actual curricula of the different school years and looked at the specific needs, risks and necessary abilities for persons with haemophilia. By this means we gathered about 600 typical movements and/or exercises for school sports and developed individual advice and adapted exercise solutions for sport lessons.

A study of variations in the reported haemophilia B prevalence around the world.

PubMed

Stonebraker, J S; Bolton-Maggs, P H B; Michael Soucie, J; Walker, I; Brooker, M

2012-05-01

The objectives of this article were to study the reported prevalence of haemophilia B (HB) on a country-by-country basis and to analyse whether the prevalence of HB varied by national economy. The prevalence of HB is the proportion of diagnosed, reported cases of HB in a population at a specific point of time. We collected data on the HB prevalence for 105 countries from the World Federation of Hemophilia annual global surveys. Our results showed that the HB prevalence varied considerably among countries, even among the wealthiest of countries. The HB prevalence (per 100 000 males) for the highest income countries was 2.69 ± 1.61 (mean ± SD), whereas the prevalence for the rest of the world was 1.20 ± 1.33 (mean ± SD). Ireland had the highest reported HB prevalence of 8.07 per 100 000 males. There was a strong trend of increasing HB prevalence (per 100 000 males) over time. Prevalence data reported from the WFH compared well with prevalence data from the literature. The WFH annual global surveys have some limitations, but they are the best available source of worldwide haemophilia data. Prevalence data are extremely valuable information for the planning efforts of national healthcare agencies in setting priorities and allocating resources for the treatment of HB. © 2011 Blackwell Publishing Ltd.

Effectiveness of a balance training home exercise programme for adults with haemophilia: a pilot study.

PubMed

Hill, K; Fearn, M; Williams, S; Mudge, L; Walsh, C; McCarthy, P; Walsh, M; Street, A

2010-01-01

Adults with haemophilia and other bleeding disorders often develop lower limb musculoskeletal problems associated with bleeds into joints and muscles, which may affect balance performance and increase likelihood of falling. The aim of this study was to evaluate the effectiveness of an individualized balance and strength home exercise programme on improving balance and related outcomes for adults with haemophilia and other bleeding disorders. Twenty male adults with haemophilia and other bleeding disorders (mean age 39.4 years, 95% CI = 33.7-45.1) were recruited to participate. They underwent a comprehensive clinical and force platform assessment of balance and related measures. Based on assessment findings, the assessing physiotherapist provided an individualized home exercise programme of balance, strengthening and walking exercises. Re-assessment occurred after the 4-month exercise programme. Twelve participants (60%) completed the programme and were re-assessed. There were no safety problems or dropouts associated with the exercise programme aggravating joint status. Although there were no statistically significant changes in any of the measures (adjusted for multiple comparisons), there were improvements of between 5% and 22% on 10 of the 16 measures, with the Neurocom modified Clinical Test of Sensory Interaction on Balance (P = 0.036) and Timed Sit to Stand (P = 0.064) approaching significance. A tailored home exercise programme targeting balance, strengthening and walking is feasible for adults with haemophilia and other bleeding disorders. These results suggest that positive physical outcomes including improved balance and mobility may be achieved with this type of programme.

Physical activity for prevention of osteoporosis in patients with severe haemophilia on long-term prophylaxis.

PubMed

Khawaji, M; Astermark, J; Akesson, K; Berntorp, E

2010-05-01

Physical activity has been considered as an important factor for bone density and as a factor facilitating prevention of osteoporosis. Bone density has been reported to be reduced in haemophilia. To examine the relation between different aspects of physical activity and bone mineral density (BMD) in patients with severe haemophilia on long-term prophylaxis. The study group consisted of 38 patients with severe haemophilia (mean age 30.5 years). All patients received long-term prophylaxis to prevent bleeding. The bone density (BMD g cm(-2)) of the total body, lumbar spine, total hip, femoral neck and trochanter was measured by dual energy X-ray absorptiometry. Physical activity was assessed using the self-report Modifiable Activity Questionnaire, an instrument which collects information about leisure and occupational activities for the prior 12 months. There was only significant correlation between duration and intensity of vigorous physical activity and bone density at lumber spine L1-L4; for duration (r = 0.429 and P = 0.020) and for intensity (r = 0.430 and P = 0.019); whereas no significant correlation between all aspects of physical activity and bone density at any other measured sites. With adequate long-term prophylaxis, adult patients with haemophilia are maintaining bone mass, whereas the level of physical activity in terms of intensity and duration play a minor role. These results may support the proposition that the responsiveness to mechanical strain is probably more important for bone mass development in children and during adolescence than in adults and underscores the importance of early onset prophylaxis.

Non-genetic risk factors in haemophilia A inhibitor management - the danger theory and the use of animal models.

PubMed

Lövgren, K M; Søndergaard, H; Skov, S; Wiinberg, B

2016-09-01

In haemophilia A (HA) management, antidrug antibodies, or inhibitors, are a serious complication that renders factor VIII (FVIII) replacement therapy ineffective, increases morbidity and reduces quality of life for affected patients. Inhibitor development aetiology is multifactorial and covers both genetic and therapy related risk factors. Many therapy-related risk factors have proven difficult to confirm due to several confounding factors and the small study populations available. However, clinical studies indicate that e.g. on-demand treatment and surgery affect inhibitor development, and explanations for this association are being investigated. A potential explanation is the danger signal effect, where the immune response is activated by endogenous or exogenous danger or damage signals present at the time and site of FVIII administration. The danger theory explains how alarm signals from stressed, injured or dying cells can activate an immune reaction, without the involvement of foreign antigens. Bleeds, trauma, surgery or concomitant infection could be events initiating danger signalling in HA patients, resulting in an immune reaction towards administered FVIII that otherwise would pass unnoticed. This role of danger in HA inhibitor formation has previously been suggested, but a thorough discussion of this subject is lacking. The present review will discuss the potential role of danger signals in haemophilia and inhibitor development, with focus on treatment related risk factors with a suspected danger signal aetiology; on-demand treatment, treatment during major bleeds or surgery, and treatment during infection or vaccination. Clinical studies as well as animal experiments addressing these factors will be reviewed. © 2016 John Wiley & Sons Ltd.

Osteoporosis in haemophilia - an underestimated comorbidity?

PubMed

Wallny, T A; Scholz, D T; Oldenburg, J; Nicolay, C; Ezziddin, S; Pennekamp, P H; Stoffel-Wagner, B; Kraft, C N

2007-01-01

A relationship between haemophilia and osteoporosis has been suggested, leading to the initiative for a larger study assessing this issue. Bone mineral density (BMD) was measured by osteodensitometry using dual energy X-ray absorptiometry (DEXA) in 62 male patients with severe haemophilia A; mean age 41 +/- 13.1 years, mean body mass index (BMI) 23.5 +/- 3.6 kg m(-2). Using the clinical score suggested by the World Federation of Hemophilia, all patients were assessed to determine the severity of their arthropathy. A reduced BMD defined as osteopenia and osteoporosis by World Health Organization criteria was detected in 27/62 (43.5%) and 16/62 (25.8%) patients, respectively. Fifty-five of sixty-two (88.7%) patients suffered from haemophilic arthropathy. An increased number of affected joints and/or an increased severity were associated with lower BMD in the neck of femur. Pronounced muscle atrophy and loss of joint movement were also associated with low BMD. Furthermore, hepatitis C, low BMI and age were found to be additional risk factors for reduced BMD in the haemophiliac. Our data shows that in haemophilic patients osteoporosis represents a frequent concomitant observation. The main cause for reduced bone mass in the haemophiliac is most probably the haemophilic arthropathy being typically associated with chronic pain and loss of joint function subsequently leading to inactivity. Further studies including control groups are necessary to elucidate the impact of comorbidities such as hepatitis C or HIV on the development of osteoporosis in the haemophiliac.

Recombinant factor VIII Fc fusion protein for immune tolerance induction in patients with severe haemophilia A with inhibitors-A retrospective analysis.

PubMed

Carcao, M; Shapiro, A; Staber, J M; Hwang, N; Druzgal, C; Lieuw, K; Belletrutti, M; Thornburg, C D; Ahuja, S P; Morales-Arias, J; Dumont, J; Miyasato, G; Tsao, E; Jain, N; Pipe, S W

2018-03-01

Immune tolerance induction (ITI) is the gold standard for eradication of factor VIII inhibitors in severe haemophilia A; however, it usually requires treatment for extended periods with associated high burden on patients and healthcare resources. Review outcomes of ITI with recombinant factor VIII Fc fusion protein (rFVIIIFc) in patients with severe haemophilia A and high-titre inhibitors. Multicentre retrospective chart review of severe haemophilia A patients treated with rFVIIIFc for ITI. Of 19 patients, 7 were first-time ITI and 12 were rescue ITI. Of 7 first-time patients, 6 had at least 1 high-risk feature for ITI failure. Four of 7 first-time patients were tolerized in a median of 7.8 months. The remaining 3 patients continue on rFVIIIFc ITI. Of 12 rescue patients, 7 initially achieved a negative Bethesda titre (≤0.6) in a median of 3.3 months, 1 had a decrease in Bethesda titre and continues on rFVIIIFc ITI and 4 have not demonstrated a decrease in Bethesda titre. Of these 4, 3 continue on rFVIIIFc ITI and 1 switched to bypass therapy alone. Two initially responsive patients transitioned to other factors due to recurrence. Overall, 16 of 19 patients remain on rFVIIIFc (prophylaxis or ITI). For those still undergoing ITI, longer follow-up is needed to determine final outcomes. No adverse events reported. Recombinant factor VIII Fc fusion protein demonstrated rapid time to tolerization in high-risk first-time ITI patients. For rescue ITI, rFVIIIFc showed therapeutic benefit in some patients who previously failed ITI with other products. These findings highlight the need to further evaluate the use of rFVIIIFc for ITI. © 2018 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Participation and risk-taking behaviour in sports in children with haemophilia.

PubMed

Köiter, J; van Genderen, F R; Brons, P P T; Nijhuis-van der Sanden, M W G

2009-05-01

The aim of this study was to investigate participation in sports activities and risk-taking behaviour in children with haemophilia and the relationship to personal and health related factors. Ninety-nine children (mean age 12.6 years) completed questionnaires regarding participation in sports and physical education, medication, health related quality of life, and perceived motor competence. Furthermore, weight, height, active range of motion, pain, and muscle strength were assessed. Based on a risk exposure factor (REF) we defined subgroups with low, medium, and high risk when participating in sport. Most children participate in sport five times a week (mean 140 min per week), and little absence during school sports was reported. In general, prophylaxis was not tailored to sport activities. Boys with haemophilia preferred other sports than their Dutch contemporaries. The top-5 being soccer, swimming, tennis, gymnastics, and cardio-fitness for the former; soccer, gymnastics, tennis, hockey, and swimming for the latter. Significant differences between the low risk group and both other groups were found for sport intensity, total energy expenditure (EE) and average risk factor (ARF), however the medium and high-risk groups did not differ in ARF. REF and sport participation increased associated with increasing interest in athletic and motor activities. No significant differences were found between REF groups regarding age, Z-BMI, Z-AROM, Z-Muscle force, and the presence of painful joints. As in normal peers motivation to participate in sport depends upon the enthusiasm and interest, in children with haemophilia choice of sports differs, probably related to sport advice.

A case of Munchausen syndrome with claims of trauma and haemophilia.

PubMed Central

Park, G; Huang, A; Wright, S

1996-01-01

A case of Munchausen syndrome presented with both factitious trauma and factitious haemophilia. He was treated inappropriately with factor VIII concentrate before the history of the presenting complaint could be validated. Clinical suspicion remains the most important aid to diagnosis. Images Figure 1 PMID:8832359

Impact of multiple joint impairments on the energetics and mechanics of walking in patients with haemophilia.

PubMed

Lobet, S; Detrembleur, C; Hermans, C

2013-03-01

Few studies have assessed the changes produced by multiple joint impairments (MJI) of the lower limbs on gait in patients with haemophilia (PWH). In patients with MJI, quantifiable outcome measures are necessary if treatment benefits are to be compared. This study was aimed at observing the metabolic cost, mechanical work and efficiency of walking among PWH with MJI and to investigate the relationship between joint damage and any changes in mechanical and energetic variables. This study used three-dimensional gait analysis to investigate the kinematics, cost, mechanical work and efficiency of walking in 31 PWH with MJI, with the results being compared with speed-matched values from a database of healthy subjects. Regarding energetics, the mass-specific net cost of transport (C(net)) was significantly higher for PWH with MJI compared with control and directly related to a loss in dynamic joint range of motion. Surprisingly, however, there was no substantial increase in mechanical work, with PWH being able to adopt a walking strategy to improve energy recovery via the pendulum mechanism. This probable compensatory mechanism to economize energy likely counterbalances the supplementary work associated with an increased vertical excursion of centre of mass (CoM) and lower muscle efficiency of locomotion. Metabolic variables were probably the most representative variables of gait disability for these subjects with complex orthopaedic degenerative disorders. © 2012 Blackwell Publishing Ltd.

Content comparison of haemophilia specific patient-rated outcome measures with the international classification of functioning, disability and health (ICF, ICF-CY)

PubMed Central

2010-01-01

Background Patient-Reported Outcomes (PROs) are considered important outcomes because they reflect the patient's experience in clinical trials. PROs have been included in the field of haemophilia only recently. Purpose Comparing the contents of PROs measures used in haemophilia, based on the ICF/ICF-CY as frame of reference. Methods Haemophilia-specific PROs for adults and children were selected on the grounds of international accessibility. The content of the selected instruments were examined by linking the concepts within the items of these instruments to the ICF/ICF-CY. Results Within the 5 selected instruments 365 concepts were identified, of which 283 concepts were linked to the ICF/ICF CY and mapped into 70 different categories. The most frequently used categories were "b152: Emotional functions" and "e1101: Drugs". Conclusions The present paper provides an overview on current PROs in haemophilia and facilitates the selection of appropriate instruments for specific purposes in clinical and research settings. This work was made possible by the grant of the European Murinet Project (Multidisciplinary Research Network on Health and Disability in Europe). PMID:21108796

Evaluation of bone mineral density and related parameters in patients with haemophilia: a single center cross-sectional study

PubMed Central

Kiper Unal, Hatice Demet; Comert Ozkan, Melda; Atilla, Fatos Dilan; Demirci, Zuhal; Soyer, Nur; Yildirim Simsir, Ilgin; Omur, Ozgur; Capaci, Kazim; Saydam, Guray; Sahin, Fahri

2017-01-01

Haemophilia has been associated with low bone mineral density (BMD) probably due to some predisposing factors. The aim of this study was to evaluate the relationship between BMD and potential clinical predictors in adult haemophilic patients. Fortynine patients with moderate and severe haemophilia were enrolled. BMD was measured by Dual Energy X-Ray Absorptiometry (DXA) and blood tests were performed for vitamin D, calcium, phosphore, alkaline phosphatase and parathormone levels. Functional Independence Score in Haemophilia (FISH) and Haemophilia Joint Health Score (HJHS) were used to assess musculoskeletal functions. Body mass index (BMI), Hepatitis C virus (HCV)/Human immunodeficiency virus (HIV) seropositivity and smoking status were also recorded. BMD was found lower than expected for reference age in 34.8% of patients of less than 50 years old. In patients older than 50 years, 66.6% of them had osteoporosis and 33.3% of them had normal BMD. FISH score was statistically significant correlated with BMD of total hip (TH) and femur neck (FN) but not with lumbar spine (LS). In eligible patients, there was also a statistically significant correlation between BMD of TH and HJHS. Vitamine D deficiency was common and found in 77.5% of patients, although there was no significant correlation with BMD. Also no correlation was found between BMD and blood tests, HCV/HIV status, BMI and smoking. This study confirmed that patients with haemophilia have an increased prevelance of low BMD even in younger group. Our results showed that there are significant correlations between FISH score and BMD of TH and FN and also between HJHS score and BMD of TH. Thus, using scoring systems may be beneficial as a simple predictors of BMD to reflect the severity of haemophilic arthropathy. PMID:29181264

Evaluation of bone mineral density and related parameters in patients with haemophilia: a single center cross-sectional study.

PubMed

Kiper Unal, Hatice Demet; Comert Ozkan, Melda; Atilla, Fatos Dilan; Demirci, Zuhal; Soyer, Nur; Yildirim Simsir, Ilgin; Omur, Ozgur; Capaci, Kazim; Saydam, Guray; Sahin, Fahri

2017-01-01

Haemophilia has been associated with low bone mineral density (BMD) probably due to some predisposing factors. The aim of this study was to evaluate the relationship between BMD and potential clinical predictors in adult haemophilic patients. Fortynine patients with moderate and severe haemophilia were enrolled. BMD was measured by Dual Energy X-Ray Absorptiometry (DXA) and blood tests were performed for vitamin D, calcium, phosphore, alkaline phosphatase and parathormone levels. Functional Independence Score in Haemophilia (FISH) and Haemophilia Joint Health Score (HJHS) were used to assess musculoskeletal functions. Body mass index (BMI), Hepatitis C virus (HCV)/Human immunodeficiency virus (HIV) seropositivity and smoking status were also recorded. BMD was found lower than expected for reference age in 34.8% of patients of less than 50 years old. In patients older than 50 years, 66.6% of them had osteoporosis and 33.3% of them had normal BMD. FISH score was statistically significant correlated with BMD of total hip (TH) and femur neck (FN) but not with lumbar spine (LS). In eligible patients, there was also a statistically significant correlation between BMD of TH and HJHS. Vitamine D deficiency was common and found in 77.5% of patients, although there was no significant correlation with BMD. Also no correlation was found between BMD and blood tests, HCV/HIV status, BMI and smoking. This study confirmed that patients with haemophilia have an increased prevelance of low BMD even in younger group. Our results showed that there are significant correlations between FISH score and BMD of TH and FN and also between HJHS score and BMD of TH. Thus, using scoring systems may be beneficial as a simple predictors of BMD to reflect the severity of haemophilic arthropathy.

Safety and efficacy of turoctocog alfa (NovoEight®) during surgery in patients with haemophilia A: results from the multinational guardian™ clinical trials

PubMed Central

Santagostino, E; Lentz, S R; Misgav, M; Brand, B; Chowdary, P; Savic, A; Kilinc, Y; Amit, Y; Amendola, A; Solimeno, L P; Saugstrup, T; Matytsina, I

2015-01-01

Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prevention and treatment of bleeding episodes in patients with haemophilia A. The present investigations from the multinational, open-label guardian™ clinical trials assessed the haemostatic response of turoctocog alfa (NovoEight®), a rFVIII product, in patients with severe haemophilia A (FVIII ≤ 1%) undergoing surgery. All patients had a minimum of 50 exposure days to any FVIII product prior to surgery and no history of inhibitors. A total of 41 procedures (13 orthopaedic, 19 dental and 9 general) were performed in 33 patients aged 4–59 years. Of the 41 procedures, 15 were major surgeries in 13 patients and 26 were minor surgeries in 21 patients. The success rate for haemostatic response was 100% (success was defined as ‘excellent’ or ‘good’ haemostatic outcome). Turoctocog alfa consumption on the day of surgery ranged from 27 to 153 IU kg−1. The mean daily dose declined over time, while retaining adequate FVIII coverage as measured by trough levels. Overall, no safety issues were identified. No thrombotic events were observed and none of the patients developed FVIII inhibitors. In conclusion, the present results show that turoctocog alfa was effective in controlling blood loss by obtaining a sufficient haemostatic response in patients with severe haemophilia A undergoing surgery. PMID:25273984

Methodologies for data collection in congenital haemophilia with inhibitors (CHwI): critical assessment of the literature and lessons learned from recombinant factor VIIa.

PubMed

Kessler, C M; Benchikh El Fegoun, S; Worster, A

2018-05-09

To systematically review the effectiveness of on-demand treatment with recombinant coagulation factor VIIa (rFVIIa) in congenital haemophilia with inhibitors and, if feasible, perform a meta-analysis of the data. Publications from Embase ® , MEDLINE ® , MEDLINE ® In-Process and the Cochrane Central Register of Controlled Trials were searched. Selected publications were reviewed for inclusion by two independent expert reviewers. Discrepancies were reconciled by a third independent reviewer. Data from selected studies were extracted using a predefined grid to ensure uniform and comparable results were captured. A systematic search (cut-off date of 2 May 2016) identified 20 studies (13 observational; seven randomized controlled trials). All studies were of sufficient quality to include in this analysis and comprised 1221 participants, with 5981 bleeds in 746 individuals treated with rFVIIa. Haemostatic overall effectiveness of the individual studies identified ranged from 68% to 100% at ≤12 hours, 86% to 96% at 13-24 hours and 76% to 99% at 24-48 hours with rFVIIa <100 μg/kg, with similar rates reported for the ≥250 μg/kg dose. However, heterogeneity between the studies precluded pooling of results. Data from the individual studies confirmed that rFVIIa is an effective therapy for the on-demand treatment of bleeds in congenital haemophilia with inhibitors. However, the high levels of heterogeneity between studies precluded pooling of results for a valid, reliable or precise summary measure. There remains a need to implement standardized clinical definitions and measurements for the effectiveness and safety of haemophilia therapies in future clinical trials. © 2018 John Wiley & Sons Ltd.

The effect of Nordic Walking on joint status, quality of life, physical ability, exercise capacity and pain in adult persons with haemophilia.

PubMed

Salim, Maryem; Brodin, Elisabeth; Spaals-Abrahamsson, Yvonne; Berntorp, Erik; Zetterberg, Eva

2016-06-01

Nordic Walking is an exercise form requiring significant energy consumption, but where the use of poles minimizes the risk of injury. The aim of this pilot study was to examine the effect of 3 months of Nordic Walking on males (>40 years of age) with haemophilia, regarding joint function (Haemophilia Joint Health Score), physical ability (Haemophilia Exercise Project - Test-Questionnaire), exercise capacity (6-min walking test), pain (visual analogue scale) and quality of life (the Swedish version of The Short Form Health Survey, SF-36). Pre-interventional and post-interventional scores of above-mentioned parameters were analysed, using Wilcoxon Signed Ranks Test. Eleven participants were recruited to the study. Statistically significant improvements were observed in physical ability (P value: 0.01) and body perception (P value: 0.02). The intervention did not increase number of bleedings or factor consumption. This is the first study ever evaluating Nordic Walking in persons with haemophilia. Our results suggest that Nordic Walking is safe and efficient, also in patients with haemophilic arthropathy.

Comprehensive elements of a physiotherapy exercise programme in haemophilia--a global perspective.

PubMed

Blamey, G; Forsyth, A; Zourikian, N; Short, L; Jankovic, N; De Kleijn, P; Flannery, T

2010-07-01

Exercise programmes for people with haemophilia are usually designed and implemented to help manage the recovery after a haemarthrosis or a muscle bleed, or as a tool to help prevent bleeding episodes from occurring. In this article, we have identified individual components of exercise that are often applied as separate entities, but may also need to be implemented in concert for optimized impact. Although it may be necessary on occasion to bias an exercise programme towards one component over the others, it is important to recognize that the various elements of exercise are not mutually exclusive. Decreased flexibility, strength and proprioception, will result in an impairment of balance and a loss of function. Programme design should whenever possible be guided by proven methodology in terms of how each component is incorporated, and more specifically how long to perform the exercise for and how many repetitions should be performed. We recognize, however, that this is not always possible and that there is significant value in drawing from the experience of clinicians with specialized training in the management of haemophilia. In this study, both perspectives are presented, providing reference-based reviews of the mechanics of the various elements of exercise as well as the expert opinions of the authors. Research that has been completed using patients with conditions other than haemophilia may or may not have a direct application with the bleeding disorders population, but the programme design based on principles of tissue healing in addition to disease specific knowledge should be encouraged.

A haemophilia disease management programme targeting cost and utilization of specialty pharmaceuticals.

PubMed

Duncan, N; Roberson, C; Lail, A; Donfield, S; Shapiro, A

2014-07-01

The high cost of clotting factor concentrate (CFC) used to treat haemophilia and von Willebrand disease (VWD) attracts health plans' attention for cost management strategies such as disease management programmes (DMPs). In 2004, Indiana's high risk insurance health plan, the Indiana Comprehensive Health Insurance Association, in partnership with the Indiana Hemophilia and Thrombosis Center developed and implemented a DMP for beneficiaries with bleeding disorders. This report evaluates the effectiveness of the DMP 5 years post implementation, with specific emphasis on the cost of CFC and other medical expenditures by severity of disease. A pre/post analysis was used. The main evaluation measures were total cost, total outpatient CFC IU dispensed and adjusted total outpatient CFC cost. Summary statistics and mean and median plots were calculated. Overall, 1000 non-parametric bootstrap replicates were created and percentile confidence limits for 95% confidence intervals (CI) are reported. Mean emergency department (ED) visits and mean and median duration of hospitalizations are also reported. The DMP was associated with a significant decrease in mean annualized total cost including decreased CFC utilization and cost in most years in the overall group, and specifically in patients with severe haemophilia. Patients with mild and moderate haemophilia contributed little to overall programme expenditures. This specialty health care provider-administered DMP exemplifies the success of targeted interventions developed and implemented through a health care facility expert in the disease state to curb the cost of specialty pharmaceuticals in conditions when their expenditures represent a significant portion of total annual costs of care. © 2014 John Wiley & Sons Ltd.

Low-factor consumption for major surgery in haemophilia B with long-acting recombinant glycoPEGylated factor IX.

PubMed

Escobar, M A; Tehranchi, R; Karim, F A; Caliskan, U; Chowdary, P; Colberg, T; Giangrande, P; Giermasz, A; Mancuso, M E; Serban, M; Tsay, W; Mahlangu, J N

2017-01-01

Surgery in patients with haemophilia B carries a high risk of excessive bleeding and requires adequate haemostatic control until wound healing. Nonacog beta pegol, a long-acting recombinant glycoPEGylated factor IX (FIX), was used in the perioperative management of patients undergoing major surgery. To evaluate the efficacy and safety of nonacog beta pegol in patients with haemophilia B who undergo major surgery. This was an open-label, multicentre, non-controlled surgery trial aimed at assessing peri- and postoperative efficacy and safety of nonacog beta pegol in 13 previously treated patients with haemophilia B. All patients received a preoperative nonacog beta pegol bolus injection of 80 IU kg -1 . Postoperatively, the patients received fixed nonacog beta pegol doses of 40 IU kg -1 , repeated at the investigator's discretion. Safety assessments included monitoring of immunogenicity and adverse events. Intraoperative haemostatic effect was rated 'excellent' or 'good' in all 13 cases. Apart from the preoperative injection, none of the patients needed additional doses of nonacog beta pegol on the day of surgery. The median number of postoperative doses of nonacog beta pegol was 2.0 from days 1 to 6 and 1.5 from days 7 to 13. No unexpected intra- or postoperative complications were observed including deaths or thromboembolic events. No patients developed inhibitors. These results indicated that nonacog beta pegol was safe and effective in the perioperative setting, allowing major surgical interventions in patients with haemophilia B with minimal peri- and postoperative concentrate consumption and infrequent injections as reported with standard FIX products. © 2016 John Wiley & Sons Ltd.

Design Considerations for an Intensive Autism Treatment Centre

ERIC Educational Resources Information Center

Deochand, Neil; Conway, Alissa A.; Fuqua, R. Wayne

2015-01-01

Individuals with autistic spectrum disorder (ASD) who display severe and challenging behaviour sometimes require centre-based intensive applied behaviour analysis (ABA) therapy to meet their health, safety and educational needs. Unfortunately, despite the need for centre-based treatment, there is a paucity of empirical research on building and…

Complications of haemophilia in babies (first two years of life): a report from the Centers for Disease Control and Prevention Universal Data Collection System

PubMed Central

KULKARNI, R.; PRESLEY, R. J.; LUSHER, J. M.; SHAPIRO, A. D.; GILL, J. C.; MANCO-JOHNSON, M.; KOERPER, M. A.; ABSHIRE, T. C.; DIMICHELE, D.; HOOTS, W. K.; MATHEW, P.; NUGENT, D. J.; GERAGHTY, S.; EVATT, B. L.; SOUCIE, J. M.

2016-01-01

Aim To describe the prevalence and complications in babies ≤2 years with haemophilia. Methods We used a standardized collection tool to obtain consented data on eligible babies aged ≤2 years with haemophilia enrolled in the Centers for Disease Control and Prevention Universal Data Collection System surveillance project at US Hemophilia Treatment Centers (HTCs). Results Of 547 babies, 82% had haemophilia A, and 70% were diagnosed within one month of birth. Diagnosis was prompted by known maternal carrier status (40%), positive family history (23%), bleeding (35%) and unknown 2%; 81% bled during the first two years. The most common events were bleeding (circumcision, soft tissue, oral bleeding) and head injury. There were 46 episodes of intracranial haemorrhage (ICH) in 37 babies (7%): 18 spontaneous, 14 delivery related, 11 traumatic, 2 procedure related and 1 unknown cause. Of the 176 central venous access devices (CVADs) in 148 (27%) babies, there were 137 ports, 22 surgically inserted central catheters and 20 peripherally inserted central catheters. Ports had the lowest complication rates. Inhibitors occurred in 109 (20%) babies who experienced higher rates of ICH (14% vs. 5%; P = 0.002), CVAD placement (61% vs. 19%; P < 0.001) and CVAD complications (44% vs. 26%; P < 0.001). The most common replacement therapy was recombinant clotting factor concentrates. Conclusion Bleeding events in haemophilic babies ≤2 years were common; no detectable difference in the rates of ICH by the mode of delivery was noted. Neonatal factor exposure did not affect the inhibitor rates. Minor head trauma, soft tissue and oropharyngeal bleeding were the leading indications for treatment. PMID:27813214

How fit are children and adolescents with haemophilia in Germany? Results of a prospective study assessing the sport-specific motor performance by means of modern test procedures of sports science.

PubMed

Seuser, A; Boehm, P; Ochs, S; Trunz-Carlisi, E; Halimeh, S; Klamroth, R

2015-07-01

There are a lot of publications on the physical fitness of patients with haemophilia (PWH), however, most studies only reflect individual sport-specific motor capacities or focus on a single fitness ability. They involve small patient populations. In this respect principal objective of this study was to compare the physical fitness in all respects and the body composition of young PWH to healthy peers based on the most valid data we could get. Twenty-one German haemophilia treatment centres were visited from 2002 to 2009. PWH between 8 and 25 years were included. They performed a five-stage fitness test covering the sport-specific motor capacities for coordination, measured by one leg stand, strength, aerobic fitness and mobility as well as body composition. The patients' results were compared with age- and gender-specific reference values of healthy subjects. Two hundred and eighty-five PWH (mean age 13.2 ± 4.5 years, 164 PWH with severe disease) were included prospectively in the study. PWH are significantly below the reference values of healthy subjects in the one-leg stand test, the mobility of the lower extremity, the strength ratio of chest and back muscles and the endurance test. In body composition, the back strength and the mobility of the upper extremity PWH are significantly above the reference values. There are no significant differences in abdominal strength. In conclusion we found specific differences in different fitness abilities between PWH and healthy subjects. Knowing this, we are able to work out exercise programmes to compensate the diminished fitness abilities for our PWH. © 2015 John Wiley & Sons Ltd.

An economic model of haemophilia in Mexico.

PubMed

Martínez-Murillo, C; Quintana, S; Ambriz, R; Benitez, H; Berges, A; Collazo, J; Esparza, A; Pompa, T; Taboada, C; Zavala, S; Larochelle, M R; Bentkover, J D

2004-01-01

A model was developed to assess the lifetime costs and outcomes associated with haemophilia in Mexico. A retrospective chart review of 182 type A haemophiliacs was conducted for patients aged 0-34 years receiving one of three treatments: (i) cryoprecipitate at clinic; (ii) concentrate at home; or (iii) concentrate at clinic. Patients treated at home experienced 30% less joint damage, used 13-54% less factor VIII, had four times fewer clinic visits, and utilized half as many hospital days than those treated at a clinic. For cryoprecipitate at clinic patients, the annual incidence rates of HCV and HIV were calculated to be 3.6% and 1.4% respectively. The life expectancy for patients receiving cryoprecipitate and those receiving concentrate was estimated to be 49 years and 69 years respectively, with 58% of cryoprecipitate patients predicted to die of AIDS before age 69. Across the lifespan, the average annual cost of care was US$11,677 (MN$110,464) for cryoprecipitate at clinic patients, US$10,104 (M$95,580) for concentrate at home patients and US$18,819 (MN$178,027) for concentrate at clinic patients. Using a 5% discount rate, the incremental lifetime cost per year of life added for treatment with concentrate at home compared with cryoprecipitate at a clinic was US$738 (MN$6981). Rank order stability analysis demonstrated that the model was most sensitive to the cost of fVIII. These results indicate that treatment with concentrate at home compared with cryoprecipitate at a clinic substantially improves clinical outcomes at reduced annual cost levels.

First analysis of 10-year trends in national factor concentrates usage in haemophilia: data from CHARMS, the Canadian Hemophilia Assessment and Resource Management System

PubMed Central

Traore, A N; Chan, A K C; Webert, K E; Heddle, N; Ritchie, B; St-Louis, J; Teitel, J; Lillicrap, D; Iorio, A; Walker, I

2014-01-01

The Canadian Hemophilia Assessment and Resource Management System (CHARMS) tracks factor concentrates (FC) from the sole suppliers, Canadian Blood Services (CBS) and Hema-Quebec (HQ), to hospitals and to patients’ homes. Patients FC infusion data are entered into CHARMS at Canadian Hemophilia Treatment Centres (HTCs) then exported to the national database (CentrePoint). From 2000 to 2009, 2260 registered haemophilia A or B patients received FVIII (1 009 097 765 IU) and FIX (272 406 859 IU). Over 91% of FVIII and over 84% of FIX was infused at home. Utilization of FVIII progressively increased; this was accounted for by an increase in the number of patients treated (r = 0.97; P < 0.001), there being a linear relationship between the increase in utilization and the increase in number of patients treated (P < 0.001). There was also a correlation with the annual amount used per patient (r = 0.95; P < 0.001). Utilization of FIX did not increase over time. The highest proportional utilization of both FVIII and FIX was for prophylaxis, and this proportion progressively increased being, in year 10 (2009), 77% and 66% for FVIII and FIX respectively. The proportion used for bleeding remained steady; in year 10 that proportion was 14% for FVIII and 26% for FIX, the use per patient for bleeding decreasing. The HTC-based CHARMS tracking system is essential, in Canada, for analysing indications for infusion, for predicting utilization and planning for future needs. PMID:24948405

Orthopaedic management of haemophilia arthropathy of the ankle.

PubMed

Pasta, G; Forsyth, A; Merchan, C R; Mortazavi, S M J; Silva, M; Mulder, K; Mancuso, E; Perfetto, O; Heim, M; Caviglia, H; Solimeno, L

2008-07-01

radiographic findings. Joint fusion, or arthrodesis, is the treatment of choice in the advanced stages of ankle arthropathy although total ankle replacement is currently available. Early ankle replacement components were associated with a poor outcome, but as implant designs have improved, there have been successful outcomes achieved. As the ankle is a commonly affected joint in many individuals with haemophilia, it is important to add to the knowledge base to validate indications and timing of surgical and non-surgical interventions in ankle arthropathy.

Combination of FVIII and by-passing agent potentiates in vitro thrombin production in haemophilia A inhibitor plasma.

PubMed

Klintman, Jenny; Astermark, Jan; Berntorp, Erik

2010-11-01

The by-passing agents, recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (APCC), are important tools in the treatment of patients with haemophilia A and high-responding inhibitory antibodies. It has been observed clinically that in some patients undergoing immune tolerance induction the bleeding frequency decreases, hypothetically caused by a transient haemostatic effect of infused FVIII not measurable ex vivo. We evaluated how by-passing agents and factor VIII (FVIII) affect thrombin generation (TG) in vitro using plasma from 11 patients with severe haemophilia A and high titre inhibitors. Samples were spiked with combinations of APCC, rFVIIa and five different FVIII products. Combination of APCC and FVIII showed a synergistic effect in eliciting TG (P<0·005) for four FVIII products. When rFVIIa and FVIII were combined the interaction between the preparations was found to be additive. APCC and rFVIIa were then combined without FVIII, resulting in an additive effect on thrombin production. Each product separately increased TG above baseline. In conclusion, the amount of thrombin formed in vitro by adding a by-passing agent, was higher in the presence of FVIII. Our findings support the use of FVIII in by-passing therapy to optimize the haemostatic effect. © 2010 Blackwell Publishing Ltd.

Travel behaviour of patients with haemophilia.

PubMed

Ringwald, Juergen; Rudolph, Pamela; Biner, Melanie; Fießler, Cornelia; Mayr, Andreas; Lohmann, Martin; Strobel, Julian; Eckstein, Reinhold; Kurnik, Karin

2013-01-01

We aimed to identify socio-demographic, or illness-specific variables, influencing travel behaviour of haemophilic patients. A standardised questionnaire was sent to more than 2000 members of two German Haemophilia associations. Multivariable logistic regression with the outcomes frequent (at least two journeys per year) and long-haul travel (outside of Europe) was applied separately on adult patients and patients younger than 18 years. Among 345 adults, high education level, living in a partnership or travelling alone was significantly associated with frequent travel with odds ratios (ORs)/95%-confidence intervals (95%-CI) of 3.10/1.72-5.80, 1.99/1.10-3.62 and 1.73/1.01-3.62, respectively. High education level and self-application of clotting factors were significant variables for long-haul travel (OR/95%-CI: 2.45/1.43-4.26 and 3.25/1.33-8.52, respectively). Among 144 non-adults, a younger age or performing permanent prophylactic treatment was significantly associated with a lower likelihood for long-haul travel (OR/95%-CI: 0.51/0.22-0.95 and 0.10/0.01-0.65, respectively). Longer awareness of the disease increased the likelihood for long-haul travel (OR/95%-CI: 1.06/1.01-1.14). High education level and self-application of clotting factors influence travel intensity of adult patients most strikingly. Parents of very young patients on permanent prophylactic treatment might need special education to facilitate holiday travel for these families. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gene therapy for haemophilia: prospects and challenges to prevent or reverse inhibitor formation.

PubMed

Scott, David W; Lozier, Jay N

2012-02-01

Monogenic hereditary diseases, such as haemophilia A and B, are ideal targets for gene therapeutic approaches. While these diseases can be treated with protein therapeutics, such as factor VIII (FVIII) or IX (FIX), the notion that permanent transfer of the genes encoding these factors can cure haemophilia is very attractive. An underlying problem with a gene therapy approach, however, is the patient's immune response to the therapeutic protein (as well as to the transmission vector), leading to the formation of inhibitory antibodies. Even more daunting is reversing an existing immune response in patients with pre-existing inhibitors. In this review, we will describe the laboratory and clinical progress, and the challenges met thus far, in achieving the goal of gene therapy efficacy, with a focus on the goal of tolerance induction. Published 2011. This article is a US Government work and is in the public domain in the USA.

Tests for qualitative treatment-by-centre interaction using a 'pushback' procedure.

PubMed

Ciminera, J L; Heyse, J F; Nguyen, H H; Tukey, J W

1993-06-15

In multicentre clinical trials using a common protocol, the centres are usually regarded as being a fixed factor, thus allowing any treatment-by-centre interaction to be omitted from the error term for the effect of treatment. However, we feel it necessary to use the treatment-by-centre interaction as the error term if there is substantial evidence that the interaction with centres is qualitative instead of quantitative. To make allowance for the estimated uncertainties of the centre means, we propose choosing a reference value (for example, the median of the ordered array of centre means) and converting the individual centre results into standardized deviations from the reference value. The deviations are then reordered, and the results 'pushed back' by amounts appropriate for the corresponding order statistics in a sample from the relevant distribution. The pushed-back standardized deviations are then restored to the original scale. The appearance of opposite signs among the destandardized values for the various centres is then taken as 'substantial evidence' of qualitative interaction. Procedures are presented using, in any combination: (i) Gaussian, or Student's t-distribution; (ii) order-statistic medians or outward 90 per cent points of the corresponding order statistic distributions; (iii) pooling or grouping and pooling the internally estimated standard deviations of the centre means. The use of the least conservative combination--Student's t, outward 90 per cent points, grouping and pooling--is recommended.

Participation in sports and physical activity of haemophilia patients.

PubMed

Fromme, A; Dreeskamp, K; Pollmann, H; Thorwesten, L; Mooren, F C; Völker, K

2007-05-01

Modern therapy options offer haemophiliacs more and more possibilities for an active participation in sports. The purpose of the present study was to investigate the attitude of these patients towards sports, their participation in school and leisure time sports activities, and differences between juveniles and adults. We investigated 44 children and adolescents (aged from 4 to 16 years) and 27 adults (aged from 18 to 72 years) with haemophilia by means of a questionnaire. 79.6% of the juvenile patients participated always or almost always in school sports, while this percentage was significantly (P < 0.05) lower in the former school time of the adults (37%). Sports play an important or very important role in leisure time activities for 75% of the adolescent and 55.5% of the adult haemophiliacs (P < 0.05). Bleeding complications occurred in 17.6% of all patients; there was no correlation with any particular type of sports. There were only slight differences between both groups, regarding their motivation to participate in sports activities. The main reasons involved social aspects and having fun. The results show that the modern therapy of haemophilia probably leads to a more positive attitude towards sports and to a wider spectrum of practised sports. This, however, may be associated with an increasing potential of health risks, which require a high level of sports medical care.

Genetic risk factors for inhibitors in haemophilia A.

PubMed

Bardi, Edit; Astermark, Jan

2015-02-01

The current most serious side effect of haemophilia treatment is inhibitor development. Significant progress has been made over the last decades to understand why this complication occurs in some patients and it seems clear that both genetic and non-genetic factors are involved. Several issues however remain to be settled. A review was undertaken to summarise some key findings regarding the current view and available data on genetic markers of potential importance within this area. The causative F8 mutation, together with the HLA class II alleles, plays a pivotal pathophysiological role in inhibitor development. The types of mutation most frequently associated with inhibitors are large deletions, nonsense mutations, inversions, small deletions/insertions without A-runs, splice-site mutations at conserved nucleotides and certain missense mutations. Regarding HLA class II allele, it has been hard to consistently identify risk alleles. Ethnicity has consistently been associated with inhibitor risk, but the causality of this has so far not been resolved. Among immune regulatory molecules, several polymorphic molecules have been suggested to be of importance. Most of these need additional studies and immune system challenges have to be fully evaluated. Inhibitor risk should be further defined, as patients in the future may be offered non-immunogenic treatments. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Role of exercise and physical activity on haemophilic arthropathy, fall prevention and osteoporosis.

PubMed

Forsyth, A L; Quon, D V; Konkle, B A

2011-09-01

In older men with haemophilia, arthropathy resulting from a lifetime of intra-articular bleeding contributes to the loss of independence and increased morbidity that occurs with age. A regular exercise programme that incorporates aerobics, strength training and balance and flexibility activities is a key component of successful ageing, helping to improve functional mobility and reduce the risk of falls, osteoporosis and osteoporotic fractures. Because of the special challenges associated with haemophilia, which include both the underlying coagulopathy and, in many cases, extensive joint damage, patients beginning an exercise regimen should be referred to appropriately trained physiotherapists (preferably someone associated with a haemophilia treatment centre) for evaluation, education and instruction and follow-up. Various assistive devices may make exercise easier to perform and more comfortable. © 2011 Blackwell Publishing Ltd.

Determinants of drug costs in hopitalised patients with haemophilia: impact of recombinant activated factor VII.

PubMed

Galanaud, Jean Philippe; Pelletier-Fleury, Nathalie; Logerot-Lebrun, Hélène; Lambert, Thierry

2003-01-01

To analyse the determinants of anti-haemophilic drug costs in hospitalised patients with haemophilia and to estimate the impact of recombinant activated factor VII (rFVIIa) therapy on this expenditure. The perspective of the study was from the viewpoint of the hospital. A prospective study was carried out. All patients with haemophilia who were hospitalised in 1999 in Bicêtre public hospital, Paris, France were included in the cohort. For each of the 96 patients (154 hospital stays), we estimated the costs of anti-haemophilic drugs (coagulation concentrates) used. Costs were then stratified by different variables (severity of the disease, presence of a circulating inhibitor to coagulation factors, etc.) and a multivariate model was developed to determine the relationship between these variables and total anti-haemophilic drug costs, while controlling for potential confounders. Our study revealed: (i) the independent role of the five following variables in contributing to high anti-haemophilic drug expenditure: presence of a circulating inhibitor to coagulation factors, odds ratio (OR) = 16.9 (95% CI: 4.3-66); severity of the disease (factor VIII or factor IX < or =0.01 IU/mL), OR = 3.7 (95% CI: 1.6-8.6); length of hospital stay >4 days, OR = 8 (95% CI: 2.2-29.4); age >18 years old, OR = 6.2 (95% CI: 1.6-24.5); and surgical reasons for hospitalisation (whether surgery was haemophilia related [OR = 35.7 (95% CI: 7.3-175)] or not [OR = 5.4 (95% CI: 1.3-22.5)]); (ii) the large share that rFVIIa represented in this expenditure on medicines: rFVIIa was used in 20.1% of hospital stays and accounted for 56.2% of the total anti-haemophilic drug costs, which were estimated at 4,384,732 Euros (2000 values). Our data underline the heavy cost of the treatment of haemophilic patients with an inhibitor to coagulation factors. But, to the question of whether the high expenditure linked to rFVIIa utilisation will be balanced out by later benefits, it is not yet possible to reply

The use of a co-design model in improving timely bleed reporting by adults with haemophilia living in the Auckland region of New Zealand.

PubMed

d'Young, A I; Young, L; Ockelford, P A; Brasser, M; Slavin, K; Manson, L; Preston, S

2014-05-01

Many adult patients diagnosed with phenotypically moderate and severe haemophilia living in the Auckland region of New Zealand do not report bleeding episodes within a timeframe that allows for optimal assessment and management. This can result in poor clinical outcomes for patients and poor oversight of the use of expensive clotting factor concentrates. Our goal was to improve both the number and speed at which bleeding episodes were reported to our centre, improving access to care and clinical oversight of the use of expensive factor concentrates and aiding the development of a care partnership with patients. We worked with 70 adult PWH living in the Auckland region of New Zealand with moderate and severe haemophilia A and B. Over a 5-month period between March and July 2013 we used a co-design model to develop and implement a range of strategies to improve the timing and frequency of bleed reporting. Mean bleed reporting time was reduced threefold, with a threefold increase in the number of bleeds reported per month. We reduced the number of bleeding episodes reported outside of a prespecified 48-h time limit by 68%. We significantly improved bleed reporting and time to report, indicating improved access to our services, improved clinical oversight and improved accountability to our national funder. We have achieved a care partnership and a reduction in factor consumption for the study population without compromising the quality of care they receive. © 2013 John Wiley & Sons Ltd.

Addiction research centres and the nurturing of creativity: National Drug Dependence Treatment Centre, India--a profile.

PubMed

Ray, Rajat; Dhawan, Anju; Chopra, Anita

2013-10-01

The National Drug Dependence Treatment Centre (NDDTC) is a part of the All India Institute of Medical Sciences, a premier autonomous medical university in India. This article provides an account of its origin and its contribution to the field of substance use disorder at the national and international levels. Since its establishment, the NDDTC has played a major role in the development of various replicable models of care, the training of post-graduate students of psychiatry, research, policy development and planning. An assessment of the magnitude of drug abuse in India began in the early 1990s and this was followed by a National Survey on Extent, Patterns and Trends of Drug Abuse in 2004. Several models of clinical care have been developed for population subgroups in diverse settings. The centre played an important role in producing data and resource material which helped to scale up opioid substitution treatment in India. A nationwide database on the profile of patients seeking treatment (Drug Abuse Monitoring System) at government drug treatment centres has also been created. The centre has provided valuable inputs for the Government of India's programme planning. Besides clinical studies, research has also focused on pre-clinical studies. Capacity-building is an important priority, with training curricula and resource material being developed for doctors and paramedical staff. Many of these training programmes are conducted in collaboration with other institutions in the country. The NDDTC has received funding from several national and international organizations for research and scientific meetings, and, most recently (2012), it has been designated as a World Health Organization Collaborating Centre on Substance Abuse. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

The importance of mRNA structure in determining the pathogenicity of synonymous and non-synonymous mutations in haemophilia

PubMed Central

Hamasaki-Katagiri, Nobuko; Lin, Brian C.; Simon, Jonathan; Hunt, Ryan C.; Schiller, Tal; Russek-Cohen, Estelle; Komar, Anton A.; Bar, Haim; Kimchi-Sarfaty, Chava

2016-01-01

Introduction Mutational analysis is commonly used to support the diagnosis and management of haemophilia. This has allowed for the generation of large mutation databases which provide unparalleled insight into genotype-phenotype relationships. Haemophilia is associated with inversions, deletions, insertions, nonsense and missense mutations. Both synonymous and non-synonymous mutations influence the base pairing of messenger RNA (mRNA), which can alter mRNA structure, cellular half-life and ribosome processivity/elongation. However, the role of mRNA structure in determining the pathogenicity of point mutations in haemophilia has not been evaluated. Aim To evaluate mRNA thermodynamic stability and associated RNA prediction software as a means to distinguish between neutral and disease-associated mutations in haemophilia. Methods Five mRNA structure prediction software programs were used to assess the thermodynamic stability of mRNA fragments carrying neutral vs. disease-associated and synonymous vs. non-synonymous point mutations in F8, F9 and a third X-linked gene, DMD (dystrophin). Results In F8 and DMD, disease-associated mutations tend to occur in more structurally stable mRNA regions, represented by lower MFE (minimum free energy) levels. In comparing multiple software packages for mRNA structure prediction, a 101–151 nucleotide fragment length appears to be a feasible range for structuring future studies. Conclusion mRNA thermodynamic stability is one predictive characteristic, which when combined with other RNA and protein features, may offer significant insight when screening sequencing data for novel disease-associated mutations. Our results also suggest potential utility in evaluating the mRNA thermodynamic stability profile of a gene when determining the viability of interchanging codons for biological and therapeutic applications. PMID:27933712

RCT - subjective physical performance and quality of life after a 6-month programmed sports therapy (PST) in patients with haemophilia.

PubMed

Runkel, B; Von Mackensen, S; Hilberg, T

2017-01-01

Musculoskeletal bleedings lead to limitations in the locomotor system and consequently, in health-related quality of life (HRQoL) in patients with haemophilia (PwH). Sports therapy is increasingly recommended to improve their physical performance. Until today, randomised controlled studies investigating changes in physical performance in PwH are rare. This study investigates the impact of programmed sports therapy on the subjective physical performance and the HRQoL in PwH. A randomised controlled trial (RCT) was conducted with a training intervention for over 6 months. For this purpose, 64 PwH with moderate (n = 5) or severe (n = 59) haemophilia A (n = 57) or B (n = 7) were randomised into two groups - intervention (IG) or control group (CG). The HRQoL was assessed with the SF-36 questionnaire and the disease-specific Haem-A-QoL before and after the intervention. The subjective physical performance was tested by the HEP-Test-Q. After the 6-month training intervention, PwH in the IG subjectively reported significant better 'endurance' (P = 0.000) in the HEP-Test-Q compared to the CG. In the SF-36, a significant difference in the domains 'general health perceptions' (P = 0.005) and 'mental health' (P = 0.001) was detected. The haemophilia-specific HRQoL questionnaire showed a significant improvement in the dimensions 'feeling' (P = 0.049), 'work' (P = 0.046) and 'family' (P = 0.040). In the first RCT evaluating the impact of a 6-month training intervention on the subjective perception of PwH, an increase in subjective physical performance and some domains of HRQoL was demonstrated in the IG. Specific sports therapy should be included into the comprehensive treatment under supervision and monitoring by experienced staff. © 2016 John Wiley & Sons Ltd.

Development and preliminary testing of a Paediatric Version of the Haemophilia Activities List (pedhal).

PubMed

Groen, W G; van der Net, J; Helders, P J M; Fischer, K

2010-03-01

Worldwide, children with haemophilia suffer from limitations in performing activities of daily living. To measure such limitations in adults a disease-specific instrument, the Haemophilia Activities List (HAL), was created in 2004. The aim of this study was to adapt the HAL for children with haemophilia and to assess its psychometric properties. The structure and the main content were derived from the HAL. Additionally, items of the Childhood Health Assessment Questionnaire and the Activity Scale for Kids were considered for inclusion. This version was evaluated by health professionals (n = 6), patients (n = 4), and parents (n = 3). A pilot test in a sample of 32 Dutch children was performed to assess score distribution, construct validity (Spearman's rho) and reproducibility. Administration of the pedhal was feasible for children from the age of 4 years onwards. The pedhal scores of the Dutch children were in the high end of the scale, reflecting a good functional status. Most subscales showed moderate associations with the joint examination (rho = 0.42-0.63) and moderate-to-good associations with the physical function subscale of the CHQ-50 (rho = 0.48-0.74). No significant associations were found for the pedhal and the subscales mental health and behaviour, except for the subscales leisure and sport and mental health (rho = 0.47). Test-retest agreement was good. The pedhal is a promising tool, but further testing in populations with a higher level of disability is warranted to study the full range of its psychometric properties.

Self-reported prevalence, description and management of pain in adults with haemophilia: methods, demographics and results from the Pain, Functional Impairment, and Quality of life (P-FiQ) study.

PubMed

Witkop, M; Neff, A; Buckner, T W; Wang, M; Batt, K; Kessler, C M; Quon, D; Boggio, L; Recht, M; Baumann, K; Gut, R Z; Cooper, D L; Kempton, C L

2017-07-01

Haemophilia is characterized by frequent haemarthrosis, leading to acute/chronic joint pain. To assess self-reported prevalence, description and management of pain in adult males with mild-to-severe haemophilia and history of joint pain/bleeding. Participants completed a pain survey and five patient-reported outcome instruments assessing pain, functional impairment and health-related quality of life (HRQoL). Of 381 participants enrolled, median age was 34 years; 77% had haemophilia A, 71% had severe disease and 65% were overweight/obese. Many (56%) were not receiving routine infusions; 30% never received routine infusions. During the prior 6 months, 20% experienced acute pain, 34% chronic pain and 32% both acute/chronic pain. Subjects with both acute/chronic pain (vs. none, acute or chronic) were more likely to be depressed (30% vs. 0-15%), obese (35% vs. 20-29%) and have lower HRQoL (mean EQ-5D visual analog scale, 69 vs. 83-86) and function (median overall Hemophilia Activities List, 60 vs. 88-99). Most common analgesics used for acute/chronic pain during the prior 6 months were acetaminophen (62%/55%) and non-steroidal anti-inflammatory drugs (34%/49%); most common non-pharmacologic strategies were ice (65%/33%) and rest (51%/33%). Hydrocodone-acetaminophen was the most common opioid for both acute/chronic pain (30%); other long-acting opioids were infrequently used specifically for chronic but not acute pain (morphine, 7%; methadone, 6%; fentanyl patch, 2%). Patients with chronic pain, particularly those with both acute/chronic pain, frequently experience psychological issues, functional disability and reduced HRQoL. Treatment strategies for acute pain (e.g. routine infusions to prevent bleeding) and for chronic pain (e.g. long-acting opioids) may be underused. © 2017 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Immune tolerance induction in patients with haemophilia a and inhibitors: effectiveness and cost analysis in an European Cohort (The ITER Study).

PubMed

Rocino, A; Cortesi, P A; Scalone, L; Mantovani, L G; Crea, R; Gringeri, A

2016-01-01

Although immune tolerance induction (ITI) is considered the first choice treatment to eradicate inhibitors in haemophilia A patients, little is known about outcomes determinants and cost magnitude. A retrospective, multicentre study was conducted to assess the relationship between ITI outcome, clinical and treatment characteristics and cost of ITI treatment in haemophilia A patients. Data from 12 months before inhibitor diagnosis to 12 months after ITI completion were collected. Treatment cost was calculated in the third-party perspective and expressed as mean € per patient-month. Cox regression models were used to identify predictors of better outcome and the time taken to achieve tolerance. Seventy-one patients, aged 0.4-41 years (median: 3.8 years) at ITI start, were enrolled. Undetectable inhibitor was achieved in 84.5% of patients and inhibitor eradication with normal factor VIII (FVIII) pharmacokinetics in 74.2%. Median time to successful tolerance was 10.7 months (range 2.0-90.0 months). Peak inhibitor level on ITI was a significant predictor of ITI success. Breakthrough bleeding event incidence during ITI was associated with time to success. The mean cost of treatment for the time period between inhibitor diagnosis and ITI start was €3188 per patient-month (92.1% for bypassing agents), and €60 078 during ITI (76.8% for FVIII use in ITI). Immune tolerance induction in this patient cohort was successful in 84.5% of patients with a mean cost of €60 000 per patient-month. This high cost is dwarfed by comparison with the prospect of lifelong care of an inhibitor patient, in addition to gains in life expectancy and health-related quality of life. © 2015 John Wiley & Sons Ltd.

Mode of delivery and risk of intracranial haemorrhage in newborns with severe haemophilia A: a multicentre study in Gulf region.

PubMed

Nazir, H F; Al Lawati, T; Beshlawi, I; AlSharidah, S; Elshinawy, M; Alkasim, F; Khanani, M F; Tarawa, A; Al Subhi, T; Alrawas, A; Al Riyami, W; Al Kindi, S; Al Saadi, K; Al-Lamki, S; Wali, Y

2016-05-01

The optimum mode of delivery in a known carrier of a haemophilia A is still an issue of debate. This study was conducted to report a multicentre experience in Gulf Cooperation Council (GCC) on the incidence of intracranial haemorrhage (ICH) in newborns with severe haemophilia A delivered by different modalities. We have conducted a retrospective/prospective multicentre cohort study including a total of seven hospitals distributed in four GCC countries between 1998 and Jan 2015. A total of 163 patient with severe haemophilia A (factor VIII <1%) were enrolled in this study, age ranged between 2 weeks to 18 years. Most of the patients were born by spontaneous vaginal delivery (SVD) (131, 80.4%), whereas 26 patients (16%) were born by CS and only six patients were born by instrumental delivery (3.7%), five of them by vacuum and one was delivered using forceps. Five out of 163 patients developed ICH during the first 2 weeks of life (3.1%). Two of them were born by SVD (2/131; 1.5%) and two were born by instrumental delivery (2/6; 33.3%). Only one patient among those who were born by caesarean section developed ICH (1/26; 3.8%). Assisted vaginal delivery was associated with a significant risk of ICH, in comparison to SVD and CS (P = 0.0093). Normal vaginal delivery is still considered a safe journey through the birth canal for haemophilic newborns particularly in this area of the world. Larger prospective studies might be needed to define an evidence-based optimal mode of delivery for the haemophilia carrier expecting an affected child. © 2015 John Wiley & Sons Ltd.

Patient or treatment centre? Where are efforts invested to improve cancer patients' psychosocial outcomes?

PubMed Central

Carey, ML; Clinton-McHarg, T; Sanson-Fisher, RW; Campbell, S; Douglas, HE

2011-01-01

The psychosocial outcomes of cancer patients may be influenced by individual-level, social and treatment centre predictors. This paper aimed to examine the extent to which individual, social and treatment centre variables have been examined as predictors or targets of intervention for psychosocial outcomes of cancer patients. Medline was searched to find studies in which the psychological outcomes of cancer patient were primary variables. Papers published in English between 1999 and 2009 that reported primary data relevant to psychosocial outcomes for cancer patients were included, with 20% randomly selected for further coding. Descriptive studies were coded for inclusion of individual, social or treatment centre variables. Intervention studies were coded to determine if the unit of intervention was the individual patient, social unit or treatment centre. After random sampling, 412 publications meeting the inclusion criteria were identified, 169 were descriptive and 243 interventions. Of the descriptive papers 95.0% included individual predictors, and 5.0% social predictors. None of the descriptive papers examined treatment centre variables as predictors of psychosocial outcomes. Similarly, none of the interventions evaluated the effectiveness of treatment centre interventions for improving psychosocial outcomes. Potential reasons for the overwhelming dominance of individual predictors and individual-focused interventions in psychosocial literature are discussed. PMID:20646035

Influence of class I and II HLA alleles on inhibitor development in severe haemophilia A patients from the south of Brazil.

PubMed

De Barros, M F; Herrero, J C M; Sell, A M; De Melo, F C; Braga, M A; Pelissari, C B; Machado, J; De Souza Schiller, S; De Souza Hirle, L; Visentainer, J E L

2012-05-01

Congenital haemophilia A is a chromosome-linked recessive disorder caused by the deficiency or reduction of factor VIII (FVIII) pro-coagulant activity. During treatment, some patients develop alloantibodies (FVIII inhibitors) that neutralize the action of exogenously administered FVIII. Currently, the presence of these inhibitors is the most serious adverse event found in replacement therapy. Some studies have suggested that genetic factors influence the development of the FVIII coagulation inhibitors. To identify the class I and II alleles that may be influencing the formation of inhibitors in severe haemophilic patients. Genotyping of the class I (HLA-A, -B and -C) and class II (HLA-DRB1, -DQA1 and -DQB1) alleles of 122 patients with severe haemophilia A, including 36 who had developed antibodies to factor VIII, was performed. After the comparison of the group without inhibitors and the group with inhibitors, HLA-C*16 [Odds ratio (OR) = 7.73; P = 0.0092] and HLA-DRB1*14 (OR = 4.52; P = 0.0174) were found to be positively associated with the formation of the inhibitors. These results confirm that HLA alleles are involved in inhibitor production and could be used as a tool for recognition of groups at high risk of possible inhibitor development in Southern Brazilian haemophilic patients. © 2011 Blackwell Publishing Ltd.

Multi-centre audit of VMAT planning and pre-treatment verification.

PubMed

Jurado-Bruggeman, Diego; Hernández, Victor; Sáez, Jordi; Navarro, David; Pino, Francisco; Martínez, Tatiana; Alayrach, Maria-Elena; Ailleres, Norbert; Melero, Alejandro; Jornet, Núria

2017-08-01

We performed a multi-centre intercomparison of VMAT dose planning and pre-treatment verification. The aims were to analyse the dose plans in terms of dosimetric quality and deliverability, and to validate whether in-house pre-treatment verification results agreed with those of an external audit. The nine participating centres encompassed different machines, equipment, and methodologies. Two mock cases (prostate and head and neck) were planned using one and two arcs. A plan quality index was defined to compare the plans and different complexity indices were calculated to check their deliverability. We compared gamma index pass rates using the centre's equipment and methodology to those of an external audit (global 3D gamma, absolute dose differences, 10% of maximum dose threshold). Log-file analysis was performed to look for delivery errors. All centres fulfilled the dosimetric goals but plan quality and delivery complexity were heterogeneous and uncorrelated, depending on the manufacturer and the planner's methodology. Pre-treatment verifications results were within tolerance in all cases for gamma 3%-3mm evaluation. Nevertheless, differences between the external audit and in-house measurements arose due to different equipment or methodology, especially for 2%-2mm criteria with differences up to 20%. No correlation was found between complexity indices and verification results amongst centres. All plans fulfilled dosimetric constraints, but plan quality and complexity did not correlate and were strongly dependent on the planner and the vendor. In-house measurements cannot completely replace external audits for credentialing. Copyright © 2017 Elsevier B.V. All rights reserved.

Haemophilia Joint Health Score in healthy adults playing sports.

PubMed

Sluiter, D; Foppen, W; de Kleijn, P; Fischer, K

2014-03-01

To evaluate outcome of prophylactic clotting factor replacement in children with haemophilia, the Haemophilia Joint Health Score (HJHS) was developed aiming at scoring early joint changes in children aged 4-18. The HJHS has been used for adults on long-term prophylaxis but interpretation of small changes remains difficult. Some changes in these patients may be due to sports-related injuries. Evaluation of HJHS score in healthy adults playing sports could improve the interpretation of this score in haemophilic patients. The aim of this study was to evaluate the HJHS scores in a cohort of young, healthy men participating in sports. Concomitant with a project collecting MRI images of ankles and knees in normal young adults, HJHS scores were assessed in 30 healthy men aged 18-26, participating in sports one to three times per week. One physiotherapist assessed their clinical function using the HJHS 2.1. History of joint injuries was documented. MRI images were scored by a single radiologist, using the International Prophylaxis Study Group additive MRI score. Median age of the study group was 24.3 years (range 19.0-26.4) and median frequency of sports activities was three times per week (range 1-4). Six joints (five knees, one ankle) had a history of sports-related injury. The median overall HJHS score was 0 out of 124 (range 0-3), with 60% of subjects showing no abnormalities on HJHS. All joints were normal on MRI. These results suggest that frequent sports participation and related injuries are not related with abnormalities in HJHS scores. © 2013 John Wiley & Sons Ltd.

The Patient Reported Outcomes, Burdens and Experiences (PROBE) Project: development and evaluation of a questionnaire assessing patient reported outcomes in people with haemophilia.

PubMed

Skinner, M W; Chai-Adisaksopha, C; Curtis, R; Frick, N; Nichol, M; Noone, D; O'Mahony, B; Page, D; Stonebraker, J S; Iorio, A

2018-01-01

The interest of health care agencies, private payers and policy makers for patient-reported outcomes (PRO) is continuously increasing. There is a substantial need to improve capacity to collect and interpret relevant PRO data to support implementation of patient-centered research and optimal care in haemophilia. The Patient Reported Outcomes, Burdens and Experiences (PROBE) Project aims to develop a patient-led research network, to develop a standardized questionnaire to gather patient-reported outcomes and to perform a feasibility study of implementing the PROBE questionnaire. A pilot questionnaire was developed using focus group methodology. Content and face validity were assessed by a pool of persons living with haemophilia (PWH) and content experts through interactive workshops. The PROBE questionnaire was translated with the forward-backward approach. PROBE recruited national haemophilia patient non-governmental organizations (NGOs) to administer the questionnaire to people with and without haemophilia. PROBE measured the time to complete the questionnaire and gathered feedback on its content and clarity; staff time and cost required to implement the questionnaire were also collected. The PROBE questionnaire is comprised of four major sections (demographic data, general health problems, haemophilia-related health problems and health-related quality of life using EQ-5D-5L and EQ-VAS). Seventeen NGOs participated in the pilot study of the PROBE Project, recruiting 656 participants. Of these, 71% completed the questionnaire within 15 min, and all participants completed within 30 min. The median total staff and volunteer time required for the NGOs to carry out the study within their country was 9 h (range 2 to 40 h). NGO costs ranged from $22.00 to $543.00 USD per country, with printing and postage being the most commonly reported expenditures. The PROBE questionnaire assesses patient-important reported outcomes in PWH and control participants, with a

Using concept mapping to design an indicator framework for addiction treatment centres.

PubMed

Nabitz, Udo; van Den Brink, Wim; Jansen, Paul

2005-06-01

The objective of this study is to determine an indicator framework for addiction treatment centres based on the demands of stakeholders and in alignment with the European Foundation for Quality Management (EFQM) Excellence Model. The setting is the Jellinek Centre based in Amsterdam, the Netherlands, which serves as a prototype for an addiction treatment centre. Concept mapping was used in the construction of the indicator framework. During the 1-day workshop, 16 stakeholders generated, prioritized and sorted 73 items concerning quality and performance. Multidimensional scaling and cluster analysis was applied in constructing a framework consisting of two dimensions and eight clusters. The horizontal axis of the indicator framework is named 'Organization' and has two poles, namely, 'Processes' and 'Results'. The vertical axis is named ' Task' and the poles are named 'Efficient treatment' and 'Prevention programs'. The eight clusters in the two-dimensional framework are arranged in the following, prioritized sequence: 'Efficient treatment network', 'Effective service', ' Target group', 'Quality of life', 'Efficient service', 'Knowledge transfer', 'Reducing addiction related problems', and 'Prevention programs'. The most important items in the framework are: 'patients are satisfied with their treatment', 'early interventions', and 'efficient treatment chain'. The indicator framework aligns with three clusters of the results criteria of the EFQM Excellence Model. It is based on the stakeholders' perspectives and is believed to be specific for addiction treatment centres. The study demonstrates that concept mapping is a suitable strategy for generating indicator frameworks.

Shared topics on the experience of people with haemophilia living in the UK and the USA and the influence of individual and contextual variables: Results from the HERO qualitative study

PubMed Central

Palareti, Laura; Potì, Silvia; Cassis, Frederica; Emiliani, Francesca; Matino, Davide; Iorio, Alfonso

2015-01-01

The study illuminates the subjective experience of haemophilia in people who took part in the Haemophilia Experience, Results and Opportunities (HERO) initiative, a quali-quantitative research program aimed at exploring psychosocial issues concerning this illness around the world. Applying a bottom-up analytic process with the help of software for textual data, we investigated 19 interviews in order to describe the core themes and the latent factors of speech, to explore the role of different variables in shaping the participants’ illness experiences. The five themes detected are feeling different from others, body pain, acquisition of knowledge and resources, family history, and integration of care practices in everyday life. We illustrate how nationality, age, family situation, the use of prophylaxis or on-demand treatment, and the presence of human immunodeficiency virus or hepatitis C virus affect the experience of our participants in different ways. Findings are used to bring insights on research, clinical practice, and psychosocial support. PMID:26578360

Tranexamic Acid in Control of Haemorrhage after Dental Extraction in Haemophilia and Christmas Disease

PubMed Central

Forbes, C. D.; Barr, R. D.; Reid, G.; Thomson, C.; Prentice, C. R. M.; Nicol, G. P. Mc; Douglas, A. S.

1972-01-01

In a double-blind trial tranexamic acid (AMCA, Cyclokapron), 1 g three times a day for five days, significantly reduced blood loss and transfusion requirements after dental extraction in patients with haemophilia and Christmas disease. No side effects were seen in either group of patients. Screening tests showed no toxic action of tranexamic acid on the liver, kidney, or heart. PMID:4553818

Safety and effectiveness of room temperature stable recombinant factor VIIa in patients with haemophilia A or B and inhibitors: Results of a multinational, prospective, observational study.

PubMed

Kavakli, K; Demartis, F; Karimi, M; Eshghi, P; Neme, D; Chambost, H; Sommer, L; Zak, M; Benson, G

2017-07-01

A room temperature stable formulation of recombinant activated factor VII (NovoSeven ® ), allowing convenient storage and therefore improved treatment access, has been developed. Bioequivalence to the previous NovoSeven ® was demonstrated in healthy humans, leading to European approval (2008). Although no confirmed cases of neutralising antibodies to rFVIIa in patients with haemophilia A or B have been observed with the original formulation, changes in formulation or storage condition may alter immunogenicity. SMART-7™ was designed to investigate the safety of NovoSeven ® in a real-world setting in patients with haemophilia A or B with inhibitors. Study medication was not provided by the sponsor, and treatment was at the discretion of the treating physician, in accordance with the local label. Patient baseline information was collected at enrolment. Information on safety, drug exposure and bleeding episodes was collected and FVII antibody screening was encouraged at baseline and performed at the investigator's discretion. Fifty-one patients were enrolled and 31 completed the study. Forty-one adverse events (AEs) were reported in 23 patients; 25 AEs in 14 patients were serious. No thromboembolic events were observed. Although four cases of reduced therapeutic response were reported, FVII antibody screening was negative. Forty-eight patients experienced 618 bleeding episodes and 93.4% of 609 evaluated bleeds were stopped by treatment. Of the 538 bleeding episodes treated with NovoSeven ® monotherapy, 94.2% stopped by end of treatment. Data collected during the SMART-7™ study revealed no treatment-related safety issues and no FVII-binding antibodies for patients treated with NovoSeven ® under real-world conditions. © 2017 John Wiley & Sons Ltd.

Adherence to prophylaxis and quality of life in children and adolescents with severe haemophilia A.

PubMed

García-Dasí, M; Aznar, J A; Jiménez-Yuste, V; Altisent, C; Bonanad, S; Mingot, E; Lucía, F; Giménez, F; López, M Fernanda; Marco, P; Pérez, R; Fernández, M Á; Paloma, M J; Galmes, B; Herrero, S; García-Talavera, J A

2015-07-01

Treatment adherence in adolescents with chronic diseases is around 50%, and failure is more common in preventive therapy. In haemophilia, contradictory results are reported by the published studies. The objective of this study was to evaluate adherence with factor VIII (FVIII) prophylaxis in Spanish patients with severe haemophilia A between age 6 and 20 years. Data were collected retrosp-ectively in the previous 2 years. The primary endpoint was the absolute adherence index (AAI), and the endpoints were related to clinical status, age, prophylaxis regimen, responsibility for factor administration and quality of life (QoL), assessed by the Haemo-QoL questionnaires. A total of 78 patients from 14 Spanish hospitals were recruited. Adherence ranged between -64.4 and 66.7 (mean -3.08). No differences were observed between children and adolescents (7.11 vs. 6.39; P = 0.809). A statistically significant association (P < 0.010) between infra adherent group and target joint was found, as was a statistically significant difference (P < 0.010) between the number of bleeding episodes experienced by the adherent group (mean 1.4) and by infra adherents (mean 4.5). There was no significant difference between AAI and prophylactic regimen (6.35 vs. 6.96, P = 0.848), neither between AAI and the person responsible for factor administration (5.57 vs. 8.79, P = 0.326). The Haemo-QoL scores (8-12 years) were related to adherence level (P < 0.05). Adherence was approximately ideal and patients perceived a high QoL. Because of the repercussions for compliance, it is essential to work during puberty on emotional and self-acceptance aspects of the disease, as well as coping, and the patient's family, school and health team relationships. © 2015 John Wiley & Sons Ltd.

First report on the safety and efficacy of an extended half-life glycoPEGylated recombinant FVIII for major surgery in severe haemophilia A.

PubMed

Hampton, K; Chowdary, P; Dunkley, S; Ehrenforth, S; Jacobsen, L; Neff, A; Santagostino, E; Sathar, J; Takedani, H; Takemoto, C M; Négrier, C

2017-09-01

N8-GP (turoctocog alfa pegol) is an extended half-life glycoPEGylated recombinant factor VIII (FVIII) product developed for the prevention and treatment of bleeds in haemophilia A patients. This is a planned interim analysis of pathfinder™3, an international, open-label, Phase 3 trial evaluating the efficacy and safety (including immunogenicity) of N8-GP administered before, during and after major surgery in severe haemophilia A patients aged ≥12 years. Sixteen patients who underwent 18 major surgical procedures (including synovectomy, joint replacement and ankle arthrodesis) were included here. Postoperative assessments were conducted daily for days 1-6, and once for days 7-14. Primary endpoint was N8-GP haemostatic efficacy, assessed after completion of surgery using a four-point scale ('excellent', 'good', 'moderate', 'none'). Haemostasis was successful (rated 'excellent' or 'good') on completion of surgery in 17 (94.4%) procedures and rated as 'moderate' (5.6%) for one surgery in a patient with multiple comorbidities who needed an intraoperative N8-GP dose (20.7 IU kg -1 ). In the postoperative period, three bleeds occurred (one during days 1-6; two during days 7-14); all were successfully treated with N8-GP. Mean N8-GP consumption on day of surgery was 80.0 IU kg -1 ; patients received a mean of 1.7 doses (median: 2, range: 1-3). No safety concerns were identified. The data showed that N8-GP was effective and well tolerated for the prevention and treatment of bleeds during major surgery; such FVIII products with extended half-lives may modify current treatment schedules, enabling fewer infusions and earlier patient discharge. © 2017 John Wiley & Sons Ltd.

Challenges in the management of haemophilia on transition from adolescence to adulthood.

PubMed

Brand, Brigitte; Dunn, Spencer; Kulkarni, Roshni

2015-12-01

Patients with haemophilia undergo many transitions during their lives, but the period between adolescence and adulthood is particularly challenging. During this time, the patient must deal with all of the typical biological, social and emotional changes associated with this phase of life, whilst at the same time, adapting his lifestyle to the needs of his condition, transferring from paediatric to adult services and, most importantly, accepting increasing (and ultimately full) responsibility for managing his condition. Parents may also find their diminishing role equally challenging. Perhaps not surprisingly, given the challenges that adolescents face, treatment adherence during this time is generally low, which can lead to recurrent joint bleeds, chronic pain and reduced quality of life. To address the challenges, it is critical that a transition programme is put in place that meets the needs of not only the patient, but also his parents and healthcare providers. Key elements of the plan are a multidisciplinary approach, early planning, patient education and appropriate follow-up. A successful programme will equip all parties with the skills to deal with the challenges of transition from adolescence to adulthood, ensuring that the benefits of treatment in childhood are maintained, thus optimising health outcomes and quality of life. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cost-effectiveness analysis of pharmacokinetic-driven prophylaxis vs. standard prophylaxis in patients with severe haemophilia A.

PubMed

Iannazzo, Sergio; Cortesi, Paolo A; Crea, Roberto; Steinitz, Katharina; Mantovani, Lorenzo G; Gringeri, Alessandro

2017-09-01

: The objective of this study was to assess the cost-effectiveness of pharmacokinetic-driven prophylaxis in severe haemophilia A patients. A microsimulation model was developed to evaluate the cost-effectiveness of pharmacokinetic-driven prophylaxis vs. standard prophylaxis and estimate cost, annual joint bleed rate (AJBR), and incremental cost-effectiveness ratio over a 1-year time horizon for a hypothetical population of 10 000 severe haemophilia A patients. A dose of 30 IU/kg per 48 h was assumed for standard prophylaxis. Pharmacokinetic prophylaxis was individually adjusted to maintain trough levels at least 1 and 5 IU/dl or less. AJBR was estimated on the relationship between factor VIII (FVIII) levels and bleeding rate reported in the literature. Sensitivity analyses were performed to assess the stability of the model and the reliability of results. The FVIII dose was reduced in the 27.8% of patients with a trough level more than 5 IU/dl on standard prophylaxis, with a negligible impact on AJBR (+0.1 bleed/year). The FVIII dose was increased in the 10.6% of patients with trough levels less than 1 IU/dl on standard prophylaxis, with a significant reduction of AJBR (-1.9 bleeds/year). On average, overall, pharmacokinetic-driven prophylaxis was shown to decrease the AJBR from 1.012 to 0.845 with a slight reduction of the infusion dose of 0.36 IU/kg, with total saving of 5 197&OV0556; per patient-year. Pharmacokinetic-driven prophylaxis was preferable (i.e. more effective and less costly) compared with standard prophylaxis, with savings of 31 205&OV0556; per bleed avoided. Pharmacokinetic-driven prophylaxis, accounting for patients' individual pharmacokinetic variability, appears to be a promising strategy to improve outcomes with efficient use of available resources in severe haemophilia A patients.

Risks and challenges of orthopaedic invasive interventions in haemophilia in a low-resource country. A single-center experience.

PubMed

Serban, M; Poenaru, D; Patrascu, J; Ursu, E; Savescu, D; Ionita, H; Jinca, C; Pop, L; Talpos-Niculescu, S; Ritli, L; Arghirescu, S; Mihailov, D; Schramm, W

2014-01-01

Haemophilic arthropathy is a defining feature and a debilitating condition of persons with haemophilia (PwH) in low resource countries. Orthopaedic surgery is unavoidable for patients with high occurrence of joint damage. We aimed to evaluate the spectrum and outcome of invasive orthopaedic therapies in PwH and von Willebrand diseases (VWD). Our descriptive observational retrospective study included 131 invasive surgical procedures, performed on 76 consecutive patients, most of them (93.4%) with severe disease, treated in Timisoara's Haemophilia Center over a period of 12 years; 17.1% had pre-operation anti-FVIII inhibitors. Invasive elective procedures were predominant (90.8%) as compared to emergency measures (9.2%); according to their invasiveness, 20.6% of interventions were major, 44.3% intermediate and 35.1% minor. Results were good in the majority of cases; significantly reduced joint bleed rate and pain score were the most consistent achievements. The greatest proportion of complications occurred after major (66.7%), compared to moderate (25.6%) and minor (7.7%) interventions. The main threatening complication was the development (3.8%) or increase (4.6%) of inhibitor titer. Local bacterial infections and wound dehiscence complicated the evolution in 4.6% and 0.8 % of cases, respectively; we noticed no blood-borne infections or thrombotic accidents. Low dosage (10.7%) and short duration of substitution (21.4%) led to increased post-surgical bleeding and post-haemorrhagic anaemia. Surgery is a highly demanding intervention in haemophilia, which cannot be ignored in a low resource country. It represents a life or limb-saving and quality of life-improving measure.

Inhibitors in haemophilia A: a perspective on clotting factor products as a potential contributing factor.

PubMed

Mathew, P; Dinter, H; Church, N; Humphries, T J; Kulkarni, R

2016-05-01

The occurrence of a neutralizing antibody in previously untreated patients (PUPs) with haemophilia A appears to be the result of an intricate interplay of both genetic and environmental factors. Recently, the type of factor VIII (FVIII) product used in the PUPs population has been implicated as a risk factor for inhibitor development. The aim of this review was to explore in a systematic manner potential hypotheses for the product-related findings in these studies (i.e. differences in the expression system of the cell lines used to produce recombinant FVIII [rFVIII], differences in the administered antigen load or changes in clinical practice over time). Review of the available clinical studies illustrates the high degree of variability for the risk of inhibitor development for the same products across different studies. Differences in cell lines or antigen load were not found to provide a reasonable explanation. The possibility of changes in clinical practice over time and patient selection bias (i.e. the preferential use of one product over another in patients at higher risk for inhibitors) offers a potential explanation and should be carefully considered when evaluating the studies. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

An exploratory qualitative assessment of self-reported treatment outcomes and satisfaction among patients accessing an innovative voluntary drug treatment centre in Malaysia.

PubMed

Ghani, Mansur A; Brown, Shan-Estelle; Khan, Farrah; Wickersham, Jeffrey A; Lim, Sin How; Dhaliwal, Sangeeth K; Kamarulzaman, Adeeba; Altice, Frederick L

2015-02-01

In Malaysia, compulsory drug detention centres (CDDCs) hold suspected drug users for two years without adjudication. Acute detoxification without healthcare access has been documented. CDDCs are criticized globally due to ineffectiveness in treating addiction and human rights violations. In response, the Malaysian government began transitioning these facilities into voluntary drug treatment centres known as "Cure and Care" (C&C) centres that embrace a holistic treatment-based approach to drug addiction rehabilitation. An explorative qualitative study was undertaken to explore patient perspectives and satisfaction regarding treatment and services at the new Cure and Care centre in Kota Bharu, Malaysia. A convenience sample of 20 patients was recruited to participate in semi-structured in-depth interviews. Content analysis was used to identify the salient themes. Patients identified methadone treatment, psychosocial programs, religious instruction, and recreational activities as important factors contributing to treatment success for addressing both health and addiction needs. Though many had previously been in a CDDC, adherence to treatment in the C&C centre was perceived to be facilitated by the degree of social support, the voluntary nature and the array of new programs available for selection. C&Cs represents a dramatic shift in the Malaysian government's approach to drug addiction. Our findings demonstrate positive patient experiences associated with the holistic treatment-based approach of these centres. This exploratory study provides additional evidence to document this ongoing policy transition and may guide continued expansion of new holistic drug treatment programs across the country. Copyright © 2014 Elsevier B.V. All rights reserved.

An Exploratory Qualitative Assessment of Self-Reported Treatment Outcomes and Satisfaction Among Patients Accessing an Innovative Voluntary Drug Treatment Centre in Malaysia

PubMed Central

Ghani, Mansur A.; Brown, Shan-Estelle; Khan, Farrah; Wickersham, Jeffrey A.; Lim, Sin How; Dhaliwal, Sangeeth K.; Kamarulzaman, Adeeba; Altice, Frederick L.

2014-01-01

Background In Malaysia, compulsory drug detention centres (CDDCs) hold suspected drug users for two years without adjudication. Acute detoxification without healthcare access has been documented. CDDCs are criticized globally due to ineffectiveness in treating addiction and human rights violations. In response, the Malaysian government began transitioning these facilities into voluntary drug treatment centres known as “Cure and Care” (C&C) centres that embrace a holistic treatment-based approach to drug addiction rehabilitation. Methods An explorative qualitative study was undertaken to explore patient perspectives and satisfaction regarding treatment and services at the new Cure and Care centre in Kota Bharu, Malaysia. A convenience sample of 20 patients was recruited to participate in semi-structured in-depth interviews. Content analysis approach was used to identify the salient themes. Results Patients identified methadone treatment, psychosocial programs, religious instruction, and recreational activities as important factors contributing to treatment success for addressing both health and addiction needs. Though many had previously been in a CDDC, adherence to treatment in the C&C centre was perceived to be facilitated by the degree of social support, the voluntary nature and the array of new programs available for selection. Conclusion C&Cs represents a dramatic shift in the Malaysian government’s approach to drug addiction. Our findings demonstrate positive patient experiences associated with the holistic treatment-based approach of these centres. This exploratory study provides additional evidence to document this ongoing policy transition and may guide continued expansion of new holistic drug treatment programs across the country. PMID:25577322

The effect of cooling on coagulation and haemostasis: should "Ice" be part of treatment of acute haemarthrosis in haemophilia?

PubMed

Forsyth, A L; Zourikian, N; Valentino, L A; Rivard, G E

2012-11-01

Repeated haemarthroses and the consequences of blood in the joint contribute to blood induced joint disease (BIJD) in people with haemophilia (PWH). Prevention of bleeding, through medical management, is the standard of care in developed countries, but is not universally available due to financial and other barriers. Ice application, as part of R.I.C.E. (Rest, Ice, Compression, Elevation) or alone, is commonly recommended as an adjunct treatment to decrease bleeding, pain, tissue metabolism, oedema, and inflammation. This article will review evidence regarding local cooling by commonly used ice application methods, to decrease the temperature of the skin and intra-articular (IA) joint space and the resultant effects on haemostasis and coagulation. The general literature was reviewed for articles in English describing temperatures achievable in the skin and IA space using clinically relevant ice protocols, and the effect of cooling on haemostasis and coagulation. The literature demonstrates that typical methods of ice application can cool both the skin and IA space. Published, general literature studies have also consistently demonstrated that experimental cooling of blood and/or tissue, both in vitro and in vivo in humans and in animal models, can significantly impair coagulation and prolong bleeding. In PWH with acute haemarthrosis, ice application has potential to increase haemorrhage morbidity by further impairing coagulation and haemostasis. Ice has not been shown to improve overall outcome, stop bleeding nor swelling from haemarthrosis. Although ice can help manage acute, haemarthrosis-related pain, there are other available interventions that will not impair coagulation and haemostasis. © 2012 Blackwell Publishing Ltd.

Using benchmarking to identify inter-centre differences in persistent ductus arteriosus treatment: can we improve outcome?

PubMed

Jansen, Esther J S; Dijkman, Koen P; van Lingen, Richard A; de Vries, Willem B; Vijlbrief, Daniel C; de Boode, Willem P; Andriessen, Peter

2017-10-01

The aim of this study was to identify inter-centre differences in persistent ductus arteriosus treatment and their related outcomes. Materials and methods We carried out a retrospective, multicentre study including infants between 24+0 and 27+6 weeks of gestation in the period between 2010 and 2011. In all centres, echocardiography was used as the standard procedure to diagnose a patent ductus arteriosus and to document ductal closure. In total, 367 preterm infants were included. All four participating neonatal ICU had a comparable number of preterm infants; however, differences were observed in the incidence of treatment (33-63%), choice and dosing of medication (ibuprofen or indomethacin), number of pharmacological courses (1-4), and the need for surgical ligation after failure of pharmacological treatment (8-52%). Despite the differences in treatment, we found no difference in short-term morbidity between the centres. Adjusted mortality showed independent risk contribution of gestational age, birth weight, ductal ligation, and perinatal centre. Using benchmarking as a tool identified inter-centre differences. In these four perinatal centres, the factors that explained the differences in patent ductus arteriosus treatment are quite complex. Timing, choice of medication, and dosing are probably important determinants for successful patent ductus arteriosus closure.

Comparative dosimetry study of three UK centres implementing total skin electron treatment through external audit.

PubMed

Misson-Yates, S; Gonzalez, R; McGovern, M; Greener, A

2015-05-01

This article describes the external audit measurements conducted in two UK centres implementing total skin electron beam therapy (TSEBT) and the results obtained. Measurements of output, energy, beam flatness and symmetry at a standard distance (95 or 100 cm SSD) were performed using a parallel plate chamber in solid water. Similarly, output and energy measurements were also performed at the treatment plane for single and dual fields. Clinical simulations were carried out using thermoluminescent dosemeters (TLDs) and Gafchromic® film (International Specialty Products, Wayne, NJ) on an anthropomorphic phantom. Extended distance measurements confirmed that local values for the beam dosimetry at Centres A and B were within 2% for outputs and 1-mm agreement of the expected depth at which the dose is 50% of the maximum for the depth-dose curve in water (R50,D) value. Clinical simulation using TLDs) showed an agreement of -1.6% and -6.7% compared with the expected mean trunk dose for each centre, respectively, and a variation within 10% (±1 standard deviation) across the trunk. The film results confirmed that the delivery of the treatment technique at each audited centre complies with the European Organisation for Research and Treatment of Cancer recommendations. This audit methodology has proven to be a successful way to confirm the agreement of dosimetric parameters for TSEBT treatments at both audited centres and could serve as the basis for an audit template to be used by other audit groups. TSEBT audits are not established in the UK owing to a limited number of centres carrying out the treatment technique. This article describes the audits performed at two UK centres prior to their clinical implementation.

Comparative dosimetry study of three UK centres implementing total skin electron treatment through external audit

PubMed Central

Gonzalez, R; McGovern, M; Greener, A

2015-01-01

Objective: This article describes the external audit measurements conducted in two UK centres implementing total skin electron beam therapy (TSEBT) and the results obtained. Methods: Measurements of output, energy, beam flatness and symmetry at a standard distance (95 or 100 cm SSD) were performed using a parallel plate chamber in solid water. Similarly, output and energy measurements were also performed at the treatment plane for single and dual fields. Clinical simulations were carried out using thermoluminescent dosemeters (TLDs) and Gafchromic® film (International Specialty Products, Wayne, NJ) on an anthropomorphic phantom. Results: Extended distance measurements confirmed that local values for the beam dosimetry at Centres A and B were within 2% for outputs and 1-mm agreement of the expected depth at which the dose is 50% of the maximum for the depth–dose curve in water (R50,D) value. Clinical simulation using TLDs) showed an agreement of −1.6% and −6.7% compared with the expected mean trunk dose for each centre, respectively, and a variation within 10% (±1 standard deviation) across the trunk. The film results confirmed that the delivery of the treatment technique at each audited centre complies with the European Organisation for Research and Treatment of Cancer recommendations. Conclusion: This audit methodology has proven to be a successful way to confirm the agreement of dosimetric parameters for TSEBT treatments at both audited centres and could serve as the basis for an audit template to be used by other audit groups. Advances in knowledge: TSEBT audits are not established in the UK owing to a limited number of centres carrying out the treatment technique. This article describes the audits performed at two UK centres prior to their clinical implementation. PMID:25761213

Immunogenicity, efficacy and safety of Nuwiq® (human-cl rhFVIII) in previously untreated patients with severe haemophilia A-Interim results from the NuProtect Study.

PubMed

Liesner, R J; Abashidze, M; Aleinikova, O; Altisent, C; Belletrutti, M J; Borel-Derlon, A; Carcao, M; Chambost, H; Chan, A K C; Dubey, L; Ducore, J; Fouzia, N A; Gattens, M; Gruel, Y; Guillet, B; Kavardakova, N; El Khorassani, M; Klukowska, A; Lambert, T; Lohade, S; Sigaud, M; Turea, V; Wu, J K M; Vdovin, V; Pavlova, A; Jansen, M; Belyanskaya, L; Walter, O; Knaub, S; Neufeld, E J

2018-03-01

Nuwiq ® (Human-cl rhFVIII) is a fourth generation recombinant FVIII, produced in a human cell line, without chemical modification or protein fusion. No inhibitors developed in studies with Nuwiq ® in 201 previously treated patients with haemophilia A (HA). The immunogenicity, efficacy and safety of Nuwiq ® in previously untreated patients (PUPs) with severe HA are being assessed in the ongoing NuProtect study. The study, conducted across 38 centres worldwide, is evaluating 110 true PUPs of all ages and ethnicities enrolled for study up to 100 exposure days (EDs) or 5 years maximum. The primary objective is to assess the immunogenicity of Nuwiq ® (inhibitor activity ≥0.6 BU) using the Nijmegen-modified Bethesda assay at a central laboratory. Data for 66 PUPs with ≥20 EDs from a preplanned interim analysis were analysed. High-titre (HT) inhibitors developed in 8 of 66 patients after a median of 11.5 EDs (range 6-24). Five patients developed low-titre inhibitors (4 transient). The cumulative incidence (95% confidence interval) was 12.8% (4.5%, 21.2%) for HT inhibitors and 20.8% (10.7%, 31.0%) for all inhibitors. During inhibitor-free periods, median annualized bleeding rates during prophylaxis were 0 for spontaneous bleeds and 2.40 for all bleeds. Efficacy was rated as "excellent" or "good" in treating 91.8% of bleeds. Efficacy of surgical prophylaxis was "excellent" or "good" for 8 (89%) procedures and "moderate" for 1 (11%). No tolerability concerns were evident. These interim data show a cumulative incidence of 12.8% for HT inhibitors and convincing efficacy and tolerability in PUPs treated with Nuwiq ® . © 2017 The Authors. Haemophilia published by John Wiley & Sons Ltd.

PK-guided personalized prophylaxis with Nuwiq® (human-cl rhFVIII) in adults with severe haemophilia A.

PubMed

Lissitchkov, T; Rusen, L; Georgiev, P; Windyga, J; Klamroth, R; Gercheva, L; Nemes, L; Tiede, A; Bichler, J; Knaub, S; Belyanskaya, L; Walter, O; Pasi, K J

2017-09-01

Nuwiq ® (human-cl rhFVIII) is a 4 th generation recombinant human FVIII, without chemical modification or protein fusion, produced in a human cell-line. This study (NuPreviq) was a prospective, open-label, multicentre, phase IIIb study of the efficacy and safety of personalized prophylaxis with Nuwiq ® in 66 previously treated adults with severe haemophilia A. NuPreviq had three phases: (i) a 72-h pharmacokinetic (PK) phase; (ii) a 1-3 month standard prophylaxis phase; and (iii) a 6-month personalized prophylaxis phase. The personalized prophylaxis regimen was based on individual PK modelling for each patient according to whether their PK profile most closely fitted a two- or one-compartment model (NuPreviq approach). In cases of uncertainty, a noncompartment model was applied. The median dosing interval during personalized prophylaxis was 3.5 days, with 57% of patients on ≤2 weekly dosing. Mean annualized bleeding rates during personalized prophylaxis were 1.45 (median [interquartile range, IQR]: 0 [0, 1.9]) for all bleeds, 0.79 (median [IQR]: 0 [0, 0]) for spontaneous bleeds, and 0.91 (median [IQR]: 0 [0, 0]) for joint bleeds. During personalized prophylaxis, 83.1% of patients were spontaneous bleed-free. Compared with standard prophylaxis, median weekly prophylaxis dose was reduced by 7.2% from 100.0 to 92.8 IU kg -1 during the last 2 months of personalized prophylaxis. There were no FVIII inhibitors or treatment-related serious or severe adverse events. PK-guided personalized prophylaxis with Nuwiq ® provided bleeding protection and enabled the dosing interval to be extended to twice weekly or less in many patients and an overall dose reduction. © 2017 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

How is medical decision‐making shared? The case of haemophilia patients and doctors: the aftermath of the infected blood affair in France

PubMed Central

Fillion, Emmanuelle

2003-01-01

Abstract Objective  This article looks at how users and doctors in France have rethought the question of shared decision‐making in the clinical field of haemophilia following a major crisis – that of the infected blood affair. Design  We did a qualitative survey based on semi‐structured interviews in three regions of France. Setting and participants  The interviews covered 31 clinical doctors of haemophilia and 31 users: 21 adult males with severe haemophilia (21/31), infected (14/21) or not (7/21) with HIV, the infected wife of one of the latter (1/31) and nine parents of young patients with severe haemophilia (9/31), either HIV positive (6/9) or negative (3/9). Results and conclusions  The results show the infected blood affair to be a major individual and collective ordeal. It has caused users and doctors to rethink their roles within clinical relationships and to develop new ways of sharing medical decision‐making. Prior to the crisis, the dominant model was based upon a distinction between the medical aspect, governed by the doctors, and the psychosocial aspect, which involved the patients and their families. Since the crisis, medicoscientific knowledge has been shared between users and doctors. This general trend nevertheless permits the existence of different patient, family and doctor profiles which in turn correspond to different notions of what a clinical decision should be. Some users remain attached to the idea of complementarity between doctors and patients (new partnership model), whilst others put doctors and patients on an equal footing (negotiation model). On the doctors’ side, whilst some still prefer the initial model for therapeutic decision‐making, the majority have reassessed their perceptions and viewpoints. A certain number believe that decisions should be made by both doctor and patient in accordance with scientific procedures (decision‐making controlled by scientific standards) or regulatory procedures (decision�

Parent participation in paediatric rehabilitation treatment centres in the Netherlands: a parents' viewpoint.

PubMed

Siebes, R C; Wijnroks, L; Ketelaar, M; van Schie, P E M; Gorter, J W; Vermeer, A

2007-03-01

The importance of family-centred care and services has been increasingly emphasized in paediatric rehabilitation. One aspect of family-centred care is parent involvement in their child's treatment. The aims of this study were (1) to describe how, and to what extent parents are involved in the paediatric rehabilitation treatment process in the Netherlands; (2) to determine the level of parents' satisfaction about the services they and their child have received; and (3) to describe what ideas parents have to enhance their involvement in the treatment process. A total of 679 parents of children aged 1-20 years who participated in our longitudinal study on family centred care in the Netherlands. The children had various diagnoses and were treated in nine out of 23 Dutch paediatric rehabilitation centres. A random sample of 75 parents was interviewed within 4 weeks after completion of the Measure of Processes of Care and the Client Satisfaction Questionnaire. A Quality of Care cycle with six stages was used to structure the evaluation. The data showed that parents are involved in all stages of their child's rehabilitation process in various ways. The average level of parent satisfaction about the services received was high. According to the interviewed parents, the communication between professionals and parents, parents' involvement in goal setting, and parents' involvement in treatment could be improved upon. Parents are to a large extent involved in all stages of the treatment process in Dutch paediatric rehabilitation settings. Although parents valued the services received, they suggested various ways to enhance parent participation.

Functional outcomes following ankle arthrodesis in males with haemophilia: analyses using the CDC's Universal Data Collection surveillance project.

PubMed

Lane, H; Siddiqi, A-E-A; Ingram-Rich, R; Tobase, P; Scott Ward, R

2014-09-01

In persons with haemophilia (PWH), repeated ankle haemarthroses lead to pain, loss of joint range of motion (ROM), and limitations in activity and participation in society. PWH are offered ankle arthrodesis (AA) to eliminate pain. In our experience, PWH are hesitant to proceed to AA due to concerns regarding gait anomalies, functional decline and complete loss of ROM. The aim of this study was to report outcomes in ROM, assistive device (AD)/wheelchair use, activity scale and work/school absenteeism for participants in the CDC's Universal Data Collection surveillance project (UDC) pre- and post- AA. Males with haemophilia enrolled in the UDC with first report of AA (1998-2010) were selected. Descriptive statistics were calculated using data from the annual study visit pre-AA and the follow-up visit (~12-24 months) post-AA. The 68 subjects who fulfilled the criteria were: mean age 36.9 years (SD = 12.9); 85.3% white; 85.3% haemophilia A; 72% severe, 20.6% moderate; and 10.3% with inhibitor once during the study period. Mean loss in total arc of ankle motion was 17.02° (SD = 21.8, P ≤ 0.01) pre- compared to post-AA. For 61.8%, there was no change in use of AD for ambulation/mobility. For 85.3%, there was no change in use of a wheelchair. On a self-reported activity scale, 11.8% improved, 8.8% worsened and 79.4% did not change. Work/school absenteeism averaged 2.7 (SD = 6.4) pre- and 1.5 (SD = 6.4, P = 0.26) days per year post-AA. While ankle ROM was significantly reduced post-AA, for most subjects, there was no change in use of AD/wheelchair for ambulation/mobility. Physical activity was maintained and work/school absenteeism remained stable. © 2014 John Wiley & Sons Ltd.

Controlled, cross-sectional MRI evaluation of joint status in severe haemophilia A patients treated with prophylaxis vs. on demand

PubMed Central

Oldenburg, J; Zimmermann, R; Katsarou, O; Theodossiades, G; Zanon, E; Niemann, B; Kellermann, E; Lundin, B

2015-01-01

In patients with haemophilia A, factor VIII (FVIII) prophylaxis reduces bleeding frequency and joint damage compared with on-demand therapy. To assess the effect of prophylaxis initiation age, magnetic resonance imaging (MRI) was used to evaluate bone and cartilage damage in patients with severe haemophilia A. In this cross-sectional, multinational investigation, patients aged 12–35 years were assigned to 1 of 5 groups: primary prophylaxis started at age <2 years (group 1); secondary prophylaxis started at age 2 to <6 years (group 2), 6 to <12 years (group 3), or 12−18 years (group 4); or on-demand treatment (group 5). Joint status at ankles and knees was assessed using Compatible Additive MRI scoring (maximum and mean ankle; maximum and mean of all 4 joints) and Gilbert scores in the per-protocol population (n = 118). All prophylaxis groups had better MRI joint scores than the on-demand group. MRI scores generally increased with current patient age and later start of prophylaxis. Ankles were the most affected joints. In group 1 patients currently aged 27−35 years, the median of maximum ankle scores was 0.0; corresponding values in groups 4 and 5 were 17.0 and 18.0, respectively [medians of mean index joint scores: 0.0 (group 1), 8.1 (group 2) and 13.8 (group 4)]. Gilbert scores revealed outcomes less pronounced than MRI scores. MRI scores identified pathologic joint status with high sensitivity. Prophylaxis groups had lower annualized joint bleeds and MRI scores vs. the on-demand group. Primary prophylaxis demonstrated protective effects against joint deterioration compared with secondary prophylaxis. PMID:25470205

Pain sensitivity in patients with haemophilia following moderate aerobic exercise intervention.

PubMed

Krüger, S; Weitz, C; Runkel, B; Hilberg, T

2016-11-01

Physical activity is influenced by pain and vice versa. Although studies recommend exercise therapy for patients with haemophilia (PwH), the influence of physical activity on the pain condition in PwH has not been investigated so far. Aim of this study was to examine the effect of a treadmill intervention with self-chosen velocity on the acute pain sensitivity in PwH. Twenty PwH [aged 24-58 years, moderate (n = 3) to severe (n = 17) haemophilia A (n = 17) or B (n = 3)] and 20 control subjects (aged 26-61 years) were included in this study. Eighteen PwH and all controls completed a treadmill intervention for 30 min. Pressure pain thresholds (PPT) in Newton (N) were measured at both the knees, ankles and elbows, sternum and forehead before (pre) and immediately after walking (post). PwH and controls walked with comparable speed (mean speed in km h -1 ; PwH: 3.5, controls: 3.8), resulting in significantly different values of performance-related parameters such as heart rate (mean heart rate per minute; PwH: 102, controls: 86; P ≤ 0.01). Compared to baseline values, PPT remained unaltered at all landmarks in both groups after walking (e.g. pre/post in Newton; knee right: PwH: 63.1/63.0, controls: 93.8/93.8; left knee: PwH: 62.1/62.7, controls: 90.0/93.4), indicating a non-increasing pain condition. Findings of unaltered PPT following moderate aerobic exercise showed initial evidence that PwH are able to perform an endurance exercise with self-chosen velocity for 30 min as recommended, without increasing the acute pain condition. By doing so, PwH can benefit from the positive effects of endurance exercise. © 2016 John Wiley & Sons Ltd.

Cost analysis of prophylaxis with activated prothrombin complex concentrate vs. on-demand therapy with activated factor VII in severe haemophilia A patients with inhibitors, in Spain.

PubMed

Villarrubia, R; Oyagüez, I; Álvarez-Román, M T; Mingot-Castellano, M E; Parra, R; Casado, M A

2015-05-01

A cost analysis model was developed to compare annual cost of prophylaxis with activated prothrombin complex concentrate (aPCC) vs. on-demand therapy with activated recombinant factor VII (rFVIIa) in severe haemophilia A patients with inhibitors for the Spanish National Health System (NHS). Model inputs were drug cost for prophylaxis (aPCC) and for on-demand treatment (rFVIIa or aPCC); bleeding episodes management (excluding bypassing agent cost); surgical costs and disease management (excluding bleeding episodes). Annual bleeding episodes treated on-demand was assumed to be 25, whereas breakthrough bleeds on prophylaxis was 8. Dose for prophylaxis was 75.72 U kg(-1) , three times per week. The total on-demand dose/bleeding episode was 679.66 μg kg(-1) (rFVIIa) and 235.28 U kg(-1) (aPCC). The average bleeding cost (€2998) considered different bleeding sites (62.5% joints, 28.6% muscles and soft tissues, 3.6% mucocutaneous tissues and 5.4% other areas). A 7.5% deduction was applied to ex-factory drug prices. Unitary costs (€2013) derived from local databases. Sensitivity analyses (SA) were performed. Annual cost of aPCC prophylaxis (€524,358) was 16% lower than on-demand treatment with rFVIIa (€627,876). Yearly drug costs were €497,017 for aPCC (€73,166 for on-demand treatment and €423,850 for prophylaxis), and €548,870 for rFVIIa. Disease management cost (€2645 per year) and surgical procedures (€708 per year) were common for both strategies. In the SA prophylactic treatment led to savings between €26,225 and €-1,008,960. Prophylaxis with aPCC reduces number of bleeding episodes in severe haemophilia A patients with inhibitors. aPCC prophylaxis resulted in savings in excess of €100,000 per-patient per year, being 16% less costly than on-demand treatment with rFVIIa, for the Spanish NHS. © 2015 John Wiley & Sons Ltd.

[Five years of ROM in substance abuse treatment centres in the Netherlands].

PubMed

Oudejans, S C C; Schippers, G M; Spits, M E; Stollenga, M; van den Brink, W

2012-01-01

Three substance abuse treatment centres set up a benchmarking project for routine outcome management (ROM) of structured cognitive behavioral treatments for outpatients with a substance use disorder. To present the results of five years benchmarking. All patients were included at intake and the follow-up assessment was performed by a call-center nine months later. Twice a year aggregated data were fed back to management and treatment teams. Since 2005, clinical outcome data, including substance abuse data, have been collected for more than half of all 15.786 treated patients. At follow-up, nine months after intake, 23% was abstinent, 28% reported moderate substance use and 49% reported excessive substance use. The Dutch centres for the treatment of substance abuse were successful in setting up ROM projects to monitor and compare the development and the effects of outpatient addiction treatments. The clinical results are acceptable and correspond to the results of the American project called match. It is not yet clear whether the biannual feedback of aggregated outcomes to management and treatment teams has contributed to the creation of learning organisations, but it has provided transparency and has made it possible for teams to learn from the outcomes.

Recombinant FVIIa (NovoSeven) continuous infusion and total hip replacement in patients with haemophilia and high titre of inhibitors to FVIII: experience of two cases.

PubMed

Tagariello, G; De Biasi, E; Gajo, G B; Risato, R; Radossi, P; Davoli, P G; Traldi, A

2000-09-01

In this report we describe our experience of total hip replacement in two patients with severe haemophilia A and high titres of inhibitors to FVIII. We used rFVIIa replacement therapy by continuous infusion to perform the surgery. The total amount of rFVIIa used in these two patients was very similar but the manner of administration was quite different. In our experience, it is an advantage to use a higher dose for shorter periods than a lower dose for a longer treatment period. Tranexamic acid by continuous infusion, and parallel saline infusion were useful for good haemostasis and avoided local thrombophlebitis in the side of rFVIIa infusion.

Cognitive behaviour therapy for chronic fatigue syndrome: Differences in treatment outcome between a tertiary treatment centre in the United Kingdom and the Netherlands.

PubMed

Worm-Smeitink, M; Nikolaus, S; Goldsmith, K; Wiborg, J; Ali, S; Knoop, H; Chalder, T

2016-08-01

Cognitive behaviour therapy (CBT) reduces fatigue and disability in chronic fatigue syndrome (CFS). However, outcomes vary between studies, possibly because of differences in patient characteristics, treatment protocols, diagnostic criteria and outcome measures. The objective was to compare outcomes after CBT in tertiary treatment centres in the Netherlands (NL) and the United Kingdom (UK), using different treatment protocols but identical outcome measures, while controlling for differences in patient characteristics and diagnostic criteria. Consecutively referred CFS patients who received CBT were included (NL: n=293, UK: n=163). Uncontrolled effect sizes for improvement in fatigue (Chalder Fatigue Questionnaire), physical functioning (SF-36 physical functioning subscale) and social functioning (Work and Social Adjustment Scale) were compared. Multiple regression analysis was used to examine whether patient differences explained outcome differences between centres. Effect sizes differed between centres for fatigue (Cohen's D NL=1.74, 95% CI=1.52-1.95; UK=0.99, CI=0.73-1.25), physical functioning (NL=0.99, CI=0.81-1.18; UK=0.33, CI=0.08-0.58) and social functioning (NL=1.47, CI=1.26-1.69; UK=0.61, CI=0.35-0.86). Patients in the UK had worse physical functioning at baseline and there were minor demographic differences. These could not explain differences in centre outcome. Effectiveness of CBT differed between treatment centres. Differences in treatment protocols may explain this and should be investigated to help further improve outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Daclatasvir/peginterferon lambda-1a/ribavirin in patients with chronic HCV infection and haemophilia who are treatment naïve or prior relapsers to peginterferon alfa-2a/ribavirin.

PubMed

Santagostino, E; Pol, S; Olveira, A; Reesink, H W; van Erpecum, K; Bogomolov, P; Xu, D; Critelli, L; Srinivasan, S; Cooney, E

2016-09-01

This study explores the potential role of a novel interferon-containing regimen for treatment of patients with chronic hepatitis C (CHC) and underlying haemophilia. This trial (NCT01741545) was an open-label, non-randomized phase 3 study, which included adult haemophiliacs with hepatitis C virus (HCV). Patients with HCV genotypes (GT)-2 or -3 were treated with Lambda-IFN/ribavirin (RBV)/daclatasvir (DCV) for 12 weeks (cohort A). Patients with HCV GT-1b or -4 were treated with Lambda-IFN/RBV/DCV for 12 weeks, followed by Lambda-IFN/RBV for an additional 12 weeks (cohort B). The primary endpoint was the proportion of patients with a sustained virologic response at post-treatment follow-up week 12 (SVR12). Clinical development of Lambda-IFN was discontinued during this trial leading to study termination before a 24-week post-treatment follow-up was obtained for all participants. Overall, 51 patients were treated (cohort A, n = 12; cohort B, n = 39). The proportion of patients achieving SVR12 was 92% in cohort A and 90% in cohort B. Therapy was generally well tolerated. The most common adverse events (AEs) were related to elevations in serum transaminases and/or bilirubin. Five serious AEs, four discontinuations due to AEs, and no deaths were reported. The rate of grade 3-4 bilirubin elevations was 17-18% across cohorts. Lambda-IFN/RBV/DCV treatment demonstrated a high SVR rate and was generally well tolerated with a safety profile consistent with expectations for this special patient population. This study supports use of DCV as part of a combination treatment regimen for haemophiliacs with CHC. © 2016 John Wiley & Sons Ltd.

Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study.

PubMed

Powell, Jerry; Martinowitz, Uri; Windyga, Jerzy; Di Minno, Giovanni; Hellmann, Andrzej; Pabinger, Ingrid; Maas Enriquez, Monika; Schwartz, Lawrence; Ingerslev, Jørgen

2012-11-01

The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79-4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79-4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79-4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79-4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79-4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79-4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. The investigational treatment arm was prematurely discontinued due to failure to achieve the primary endpoint.

Bioequivalence between two serum-free recombinant factor VIII preparations (N8 and ADVATE®)--an open-label, sequential dosing pharmacokinetic study in patients with severe haemophilia A.

PubMed

Martinowitz, U; Bjerre, J; Brand, B; Klamroth, R; Misgav, M; Morfini, M; Santagostino, E; Tiede, A; Viuff, D

2011-11-01

Recombinant coagulation factor VIII (rFVIII) concentrates provide a safe and efficacious replacement therapy for treatment and prevention of bleeding in patients with severe haemophilia A. The aim of this study was to compare the pharmacokinetic (PK) and safety profiles of two serum-free rFVIII products: N8, a new rFVIII manufactured by Novo Nordisk and Advate(®), a marketed product. Patients with severe haemophilia A with >150 exposure days to FVIII, without current or past inhibitors, were enrolled in an open-label, first human dose (FHD), multicentre trial. Twenty-three patients first received a single dose of 50 IU kg(-1) body weight Advate(®) followed by 50 IU kg(-1) body weight N8 at the next visit. A 4-day washout period was required prior to each dosing. Blood samples for PK and safety analyses were drawn prior to dosing and at intervals up until 48 h postdosing. The PK parameters were based on FVIII clotting activity (FVIII:C) measurements. Occurrence of adverse events was closely monitored. The mean profiles of FVIII:C and all primary and secondary parameters for Advate(®) and N8 were comparable. The 90% CI for the treatment ratio (Advate(®)/N8) for all primary endpoints (incremental recovery, t(1/2), AUC and Cl), and the secondary endpoints (AUC(last) and C(max)) were within the bioequivalence interval of 0.8-1.25. There were no safety concerns in the study and no reports of inhibitor formation in the 72-h period following exposure to a single N8 dose. In conclusion, N8 is bioequivalent to Advate(®). Furthermore, N8 is well tolerated in the FHD trial. © 2011 Blackwell Publishing Ltd.

Haemophilia A: carrier detection and prenatal diagnosis by linkage analysis using DNA polymorphism.

PubMed Central

Tuddenham, E G; Goldman, E; McGraw, A; Kernoff, P B

1987-01-01

Restriction fragment length polymorphisms (RFLPs) within or close to the factor VIII locus are very useful for genetic linkage analysis. Such RFLPs allow a mutant allele to be tracked in a family, segregating haemophilia A even when, as is usually the case, the precise mutation causing failure to synthesise factor VIII is unknown. To date two markers tightly linked to the factor VIII locus have been described, one of which is highly polymorphic and therefore informative in most kindreds. A significant crossover rate, however, does not make diagnosis absolute. Three intragenic RFLPs have been defined, which, taken together, are informative in about 70% of women, providing virtually deterministic genetic diagnosis. PMID:2889753

Knee flexion contracture treated with botulinum toxin type A in patients with haemophilia (PWH).

PubMed

Daffunchio, C; Caviglia, H; Nassif, J; Morettil, N; Galatro, G

2016-01-01

Knee flexion contracture (KFC) remains a common complication of haemoarthrosis in children and young adults with haemophilia. If the KFC is not treated properly it produces disability, postural and gait abnormalities. Evaluate the effectiveness of conservative treatment of KFC with Botulinum toxin type A (BTX-A) in PWH. Seventeen patients were treated, with 21 affected knees. Mean age was 26 years. The mean follow up was 12 months. We evaluated flexion and KFC pretreatment BTX-A and up to 12 months posttreatment. BTX-A application was in hamstring and calf muscles. To evaluate the function, a questionnaire about different activities was made, and it was checked 3, 6 and 12 months after BTX-A. According to the degree of KFC, knees were divided into 3 groups: Group 1: -10° to -30° (n = 10), Group 2: -31° to -45° (n = 6) Group 3: -46° or more (n = 5). The average KFC improved from -38° to -24°. The improvement was 14° (P < 0.001). The average KFC improvement was 9° in group 1, 17° in group 2, and 23° in group 3. There was a high correlation between the improvement in KFC and the total score of the questionnaire R = 0.77. Treatment of KFC with BTX-A improves knee-related functional activities, with the advantage of being a low-cost procedure and easy to apply. © 2015 John Wiley & Sons Ltd.

Natural progression of blood-induced joint damage in patients with haemophilia: clinical relevance and reproducibility of three-dimensional gait analysis.

PubMed

Lobet, S; Detrembleur, C; Francq, B; Hermans, C

2010-09-01

A major complication in haemophilia is the destruction of joint cartilage because of recurrent intraarticular and intramuscular bleeds. Therefore, joint assessment is critical to quantify the extent of joint damage, which has traditionally been evaluated using both radiological and clinical joint scores. Our study aimed to evaluate the natural progression of haemophilic arthopathy using three-dimensional gait analysis (3DGA) and to assess the reproducibility of this technique. We hypothesized that the musculoskeletal function was relatively stable in patients with haemophilia. Eighteen adults with established haemophilic arthropathies were evaluated twice by 3DGA (mean follow-up: 18 +/- 5 weeks). Unexpectedly, our findings revealed infraclinical deterioration of gait pattern, characterized by a 3.2% decrease in the recovery index, which is indicative of the subject's ability to save energy while walking. A tendency towards modification of segmental joint function was also observed. Gait analysis was sufficiently reproducible with regards to spatiotemporal parameters as well as kinetic, mechanical and energetic gait variables. The kinematic variables were reproducible in both the sagittal and frontal planes. In conclusion, 3DGA is a reproducible tool to assess abnormal gait patterns and monitor natural disease progression in haemophilic patients.

Service users' expectations of treatment and support at the Community Mental Health Centre in their recovery.

PubMed

Biringer, Eva; Davidson, Larry; Sundfør, Bengt; Ruud, Torleif; Borg, Marit

2017-09-01

Focus on service users' needs, coping and empowerment, user involvement, and comprehensiveness are supposed to be key elements of the Community Mental Health Centres in Norway. Taking a user-oriented approach means acknowledging the individual's own expectations, aims and hopes. However, studies that have investigated service users' expectations of treatment and support at Community Mental Health Centres are hard to find. The aim of the study was therefore to explore service users' expectations at the start of treatment at a Community Mental Health Centre. Within a collaborative framework, taking a hermeneutic-phenomenological approach, ten service users participated in in-depth interviews about their expectations, hopes and aims for treatment and recovery. The participants sought help due to various mental health issues that had interfered with their lives and created disability and suffering. A data-driven stepwise approach in line with thematic analysis was used. The study was approved by the Norwegian Social Science Data Services. The following four main themes representing participants' expectations at the start of treatment were elicited: hope for recovery, developing understanding, finding tools for coping and receiving counselling and practical assistance. Participants' expectations about treatment were tightly interwoven with their personal aims and hopes for their future life, and expectations were often related to practical and financial problems, the solution of which being deemed necessary to gain a safe basis for recovery in the long run. The transferability of the results may be limited by the small number of participants. The study emphasises how important it is that service users' personal aims and expectations guide the collaborative treatment process. In addition to providing treatment aimed at improving symptoms, Community Mental Health Centres should take a more comprehensive approach than today by providing more support with family issues

Risks and benefits of sports and fitness activities for people with haemophilia.

PubMed

Mulder, K; Cassis, F; Seuser, D R A; Narayan, P; Dalzell, R; Poulsen, W

2004-10-01

Physical activity is a key component of a healthy lifestyle. Exercise and physical activity have been shown to help maintain a healthy body weight, reduce stress, increase self-esteem and feelings of wellbeing, control blood pressure, and prevent heart disease and diabetes. Children with haemophilia may feel restricted from competing in sports through parental concern or pain and difficulty in moving, or they may rebel against such restrictions, thus leaving themselves open to serious injury. Several groups have attempted to classify sports activities with regard to the level of risk involved; however, these are not consistent. It is important to match the child's abilities with the sport in which they want to take part, and suggest alternatives if this is not possible. Prevention of injury should not depend solely on use of factor concentrates.

Cost-effectiveness analysis of late prophylaxis vs. on-demand treatment for severe haemophilia A in Italy.

PubMed

Coppola, A; D'Ausilio, A; Aiello, A; Amoresano, S; Toumi, M; Mathew, P; Tagliaferri, A

2017-05-01

Long-term regular administrations of factor VIII (FVIII) concentrate (prophylaxis) initiated at an early age prevents bleeding in patients with severe haemophilia A (HA). The 5-year prospective Italian POTTER study provided evidence of benefits in adolescents and adults of late prophylaxis (LP) vs. on-demand therapy (OD) in reducing bleeding episodes and joint morbidity and improving quality of life; however, costs were increased. The aim of this study was to determine the cost-effectiveness of LP vs. OD with sucrose-formulated recombinant FVIII in adolescents and adults with severe HA in Italy. A Markov model evaluated lifetime cost-effectiveness of LP vs. OD in patients with severe HA in Italy, from both the healthcare and societal perspectives. Clinical input parameters were taken from the POTTER study and published literature. Health utility values were assigned to each health state as measured by the joint disease severity Pettersson score. Costs were expressed in Euro (€) 2014, including drug and other medical costs. Sensitivity analyses were performed considering societal perspective (including productivity lost) and varying relative risk of bleeding episodes between regimens. Clinical outcomes and costs were discounted at 6% according to previous studies. Lifetime incremental discounted quality-adjusted life-years (QALYs) were +4.26, whereas incremental discounted costs were +€229,694 from a healthcare perspective, with estimated incremental cost-effectiveness ratios (ICERs) equal to €53,978/QALY. Sensitivity analyses confirmed the base-case results showing lower ICERs with the societal perspective. Late prophylaxis vs. on-demand therapy results in a cost-effective approach with ICERs falling below the threshold considered acceptable in Italy. © 2017 John Wiley & Sons Ltd.

Cost-utility of a six-month programmed sports therapy (PST) in patients with haemophilia.

PubMed

Koeberlein-Neu, J; Runkel, B; Hilberg, T

2018-03-30

Recurrent musculoskeletal haemorrhages in people with haemophilia (PwH) lead to restrictions in the locomotor system and, as a result, in physical performance, too. Due to its physical and psychological benefits, sport is increasingly re-commended for haemophilic patients. Evidence on the cost-effectiveness of sports therapy is still lacking. The aim of this study was to determine the cost-effectiveness of a 6-month programmed sports therapy (PST). The cost-effectiveness of the 6-month PST was assessed from a societal perspective alongside a RCT using cost-utility analysis. The analysis included 50 PwH with moderate-to-severe haemophilia A and B and a training period over 6 months. The health-related quality of life was measured with the EuroQoL-domain questionnaire. Resource utilization was assessed by questionnaire before and after the intervention. A cost-effectiveness acceptability curve was constructed, and sensitivity analyses were performed. During the 6-month study period, mean adjusted total healthcare costs were lower (mean difference: -22 805 EUR; 95%-CI: -73 944-48 463; P = .59) and the number of QALYs was higher in the intervention group (mean difference: 0.3733; 95%-CI: 0.0014-0.0573; P = .04). The probability of an incremental cost-effectiveness ratio <50 000 EUR per QALY was 71%. The performed sensitivity analysis confirmed these results. Results showed that the PST is effective in terms of a significant gain of QALYs. Furthermore, results weakly indicate the potential of the PST to reduce healthcare costs. Future studies should expand the observation period to have a closer look at the influence of PST on lifetime costs. © 2018 John Wiley & Sons Ltd.

Effects of unstratified and centre-stratified randomization in multi-centre clinical trials.

PubMed

Anisimov, Vladimir V

2011-01-01

This paper deals with the analysis of randomization effects in multi-centre clinical trials. The two randomization schemes most often used in clinical trials are considered: unstratified and centre-stratified block-permuted randomization. The prediction of the number of patients randomized to different treatment arms in different regions during the recruitment period accounting for the stochastic nature of the recruitment and effects of multiple centres is investigated. A new analytic approach using a Poisson-gamma patient recruitment model (patients arrive at different centres according to Poisson processes with rates sampled from a gamma distributed population) and its further extensions is proposed. Closed-form expressions for corresponding distributions of the predicted number of the patients randomized in different regions are derived. In the case of two treatments, the properties of the total imbalance in the number of patients on treatment arms caused by using centre-stratified randomization are investigated and for a large number of centres a normal approximation of imbalance is proved. The impact of imbalance on the power of the study is considered. It is shown that the loss of statistical power is practically negligible and can be compensated by a minor increase in sample size. The influence of patient dropout is also investigated. The impact of randomization on predicted drug supply overage is discussed. Copyright © 2010 John Wiley & Sons, Ltd.

Treatment of dysplastic Barrett’s Oesophagus in lower volume centres after structured training

PubMed Central

Chadwick, Georgina; Faulkner, Jack; Ley-Greaves, Robert; Vlavianos, Panagiotis; Goldin, Rob; Hoare, Jonathan

2015-01-01

AIM: To investigate whether dysplastic Barrett’s Oesophagus can be safely and effectively treated endoscopically in low volume centres after structured training. METHODS: After attending a structured training program in Amsterdam on the endoscopic treatment of dysplastic Barrett’s Oesophagus, treatment of these patients was initiated at St Marys Hospital. This is a retrospective case series conducted at a United Kingdom teaching Hospital, of patients referred for endoscopic treatment of Barrett’s oesophagus with high grade dysplasia or early cancer, who were diagnosed between January 2008 and February 2012. Data was collected on treatment provided (radiofrequency ablation and endoscopic resection), and success of treatment both at the end of treatment and at follow up. Rates of immediate and long term complications were assessed. RESULTS: Thirty-two patients were referred to St Marys with high grade dysplasia or intramucosal cancer within a segment of Barrett’s Oesophagus. Twenty-seven met the study inclusion criteria, 16 of these had a visible nodule at initial endoscopy. Treatment was given over a median of 5 mo, and patients received a median of 3 treatment sessions over this time. At the end of treatment dysplasia was successfully eradicated in 96% and intestinal metaplasia in 88%, on per protocol analysis. Patients were followed up for a median of 18 mo. At which time complete eradication of dysplasia was maintained in 86%. Complications were rare: 2 patients suffered from post-procedural bleeding, 4 cases were complicated by oesophageal stenosis. Recurrence of cancer was seen in 1 case. CONCLUSION: With structured training good outcomes can be achieved in low volume centres treating dysplastic Barrett’s Oesophagus. PMID:25610536

Dr Jekels' health resort in Bystra near Bielsko: the first treatment centre which adopted psychoanalysis in Poland.

PubMed

Dembińska, Edyta; Rutkowski, Krzysztof

2017-08-29

The paper sets out to present the history of a health resort and hydrotherapy centre in Bystra near Bielsko from 1898 to 1912. At that time Dr Ludwik Jekels, one of the Polish psychoanalysis forerunners, was the owner of the centre. Initially, Dr Jekels was very enthusiastic about climatic treatment and hydrotherapy, until 1905 when he got interested in psychoanalysis. Shortly afterwards he became its staunch supporter and adopted it as a curative procedure in his health resort. That was the first documented case of psychoanalysis use in Poland. This paper presents the development of the therapeutic centre in Bystra and the characteristic of typical patients receiving treatment there. It also briefly reports on medical histories of the conditions of patients who received psychoanalytic treatment. The paper also focuses on another significant area of Dr Jekels'contact with Sigmund Freud ranging from an accidental meeting in Vienna around 1898, through the summer of 1910 when Jekels looked after Freud's daughters in his spa, to 1912 which saw Jekels'receiving psychoanalytic treatment from Freud. It also presents a detailed analysis of hypotheses why Jekels decided to sell the health resort and move to Vienna. Finally, the significance of Jekels'currently underrated therapeutic work for the development of the Polish psychoanalysis is reiterated.

The manufacture of blood plasma products in Scotland: a brief history.

PubMed

Foster, Peter R

2016-02-01

A number of essential clinical products are derived from human blood plasma, including immunoglobulin products for the treatment of infections and disorders of immunity; albumin for protein and fluid replacement and coagulation factors for the treatment of haemophilia and other disorders of haemostasis. For many years, these protein pharmaceuticals were manufactured by the Scottish National Blood Transfusion Service (SNBTS) at its Scottish Protein Fractionation Centre (PFC) in Edinburgh, a contribution which ended with the closure of the PFC in 2008. The origins and development of plasma fractionation in Scotland are summarised in this article, as well as issues which contributed to the closure of the PFC. © The Author(s) 2015.

[National health fund and morbidity-based risk structure equalization with focus on haemophilia].

PubMed

König, T

2010-11-01

The Gesundheitsfonds (national health fund) was established in Germany on January 1st, 2009, in combination with the morbidity-based risk structure equalization (RSA) in order to manage the cash flow between the statutory health insurances. The RSA equalizes income differences due to the varying levels of contributory income of the members of a health insurance (basic wage totals) and expenditure differences due to varying distribution of morbidity risks across different health insurances, as well as the varying numbers of non-contributing insured family members. Additionally, insured persons are allocated to morbidity groups according to a classification model based upon diagnoses and prescriptions anticipating medical expenses in the subsequent year. Haemophilia falls, among 80 disease entities, in the morbidity group which generates the highest risk supplement. Matching of prescribed drugs with disease entities facilitates disease grading and improves the accuracy of risk supplements.

Dosimetric inter-institutional comparison in European radiotherapy centres: Results of IAEA supported treatment planning system audit.

PubMed

Gershkevitsh, Eduard; Pesznyak, Csilla; Petrovic, Borislava; Grezdo, Joseph; Chelminski, Krzysztof; do Carmo Lopes, Maria; Izewska, Joanna; Van Dyk, Jacob

2014-05-01

One of the newer audit modalities operated by the International Atomic Energy Agency (IAEA) involves audits of treatment planning systems (TPS) in radiotherapy. The main focus of the audit is the dosimetry verification of the delivery of a radiation treatment plan for three-dimensional (3D) conformal radiotherapy using high energy photon beams. The audit has been carried out in eight European countries - Estonia, Hungary, Latvia, Lithuania, Serbia, Slovakia, Poland and Portugal. The corresponding results are presented. The TPS audit reviews the dosimetry, treatment planning and radiotherapy delivery processes using the 'end-to-end' approach, i.e. following the pathway similar to that of the patient, through imaging, treatment planning and dose delivery. The audit is implemented at the national level with IAEA assistance. The national counterparts conduct the TPS audit at local radiotherapy centres through on-site visits. TPS calculated doses are compared with ion chamber measurements performed in an anthropomorphic phantom for eight test cases per algorithm/beam. A set of pre-defined agreement criteria is used to analyse the performance of TPSs. TPS audit was carried out in 60 radiotherapy centres. In total, 190 data sets (combination of algorithm and beam quality) have been collected and reviewed. Dosimetry problems requiring interventions were discovered in about 10% of datasets. In addition, suboptimal beam modelling in TPSs was discovered in a number of cases. The TPS audit project using the IAEA methodology has verified the treatment planning system calculations for 3D conformal radiotherapy in a group of radiotherapy centres in Europe. It contributed to achieving better understanding of the performance of TPSs and helped to resolve issues related to imaging, dosimetry and treatment planning.

In-hospital rehabilitation after multiple joint procedures of the lower extremities in haemophilia patients: clinical guidelines for physical therapists.

PubMed

De Kleijn, P; Fischer, K; Vogely, H Ch; Hendriks, C; Lindeman, E

2011-11-01

This project aimed to develop guidelines for use during in-hospital rehabilitation after combinations of multiple joint procedures (MJP) of the lower extremities in persons with haemophilia (PWH). MJP are defined as surgical procedures on the ankles, knees and hips, performed in any combination, staged, or during a single session. MJP that we studied included total knee arthroplasty, total hip arthroplasty and ankle arthrodesis. Literature on rheumatoid arthritis demonstrated promising functional results, fewer hospitalization days and days lost from work. However, the complication rate is higher and rehabilitation needs optimal conditions. Since 1995, at the Van Creveldkliniek, 54 PWH have undergone MJP. During the rehabilitation in our hospital performed by experienced physical therapists, regular guidelines seemed useless. Guidelines will guarantee an optimal physical recovery and maximum benefit from this enormous investment. This will lead to an optimal functional capability and optimal quality of life for this elderly group of PWH. There are no existing guidelines for MJP, in haemophilia, revealed through a review of the literature. Therefore, a working group was formed to develop and implement such guidelines and the procedure is explained. The total group of PWH who underwent MJP is described, subdivided into combinations of joints. For these subgroups, the number of days in hospital, complications and profile at discharge, as well as a guideline on the clinical rehabilitation, are given. It contains a general part and a part for each specific subgroup. © 2011 Blackwell Publishing Ltd.

Prevalence of IgG antibodies to human parvovirus B19 in haemophilia children treated with recombinant factor (F)VIII only or with at least one plasma-derived FVIII or FIX concentrate: results from the French haemophilia cohort.

PubMed

Gaboulaud, Valérie; Parquet, Armelle; Tahiri, Cedric; Claeyssens, Ségolène; Potard, Valérie; Faradji, Albert; Peynet, Jocelyne; Costagliola, Dominique

2002-02-01

Human parvovirus B19 (B19) has been transmitted by some brands of virally attenuated plasma-derived factor VIII (FVIII) or IX (FIX) concentrates. To quantify the differences of human parvovirus B19 risk transmission between albumin-stabilized recombinant factor and plasma-derived factor, we studied the prevalence of IgG antibodies to B19 (anti-B19) in 193 haemophiliac children between 1 and 6-years of age who had previously been treated with albumin-stabilized recombinant FVIII only (n = 104), and in children previously treated with solvent/detergent high-purity non-immunopurified and non-nanofiltered FVIII or IX concentrates (n = 89). Association between the prevalence of anti-B19 and the treatment group was analysed using multivariate logistic regression. Age, severity and type of haemophilia, number of cumulative days of exposure to factor VIII or IX, previous history of red blood cells or plasma transfusion were considered as potential confounding variables. A higher prevalence of anti-B19 was found in children previously treated with solvent/detergent high-purity non-immunopurified and non-nanofiltered FVIII or IX concentrates than in children treated with albumin- stabilized recombinant FVIII only (OR: 22.3; CI: 7.9-62.8), independently of the other factors studied.

A patient-centred approach to treatment with incretin-based agents in patients with type 2 diabetes.

PubMed

Cornell, Susan A

2013-06-01

The 2012 position statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommends a haemoglobin A1c level of <7% for most patients with type 2 diabetes (T2D). Initial therapy consists of lifestyle changes plus metformin, with an emphasis on a patient-centred approach to management. Addition of incretin-based therapy is recommended as an add-on after metformin failure, and later on in combination with basal insulin. Basal insulin is recommended from the onset in patients with A1c ≥10%. The possibility of incorporating incretin-based therapy in the patient-centred approach will be investigated both in the literature and clinical experience. Incretin-based therapy targets multiple dysfunctional organ systems in T2D and provides sustained glycaemic control, with extraglycaemic benefits and low risk of hypoglycaemia. To initiate an incretin-based therapy that best fits an individual patient's needs, the patient's A1c level, preference and comorbid conditions should be considered along with any drug safety and adherence-related issues. There is good evidence to support the patient-centred approach to T2D management. This approach allows patient treatment goals and personal preferences to be matched with the clinical profile(s) of one or more agents to formulate a treatment plan that can best achieve the goals. Incretin-based therapies are an important class of agents to consider after metformin monotherapy failure and later in combination with basal insulin. By matching patient needs with the clinical profiles of the various treatment options, pharmacists can actively engage in the practice of patient-centred care and management. © 2013 Blackwell Publishing Ltd.

Investigation of inflicted injury in a young girl reveals mild haemophilia A and Turner's syndrome.

PubMed

Williams, V K; Suppiah, R; Coppin, B; Nicholls, C M; Simsek, A; McGregor, L K

2012-02-01

A 2-year-old girl presented to casualty with a right knee effusion after apparently minor trauma. Inflicted injury was suspected and full forensic coagulation studies were performed which revealed a mild deficiency of factor VIII. Screening of the exons and intron/exon boundaries of F8 gene indicated that the child appeared to be homozygous for the missense mutation c.5123G>A (p.Arg1708His) in exon 14 of the F8 gene. This mutation has been reported to be associated with mild haemophilia A. The possibility of hemizygosity had been masked by the test kit employed but referral to the genetics service and subsequent array CGH resulted in a diagnosis of Turner syndrome. © 2011 Blackwell Publishing Ltd.

Effects of short-term resistance training and pulsed electromagnetic fields on bone metabolism and joint function in severe haemophilia A patients with osteoporosis: a randomized controlled trial.

PubMed

Parhampour, Behrouz; Torkaman, Giti; Hoorfar, Hamid; Hedayati, Mehdi; Ravanbod, Roya

2014-05-01

To assess the effects of short-term resistance training and pulsed electromagnetic fields on bone metabolism and joint function in patients with haemophilia with osteoporosis. A randomized, controlled, patient and blood sample assessor-blinded, six-week trial, three times weekly. Hospital outpatients with severe haemophilia A and osteoporosis. Forty-eight patients were randomly assigned to resistance training (RT, n = 13), combined resistance training with pulsed electromagnetic fields (RTPEMF, n = 12), pulsed electromagnetic fields (PEMF, n = 11) and control (n = 12) groups. The RT group received 30-40 minutes of resistance exercises and placebo pulsed electromagnetic fields. The RTPEMF group received the same exercises with lower repetition and 30 minutes of pulsed electromagnetic fields. The PEMF group was exposed to 60 minutes of pulsed electromagnetic fields (30 Hz and 40 Gauss). Bone-specific alkaline phosphatase, N-terminal telopeptide of type 1 collagen, and joint function, using the modified Colorado Questionnaire, were measured before and after the programme. The absolute change of bone-specific alkaline phosphatase was significant in the RT and RTPEMF groups compared with the control group (25.41 ± 14.40, 15.09 ± 5.51, and -4.73 ± 2.93 U/L, respectively). The absolute changes in the total score for joint function were significant for knees, ankles, and elbows in the RT group (9.2 ± 1.38, 5.1 ± 0.5, and 3.2 ± 0.8, respectively) and the RTPEMF group (7.7 ± 1.0, 3.3 ± 0.6, and 2.5 ± 0.7, respectively) compared to the PEMF and control groups. This value was significant for knee joints in the PEMF group compared to the control group (3.4 ± 0.5 and 0.66 ± 0.4, respectively). Resistance training is effective for improving bone formation and joint function in severe haemophilia A patients with osteoporosis.

Recombinant factor concentrates may increase inhibitor development: a single centre cohort study.

PubMed

Strauss, T; Lubetsky, A; Ravid, B; Bashari, D; Luboshitz, J; Lalezari, S; Misgav, M; Martinowitz, U; Kenet, G

2011-07-01

Recent reports have raised concerns regarding potential risk factors for inhibitor development. In Israel, all haemophilia patients (n = 479) are followed by the National Hemophilia Center. Most children are neonatally exposed to factor concentrate (due to circumcision performed at the age of 8 days). The impact of early exposure and recombinant FVIII products (rFVIII) administration (approved in Israel since 1996) upon inhibitor occurrence in our cohort of haemophilia A (HA) patients was analysed. Two hundred ninety-two consecutive paediatric cases with a first symptomatic onset of HA were enrolled and followed over a median time of 7 years [min-max: 9 months to 17 years]. Study endpoint was inhibitor development against factor VIII. In addition, the treatment regimens applied, i.e. bolus administration or 'continuous infusion' and the family history of inhibitor development were investigated. During the follow-up period 31/292 children (10.6%) developed high titre inhibitors. Inhibitors occurred in 14/43 (32.5%) HA patients neonatally exposed to rFVIII, as compared to 22/249 previously treated with Plasma Derived (PD) products (8.8%). The odds ratio for inhibitor formation in rFVIII treated HA patients was 3.43 (95% CI: 1.36-8.65). Transient inhibitor evolved among 2/43 paediatric HA patients, only among those treated with rFVIII. The risk of inhibitor detection significantly increased among HA children treated by continuous infusion (P = 0.025). Our experience shows that the risk of inhibitor formation may be increased by early exposure to recombinant concentrates. The multiple variables affecting inhibitor incidence deserve further attention by larger prospective studies. © 2011 Blackwell Publishing Ltd.

Treatment of fibromyalgia at the Maharishi Ayurveda Health Centre in Norway. A six-month follow-up study.

PubMed

Rasmussen, L B; Mikkelsen, K; Haugen, M; Pripp, A H; Førre, Ø T

2009-01-01

Treatments offered at the Maharishi Ayurveda Health Centre in Norway are based on Maharishi Vedic medicine, which is also known as Maharishi Ayurveda. It is a consciousness based revival of the ancient Ayurvedic medicine tradition in India and is established by Maharishi Mahesh Yogi, the founder of the Transcendental Meditation (TM) technique. To conduct a pilot study of the effect of the treatment program at the Health Centre on fibromyalgia patients. Thirty-one women with diagnosed fibromyalgia received an individually designed Maharishi Vedic physiological purification therapy. All subjects received personal advice on diet based on Ayurvedic principles, including a novel approach to food into-lerance, and daily routines. In addition they were offered instruction in TM (for stress and pain management and personal development) (four subjects started), and recommended Ayurvedic herbal food products for home treatment. A modified Fibromyalgia Impact Questionnaire included a visual analogue scale for each of the seven outcomes: working ability, generalised pain, tiredness, stiffness, tiredness on arising, anxiety and depression. Pre-treatment scores were compared with scores at six-month follow-up for levels of statistical significance. Twenty-eight subjects (90%) completed the follow-up. The outcome measures were reduced by 25 to 46% by the study's endpoint: working ability (p<0.002), pain (p<0.001), tiredness (p<0.001), morning tiredness (p<0.001), stiffness (p<0.005), anxiety (p<0.136), and depression (p<0.001). A group of five excellent responders including all four participants who started to practise TM, had almost no symptoms by the endpoint. Compared to the non-meditating control group the TM-subgroup showed statistically significant improvements for all outcome measures except depression. In this pilot study fibromyalgia patients undergoing treatment at Maharishi Ayurveda Health Centre in Norway showed significant improvements six months post treatment

Accidental hypothermia: rewarming treatments, complications and outcomes from one university medical centre.

PubMed

van der Ploeg, Gert-Jan; Goslings, J Carel; Walpoth, Beat H; Bierens, Joost J L M

2010-11-01

Accidental hypothermia (AH) is a complex and life threatening condition. Knowledge about epidemiology, rewarming treatments, complications and outcome is limited. This study was initiated to obtain data on causes, rewarming treatments and complications. A retrospective cohort study of all patients with a body temperature ≤ 35°C admitted to the Emergency Department (ED) of the VU university medical centre, Amsterdam, The Netherlands, between January 1, 2000 and August 31, 2008. A predefined set of epidemiological and clinical data was retrieved. Eighty-four patients were included (median age: 47 years). Categories of hypothermia included immersion (18), submersion (29) and exposure to cold (37); concomitant factors were intoxication (26), trauma (40) and homelessness (7). Temperature at admission in the ED was 31.6 ± 2.6°C (mean ± SD), lowest temperature 24.2°C. Fourteen different rewarming treatments were used resulting in a wide range of rewarming speeds. Seventy-nine complications occurred: pulmonary, renal and neurological complications in 20, 17 and 10 patients respectively. Seventeen patients had 2 or more late complications. Twenty-four patients (28.6%) died: 10 during rewarming and 14 after rewarming was completed. Prognosis was poor in older and colder patients and after indoor exposure and submersion. AH is a rare diagnosis in an inhomogeneous population, treated with a large variety of rewarming techniques. Most complications and death occurred late, after rewarming was completed. Because individual teams gain little clinical experiences, we suggest multiple centre data collection as a first step towards an evidence-based standard of care. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

RCT of a 6-month programmed sports therapy (PST) in patients with haemophilia - Improvement of physical fitness.

PubMed

Runkel, B; Czepa, D; Hilberg, T

2016-09-01

Physical fitness is of major importance for patients with haemophilia (PwH) but is highly influenced by bleeding episodes. Although some cohort studies describe an improvement of physical fitness after training intervention, randomized controlled studies (RCT) in PwH are still rare. The aim of this study was to prove the enhancement of physical work capacity in PwH by programmed sports therapy (PST). This RCT includes a training period over six months. Sixty-four PwH with moderate (n = 5) to severe (n = 59) haemophilia A (n = 57) and B (n = 7) were randomized into two groups - training intervention group (IG) and control group (CG) by block randomization. Complex strength measurements, joint score, coordination check and a 12-min walking test were carried out before and after training intervention. Significant differences were tested in M. triceps brachii (Δ+0.62 N kg(-1) ), biceps brachii (Δ+1.25 N kg(-1) ), latissimus dorsi (Δ+0.59 N kg(-1) ), rectus abdominis (Δ+0.51 N kg(-1) ), biceps femoris (right: Δ+0.68 N kg(-1) ; left: Δ+0.59 N kg(-1) ) and the quadriceps femoris (right: Δ+0.71 N kg(-1) ; left: Δ+0.55 N kg(-1) ) after intervention between the two groups (all p ≤ 0.003). Furthermore, an increase in distance (Δ+171.5 m) covered in the 12-min walking test (P = 0.011) was observed. Regarding one-leg stand, a significant improvement (P = 0.037) in the IG (Δ+2.2 s right leg) after intervention could be determined. For the first time, a study with a corresponding number of adult PwH in a RCT-design showed that programmed sport therapy with specific instructions over 6 months has a positive effect on physical performance of PwH, independent of constitution and disease process. © 2016 John Wiley & Sons Ltd.

[Cost of treatment and follow up of breast cancer: a retrospective assessment in a comprehensive cancer centre].

PubMed

Lilliu, Hervé; Stevens, Denise; Brun, Catherine; Morel, Julie; Pen, Claude Le; Bonastre, Julia; Bachelot, Florence; Davesne, Christian; Gentile, Annie; Hirlimann, Eric; Sabourin, Jean-Christophe; Berlie, Jacques; Rouëssé, Jacques

2002-06-01

Breast cancer is one of the major causes of premature death for women. Its cost management is important for both the national health insurance and the individual health care providers. The objective of this study was to assess the global medical cost of breast cancer from diagnosis to follow up in one French medical centre: centre René-Huguenin, Saint-Cloud (92). Duration of medical activities and other medical resources utilisations were collected from a retrospective cohort of 120 patients followed from January 1995 to February 2000. Unit costs were obtained from cost accounts of the Centre. The mean medical cost per patient was FF 66,067 [60,318-7,815] (USD $ 10,744 [9,809-11,679]). The mean cost varied from FF 41,875 (UDS $ 6,810) to FF 81,020 (UDS $ 13,175) depending on choice of type of therapy. The initial treatment phase was the most expensive, costing FF 48,397 [46,176-50,617] (USD $ 7,870 [7,509-8,231]) which represented 73.3% of the global cost. This study has provided an estimate of the real global cost of managing patients with breast cancer in a single French Comprehensive Cancer Centre (CLCC). The study method used is readily transposable to other treatment contexts and to other types of cancer.

Experiences from a community based substance use treatment centre in an urban resettlement colony in India.

PubMed

Balhara, Yatan Pal Singh; Ranjan, Rajeev; Dhawan, Anju; Yadav, Deepak

2014-01-01

Background. There are limited community based treatment services for drug dependence in India. Rural areas and urban resettlement colonies are in particular deficient in such services. Aims. The current study aimed at preliminary assessment of substance use disorder management services at a community based substance use treatment clinic in an urban resettlement colony. Methods. The study was carried out at community based substance use treatment centre in a resettlement colony in India. The records of the centre were chart reviewed. Results. A total of 754 patients were registered at the clinic during the study period. Heroin was the primary drug of abuse for 63% of the patients. The mean duration of follow-up for the patients with opioid and alcohol dependence was 13.47 (SD ± 10.37; range 0-39) months. A total of 220 patients of opioid dependence were prescribed substation or abstinence directed therapy. Buprenorphine (87), slow release oral morphine (SROM) (16), and dextropropoxyphene (98) were used for opioid substitution. Conclusion. It is possible to deliver substance use disorder treatment services in community setting. There is a need to develop area specific community based treatment services for substance abuse in socially disadvantaged populations such as urban resettlement colonies.

Experiences from a Community Based Substance Use Treatment Centre in an Urban Resettlement Colony in India

PubMed Central

Balhara, Yatan Pal Singh; Ranjan, Rajeev; Dhawan, Anju; Yadav, Deepak

2014-01-01

Background. There are limited community based treatment services for drug dependence in India. Rural areas and urban resettlement colonies are in particular deficient in such services. Aims. The current study aimed at preliminary assessment of substance use disorder management services at a community based substance use treatment clinic in an urban resettlement colony. Methods. The study was carried out at community based substance use treatment centre in a resettlement colony in India. The records of the centre were chart reviewed. Results. A total of 754 patients were registered at the clinic during the study period. Heroin was the primary drug of abuse for 63% of the patients. The mean duration of follow-up for the patients with opioid and alcohol dependence was 13.47 (SD ± 10.37; range 0–39) months. A total of 220 patients of opioid dependence were prescribed substation or abstinence directed therapy. Buprenorphine (87), slow release oral morphine (SROM) (16), and dextropropoxyphene (98) were used for opioid substitution. Conclusion. It is possible to deliver substance use disorder treatment services in community setting. There is a need to develop area specific community based treatment services for substance abuse in socially disadvantaged populations such as urban resettlement colonies. PMID:25431739

Diagnostic accuracy of point-of-care ultrasound for evaluation of early blood-induced joint changes: Comparison with MRI.

PubMed

Foppen, W; van der Schaaf, I C; Beek, F J A; Mali, W P T M; Fischer, K

2018-05-23

Recurrent joint bleeding is the hallmark of haemophilia. Synovial hypertrophy observed with Magnetic Resonance Imaging (MRI) is associated with an increased risk of future joint bleeding. The aim of this study was to investigate whether point-of-care ultrasound (POC-US) is an accurate alternative for MRI for the detection of early joint changes. In this single centre diagnostic accuracy study, bilateral knees and ankles of haemophilia patients with no or minimal arthropathy on X-rays were scanned using POC-US and 3 Tesla MRI. POC-US was performed by 1 medical doctor, blinded for MRI, according to the "Haemophilia Early Arthropathy Detection with Ultrasound" (HEAD-US) protocol. MRIs were independently scored by 2 radiologists, blinded for clinical data and ultrasound results. Diagnostic accuracy parameters were calculated with 95% confidence intervals (CI). Knees and ankles of 24 haemophilia patients (96 joints), aged 18-34, were studied. Synovial hypertrophy on MRI was observed in 20% of joints. POC-US for synovial tissue was correct (overall accuracy) in 97% (CI: 91-99) with a positive predictive value of 94% (CI: 73-100) and a negative predictive value of 97% (CI: 91-100). The overall accuracy of POC-US for cartilage abnormalities was 91% (CI: 83-96) and for bone surface irregularities 97% (CI: 91-99). POC-US could accurately assess synovial hypertrophy, bone surface irregularities and cartilage abnormalities in haemophilia patients with limited joint disease. As POC-US is an accurate and available alternative for MRI, it can be used for routine evaluation of early joint changes. © 2018 The Authors. Haemophilia published by John Wiley & Sons Ltd.

New associations: INFG and TGFB1 genes and the inhibitor development in severe haemophilia A.

PubMed

de Alencar, J B; Macedo, L C; de Barros, M F; Rodrigues, C; Shinzato, A H; Pelissari, C B; Machado, J; Sell, A M; Visentainer, J E L

2015-07-01

The development of factor VIII (FVIII) inhibitor is the main complication of replacement therapy in patients with haemophilia A (HA). A ratio of 5-7% of individuals HA develops antibodies (inhibitors) against the FVIII infused during the treatment, thereby reducing their pro-coagulant activity. The immunomodulatory cytokine genes have been related to the risk of development of alloantibodies in several studies, mainly in HA with severe form. We investigated the polymorphisms in regulatory regions of cytokine genes (IL1A, IL1B, IL1R, IL1RA, IL4RA, IL12, INFG, TGFB1, TNF, IL2, IL4, IL6, IL10) that could influence the risk of developing inhibitors in patients with severe HA. The genotyping of cytokine genes of 117 patients with HA was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP) using the protocol recommended by the manufacturer (Invitrogen kit Cytokines(®) , Canoga Park, USA) RESULTS: From the cohort of 117 patients with severe HA, 35 developed inhibitors. There was a higher frequency of +874 T allele in INFG and of +869 TT and TG/TG in TGFB1 genes on patients with inhibitors. This suggests that polymorphisms in INFG and in TGFB1 genes are related to risk of developing inhibitor, and could contribute to a genetic profile of the individual HA for the risk of inhibitors development to FVIII. © 2015 John Wiley & Sons Ltd.

Factor (F)VIII/VIIa enhances global haemostatic function in the co-presence of bypassing agents and FVIII among patients with haemophilia A with inhibitor.

PubMed

Nogami, Keiji; Matsumoto, Tomoko; Yada, Koji; Ogiwara, Kenichi; Furukawa, Shoko; Shida, Yasuaki; Takeyama, Masahiro; Shima, Midori

2018-05-01

Bypassing therapy is essential for the haemostatic management of patients with haemophilia A with inhibitor (PWHA-inh), but the therapeutic effects are inconsistent. We previously reported that activated prothrombin complex concentrates (aPCC) activated factor (F)VIIIin vitro, and was mediated mainly by the activated FVII (FVIIa) contained in aPCC. We have extended those studies to assess global coagulation in whole blood from 18 PWHA-inh in the co-presence of aPCC and FVIII using Ca 2+ -triggered rotational thromboelastometry. The clot times (CTs) in the presence of both aPCC (0·05 iu/ml) and recombinant (r)FVIII (1 iu/ml) ex vivo were shortened compared to the aPCC alone (P < 0·01). These enhancing effects of rFVIII were observed, irrespective of recognizing inhibitor epitopes; however, the clot formation time and 'α'-angle were not significantly different. In samples from 7 PWHA-inh post-infusion of aPCC (70-80 iu/kg), only the CTs were shortened in the presence of rFVIIIex vivo compared to its absence (P < 0·05), indicating that the enhanced activity centred on the initiation phase of coagulation. Furthermore, experiments in the co-presence of rFVIIa and rFVIII demonstrated that FVIII accelerated only the CTs. We concluded that FVIII/FVIIa-related coagulation mechanism enhanced global haemostatic function by the co-presence of bypassing agents and FVIII in PWHA-inh. © 2018 John Wiley & Sons Ltd.

Independent sector treatment centres: the first independent evaluation, a Scottish case study.

PubMed

Pollock, Allyson M; Kirkwood, Graham

2009-07-01

The pound5 billion English Independent Sector Treatment Centre (ISTC) programme remains unevaluated because of a lack of published contract data and poor quality data returns. Scotland has a three-year pilot ISTC, the Scottish Regional Treatment Centre (SRTC), the contract for which is now in the public domain. This study aims to conduct an independent evaluation of the performance of the SRTC during the first year of operation. A retrospective analysis of the SRTC comparing activity as reported by hospital episode statistics returned to ISD Scotland with: volume and cost data in the SRTC contract; a 10-month audit carried out by management consultants Price Waterhouse Coopers (PWC); and an internal NHS Tayside performance report. All day-case and inpatient activity at the SRTC from 1 December 2006 to 31 January 2008. Activity and cost. The annual contract was based on patient referrals to the SRTC and not actual treatments. The contract was awarded on the basis of 2624 referrals a year, total value of pound5,667,464. According to ISD data, the SRTC performed 831 procedures (32% of annual contract) in the first 13 months worth pound1,035,603 (18%). PWC's figures report 2200 referrals (84%) to the SRTC at a cost of 2,642,000 (47%) in the first 10 months. Basing the SRTC contract on payments for referrals rather than actual treatment represents a major departure from normal standards of reporting and commissioning and may have resulted in over-payment for referrals for patients who did not receive treatment of up to pound3 million in the first 10 months. The PWC report falls well below the standards one would expect of an independent evaluation and we were unable to validate PWC's analysis and the claim of value for money. If wave-one ISTCs in England perform similarly to the SRTC then as much as pound927 million may have been paid for patients who did not receive treatment. We recommend a moratorium on all ISTC contracts until the contracts have been published and

Independent sector treatment centres: the first independent evaluation, a Scottish case study

PubMed Central

Pollock, Allyson M; Kirkwood, Graham

2009-01-01

Summary Objectives The £5 billion English Independent Sector Treatment Centre (ISTC) programme remains unevaluated because of a lack of published contract data and poor quality data returns. Scotland has a three-year pilot ISTC, the Scottish Regional Treatment Centre (SRTC), the contract for which is now in the public domain. This study aims to conduct an independent evaluation of the performance of the SRTC during the first year of operation. Design A retrospective analysis of the SRTC comparing activity as reported by hospital episode statistics returned to ISD Scotland with: volume and cost data in the SRTC contract; a 10-month audit carried out by management consultants Price Waterhouse Coopers (PWC); and an internal NHS Tayside performance report. Setting All day-case and inpatient activity at the SRTC from 1 December 2006 to 31 January 2008. Main outcome measures Activity and cost. Results The annual contract was based on patient referrals to the SRTC and not actual treatments. The contract was awarded on the basis of 2624 referrals a year, total value of £5,667,464. According to ISD data, the SRTC performed 831 procedures (32% of annual contract) in the first 13 months worth £1,035,603 (18%). PWC's figures report 2200 referrals (84%) to the SRTC at a cost of 2,642,000 (47%) in the first 10 months. Conclusions Basing the SRTC contract on payments for referrals rather than actual treatment represents a major departure from normal standards of reporting and commissioning and may have resulted in over-payment for referrals for patients who did not receive treatment of up to £3 million in the first 10 months. The PWC report falls well below the standards one would expect of an independent evaluation and we were unable to validate PWC's analysis and the claim of value for money. If wave-one ISTCs in England perform similarly to the SRTC then as much as £927 million may have been paid for patients who did not receive treatment. We recommend a moratorium on all

Patient-centred outcomes research: perspectives of patient stakeholders.

PubMed

Chhatre, Sumedha; Gallo, Joseph J; Wittink, Marsha; Schwartz, J Sanford; Jayadevappa, Ravishankar

2017-11-01

To elicit patient stakeholders' experience and perspectives about patient-centred care. Qualitative. A large urban healthcare system. Four patient stakeholders who are prostate cancer survivors. Experience and perspectives of patient stakeholders regarding patient-centred care and treatment decisions. Our patient stakeholders represented a diverse socio-demographic group. The patient stakeholders identified engagement and dialogue with physicians as crucial elements of patient-centred care model. The degree of patient-centred care was observed to be dependent on the situations. High severity conditions warranted a higher level of patient involvement, compared to mild conditions. They agreed that patient-centred care should not mean that patients can demand inappropriate treatments. An important attribute of patient-centred outcomes research model is the involvement of stakeholders. However, we have limited knowledge about the experience of patient stakeholders in patient-centred outcomes research. Our study indicates that patient stakeholders offer a unique perspective as researchers and policy-makers aim to precisely define patient-centred research and care.

Impact of being overweight on factor VIII dosing in children with haemophilia A.

PubMed

Henrard, S; Hermans, C

2016-05-01

Treatment of haemophilia A (HA) requires infusions of factor VIII (FVIII) concentrates. The number of FVIII units infused to obtain a specific circulating FVIII level is calculated with the formula: [body weight (BW) (kg) × desired FVIII increase (%)]/2, with the assumption that each unit of FVIII infused per kg of BW increases the circulating FVIII level by 2%. The aim of this study was to evaluate the impact of several morphometric parameters (BW, body mass index (BMI)-for-age, height), age and type of FVIII concentrate on FVIII recovery in children with HA. A total of 66 children aged between 10 and 18 with severe HA selected from six pharmacokinetic (PK) clinical trials using two recombinant FVIII concentrates were included in the analysis. Regression tree (RT) was used to identify predictors of FVIII recovery. The median age was 14.5 years with a median FVIII recovery of 2.09 for all children. The median FVIII recovery was not significantly different between age groups. Two groups were created by RT: children with a BMI-for-age percentile

Delivering Service Quality in Alcohol Treatment: A Qualitative Comparison of Public and Private Treatment Centres by Service Users and Service Providers

ERIC Educational Resources Information Center

Resnick, Sheilagh M.; Griffiths, Mark D.

2012-01-01

In the UK, quality of care has now been placed at the centre of the National Health Service (NHS) modernisation programme. To date, there has been little research on the service quality delivery of alcohol treatment services from the perspective of both the service user and service provider. Therefore, this qualitative study explored the…

The pattern of mucocutaneous disorders in HIV-infected children attending care and treatment centres in Dar es Salaam, Tanzania.

PubMed

Panya, Millembe F; Mgonda, Yassin M; Massawe, Augustine W

2009-07-14

HIV/AIDS is associated with a wide range of mucocutaneous disorders some of which are useful in the clinical staging and prognosis of the syndrome. There is paucity of information regarding the prevalence and pattern of mucocutaneous disorders among HIV infected children attending paediatric Care and Treatment Centres (CTC) in Dar es Salaam. To determine the prevalence and pattern of mucocutaneous disorders among HIV infected children attending public paediatric 'Care and Treatment Centres' in Dar es Salaam. This was a cross sectional descriptive study involving public paediatric 'Care and Treatment Centres' in Dar es Salaam. Clinical information was obtained using a questionnaire. Dermatological examination was carried out in daylight. Investigations were taken as appropriate. Data was analysed using the Statistical Package for Social Sciences (SPSS) program version 10.0. Chi-squared and Fisher's exact tests were utilized. A p-value of less than 0.05 was considered statistically significant. Three hundred and forty seven HIV infected children (52% males) attending CTCs were recruited into the study. Mucocutaneous disorders were encountered in 85% of them. There was no gender difference in the prevalence of the infective mucocutaneous disorders but males had a higher prevalence of non-infective/inflammatory dermatoses (58%) than females (42%) (p = 0.02). Overall, mucocutaneous disorders (infective + non infective) were more prevalent in advanced stages of HIV disease. Children with advanced HIV disease had a significantly increased frequency of fungal and viral infections (43% and 25% respectively than those with less advanced disease; 24% and 13% respectively (p = 0.01). Seventy four percent of the HIV-infected children with mucocutaneous disorders were already on ART. Mucocutaneous disorders among HIV infected children attending Care and Treatment Centres are common and highly variable. Comprehensive management should also emphasize on the management of

[Overdose of modified-release paracetamol calls for changed treatment routines. New guidelines from the Swedish Poisons Information Centre].

PubMed

Höjer, Jonas; Salmonson, Helene; Sjöberg, Gunilla; Tellerup, Markus; Brogren, Jacob

2016-11-10

Overdose of modified-release paracetamol calls for changed treatment routines. New guidelines from the Swedish Poisons Information Centre  The sales of modified-release paracetamol tablets are steadily increasing in Sweden as are the number of overdose cases with this formulation. The Swedish Poisons Information Centre has noted that the standard treatment protocol with N-acetylcysteine (NAC), which is based on overdoses with immediate-release paracetamol formulations, is often inadequate in this setting. In this paper, an adult who overdosed on 66.5 grams of modified-release paracetamol tablets and developed severe liver impairment (max ALT 6,660 U/l) despite timely and rigorous NAC treatment is presented. The patient's peak S-paracetamol of 2,800 µmol/l was delayed to 19 hours post-ingestion. Moreover, a pharmacokinetic and clinical study of similar cases showed that seven (21%) of the 34 patients who received NAC treatment within 8 hours after ingestion developed liver impairment. Finally, new Swedish guidelines for management of these cases are presented. The guidelines are also available on www.giftinfo.se.

Helicobacter pylori related dyspepsia: prevalence and treatment outcomes at University Kebangsaan Malaysia-Primary Care Centre

PubMed Central

Abdul Aziz, Aznida Firzah; Hamzah, Zuhra; Tong, Seng Fah; Nadeson, Sukumar; Wan Puteh, Sharifa Ezat

2009-01-01

Background Optimum management of dyspepsia in primary care is a debatable subject. Testing for Helicobacter pylori (HP) has been recommended in primary care as this strategy will cure most underlying peptic ulcer disease and prevent future gastro duodenal disease. Methods A total of 98 patients completed Modified Glasgow Dyspepsia Severity Score Questionnaire (MGDSSQ) at initial presentation before undergoing the 13Carbon Urea Breath Test (UBT) for HP. Those with positive UBT received Eradication Therapy with oral Omeprazole 20 mg twice daily, Clarithromycin 500 mg daily and Amoxycillin 500 mg twice daily for one week followed by Omeprazole to be completed for another 4 to 6 weeks. Those with negative UBT received empirical treatment with oral Omeprazole 20 mg twice daily for 4 to 6 weeks. Patients were assessed again using the MGDSSQ at the completion of treatment and one month after stopping treatment. Results The prevalence of dyspepsia at Universiti Kebangsaan Malaysia-Primary Care Centre was 1.12% (124/11037), out of which 23.5% (23/98) was due to HP. Post treatment assessment in both HP (95.7%, 22/23) and non HP-related dyspepsia (86.7%, 65/75) groups showed complete or almost complete resolution of dyspepsia. Only about 4.3% (1/23) in the HP related dyspepsia and 13.3% (10/75) in the non HP group required endoscopy. Conclusion The prevalence of dyspepsia due to HP in this primary care centre was 23.5%. Detection of HP related dyspepsia yielded good treatment outcomes (95.7%). PMID:19435494

Treatment of fibromyalgia at the Maharishi Ayurveda Health Centre in Norway II--a 24-month follow-up pilot study.

PubMed

Rasmussen, Lars Bjørn; Mikkelsen, Knut; Haugen, Margaretha; Pripp, Are H; Fields, Jeremy Z; Førre, Øystein T

2012-05-01

Treatments offered at the Maharishi Ayurveda Health Centre in Norway are based on Maharishi Vedic Medicine (MVM). MVM is a consciousness-based revival by Maharishi Mahesh Yogi, the founder of the Transcendental Meditation (TM) program of the ancient Ayurvedic medicine tradition in India. To extend from 6 to 24 months, a pilot study of the effects of the treatment program at the Health Centre on fibromyalgia. Retesting 2 years after a clinical trial. In this intention to treat study, 31 women with a diagnosis of fibromyalgia received an individually tailored program of (1) physiological purification therapy (Maharishi Panchakarma) and (2) Ayurvedic recommendations regarding daily routine and diet including a novel approach to food intolerance. Five subjects chose to learn TM for stress reduction, pain management and personal development. All were recommended Ayurvedic herbal products for follow-up treatment. A modified Fibromyalgia Impact Questionnaire (FIQ) that included seven dimensions. Scores at 24 months follow-up were compared with pre-treatment scores. At 24-months follow-up, there were significant reductions (26% to 44%) in six of the seven fibromyalgia dimensions: impairment of working ability, pain, tiredness, morning tiredness, stiffness and anxiety. The 7th, depression, decreased 32% (borderline significant). At 24 months, the four subjects who continued practising TM, had almost no symptoms and significantly lower FIQ change scores (-92% to 97%) than the non-meditators on all outcomes. This pilot study suggests that the treatments and health promotion programs offered at the Maharishi Ayurveda Health Centre in Norway lead to long-term reductions in symptoms of fibromyalgia, which is considered a treatment-resistant condition, and further studies are warranted.

Allocation of substance use disorder patients to appropriate levels of care: feasibility of matching guidelines in routine practice in Dutch treatment centres.

PubMed

Merkx, Maarten J M; Schippers, Gerard M; Koeter, Maarten J W; Vuijk, Pieter Jelle; Oudejans, Suzan; de Vries, Carlijn C Q; van den Brink, Wim

2007-03-01

To examine the feasibility of implementing evidence-based guidelines for patient-treatment-matching to levels of care in two Dutch substance abuse treatment centres. Multi-centre observational follow-up study. Two large substance abuse treatment centres (SATCs). All 4394 referrals to the two SATCs in 2003. Baseline patient characteristics needed for treatment allocation according to protocol, treatment allocation according to matching protocol, treatment allocation according to actual level of care (LOC) entered. Comparison of recommended and actual LOC entered. Evaluation of reasons for observed differences between recommended and actual LOC entered. Data needed for treatment allocation according to protocol were available for 2269 (51.6%) patients. Data needed for evaluation of actual LOC entered were available for 1765 (40.2%) patients. Of these patients, 1089 (60.8%) were allocated according to protocol: 48.4% based on the guideline algorithm and 12.4% based on clinically justified deviations from this algorithm. The main reason for deviation was a different appraisal of addiction severity, made by the intake counsellor compared to the protocol. The feasibility of guideline-based treatment allocation is seriously limited due to inadequate data collection of patient characteristics and suboptimal guideline-based treatment allocation. As a consequence, only 24.4% of the patients could be evaluated as being matched properly to the treatment planned. The results indicate several barriers which limit the adequate implementation of patient-treatment-matching guidelines: problems in the infrastructure of data collection and storage and the inertia of intake staff who did not adhere to the guidelines for assessment and matching.

Christmas disease: diagnosis and management of a haemorrhagic diathesis following dentofacial trauma

PubMed Central

Tamagond, Sridevi B; Hugar, Santosh I; Patil, Anil; Huddar, SandhyaRani

2015-01-01

Haemorrhagic diathesis has been of much concern to health professionals including dentists. It is not infrequent that a dentist becomes the first person to diagnose a bleeding disorder while performing dental treatment. Haemophilia is an X linked disorder with a frequency of about 1:10 000 births. Haemophilia B is much less common than haemophilia A, and affects only 1:300 000 males born alive. The clinical features of haemophilia B are very similar to those of haemophilia A with a prolongation of activated partial thromboplastin time. This case report describes the dental management of a patient with an uncommon haematological disorder, namely, factor IX deficiency, which remained undiagnosed until the patient had to undergo dentofacial trauma with unexpected severe haemorrhage. Preventive dentistry remains vital to young haemophiliacs. Surgical dental procedures may be performed for haemophiliacs but they must be judiciously coordinated by dental and medical health professionals. PMID:25568261

Quality indicators for prostate radiotherapy: are patients disadvantaged by receiving treatment in a 'generalist' centre?

PubMed

Freeman, Amanda R; Roos, Daniel E; Kim, Laurence

2015-04-01

The purpose of this retrospective review was to evaluate concordance with evidence-based quality indicator guidelines for prostate cancer patients treated radically in a 'generalist' (as distinct from 'sub-specialist') centre. We were concerned that the quality of treatment may be lower in a generalist centre. If so, the findings could have relevance for many radiotherapy departments that treat prostate cancer. Two hundred fifteen consecutive patients received external beam radiotherapy (EBRT) and/or brachytherapy between 1.10.11 and 30.9.12. Treatment was deemed to be in line with evidence-based guidelines if the dose was: (i) 73.8-81 Gy at 1.8-2.0 Gy/fraction for EBRT alone (eviQ guidelines); (ii) 40-50 Gy (EBRT) for EBRT plus high-dose rate (HDR) brachytherapy boost (National Comprehensive Cancer Network (NCCN) guidelines); and (iii) 145 Gy for low dose rate (LDR) I-125 monotherapy (NCCN). Additionally, EBRT beam energy should be ≥6 MV using three-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT), and high-risk patients should receive neo-adjuvant androgen-deprivation therapy (ADT) (eviQ/NCCN). Treatment of pelvic nodes was also assessed. One hundred four high-risk, 84 intermediate-risk and 27 low-risk patients (NCCN criteria) were managed by eight of nine radiation oncologists. Concordance with guideline doses was confirmed in: (i) 125 of 136 patients (92%) treated with EBRT alone; (ii) 32 of 34 patients (94%) treated with EBRT + HDR BRT boost; and (iii) 45 of 45 patients (100%) treated with LDR BRT alone. All EBRT patients were treated with ≥6 MV beams using 3D-CRT (78%) or IMRT (22%). 84%, 21% and 0% of high-risk, intermediate-risk and low-risk patients received ADT, respectively. Overall treatment modality choice (including ADT use and duration where assessable) was concordant with guidelines for 176/207 (85%) of patients. The vast majority of patients were treated concordant with evidence-based guidelines suggesting that

Grey water treatment at a sports centre for reuse in irrigation: a case study.

PubMed

Gabarró, J; Batchelli, L; Balaguer, M D; Puig, S; Colprim, J

2013-01-01

Grey water has long been considered a promising option for dealing with water scarcity and reuse. However, factors such as lack of macronutrients and low carbon content make its treatment challenging. The aim of this paper was to investigate the applicability of sequencing batch reactor (SBR) technology to on-site grey water treatment at a sports centre for reuse in irrigation. The results demonstrated that the regenerated water complied with microbiological parameters concerning restriction of solids and organic matter removal. Denitrification was not fully accomplished, but ammonium was totally oxidised and low concentrations of nitrates were achieved. Effluent with good appearance and no odour was used in an experimental study to irrigate a grid system containing natural and artificial grass sections. The conclusion is that SBR technology offers a promising treatment for grey water.

The effect of an occupational therapy mental health day treatment centre on the use of inpatient services in the Western Cape, South Africa.

PubMed

Engelbrecht, Riekie; Plastow, Nicola; Botha, Ulla; Niehaus, Djh; Koen, Liezl

2018-04-27

The aim of this study was to determine whether attendance at an occupational therapy-led day treatment centre for mental health care users affects the use of inpatient services in South Africa. A retrospective pre-test/post-test quasi-experimental study design was used to compare admissions and days spent in hospital during the 24 months before and after attendance at the centre, using the hospital's electronic records. Total population sampling yielded data for 44 mental health care users who made first contact with the service between July 2009 and June 2010. Data were compared using the Kruskal-Wallis test, Wilcoxon Signed Ranks test and Mann-Whitney U test. There was a significant decrease in the number of admissions (z = -4.093, p = 0.00) and the number of days spent in hospital (z = -4.730, p = 0.00). Participants were admitted to psychiatric care 33 times less in the 24 months' post-intervention, indicating a medium effect (r = 0.436). They also spend 2569 days less in hospital, indicating a large effect (r = 0.504). The findings suggest that an occupational therapy-led day treatment centre could be effective in reducing the use of inpatient mental health services in South Africa. Implications for Rehabilitation Attendance at an occupational therapy-led community day treatment centre decreases the number of admissions and number of days spent in hospital and is therefore beneficial to mental health care users and service providers. The study indicates that the successful implementation of a community day treatment centre for mental health care users on the grounds of a tertiary hospital by utilising existing resources is possible.

Addiction research centres and the nurturing of creativity The Norwegian Centre for Addiction Research (SERAF).

PubMed

Bramness, Jørgen G; Clausen, Thomas; Duckert, Fanny; Ravndal, Edle; Waal, Helge

2011-08-01

The Norwegian Centre for Addiction Research (SERAF) at the University of Oslo is a newly established, clinical addiction research centre. It is located at the Oslo University Hospital and has a major focus on opioid dependency, investigating Norwegian opioid maintenance treatment (OMT), with special interest in OMT during pregnancy, mortality, morbidity and criminality before, during and after OMT and alternatives to OMT, such as the use of naltrexone implants. The well-developed health registries of Norway are core assets that also allow the opportunity for other types of substance abuse research. This research includes health services, abuse of prescription drugs and drugs of abuse in connection with traffic. The centre also focuses upon comorbidity, investigating the usefulness and limitations of psychometric instruments, drug abuse in different psychiatric treatment settings and internet-based interventions for hazardous alcohol consumption. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

Lupus anticoagulant, anticardiolipin antibodies, and human immunodeficiency virus in haemophilia.

PubMed Central

Cohen, H; Mackie, I J; Anagnostopoulos, N; Savage, G F; Machin, S J

1989-01-01

The prevalence of lupus anticoagulant, using the dilute Russell's viper venom time (DRVT), was determined in 22 patients with mild to severe haemophilia A to see if there was any association with the presence of viral disease. Twelve haemophiliacs (58%) were lupus anticoagulant positive, with a mean patient:control ratio of 1.24 (range 1.15-1.52, normal range 0.84-1.06 which partially corrected with lysed, washed platelets). Nine of these patients were IgG or IgM, or both, anticardiolipin antibody positive and nine were human immunodeficiency virus (HIV) antibody positive, but associations between lupus anticoagulant, anticardiolipin antibodies, and HIV antibody positivity were not significant. Mixing studies of normal plasma and immune depleted factor VIII deficient plasma showed that the DRVT ratio increased when the factor VIII concentration fell below 0.15 IU/ml. There was no significant association between plasma factor VIII concentration and positive DRVT results in haemophiliacs. The addition of porcine factor VIII concentrate produced no correction in eight of the 12 with DRVTs indicative of lupus anticoagulant, suggesting that these were prolonged by antiphospholipid activity. It is concluded that the presence of lupus anticoagulant and anticardiolipin antibodies in haemophiliacs may represent an antiphospholipid response to viraemic challenge, not only to HIV but also to other viral antigens, and that a very low factor VIII concentration may produce a false positive DRVT result. PMID:2500459

Cleft lip and palate treatment of 530 children over a decade in a single centre.

PubMed

Vlastos, I M; Koudoumnakis, E; Houlakis, M; Nasika, M; Griva, M; Stylogianni, E

2009-07-01

We sought to evaluate the process of care and the outcomes of cleft lip and palate operations carried by a multidisciplinary team at a centre of craniofacial anomalies with a high patients' volume. A retrospective review of all cleft lips and/or palates cases treated in the centre from 1995 to 2007 was performed. Direct and long term complication rates, clinical, audiologic, speech intelligibility and dental arch assessments were analyzed. A total of 530 children have been operated this period in the centre (64 isolated cleft lip closures). A detailed presentation of the outcomes is performed in relation to the various types of cleft lip and palates. The majority of parents (70%) reported very good or excellent results 2-5 years after the lip closure with the Millard technique, although those with bilateral clefts were significantly less satisfied (P<0.002). Forty-two percent of children with cleft palate and otitis media with effusion were self-improved 2-8 months after palate reconstruction and 83.3% of children treated with the two flaps palatoplasty technique had a rather high or very high intelligibility score. Muscles' retropositioning had a significant effect on intelligibility (P=0.04). Children with cleft lips and palates have a variety of conditions and functional limitations even after the surgical correction of their problem that need to be evaluated and treated by several specialists. The treatment protocol utilized by the multidisciplinary team of our centre is efficient with a relative low percentage of complications and unfavorable results.

Definition of an organisational model for the prevention and reduction of health and social impacts of inherited bleeding disorders.

PubMed

Calizzani, Gabriele; Menichini, Ivana; Candura, Fabio; Lanzoni, Monica; Profili, Samantha; Tamburrini, Maria Rita; Fortino, Antonio; Vaglio, Stefania; Marano, Giuseppe; Facco, Giuseppina; Oliovecchio, Emily; Franchini, Massimo; Coppola, Antonio; Arcieri, Romano; Bon, Cinzia; Saia, Mario; Nuti, Sabina; Morfini, Massimo; Liumbruno, Giancarlo M; Di Minno, Giovanni; Grazzini, Giuliano

2014-04-01

Due to the increase in life expectancy, patients with haemophilia and other inherited bleeding disorders are experiencing age-related comorbidities that present new challenges. In order to meet current and emerging needs, a model for healthcare pathways was developed through a project funded by the Italian Ministry of Health. The project aimed to prevent or reduce the social-health burden of the disease and its complications. The National Blood Centre appointed a panel of experts comprising clinicians, patients, National and Regional Health Authority representatives. Following an analysis of the scientific and regulatory references, the panel drafted a technical proposal containing recommendations for Regional Health Authorities, which has been formally submitted to the Ministry of Health. Finally, a set of indicators to monitor haemophilia care provision has been defined. In the technical document, the panel of experts proposed the adoption of health policy recommendations summarised in areas, such as: multidisciplinary integrated approach for optimal healthcare provision; networking and protocols for emergency care; home therapy; registries/databases; replacement therapy supply and distribution; recruitment and training of experts in bleeding disorders. The recommendations became the content of proposal of agreement between the Government and the Regions. Monitoring and evaluation of haemophilia care through the set of established indicators was partially performed due to limited available data. The project provided recommendations for the clinical and organisational management of patient with haemophilia. A particular concern was given to those areas that play a critical role in the comorbidities and complications prevention. Recommendations are expected to harmonise healthcare care delivery across regional networks and building the foundation for the national haemophilia network.

Definition of an organisational model for the prevention and reduction of health and social impacts of inherited bleeding disorders

PubMed Central

Calizzani, Gabriele; Menichini, Ivana; Candura, Fabio; Lanzoni, Monica; Profili, Samantha; Tamburrini, Maria Rita; Fortino, Antonio; Vaglio, Stefania; Marano, Giuseppe; Facco, Giuseppina; Oliovecchio, Emily; Franchini, Massimo; Coppola, Antonio; Arcieri, Romano; Bon, Cinzia; Saia, Mario; Nuti, Sabina; Morfini, Massimo; Liumbruno, Giancarlo M.; Di Minno, Giovanni; Grazzini, Giuliano

2014-01-01

Introduction Due to the increase in life expectancy, patients with haemophilia and other inherited bleeding disorders are experiencing age-related comorbidities that present new challenges. In order to meet current and emerging needs, a model for healthcare pathways was developed through a project funded by the Italian Ministry of Health. The project aimed to prevent or reduce the social-health burden of the disease and its complications. Material and methods The National Blood Centre appointed a panel of experts comprising clinicians, patients, National and Regional Health Authority representatives. Following an analysis of the scientific and regulatory references, the panel drafted a technical proposal containing recommendations for Regional Health Authorities, which has been formally submitted to the Ministry of Health. Finally, a set of indicators to monitor haemophilia care provision has been defined. Results In the technical document, the panel of experts proposed the adoption of health policy recommendations summarised in areas, such as: multidisciplinary integrated approach for optimal healthcare provision; networking and protocols for emergency care; home therapy; registries/databases; replacement therapy supply and distribution; recruitment and training of experts in bleeding disorders. The recommendations became the content of proposal of agreement between the Government and the Regions. Monitoring and evaluation of haemophilia care through the set of established indicators was partially performed due to limited available data. Conclusions The project provided recommendations for the clinical and organisational management of patient with haemophilia. A particular concern was given to those areas that play a critical role in the comorbidities and complications prevention. Recommendations are expected to harmonise healthcare care delivery across regional networks and building the foundation for the national haemophilia network. PMID:24922299

Immune tolerance: critical issues of factor dose, purity and treatment complications.

PubMed

DiMichele, D M

2006-12-01

The current practice of immune tolerance induction (ITI) therapy has been largely influenced by the results of small institutional studies and three large registries. However, many questions remain. Successful outcome predictors for ITI in haemophilia A have been suggested by the analyses of two of these registries. Among these predictors, factor VIII (FVIII) dose/dosing regimen remains a controversial outcome parameter, demonstrating a strong direct relationship to ITI success in the international registry and a weaker inverse relationship in the North American registry. There is an international multicentre prospective randomized trial underway to further study the role of FVIII dose in successful ITI induction in a good risk haemophilia A inhibitor patient cohort. FVIII purity also remains an unproved ITI outcome predictor. Institutional experience with von-Willebrand-factor-containing products has suggested its therapeutic advantage in both inhibitor development and eradication. The International ITI Study, although not designed to answer this particular question, may be able to determine an impact on outcome depending on the final distribution of investigator choice of product among the study subjects. Much less is known about the influence of factor IX (FIX) dose and purity on ITI success in haemophilia B. Importantly, nephrotic syndrome has been a major determinant of ITI failure in FIX inhibitor patients, particularly those with the allergic phenotype. Unfortunately, large prospective randomized trials in this group will not be feasible. Rather, we will have to rely on prospectively collected registry data to build our knowledge base of inhibitors and ITI in haemophilia B.

Neoadjuvant/adjuvant treatment of high-risk retinoblastoma: a report from the German Retinoblastoma Referral Centre.

PubMed

Künkele, Annette; Wilm, Josephine; Holdt, Markus; Lohmann, Dietmar; Bornfeld, Norbert; Eggert, Angelika; Temming, Petra; Schulte, Johannes H

2015-07-01

Retinoblastoma can extend beyond the structures of the eye, where cells can enter the bloodstream and cause metastases. Various types of protocols for adjuvant treatment risk-adapted according to histopathological risk factors are used worldwide. Between 1997 and 2009, 420 children were diagnosed with retinoblastoma at the German Retinoblastoma Referral Centre and risk factors were assessed. Patients with post-laminar optic nerve infiltration or choroid or minor scleral invasion received six courses of adjuvant chemotherapy using vincristine, etoposide, carboplatin and cyclophosphamide (group 1). Patients with microscopic extension beyond the sclera to the resection margin of the optic nerve or potential spread due to vitrectomy received chemotherapy plus orbital radiotherapy (group 2). Neoadjuvant chemotherapy was performed in patients with local extraocular invasion detected on MRI. Following this protocol, 42 of the 420 patients and 21 referred from other centres showed high-risk histopathological factors qualifying for adjuvant therapy (57 in group 1 and 6 in group 2). Seven of the 63 patients received neoadjuvant and adjuvant treatment. During a mean follow-up of 5.8 (range 0.4-15.4) years, one of six patients in group 2 developed metastases and died. No patients died from toxicity. The 5-year overall survival was 100% for group 1 and 80% for group 2. This retrospective single-site study reveals a 10% incidence of high-risk features in children with retinoblastoma diagnosed at the German Retinoblastoma Referral Centre. Overall survival rates of 98.3% underline the safety of this adjuvant chemotherapy protocol and its efficiency in preventing metastasis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Retinal Screening Acceptance, Laser Treatment Uptake and Follow-up Response in Diabetics Requiring Laser Therapy in an Urban Diabetes Care Centre.

PubMed

Memon, Salah; Ahsan, Shahid; Alvi, Rashid; Fawwad, Asher; Basit, Abdul; Shera, Samad; Sheikh, Sikander Ali; Fahim, Muhammad Faisal

2015-10-01

To determine the acceptance of retinal screening, Laser uptake and subsequent follow-up in diabetic patients attending the Diabetes Centre of Diabetic Association of Pakistan (DAP), Karachi. Observational case series. Diabetic Centre of Diabetic Association of Pakistan (DAP), Karachi, from January 2011 to December 2012. All the diabetic patients were screened for Diabetic Retinopathy (DR) with non-Mydriatic Fundus Camera (NMFC). Patients with DR were examined by the ophthalmologist using fundus lens and slit lamp. DR was graded for severity on the basis of modified Airlie House Classification. Patients with Sight Threatening Diabetic Retinopathy (STDR) were advised Laser treatment. Each patient was followed-up for at least 6 months. The records of patients recommended Laser were retrieved, and called for re-examination. Retinal screening was accepted by all of the 8368 registered diabetics attending DAP Centre. On fundus photography, 21.2% (1777) individuals were found to have DR. Seven hundred and five (39.5%) patients were found to have STDR. Laser was advised to 96.4% (680) of STDR patients; amongst whom 70.5% (480) accepted Laser treatment. Out of 480 patients who had Laser treatment, 21.2% (107) turned out for follow-up after 6 months. Acceptance of retinal screening and Laser application was good; but follow-up was suboptional.

The experience of girls and young women with inherited bleeding disorders.

PubMed

Khair, K; Holland, M; Pollard, D

2013-09-01

Haemophilia carriers and women with inherited bleeding disorders (IBD) experience menorrhagia, bleed following dentistry, surgery, injury or childbirth. Symptoms are easily treated leading to full and active lives. Nevertheless, some girls and women suffer with abnormal bleeding for many years before diagnosis. We explored the experiences of girls and young women (aged 9-34 years) with IBD by means of focus groups which consisted of moderated discussion addressing specific aspects of bleeding, management and coping strategies. Subsequently, these issues were explored further though a paper-based questionnaire distributed via five specialist haemophilia centres in the UK. The study suggested that young women with IBD who are managed at haemophilia centres receive appropriate care and feel well supported. Although the clinic-based literature available to these women is "fit for purpose", it does not fully address the perceived needs specifically regarding sex, menorrhagia, conception and childbirth, the Pill, tattoos/piercings and so on, leading many to turn to other information sources. Most of those who responded to our survey are confident in their lives, able to manage their IBD and take pragmatic views towards the inherited nature of their condition. But there is a substantial subgroup of women who experience stigmatization, isolation and bullying and express concerns relating to fertility and conception. Overall, this cohort would benefit from opportunities for mutual support. This could be via Internet-based social networking and may be of particular value to those who are unable to seek help from traditional medical services due to religious or other cultural barriers. © 2013 John Wiley & Sons Ltd.

The British society for gynaecological endoscopy endometriosis centres project.

PubMed

Saridogan, Ertan; Byrne, Dominic

2013-01-01

Management of advanced endometriosis frequently requires a multidisciplinary team approach and international guidelines suggest treatment in centres of expertise. Due to variability of published outcome data, prospective data collection and standardisation of reporting systems have been suggested to improve our understanding of surgical outcomes. The British Society for Gynaecological Endoscopy (BSGE) Endometriosis Centres were established to manage rectovaginal endometriosis, to collect treatment and outcome data, and to provide these data to patients, clinicians and healthcare commissioners. The BSGE Endometriosis Centres Project works on the principle of voluntary participation. Centres that would like to be recognised or accredited as a BSGE Endometriosis Centre need to fulfil a number of basic requirements including working in appropriate multidisciplinary clinical teams, auditing their outcome and having sufficient workload to maintain their surgical skills. The project has already had an impact on where the patients with advanced endometriosis are treated in the United Kingdom. Patients and healthcare professionals are becoming aware of their presence and more patients with the condition are being referred to these centres. It is also expected that the accredited centre status would be required for funding by healthcare commissioners for this type endometriosis. Copyright © 2013 S. Karger AG, Basel.

Maximal and submaximal endurance performance in adults with severe haemophilia.

PubMed

Herbsleb, M; Hilberg, T

2009-01-01

Maximal exercise testing, including the determination of maximal performance and maximal oxygen uptake (VO(2max)), is considered the gold standard for assessing maximal endurance performance. The effectiveness of such testing is often reduced in haemophilic adults owing to musculoskeletal impairments or pain rather than because of cardiac exertion. The measurement of submaximal performance parameters overcomes many limitations of maximal exercise testing but a testing standard is still lacking. The aim of this study was to investigate maximal and particularly submaximal endurance performance of adult patients with severe haemophilia A and B. Eleven patients and 11 matched healthy controls were tested by spiroergometry with a specific treadmill test and the power was calculated in Watts. The haemophilic group achieved lower absolute (210 +/- 63 W) and weight-related (2.94 +/- 0.98 W kg(-1)) maximal endurance performance compared with the control group (287 +/- 50 W resp. 3.82 +/- 0.53 W kg(-1); P

Waste management in primary healthcare centres of Iran.

PubMed

Mesdaghinia, Alireza; Naddafi, Kazem; Mahvi, Amir Hossein; Saeedi, Reza

2009-06-01

The waste management practices in primary healthcare centres of Iran were investigated in the present study. A total of 120 primary healthcare centres located across the country were selected using the cluster sampling method and the current situation of healthcare waste management was determined through field investigation. The quantities of solid waste and wastewater generation per outpatient were found to be 60 g outpatient(-1) day(-1) and 26 L outpatient(-1) day(-1), respectively. In all of the facilities, sharp objects were separated almost completely, but separation of other types of hazardous healthcare solid waste was only done in 25% of the centres. The separated hazardous solid waste materials were treated by incineration, temporary incineration and open burning methods in 32.5, 8.3 and 42.5% of the healthcare centres, respectively. In 16.7% of the centres the hazardous solid wastes were disposed of without any treatment. These results indicate that the management of waste materials in primary healthcare centres in Iran faced some problems. Staff training and awareness, separation of healthcare solid waste, establishment of the autoclave method for healthcare solid waste treatment and construction of septic tanks and disinfection units in the centres that were without access to a sewer system are the major measures that are suggested for improvement of the waste management practices.

Factor VIII inhibitor in a patient with mild haemophilia A and an Asn618-->Ser mutation responsive to immune tolerance induction and cyclophosphamide.

PubMed

Vlot, André J; Wittebol, Shulamiet; Strengers, Paul F W; Turenhout, Ellen A M; Voorberg, Jan; van den Berg, H Marijke; Mauser-Bunschoten, Eveline P

2002-04-01

We describe a patient with mild haemophilia A (original value of factor VIII activity 0.30 U/ml) who developed an inhibitor (36.1 Bethesda U/ml) which cross-reacted with his endogenous factor VIII. This caused a decline in basal factor VIII level (< 0.01 U/ml) and severe haemorrhagic events. Treatment to induce immune tolerance was started with factor VIII/von Willebrand factor (VWF) concentrates, but inhibitor levels increased progressively and the patient suffered serious bleeding. Cyclophosphamide was administered and, after 8 months treatment, factor VIII levels increased to 0.20 U/ml and the inhibitor could no longer be detected. Screening of his factor VIII gene revealed a missense mutation in exon 13 that predicts substitution of Asn618-->Ser in the A2 domain of factor VIII. Immunoprecipitation analysis showed that the antibodies present in the patient's plasma reacted with metabolically labelled A2 domain and, to a lesser extent, with factor VIII light chain. Inhibitory antibodies were completely neutralized by recombinant A2 domain, whereas no neutralization was observed after the addition of factor VIII light chain (A3-C1-C2) and C2 domain. More detailed analysis showed that the majority of inhibitory antibodies were directed against residues Arg484-Ile508, a previously identified binding site for factor VIII inhibitors. Our findings suggest that immune tolerance therapy and cyclophosphamide were successful in eradicating inhibitory antibodies against a common epitope on factor VIII.

A post-marketing safety and efficacy assessment of a monoclonal antibody purified high-purity factor VIII concentrate.

PubMed

Hay, C R; Lee, C A; Savidge, G

1996-01-01

The identification of infrequent side-effects of clotting factor concentrates, undetected by clinical trials, is facilitated by post-marketing surveillance. We present a post-marketing surveillance study in which 97 patients with haemophilia A, attending three haemophilia centres, were treated over a median follow-up period of 284 days (range 1-1074), and a total follow-up period of 30,080 days, with a pasteurized immunoaffinity purified factor VIII concentrate (Monoclate-P, Armour, Collegeville, USA). 5216 infusions, using 10,527,000 units of Monoclate-P, were carried out, mostly for routine haemarthroses or prophylaxis. No new inhibitors were observed during the study. At the start of the study 60/97 were HIV seropositive, 67/97 HBs antibody positive, 12 HbsAb negative and the remainder HBsAb positive before the study period. 13/14 tested were HAV seropositive at the beginning of the study. One patient became HAV seropositive during the study period, an infection thought to be community acquired. No other seroconversions were observed. Only one mild transfusion reaction was observed. This study confirms the safety and efficacy of Monoclate-P. Post-marketing surveillance or nationally organized pharmaco-vigilance should be practiced more widely to enable identification of low-frequency side-effects of treatment.

[Creation of centres in high-volume hospitals -- promotor of communication].

PubMed

Möbius, C; Schumacher, G

2013-02-01

The number of patients with a diagnosis of cancer is alarming: according to new figures from the Robert Koch Institute about 435 000 patients are diagnosed annually in Germany. 210 000 patients die annually of this diagnosis. Even if no significant progress in prevention has been achieved, in 2020 about 25 % more cases will be diagnosed. In the last two decades it has become established that an interdisciplinary treatment of tumour patients is necessary because the variety of different treatment options depending on an individual person cannot be mastered by one physician. The goal of the centres and certification is to establish a very concentrated expertise in large case numbers and quality-assured transparent treatment. The central requirement of a maximum-care centre is thus to enable communication under appropriate conditions. Promoting not only the space requirements, centre must also develop a treatment corridor and is responsible for further education. Additionally an oncology centre has a goal in communications, namely, to offer a treatment option for all patients in each stage of the disease, and to incorporate cancer patients in clinical trials. © Georg Thieme Verlag KG Stuttgart · New York.

Abrogating fibrinolysis does not improve bleeding or rFVIIa/rFVIII treatment in a non-mucosal venous injury model in haemophilic rodents.

PubMed

Stagaard, Rikke; Flick, Matthew J; Bojko, Barbara; Goryński, Krzysztof; Goryńska, Paulina Z; Ley, Carsten D; Olsen, Lisbeth H; Knudsen, Tom

2018-05-14

Fibrinolysis may exacerbate bleeding in haemophilia A (HA). Accordingly, antifibrinolytics have been used to help maintain haemostatic control. While antifibrinolytic drugs have been proven effective in the treatment of mucosal bleeds in the oral cavity, their efficacy in non-mucosal tissues remain an open question of significant clinical interest. To determine whether inhibiting fibrinolysis improves the outcome in non-mucosal haemophilic tail vein transection (TVT) bleeding models, and to determine whether a standard ex vivo clotting/fibrinolysis assay can be used as a predictive surrogate for in vivo efficacy. A highly sensitive tail vein transection model was employed in haemophilic rodents with a suppressed fibrinolytic system to examine the effect of inhibiting fibrinolysis on bleeding in a non-mucosal tissue. In mice induced- and congenital haemophilia models were combined with fibrinolytic attenuation achieved either genetically or pharmacologically (tranexamic acid; TXA) induced. In haemophilic rats, tail bleeding was followed by whole blood rotational thromboelastometry (ROTEM) evaluation of the same animals to gauge the predictive value of such assays. The beneficial effect of systemic TXA therapy observed ex vivo could not be confirmed in vivo in haemophilic rats. Furthermore, neither intravenously administered TXA nor congenital knockout of the fibrinolytic genes plasminogen or tissue-type plasminogen activator markedly improved the TVT bleeding phenotype or response to factor therapy in haemophilic mice. The finding here suggest that inhibition of fibrinolysis is not effective in limiting the TVT bleeding phenotype of haemophilia A rodents in non-mucosal tissues. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Parental cancer: Characteristics of users of child-centred counselling versus individual psycho-oncological treatment.

PubMed

Inhestern, Laura; Geertz, Wiebke; Schulz-Kindermann, Frank; Bergelt, Corinna

2018-03-01

The aims of this study were to investigate the characteristics of users of a specific child-centred counselling service (COSIP) and to compare those to parents using an individual psycho-oncological treatment (PO). We conducted a retrospective analysis on data of users of COSIP and users of PO. Database was the routine assessment (demographic and disease-related characteristics, GAD-7, PHQ-9, EORTC QLQ-C30, and current concerns) of an outpatient psycho-oncological clinic with additional child-centred counselling. A total of 151 patients and 49 partners with children ≤21 years were included. We conducted descriptive analyses and group comparisons. Fifty-nine patients and partners used COSIP only or additionally to individual psycho-oncological service. PO users were more depressed and were more anxious than COSIP users. Patients using PO reported worse emotional functioning than patients using COSIP. Partners using PO reported worse global quality of life and more symptoms of fatigue than partners using COSIP. With regard to current concerns, patients using COSIP reported child-related issues more frequently than PO users. PO users reported symptoms of anxiety, depressive symptoms, or exhaustion more frequently than COSIP users. The findings demonstrate that patients and partners self-referring to PO or COSIP are highly burdened. COSIP users experience different psychosocial burden than PO users. As poor mental state of parents is a risk factor for the development of mental problems in children, parents using only PO may benefit from additional child-centred support. Accordingly, the need for COSIP should be assessed continuously during PO of patients with children ≤21 years. Copyright © 2017 John Wiley & Sons, Ltd.

Moderate plasma treatment enhances the quality of optically detected magnetic resonance signals of nitrogen-vacancy centres in nanodiamonds

NASA Astrophysics Data System (ADS)

Sotoma, Shingo; Igarashi, Ryuji; Shirakawa, Masahiro

2016-05-01

We demonstrate that a moderate plasma treatment increases the quality of optically detected magnetic resonance (ODMR) signals from negatively charged nitrogen-vacancy centres in nanodiamonds (NDs). We measured the statistics of the ODMR spectra of 50-nm-size NDs before and after plasma treatment. We then evaluated each ODMR spectrum in terms of fluorescence and ODMR intensities, line width and signal-to-noise (SN) ratio. Our results showed that plasma treatment for more than 10 min contributes to higher-quality ODMR signals, i.e. signals that are brighter, stronger, sharper and have a higher SN ratio. We showed that such signal improvement is due to alteration of the surface chemical states of the NDs by the plasma treatment. Our study contributes to the advancement of biosensing applications using ODMR of NDs.

Motivation for orthognathic treatment and anticipated satisfaction levels-a two-centre cross-national audit.

PubMed

Patcas, Raphael; Cunningham, Susan J; Shute, Justin; Lloyd, Timothy; Obwegeser, Joachim A; Arjomand, Lida; Sharma, Sujata

2017-06-01

This audit investigated factors which motivate patients to seek orthognathic treatment, assessed how confident patients were that they would be satisfied with the outcome of treatment, and explored possible influencing factors. Questionnaires were distributed to pre-surgical patients at two centres (United Kingdom and Switzerland); questions asked what patients wished to gain from orthognathic treatment and how confident they were that they would be satisfied with treatment outcome. Gender, age and location were recorded as demographic variables, and type of malocclusion was also recorded. A total of 202 questionnaires were returned (UK, n = 149; Switzerland, n = 53). Reported motivating factors focused on improvements in aesthetics (specified and unspecified) (UK vs. Switzerland: 91.3% vs. 83.0%), function (72.5% vs. 66.0%), psychosocial health (51.7% vs. 20.8%), speech (4.0% vs. 7.5%), alleviation of pain (5.4% vs. 17%) and normalization of breathing (1.3% vs. 7.5%). No significant relationships were observed relative to patient age, gender or malocclusion. The anticipated satisfaction levels were generally high (86.5% vs. 89.9%). Although the distribution of motivational factors varied between the two sites, it did not affect the anticipated satisfaction level. Patients were generally confident that they would be satisfied with their treatment outcome and that their reasons for seeking treatment would be addressed. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. All rights reserved.

Use of rice-based oral rehydration solution in a large diarrhoea treatment centre in Bangladesh: in-house production, use and relative cost.

PubMed

Islam, M A; Mahalanabis, D; Majid, N

1994-12-01

Glucose-based oral rehydration salt (ORS) is an appropriate and cost-effective tool to treat diarrhoeal dehydration. In patients with a high purging rate, particularly due to cholera, rice-based ORS has been shown to substantially reduce stool output compared to glucose ORS. However, it is not used in the hospitals or diarrhoea treatment centres largely because of the non-availability of a ready-to-use inexpensive packaged product and because of the problem of cooking. In a large diarrhoea treatment centre in Bangladesh (with an annual ORS consumption of approximately 140,000 litres), we have maintained in-house production of rice ORS and used it routinely for more than 600,000 patients over the last nine years. Semi-literate health workers cook rice ORS and supervise mothers in its use. Rice ORS is less costly (US $0.15 per patient treated compared with US $0.37 for glucose ORS) and is well accepted. It is an attractive alternative to glucose ORS in many fixed facility treatment centres in countries where rice is a staple and cholera is endemic. The process of its in-house preparation and use is described in this report which may assist hospitals wishing to use rice ORS in treating diarrhoea patients. Availability of a low cost ready-to-use rice ORS packet (which needs no cooking) with adequate shelf-life will increase its use at fixed facilities.

The DIY Digital Medical Centre.

PubMed

Timmis, James Kenneth; Timmis, Kenneth

2017-09-01

Healthcare systems worldwide are confronted with major economic, organizational and logistical challenges. Historic evolution of health care has led to significant healthcare sector fragmentation, resulting in systemic inefficiencies and suboptimal resource exploitation. To attain a sustainable healthcare model, fundamental, system-wide improvements that effectively network, and ensure fulfilment of potential synergies between sectors, and include and facilitate coherent strategic planning and organisation of healthcare infrastructure are needed. Critically, they must be specifically designed to sustainably achieve peak performance within the current policy environment for cost-control, and efficiency and quality improvement for service delivery. We propose creation of a new healthcare cluster, to be embedded in existing healthcare systems. It consists of (i) local 24/7 walk-in virtually autonomous do-it-yourself Digital Medical Centres performing routine diagnosis, monitoring, prevention, treatment and standardized documentation and health outcome assessment/reporting, which are online interfaced with (ii) regional 24/7 eClinician Centres providing on-demand clinical supervision/assistance to Digital Medical Centre patients. Both of these are, in turn, online interfaced with (iii) the National Clinical Informatics Centre, which houses the national patient data centre (cloud) and data analysis units that conduct patient- and population-level, personalized and predictive(-medicine) intervention optimization analyses. The National Clinical Informatics Centre also interfaces with biomedical research and prioritizes and accelerates the translation of new discoveries into clinical practice. The associated Health Policy Innovation and Evaluation Centre rapidly integrates new findings with health policy/regulatory discussions. This new cluster would synergistically link all health system components in a circular format, enable not only access by all arms of the health

Should money follow the patient: Financial implication for being the National Centre for the Treatment and Management of Pelvic and Acetabular Fractures in Ireland.

PubMed

Kelly, M E; Leonard, M; Green, C; Beggs, R; Cheung, C; McElwain, J; Morris, S

2013-12-01

Pelvic and acetabular fractures are complex injuries requiring specialist treatment. Our institution is the National Centre for Treatment and Management of these injuries. To audit all referrals to our institution over a 6-month period and calculate the cost incurred by being the national referral centre. Retrospective review of database, and subsequent allocation of Casemix points to assess total cost of treatment for each patient referred to our institution. 103 patients referred with pelvic or acetabular fracture for operative management. The furthest referral distance was 181miles. Over-all, the length of stay was 15.4 days. The average inclusive cost for a referral to our unit for operative management was €16,302. Pelvic and acetabular fractures are complex injuries that require specialist referral unit management. However for these units to remain sustainable money needs to "follow the patient". Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Profile of inhalant users seeking treatment at a de-addiction centre in north India.

PubMed

Gupta, Sunil; Nebhinani, Naresh; Basu, Debasish; Mattoo, Surendra Kumar

2014-05-01

Inhalants are substances whose chemical vapors are inhaled to produce euphoric, disinhibiting, and exciting effects. Data on inhalant abuse in India are relatively scarce. We report the demographic and clinical profile of inhalant users among the treatment seekers at a Drug De-addiction and Treatment Centre in north India. The records of treatment seekers at the Drug De-addiction and Treatment Centre, over 10 years (2002-2011) were scanned to identify 92 cases reporting inhalant use. Of these 92 cases, the complete record files were available for 87 (94.6%) cases. These case files were reviewed and the relevant data were collected and analyzed. Over the study period of 10 years, the number of cases with inhalant abuse per year rose steadily to peak at 20 cases (4.08% of new cases) in 2006 and then stabilized at 1-3 per cent of new cases annually. Of the 87 cases studied, all were males with a mean age of 18.9±4.12 yr, mean education of 9.8±3.42 yr and mean family income of Rs. 7676±7343.15 (median: Rs. 5000). Majority of subjects were unmarried (89.7%), urban resident (79.3%), and from a nuclear family (78.2%). About half of the subjects were students (50.6%). The most common inhalant used was typewriter correction fluid (73.6%) followed by typewriter diluent fluid (19.5%) and glue (6.9%). The most common reason for initiation was curiosity. The mean age of onset of inhalant use was 16.3±4.22 yr. Most subjects fulfilled the criteria for inhalant dependence (85.1%). Psychiatric co-morbidity and the family history of substance dependence were present in 26.4 and 32.9 per cent subjects, respectively. Majority of the subjects reported drug related problems, occupation and finance being the worst affected. Interpretations & conclusions: Our results showed that the inhalant users were mostly urban youth belonging to middle socio-economic class families. The principal sources of inhalant abuse were the commonly available substances like typewriter correction fluids

Relevance of Health Economics in Breast Cancer Treatment – the View of Certified Breast Centres and Their Patients

PubMed Central

Lux, Michael; Hildebrandt, Thomas; Beyer-Finkler, Elke; Bani, Mayada; Loehberg, Christian; Jud, Sebastian; Rauh, Claudia; Schrauder, Michael; Fasching, Peter; Beckmann, Matthias

2013-01-01

Summary Breast cancer centres – certified in accordance with the criteria of the German Cancer Association and the German Mastology Association – are established throughout Germany. Although the setting up of centres and the subsequent need for certification are associated with a marked increase in costs, initial data show positive effects on quality. Certified centres are cost-effective from the point of view of health economics – they lead to improved quality in processes and results without creating any increase in costs for the funding bodies. However, the organization of the necessary structures, with interdisciplinary treatment, documentation and quality-assurance measures, requires considerable resources. Increasing consolidation of inpatient services is also involved, while shortening of the patients’ hospitalization periods is leading to reduced remuneration from the funding bodies. The current cost deficits, which have resulted from the increased resources required, need to be recouped through additional charges. It will only be possible to maintain the high quality achieved if additional charges become available to cover the centres’ added costs. Good data are increasingly becoming available as a basis for negotiations on charges – e.g., with regard to the quality of results and the National Cancer Plan – as well as clear support from patients. PMID:24715838

[Report on notifications with respect to section sign 21 German Transfusion Act for 2003 and 2004].

PubMed

Waterkamp, A; Haschberger, B; Hesse, J; Heiden, M; Seitz, R

2007-02-01

Data with respect to the section sign 21 Transfusion Act concerning collection, manufacture, imports and exports show consolidation, but a non-plausible discrepancy due to the considerably lower figures of product consumption. Failure of numerous institutions to report their consumption precludes an interpretation as surplus supply. Homologous blood donations peaked in 2003 (6.8 million) with 2.4 million thereof being apheresis, which decreased to 1.6 million in 2004. Manufacture of red cells reached a peak of 4.52 million in 2004, with 74% attributable to the Red Cross. Reported consumption differs so significantly that the PEI considers utilising the legal possibility to compare the distribution lists of blood services with submitted user data. The 2.4 million litres plasma for fractionation in 2003 constitute the hitherto highest value, with a 62% share of apheresis; the latter decreased in 2004 to 50% of 1.9 million litres, paralleled by a decrease in commercial plasma centres. The new request (2004) for figures of fractionation in Germany revealed 734,224 litres, i.e. 45% of the calculated available amount on the German market. Isolated consideration of the German situation concerning plasma derivatives is impossible due to complex trade and manufacture in various federal states. Assessment of the supply situation is further impaired by missing data from users. Regarding haemophilia treatment, an improvement is intended by establishing a German Haemophilia Register.

Galileo's Treatment for the Centre of Gravity of Solids

ERIC Educational Resources Information Center

Worner, C. H.; Iommi-Amunategui, G.

2007-01-01

The appendix on the centres of gravity that appears at the end of Galileo's book, "Two New Sciences", is analysed. It is shown that the method used by Galileo in this work has an interesting reasoning and also shows preliminary ideas about scaling and advances some ideas about series convergence. In addition, we note that the geometrical language…

Review of Kinemax total knee replacements performed at the NHS treatment centre, Weston-Super-Mare: five-year results.

PubMed

Hickey, B A; Kempshall, P J; Metcalfe, A J; Forster, M C

2012-04-01

As part of the national initiative to reduce waiting times for joint replacement surgery in Wales, the Cardiff and Vale NHS Trust referred 224 patients to the NHS Treatment Centre in Weston-Super-Mare for total knee replacement (TKR). A total of 258 Kinemax TKRs were performed between November 2004 and August 2006. Of these, a total of 199 patients (232 TKRs, 90%) have been followed up for five years. This cohort was compared with 258 consecutive TKRs in 250 patients, performed at Cardiff and Vale Orthopaedic Centre (CAVOC) over a similar time period. The five year cumulative survival rate was 80.6% (95% confidence interval (CI) 74.0 to 86.0) in the Weston-Super-Mare cohort and 95.0% (95% CI 90.2 to 98.2) in the CAVOC cohort with revision for any reason as the endpoint. The relative risk for revision at Weston-Super-Mare compared with CAVOC was 3.88 (p < 0.001). For implants surviving five years, the mean Oxford knee scores (OKS) and mean EuroQol (EQ-5D) scores were similar (OKS: Weston-Super-Mare 29 (2 to 47) vs CAVOC 29.8 (3 to 48), p = 0.61; EQ-5D: Weston-Super-Mare 0.53 (-0.38 to 1.00) vs CAVOC 0.55 (-0.32 to 1.00), p = 0.79). Patients with revised TKRs had significantly lower Oxford knee and EQ-5D scores (p < 0.001). The results show a higher revision rate for patients operated at Weston-Super-Mare Treatment Centre, with a reduction in functional outcome and quality of life after revision. This further confirms that patients moved from one area to another for joint replacement surgery fare poorly.

Economic analysis of recombinant activated factor VII versus plasma-derived activated prothrombin complex concentrate in mild to moderate bleeds: haemophilia registry data from the Czech Republic.

PubMed

Salaj, Peter; Penka, Miroslav; Smejkal, Petr; Geierova, Vera; Ovesná, Petra; Brabec, Petr; Cetkovsky, Petr; Kubes, Radovan; Mesterton, Johan; Lindgren, Peter

2012-05-01

Several studies suggest that recombinant activated factor VII (rFVIIa) is more cost-effective than plasma-derived activated prothrombin complex concentrate (pd-aPCC) in haemophilia with inhibitors. However, most do not consider differences between treated patients. This study compared the pharmacoeconomics of rFVIIa versus pd-aPCC treatment of mild to moderate bleeds in inhibitor patients, taking co-variables into account. The HemoRec and HemIS registries capture exhaustive bleeding data in inhibitor patients in the Czech Republic. For each bleed, patient and bleed characteristics, treatment outcomes and bypassing agent use were retrospectively analysed, and direct costs of care per bleed calculated. Generalised Linear Model regression methods with cluster effect were employed to account for the possibility of several bleedings from the same patient. There were 108 and 53 mild to moderate bleeds in the rFVIIa and pd-aPCC groups, respectively. Although re-bleeding rates were similar in both groups, deeper analyses revealed significant differences in time to bleed resolution: 93.8% of bleeds treated with rFVIIa were resolved within ≤ 12 h, versus 60.4% with pd-aPCC (P < 0.001). Mean total cost/bleed was lower with rFVIIa (336,852 [median, 290,696] CZK; €12,760 [11,011]) than pd-aPCC (522,768 [341,310] CZK; €19,802 [12,928]) (P = 0.002). Results were maintained after controlling for potential co-variables (bleed nature, time to treatment, target joints). The lower total treatment costs per bleed with rFVIIa than pd-aPCC suggest that first-line rFVIIa is more cost-effective than pd-aPCC in mild to moderate bleeds. Time to bleed resolution was also significantly shorter with rFVIIa. These results were maintained when controlled for potential confounders. Copyright © 2012 Elsevier Ltd. All rights reserved.

The role of physical medicine and rehabilitation in haemophiliac patients.

PubMed

De la Corte-Rodriguez, Hortensia; Rodriguez-Merchan, E Carlos

2013-01-01

Physical medicine and rehabilitation aim to evaluate, diagnose and treat disability in haemophiliac patients, while preventing injury or deterioration. They also aim to maintain the greatest degree of functional capacity and independence in patients with haemophilia, or to return them to that state. Rehabilitation, together with clotting factor replacement therapy, has revolutionized the management of these patients in developed countries and reduced their morbidity/mortality rates. A knowledge of the musculoskeletal signs and symptoms of haemophilia is essential for providing a treatment which is suitable and customized. Physical medicine and rehabilitation techniques, which are based on physical means, are intended to reduce the impact which these injuries and their consequences or sequelae can have on the quality of life of patients with haemophilia. Under ideal haemostatic control conditions (primary prophylaxis), people with haemophilia could achieve good physical condition which will allow them to enjoy both physical activity and a daily life without limitations. Currently, children undergoing primary prophylaxis are quite close to this ideal situation. For these physical activities to be carried out, the safest possible situations must be sought.

Physiotherapy, rehabilitation and sports in countries with limited replacement coagulation factor supply.

PubMed

Buzzard, B M

2007-09-01

It is well documented that physiotherapy and rehabilitation benefit people with haemophilia by strengthening the key muscle groups and protecting joints from the adverse effects of repeated haemorrhages. Rehabilitation, in conjunction with the availability of replacement coagulation factor products, has revolutionized approaches to the management of patients with haemophilia in developed countries and has led to a substantial decrease in both the morbidity and mortality rates among the haemophilic population. Modern treatment approaches have also enabled persons with haemophilia to participate in sporting activities along with their peers; however, these improvements in care have not been achieved in developing nations, where health-care resources and facilities are scarce and the supply of coagulation factor products is limited. This article attempts to address the following questions about the management of haemophilic patients in developing countries: Can physiotherapy, rehabilitation and sports prevent disabilities and preserve independence? Is participation in sports activities possible in developing countries? Do countries differ with regard to guidelines for participation in sports? Should we be encouraging participation in sports or allowing patients with haemophilia to do as they choose?

An account of the real-life hepatitis C management in a single specialized viral hepatitis treatment centre in Egypt: results of treating 7042 patients with 7 different direct acting antiviral regimens.

PubMed

El Kassas, Mohamed; Alboraie, Mohamed; Omran, Dalia; Salaheldin, Mohamed; Wifi, Mohamed Naguib; ElBadry, Mohamed; El Tahan, Adel; Ezzat, Sameera; Moaz, Enass; Farid, Amir M; Omar, Heba; Abouelkhair, Mahmoud; Afify, Shimaa; Elsaeed, Kadry; Shazly, Yehia; Doss, Wahid; Esmat, Gamal

2018-05-14

A large Egyptian treatment program for HCV was launched in 2014 after the introduction of direct-acting antiviral agents (DAAs). This program depended mainly on establishing specialized independent centres for HCV treatment. These centres represent the major strengths in the Egyptian model of care, as they provide integrated care for HCV patients and have enabled Egypt to treat more than one million patients in 3 years. The New Cairo Viral Hepatitis Treatment Center (NCVHTC) is an example of these specialized centres. The Egyptian experience in the management of HCV was evaluated by analysing the data of real-life HCV management in the NCVHTC from 2014 to 2017. Results of different treatment regimens in addition to their strengths, limitations and areas for improvement are discussed in this report. A total of 7042 HCV patients have been evaluated for treatment in the NCVHTC. Among them, 5517 patients received treatment by seven different DAA regimens with excellent results. All regimens were highly effective at treating HCV in a real-life setting, apart from SOF/RBV, which was the least effective. A nationwide screening program and enhancing the follow-up of treated patients are the main missing pillars in the Egyptian model.

Comparison between diagnosis and treatment of community-acquired pneumonia in children in various medical centres across Europe with the United States, United Kingdom and the World Health Organization guidelines.

PubMed

Usonis, Vytautas; Ivaskevicius, Rimvydas; Diez-Domingo, Javier; Esposito, Susanna; Falup-Pecurariu, Oana G; Finn, Adam; Rodrigues, Fernanda; Spoulou, Vana; Syrogiannopoulos, George A; Greenberg, David

2016-01-01

The aim of this study was to review the current status and usage of guidelines in the diagnosis and treatment of community-acquired pneumonia (CAP) in European countries and to compare to established guidelines in the United States (US), United Kingdom (UK), and the World Health Organization (WHO). A questionnaire was developed and distributed by the Community-Acquired Pneumonia Paediatric Research Initiative (CAP-PRI) working group and distributed to medical centres across Europe. Out of 19 European centres, 6 (31.6 %) used WHO guidelines (3 in combination with other guidelines), 5 (26.3 %) used national guidelines, and 5 (26.3 %) used local guidelines. Chest radiograph and complete blood count were the most common diagnostic examinations, while evaluation of clinical symptoms and laboratory tests varied significantly. Tachypnoea and chest recession were considered criteria for diagnosis in all three guidelines. In US and UK guidelines blood cultures, atypical bacterial and viral detection tests were recommended. In European centres in outpatient settings, amoxicillin was used in 16 (84 %) centers, clarithromycin in 9 (37 %) centers and azithromycin in 7 (47 %) centers, whereas in hospital settings antibiotic treatment varied widely. Amoxicillin is recommended as the first drug of choice for outpatient treatment in all guidelines. Although local variations in clinical criteria, laboratory tests, and antibiotic resistance rates may necessitate some differences in standard empirical antibiotic regimens, there is considerable scope for standardisation across European centres for the diagnosis and treatment of CAP.

Recurrent haematomas of the thigh: a case of von Willebrand's disease presenting to a sports clinic

PubMed Central

Owens, S.; Baglin, T.

2000-01-01

Von Willebrand's disease is a relatively common mild form of haemophilia. It should be suspected in assessing sports injuries when excessive bleeding occurs in response to relatively mild trauma. Those with the disease should remain active but avoid contact sports. They should not take aspirin or non-steroidal anti-inflammatory drugs, which may exacerbate bleeding, and should be given supportive treatment to cover dental extraction, surgery, or significant bleeding episodes. Key Words: von Willebrand's disease; haemophilia; haematoma; sports clinic PMID:10786868

Differences in care burden of patients undergoing dialysis in different centres in the netherlands.

PubMed

de Kleijn, Ria; Uyl-de Groot, Carin; Hagen, Chris; Diepenbroek, Adry; Pasker-de Jong, Pieternel; Ter Wee, Piet

2017-06-01

A classification model was developed to simplify planning of personnel at dialysis centres. This model predicted the care burden based on dialysis characteristics. However, patient characteristics and different dialysis centre categories might also influence the amount of care time required. To determine if there is a difference in care burden between different categories of dialysis centres and if specific patient characteristics predict nursing time needed for patient treatment. An observational study. Two hundred and forty-two patients from 12 dialysis centres. In 12 dialysis centres, nurses filled out the classification list per patient and completed a form with patient characteristics. Nephrologists filled out the Charlson Comorbidity Index. Independent observers clocked the time nurses spent on separate steps of the dialysis for each patient. Dialysis centres were categorised into four types. Data were analysed using regression models. In contrast to other dialysis centres, academic centres needed 14 minutes more care time per patient per dialysis treatment than predicted in the classification model. No patient characteristics were found that influenced this difference. The only patient characteristic that predicted the time required was gender, with more time required to treat women. Gender did not affect the difference between measured and predicted care time. Differences in care burden were observed between academic and other centres, with more time required for treatment in academic centres. Contribution of patient characteristics to the time difference was minimal. The only patient characteristics that predicted care time were previous transplantation, which reduced the time required, and gender, with women requiring more care time. © 2017 European Dialysis and Transplant Nurses Association/European Renal Care Association.

From benzos to berries: treatment offered at an Aboriginal youth solvent abuse treatment centre relays the importance of culture.

PubMed

Dell, Colleen Anne; Seguin, Maureen; Hopkins, Carol; Tempier, Raymond; Mehl-Madrona, Lewis; Dell, Debra; Duncan, Randy; Mosier, Karen

2011-02-01

First Nations and Inuit youth who abuse solvents are one of the most highly stigmatized substance-abusing groups in Canada. Drawing on a residential treatment response that is grounded in a culture-based model of resiliency, this article discusses the cultural implications for psychiatry's individualized approach to treating mental disorders. A systematic review of articles published in The Canadian Journal of Psychiatry during the past decade, augmented with a review of Canadian and international literature, revealed a gap in understanding and practice between Western psychiatric disorder-based and Aboriginal culture-based approaches to treatment and healing from substance abuse and mental disorders. Differing conceptualizations of mental health and substance abuse are discussed from Western psychiatric and Aboriginal worldviews, with a focus on connection to self, community, and political context. Applying an Aboriginal method of knowledge translation-storytelling-experiences from front-line workers in a youth solvent abuse treatment centre relay the difficulties with applying Western responses to Aboriginal healing. This lends to a discussion of how psychiatry can capitalize on the growing debate regarding the role of culture in the treatment of Aboriginal youth who abuse solvents. There is significant need for culturally competent psychiatric research specific to diagnosing and treating First Nations and Inuit youth who abuse substances, including solvents. Such understanding for front-line psychiatrists is necessary to improve practice. A health promotion perspective may be a valuable beginning point for attaining this understanding, as it situates psychiatry's approach to treating mental disorders within the etiology for Aboriginal Peoples.

Patient centred care for the medical treatment of lower urinary tract symptoms in patients with benign prostatic obstruction: a key point to improve patients' care - a systematic review.

PubMed

De Nunzio, Cosimo; Presicce, Fabrizio; Lombardo, Riccardo; Trucchi, Alberto; Bellangino, Mariangela; Tubaro, Andrea; Moja, Egidio

2018-06-26

Even though evidence based medicine, guidelines and algorithms still represent the pillars of the management of chronic diseases (i.e: hypertension, diabetes mellitus), a patient centred approach has been recently proposed as a successful strategy, in particular to improve drug adherence. Aim of the present review is to evaluate the unmet needs in LUTS/BPH management and the possible impact of a patient centered approach in this setting. A National Center for Biotechnology Information (NCBI) PubMed search for relevant articles published from January 2000 until December 2016 was performed by combining the following MESH terms: patients centred medicine, patient centered care, person centered care, patient centered outcomes, value based care, shared decision making, male, Lower Urinary Tract Symptoms, Benign Prostatic Hyperplasia, treatment. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). All studies reporting on patient centred approach, shared decision making and evidence-based medicine were included in the review. All original article, reviews, letters, congress abstracts, and editorials comments were included in the review. Studies reporting single case reports, experimental studies on animal models and studies not in English were not included in the review. Overall 751 abstracts were reviewed, out of them 87 full texts were analysed resulting in 36 papers included. The evidence summarised in this systematic review confirmed how a patient centred visit may improve patient's adherence to medication. Although a patient centred model has been rarely used in urology, management of Low Urinary Tract Symptoms (LUTS) and Benign Prostatic Obstruction (BPO) may represent the perfect ground to experiment and improve this approach. Notwithstanding all the innovations in LUTS/BPO medical treatment, the real life picture is far from ideal. Recent evidence shows a dramatical low drug adherence and satisfaction to medical treatment in

Impact of aerobic exercise on haemostatic indices in paediatric patients with haemophilia.

PubMed

Kumar, Riten; Bouskill, Vanessa; Schneiderman, Jane E; Pluthero, Fred G; Kahr, Walter H A; Craik, Allison; Clark, Dewi; Whitney, Karen; Zhang, Christine; Rand, Margaret L; Carcao, Manuel

2016-06-02

This study investigated the impact of aerobic exercise on laboratory assessments of haemostatic activity in boys (5-18 years of age) with haemophilia A (HA) or B (HB), examining the hypothesis that laboratory coagulation parameters temporarily improve with exercise. Thirty subjects meeting eligibility criteria (19 HA; 11 HB; mean age: 12.8 years) were invited to participate. They underwent a replacement factor washout period and were advised against strenuous activity for three days prior to the planned intervention. At study visit, baseline blood samples were drawn prior to exercise on a stationary cycle ergometer, aiming to attain 3 minutes (min) of cycling at 85 % of predicted maximum heart rate. Blood work was repeated 5 min (t5) and 60 min (t60) post exercise completion. Samples were assessed for platelet count (PC), factor VIII activity ( C), von Willebrand antigen (VWF:Ag), ristocetin cofactor activity (VWF:RCo) and platelet function analysis (PFA-100); maximum rate of thrombus generation (MRTG) in blood was measured via thromboelastography and plasma peak thrombin generation (PTG) via calibrated automated thrombography. Mean duration of exercise was 13.9 (± 2.6) min. On average, t5 samples showed significant elevation, relative to baseline in PC, FVIII:C, VWF:Ag, VWF:RCo and PTG, while C, VWF:Ag, VWF:RCo and MRTG were significantly elevated in t60 samples. Within the cohort, participants with severe HA showed no change in C levels with exercise. The greatest improvement in haemostatic indices was observed in post-adolescent males with mild-moderate HA, who thus represent the group most likely to benefit from a reduction of bleeding risk in the setting of exercise.

Prospective surveillance study of haemophilia A patients switching from moroctocog alfa or other factor VIII products to moroctocog alfa albumin-free cell culture (AF-CC) in usual care settings.

PubMed

Parra Lopez, Rafael; Nemes, Laszlo; Jimenez-Yuste, Victor; Rusen, Luminita; Cid, Ana R; Charnigo, Robert J; Baumann, James A; Smith, Lynne; Korth-Bradley, Joan M; Rendo, Pablo

2015-10-01

This prospective, open-label, postauthorisation safety surveillance study assessed clinically significant inhibitor development in patients with severe haemophilia A transitioning from moroctocog alfa or other factor VIII (FVIII) replacement products to reformulated moroctocog alfa (AF-CC). Males aged ≥ 12 years with severe haemophilia A (FVIII:C) < 1 IU/dl), > 150 exposure days (EDs) to recombinant or plasma-derived FVIII products, and no detectable inhibitor at screening were enrolled. Primary end point was the incidence of clinically significant FVIII inhibitor development. Secondary end points included annualised bleeding rate (ABR), less-than-expected therapeutic effect (LETE), and FVIII recovery. Patients were assigned to one of two cohorts based on whether they were transitioning to moroctocog alfa (AF-CC) from moroctocog alfa (cohort 1; n=146) or from another recombinant or plasma-derived FVIII product (cohort 2; n=62). Mean number of EDs on study was 94 (range, 1-139). Six positive FVIII inhibitor results, as determined by local laboratories, were reported in four patients; none were confirmed by a central laboratory, no inhibitor-related clinical manifestations were reported, and all anti-FVIII antibody assays were negative. Median ABRs were 23.4 and 3.4 in patients categorised at baseline as following on-demand and prophylactic regimens, respectively; 86.5% of bleeding episodes resolved after one infusion. LETE incidence was 0.06% and 0.19% in the on-demand and prophylaxis settings, respectively. FVIII recovery remained constant throughout the study. No new safety concerns were identified. This study found no increased risk of clinically significant FVIII inhibitor development in patients transitioning from moroctocog alfa or other FVIII replacement products to moroctocog alfa (AF-CC).

Claims for fertility interventions: a systematic assessment of statements on UK fertility centre websites

PubMed Central

Spencer, E A; Mahtani, K R; Goldacre, B; Heneghan, C

2016-01-01

Objectives Fertility services in the UK are offered by over 200 Human Fertilisation and Embryology Authority (HFEA)-registered NHS and private clinics. While in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) form part of the National Institute for Health and Care Excellence (NICE) guidance, many further interventions are offered. We aimed to record claims of benefit for interventions offered by fertility centres via information on the centres' websites and record what evidence was cited for these claims. Methods We obtained from HFEA a list of all UK centres providing fertility treatments and examined their websites. We listed fertility interventions offered in addition to standard IVF and ICSI and recorded statements about interventions that claimed or implied improvements in fertility in healthy women. We recorded which claims were quantified, and the evidence cited in support of the claims. Two reviewers extracted data from websites. We accessed websites from 21 December 2015 to 31 March 2016. Results We found 233 websites for HFEA-registered fertility treatment centres, of which 152 (65%) were excluded as duplicates or satellite centres, 2 were andrology clinics and 5 were unavailable or under construction websites. In total, 74 fertility centre websites, incorporating 1401 web pages, were examined for claims. We found 276 claims of benefit relating to 41 different fertility interventions made by 60 of the 74 centres (median 3 per website; range 0 to 10). Quantification was given for 79 (29%) of the claims. 16 published references were cited 21 times on 13 of the 74 websites. Conclusions Many fertility centres in the UK offer a range of treatments in addition to standard IVF procedures, and for many of these interventions claims of benefit are made. In most cases, the claims are not quantified and evidence is not cited to support the claims. There is a need for more information on interventions to be made available by fertility centres

Inconsistency in health care professional work: Employment in independent sector treatment centres.

PubMed

Bishop, Simon; Waring, Justin

2011-01-01

The purpose of this paper is to investigate the impact of recent outsourcing and public-private partnership (PPPs) arrangements on the consistency of professional employment in health care. A case study methodology is applied. The paper finds that multiple arrangements for employment within the ISTC creates numerous sources for inconsistency in employment: across the workplace, within professional groups and with national frameworks for health care employment. These are identified as having implications for organisational outcomes, threatening the stability of current partnerships, and partially stymieing intended behavioural change. The study is a single case study of an independent sector treatment centre. Future research is required to investigate wider trends of employment in heterogeneous outsourcing and PPP arrangements. The paper informs both managers and clinical professionals of the unanticipated complexities and practical challenges that can arise in partnerships and outsourcing arrangements. The paper presents a unique in-depth investigation of employment within recently established ISTCs, and highlights important employment changes for the core health care workforce and high-status professionals in the evolving health care organisational landscape.

Developing substance misuse services in United Arab Emirates: the National Rehabilitation Centre experience

PubMed Central

Al Ghaferi, Hamad A.; Ali, Ahmed Y.; Gawad, Tarek A.

2017-01-01

In 2001 a directive was issued to establish the National Rehabilitation Centre (NRC) to deal with the growing problem of substance misuse in the United Arab Emirates. The NRC has achieved many goals as a treatment and rehabilitation facility as well as a drug and alcohol demand reduction response centre. It is now working towards being an international centre of excellence. PMID:29093960

The clinical features of angular cheilitis occurring during orthodontic treatment: a multi-centre observational study.

PubMed

Cross, David; Eide, May L; Kotinas, Anastasios

2010-06-01

To report the prevalence and clinical features of angular cheilitis occurring in patients undergoing orthodontic treatment. Cross-sectional, observational study. Three centres were involved; Glasgow Dental Hospital and two specialist orthodontic practices, one in Scotland and one in Greece. Six hundred and sixty consecutive patients undergoing orthodontic treatment were examined over a 9 month period. The presence and absence of angular cheilitis was recorded. A six-point clinical scale was used to describe the clinical features of angular cheilitis when present. Chi-squared tests were used to investigate the association between the presence of angular cheilitis and oral hygiene level/appliance type. Eleven per cent of orthodontic patients in this Western European population, showed signs of angular cheilitis. No correlation was found between the presence of angular cheilitis and gender. Good oral hygiene was associated with a reduced prevalence (P<0.01). Angular cheilitis is a multifactorial condition that can occur in a small percentage of patients during orthodontic treatment. Good oral hygiene may be associated with a reduced risk. A new clinical grade of angular cheilitis is suggested that may help future research. Further studies are required to investigate the microbiological features associated with angular cheilitis occurring in orthodontic patients, as well as associations with medical conditions, such as asthma.

Doxycycline in the treatment of respiratory tract infections. Results of a pan-European multi-centre trial.

PubMed

Pestel, M

1975-01-01

In the winter of 1973-4, general practitioners from seven European countries took part in a multi-centre trial of doxycycline in the treatment of infections of the respiratory tract. The carefully designed protocol was observed by all participants. A total of 1,747 patients were admitted to the trial; their ages ranged from 6 years to over 80. The commonest diagnoses (50%) were acute bronchitis and acute exacerbations of chronic bronchitis. On the recommended dosage of 200 mg doxycycline on the first day, followed by 100 mg daily thereafter (though 200 mg could be continued daily in severe cases), 87% of patients achieved good or very good results. Both subjective (pain) and objective (sputum volume and viscosity, temperature, cough) measures showed rapid improvement, usually by the third to fifth days. Side-effects were minimal and mainly gastrointestinal and caused only 4 patients to discontinue treatment. Overall, doxycycline proved its effectiveness and rapidity of action.

Luteinizing hormone-releasing hormone analogue (Buserelin) treatment for central precocious puberty: a multi-centre trial.

PubMed

Werther, G A; Warne, G L; Ennis, G; Gold, H; Silink, M; Cowell, C T; Quigley, C; Howard, N; Antony, G; Byrne, G C

1990-02-01

A multi-centre open trial of Buserelin, a luteinizing hormone-releasing hormone (LHRH) analogue, was conducted in 13 children with central precocious puberty. Eleven children (eight girls and three boys), aged 3.4-10.2 years at commencement, completed the required 12 month period of treatment. Initially all patients received the drug by intranasal spray in a dose of 1200 micrograms/day, but by the end of the 12 month period two were having daily subcutaneous injections and three were receiving an increased dose intranasally. The first month of treatment was associated in one boy with increased aggression and masturbation, and in the girls with an increase in the prevalence of vaginal bleeding. Thereafter, however, both behavioural abnormalities and menstruation were suppressed. Median bone age increased significantly during the study, but without any significant change in the ratio of height age to bone age. The median predicted adult height for the group therefore did not alter significantly over the twelve months of the study. Buserelin treatment caused a reduction in the peak luteinizing hormone and follicle-stimulating hormone (FSH) responses to LHRH, mostly to prepubertal levels, and also suppressed basal FSH. In the first weeks of treatment, the girls' serum oestradiol levels rose significantly and then fell to prepubertal or early pubertal levels. A similar pattern was seen for serum testosterone levels. Serum somatomedin-C levels, however, showed little fluctuation over the course of the study. Buserelin treatment was safe and well accepted, and offers the promise of improved linear growth potential in precocious puberty.

Regulatory challenges to global harmonization and expanded access to concentrates: how will regulators balance the increasing cost of new safety requirements with the desire to increase the availability of affordable product?

PubMed

Farrugia, A

2004-10-01

The provision of concentrates of the deficient coagulation factors is an essential component of the provision of comprehensive haemophilia care. Their safety, quality and efficacy need to be assured independently of the measures dictated by the market and the individual manufacturers. Over the past 20 years, this assurance has become the role of regulatory authorities, which in the developed world have generated a framework that assesses haemophilia products as medicines in the highest category of risk relative to other therapeutic agents. Systems of official regulation mandating standards and other measures are now coupled with voluntary standards adopted by industry bodies as additional features of a comprehensive nexus of arrangements contributing to product quality and risk minimization. Currently, the regulation of products for haemophilia in less developed economies relies on reference to decisions in the first-world authorities. This may not always result in optimal outcomes as most of the haemophilia care in the developing world is through local plasma and cryoprecipitate, which are not subject to the oversight of mainstream regulators. Furthermore, the emergence of companies based outside the developed world and seeking to supply the emerging economies of the developing world with haemophilia concentrates has necessitated new strategies for regulation that are independent of the established frameworks. Overall, the principles used by mainstream agencies may be applied in all environments seeking to assure the quality of haemophilia care. Applied properly, they can contribute to maintaining the delivery of a form of therapy that is nowadays amongst the safest in therapeutic practice. A rigid interpretation can seriously impede access to treatment, and therefore the development of independent expertise and appropriate strategies in assuring product safety and quality in the developing world is essential if patient safety and access to products can be assured.

Surgical treatment of chronic pancreatitis using Frey's procedure: a Brazilian 16-year single-centre experience.

PubMed

Gestic, Martinho Antonio; Callejas-Neto, Francisco; Chaim, Elinton Adami; Utrini, Murillo Pimentel; Cazzo, Everton; Pareja, Jose Carlos

2011-04-01

Surgical treatment of chronic pancreatitis is indicated for intractable pain. Frey's procedure is an accepted treatment for this disease. The aim of the present study was to describe a single-centre experience in the treatment of chronic pancreatitis using Frey's procedure. A retrospective analysis of 73 patients who underwent a Frey's procedure between 1991 to 2007 and had at least 1 year of follow-up. Demographics, indication for surgery, peri-operative complications and late outcomes were analysed. The median age was 39.9 years. Seventy out of the 73 (95.8%) patients were male. The median pre-operative body mass index (BMI) was 19.1 kg/m(2). All patients had abdominal pain, 34 (46.6%) of them daily and 13 (17.8%) weekly, with moderate or severe intensity in 98.6% (n= 72). The aetiology was secondary to alcohol in 70 patients (95.9%), with a median consumption of 278 g per day. The surgical morbidity rate was 28.7%; there were no deaths. Median post-operative follow-up was 77.0 months; 64 patients (91.4%) had complete pain relief and post-operative BMI was 22.4 kg/m(2) (P<0.001). All patients with pre-operative endocrine and exocrine insufficiencies showed no reversal of the situation. New onset insufficiencies appeared late. Frey's procedure was a safe and effective therapeutic option for the surgical treatment of patients with intractable pain caused by chronic pancreatitis. © 2011 International Hepato-Pancreato-Biliary Association.

Claims for fertility interventions: a systematic assessment of statements on UK fertility centre websites.

PubMed

Spencer, E A; Mahtani, K R; Goldacre, B; Heneghan, C

2016-11-27

Fertility services in the UK are offered by over 200 Human Fertilisation and Embryology Authority (HFEA)-registered NHS and private clinics. While in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) form part of the National Institute for Health and Care Excellence (NICE) guidance, many further interventions are offered. We aimed to record claims of benefit for interventions offered by fertility centres via information on the centres' websites and record what evidence was cited for these claims. We obtained from HFEA a list of all UK centres providing fertility treatments and examined their websites. We listed fertility interventions offered in addition to standard IVF and ICSI and recorded statements about interventions that claimed or implied improvements in fertility in healthy women. We recorded which claims were quantified, and the evidence cited in support of the claims. Two reviewers extracted data from websites. We accessed websites from 21 December 2015 to 31 March 2016. We found 233 websites for HFEA-registered fertility treatment centres, of which 152 (65%) were excluded as duplicates or satellite centres, 2 were andrology clinics and 5 were unavailable or under construction websites. In total, 74 fertility centre websites, incorporating 1401 web pages, were examined for claims. We found 276 claims of benefit relating to 41 different fertility interventions made by 60 of the 74 centres (median 3 per website; range 0 to 10). Quantification was given for 79 (29%) of the claims. 16 published references were cited 21 times on 13 of the 74 websites. Many fertility centres in the UK offer a range of treatments in addition to standard IVF procedures, and for many of these interventions claims of benefit are made. In most cases, the claims are not quantified and evidence is not cited to support the claims. There is a need for more information on interventions to be made available by fertility centres, to support well-informed treatment

A retrospective analysis to determine the effect of independent treatment centres on the case mix for microsurgical training.

PubMed

Barsam, A; Heatley, C J; Sundaram, V; Toma, N M G

2008-05-01

To determine the effect of Independent Sector Treatment Centres (ISTC) on microsurgical training. A novel scoring protocol for stratification of cases suitable for microsurgical training was devised. This scoring protocol was applied to all patients who underwent cataract surgery on a single consultant dedicated training list between September and November 2004. These patients are representative of patients remaining on the waiting list after ISTC selection, that is, the residual case mix. Patients who underwent cataract surgery on the same consultant list in the same period in 2003 were also analysed when there was no ISTC or other waiting list initiative in operation. Data was available for 129 patients. Seventy three patients underwent cataract surgery between September and November 2003 and 56 patients underwent cataract surgery in the same period in 2004. Using the devised scoring protocol, the mean score in the 2003 group was 1.08 +/-1.75 (range, 0.0-10.5) and for the 2004 group the mean score was 2.31 +/-2.65 (range, 0.0-4.5). A Mann-Whitney test showed that there was a statistically significant difference between the scores in the two groups (P=0.0009). With Independent Sector Treatment Centre implementation the percentage of cases suitable only for consultants increased fourfold. The decrease in suitable cases for training as shown in this study is likely to have serious consequences on microsurgical training in the UK. We recommend that the results of this study are considered in any current or future plans for ISTC continuation and expansion.

Dental arcade arteriovenous fistulas: from diagnosis to treatment with emphasis on the role of endovascular or percutaneous treatment: single centre experience.

PubMed

Saraf, Rashmi; Shrivastava, Manish; Siddhartha, W; Limaye, Uday

2014-10-01

Dental arcade arteriovenous fistula (DA-AVF) are rare. The purpose of this study was to understand the angioarchitecture of these lesions, changing strategies of endovascular treatment and to analyse the best therapeutic option which will allow normal skeletal development especially in children. Retrospective study of all the patients of DA-AVF managed at our centre over the last 16 years. Detailed analysis of the clinical features, the imaging findings, endovascular treatment and angiographic outcomes was done. Total of six patients were treated. 5 were in the mandible and one in the maxilla. Transarterial glue embolization was done in 3 patients and direct puncture of the intraosseous venous pouch in 2. Transarterial Onyx was used in 2 patients through dual lumen balloon catheter. Overall cure was achieved in 5 out of 6 patients (83%). High index of suspicion is required to diagnose it on panoramic radiographs. CT/MR/CTA can lead to early diagnosis. Transarterial Onyx embolization using dual lumen balloon catheter is a promising technique & allows excellent penetration of Onyx into the intraosseous venous pouch. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Trapezoid supracondylar femoral extension osteotomy for knee flexion contractures in patients with haemophilia.

PubMed

Mortazavi, S M J; Heidari, P; Esfandiari, H; Motamedi, M

2008-01-01

Flexion deformity of the haemophilic knee is a considerable cause of disability and may need to be managed surgically in severe cases. We have used a trapezoid supracondylar femoral extension osteotomy to correct severe knee flexion deformity. Nine severe haemophilic patients with contractures >30 degrees that were unresponsive to conservative measures underwent 11 trapezoid osteotomies. The angle of deformity was measured using anteroposterior and lateral knee X-ray films at maximum extension. Factor levels of 80-100% were achieved before the operation. A trapezoid osteotomy of the distal femur bone was performed using a lateral approach. The frontal plane angular deformity (if any) was corrected at the same time. The osteotomy site was fixed using an Arbeitsgemeinschaft für Osteo synthesefragen (AO) condylar blade plate. Following surgery, the knee was supported by a plaster splint at 20 degrees of flexion. Physiotherapy was started on third postoperative day and continued three times a week. There was no serious complication. The deformities were corrected in all of the patients and the mean range of motion increased form 68.6 degrees to 98.1 degrees . Bleeding episodes decreased in all four knees which had a bleeding score of 3 before surgery. Using the Orthopaedic Advisory Committee of the World Federation of Haemophilia scores, nine good and two fair results were obtained. All patients regained the ability to walk for both short and long distance without any aid, climb the stairs, bath, and use public transportation. Trapezoid supracondylar femoral extension osteotomy should be considered in the surgical management of severe haemophilic flexion deformity of the knee joint.

A comparison of death recording by health centres and civil registration in South Africans receiving antiretroviral treatment.

PubMed

Johnson, Leigh F; Dorrington, Rob E; Laubscher, Ria; Hoffmann, Christopher J; Wood, Robin; Fox, Matthew P; Cornell, Morna; Schomaker, Michael; Prozesky, Hans; Tanser, Frank; Davies, Mary-Ann; Boulle, Andrew

2015-01-01

There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART). Completeness of death recording was estimated using a capture-recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes. After exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3-94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2-35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004-2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults). South Africa's civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records.

Characteristics of Patients with Alcohol Dependence Seeking Baclofen Treatment in France: A Two-Centre Comparative Cohort Study.

PubMed

Simioni, Nicolas; Preda, Cristian; Deken, Valérie; Bence, Camille; Cottencin, Olivier; Rolland, Benjamin

2016-11-01

To characterize the profile of patients seeking baclofen treatment for alcohol dependence in France. We compared retrospectively baclofen seekers and baclofen non-seekers within a cohort of consecutive outpatients with alcohol dependence who attended a first appointment for alcohol treatment at two French addiction centres between September 2012 and March 2014. We documented socio-demographic characteristics; comorbid psychiatric, addiction, alcohol dependence features; patients' initial drinking goal, and referral status; and treatment retention at 6 and 12 months. Of the 289 patients identified, 107 were baclofen seekers and 182 were baclofen non-seekers. The only parameters significantly associated with baclofen seekers in multivariate analyses were a greater baseline alcohol consumption (β = 15.4, 95% CI: 0.18-30.65, P = 0.05), a controlled-drinking initial goal (OR = 14.9, 95% CI: 7.7-29, P < 0.0001) and self-referral (OR = 6.6, 95% CI: 3.7-12, P < 0.0001), baclofen seekers being eight times more likely to be self-referred and treatment-naïve (OR = 8.8, 95% CI: 4.1-18.9, P < 0.0001). Baclofen seekers were more likely to be retained in treatment at 6 months (OR = 3.5, 95% CI: 1.8-6.7, P < 0.0001) and 12 months (OR = 1.9, 95% CI: 1.1-3.2, P = 0.019). In France, the perspective of controlled drinking offered by baclofen treatment may have attracted more self-referred patients, including those without previous alcohol treatment, to attend treatment, than the usual treatment options. These findings raise the question as to whether future public health strategies on alcohol should more prominently promote some aspects of alcohol treatment, such as patient's preference and treatment options, in order to reduce the treatment gap in alcohol dependence. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Treatment outcome in patients with presumed tubercular uveitis at a tertiary referral eye care centre in Singapore.

PubMed

Ang, Leslie; Kee, Aera; Yeo, Tun Hang; Dinesh, V G; Ho, Su Ling; Teoh, Stephen C; Agrawal, Rupesh

2018-02-01

To report the clinical features and outcome of patients with presumed tubercular uveitis (TBU). Retrospective analysis of patients with presumed TBU at a tertiary referral eye care centre in Singapore between 2007 and 2012 was done. Main outcome measures were failure of complete resolution of uveitis or recurrence of inflammation. Fifty three patients with mean age of 44.18 ± 15.26 years with 54.72% being males were included. 19 (35.85%) had bilateral involvement, with panuveitis and anterior uveitis being the most common presentations. 36 (67.92%) patients received antitubercular therapy (ATT), and 28 received concurrent systemic steroids. 15 (28.30%) eyes of 11 (30.55%) patients in the ATT group and 4 (21.05%) eyes of 3 (17.64%) patients in the non-ATT group had treatment failure (p value = 0.51). The use of ATT, with or without concurrent corticosteroid, may not have a statistically significant impact in improving treatment success in patients with presumed TBU.

Relationship of reasons and fears of treatment with outcome in substance using population attending a de-addiction centre.

PubMed

Sarkar, Siddharth; Nebhinani, Naresh; Kaur, Jasveen; Kaur, Kamalpreet; Ghai, Sandhya; Basu, Debasish

2013-07-01

Substance users approach a treatment facility for a variety of reasons as well as avoid or delay in help seeking due to perceived fears with treatment facilities. Sometimes these factors might be associated with treatment outcomes. We studied the relationship of reasons and fears of treatment seeking with treatment outcome in substance users. One hundred subjects, attending the Drug Deaddiction and Treatment Centre, PGIMER, were prospectively recruited by purposive sampling. A semistructured proforma was used to gather sociodemographic and clinical data. Reasons of help-seeking and fear questionnaire, social support scale, and PGI locus of control scale were then applied. Followup data were available for 69 patients, which were classified into good or poor outcome based on relapse status. At 6 months followup, 22 patients had relapsed, while 47 patients did not relapse. A higher degree of dysfunction due to substance at baseline was associated with relapsed status at followup. Parents or guardians coming to know about resuming substance and being unemployed for a long time were the reasons associated with relapsed status, while needing to consult a doctor immediately was significantly related to abstinent status at followup. Fear of not being able to meet substance using friends was associated with a poorer outcome in the form of relapse. Reasons for treatment seeking as well as fears related to treatment have significant implications on the clinical outcome of substance abusing patients. Addressing these could help in better patient outcomes.

A vancomycin drug use evaluation and economic analysis in a cancer treatment centre.

PubMed

Dranitsaris, G; Pilla, N J; McGreer, A

1994-04-01

Princess Margaret Hospital is a 140-bed university affiliated cancer treatment centre. Vancomycin was the only formulary agent available for the treatment of methicillin-resistant gram-positive organisms. The high cost and potential toxicity of this drug warranted a closer examination of its use. The purpose of this study was to evaluate vancomycin use and to determine the economic impact when it was used contrary to newly developed hospital guidelines. A sample of 100 vancomycin orders was randomly selected from all prescriptions filled in 1992. The indication, dose, and duration of therapy for each order were compared against the hospital guidelines. The cost savings associated with altering the sample of prescriptions to meet hospital guidelines were then determined. Nine percent of the prescriptions were for nonapproved indications. The actual dose used did not meet criteria in 32% of cases and the length of therapy was beyond the approved duration in 45% of the orders. If the cases had been altered to meet the guidelines then a total savings of $13,581 would have been realized. The projected savings for the entire year (1992) would have been $100,907. The critical problem areas in vancomycin prescribing were the duration of therapy and dose. The results have provided the impetus to initiate a hospital wide prospective Drug Utilization Evaluation (DUE) study to optimize vancomycin prescribing. The program costs would be easily covered by the expected savings.

Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.

PubMed

Hua, B; Lee, A; Fan, L; Li, K; Zhang, Y; Poon, M-C; Zhao, Y

2017-05-01

Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. A cross-over study on 5 IU kg -1 FVIII daily vs. 10 IU kg -1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients. © 2017 John Wiley & Sons Ltd.

Reappearance and treatment of penicillin-susceptible Staphylococcus aureus in a tertiary medical centre.

PubMed

Chabot, Matthew R; Stefan, Mihaela S; Friderici, Jennifer; Schimmel, Jennifer; Larioza, Julius

2015-12-01

The purpose of this study was to describe trends in the prevalence and treatment patterns of penicillin-susceptible Staphylococcus aureus (SA) infections. This was a cross-sectional study of MSSA isolates from blood cultures at a tertiary-care centre between 1 January 2003 and 31 December 2012. All blood cultures positive for MSSA drawn during the study period were used to calculate the prevalence of penicillin-susceptible SA. Repeat cultures were excluded if they were isolated within 6 weeks of the index culture. The analysis was then restricted to inpatient blood cultures to assess treatment patterns. Antibiotics administered 48-96 h after the culture were analysed. A total of 446 blood cultures positive for MSSA were included in the analysis. There was a distinct trend showing an increase in the percentage of penicillin-susceptible SA over 10 years from 13.2% (95% CI 4.1%-22.3%) in 2003 to 32.4% (95% CI 17.3%-47.5%) in 2012 (P trend <0.001). During the study period, penicillin use for penicillin-susceptible SA bacteraemia increased from 0.0% in 2003-04 to 50.0% in 2011-12 (P trend = 0.007). Over a decade, there was an ∼3-fold increase in penicillin susceptibility among MSSA blood cultures at a large tertiary-care facility. Although treatment with penicillin increased over the study period, only 50% of penicillin-susceptible SA was treated with penicillin in the final study period. This study suggests that while susceptibility to penicillin appears to be returning in SA, the use of penicillin for penicillin-susceptible SA bacteraemia is low. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Clinical experience with Optivate®, high-purity factor VIII (FVIII) product with von Willebrand factor (VWF) in young children with haemophilia A.

PubMed

Matysiak, M; Bobrowska, H; Balwierz, W; Chybicka, A; Kowalczyk, J R; Shaikh-Zaidi, R; Gillanders, K; Dash, C H

2011-09-01

Optivate® is a high-purity FVIII/VWF product. Its safety, tolerability and efficacy in subjects ≥ 12 years have been demonstrated. This study was undertaken to assess Optivate® in children with haemophilia A. Twenty-five children, including one PUP (previously untreated patient), aged 1-6 years (mean 4.67 years) were treated with Optivate® for 26 weeks. Inhibitors were assessed every 3 months and viral status at the study start and end. Prophylaxis was used by five boys and on demand by twenty. The mean number of bleeds in the study was lower compared to the same period pre-study (12.0/child vs. 16.2/child), with fewer bleeds (P < 0.05) in the prophylactic subgroup (8.0/child) compared with the on-demand sub-group (13.4/child). Fourteen major bleeds were reported, all by the on-demand sub-group. Children on prophylaxis were administered a mean of 59.4 infusions; on-demand group 35.1 infusions. A total of 998 infusions were used with a mean dose of 29.1 IU kg⁻¹, and a mean of 38.6 exposure days (ED). Children < 4 years used higher doses, and reported fewer bleeds than older children. Children's Parents/Guardians rated Optivate® as helpful or very helpful in controlling 97.5% of bleeds by the prophylactic group, and in 98.5% of the bleeds in the on-demand group. Only 5 of 101 ADRs were treatment-related events (5%), all were mild and non-serious. There were no clinically significant changes in vital signs, viral transmissions or inhibitors. In young children Optivate® was well tolerated, safe and efficacious. © 2011 Blackwell Publishing Ltd.

Naltrexone versus acamprosate in the treatment of alcohol dependence: A multi-centre, randomized, double-blind, placebo-controlled trial.

PubMed

Morley, Kirsten C; Teesson, Maree; Reid, Sophie C; Sannibale, Claudia; Thomson, Clare; Phung, Nghi; Weltman, Martin; Bell, James R; Richardson, Kylie; Haber, Paul S

2006-10-01

To compare the efficacy of acamprosate and naltrexone in the treatment of alcohol dependence. A double-blind, placebo-controlled trial. Three treatment centres in Australia. A total of 169 alcohol dependent subjects were given naltrexone (50 mg/day), acamprosate (1998 mg/day) or placebo for 12 weeks. All subjects were offered manualized compliance therapy, a brief intervention that targets problems that may affect treatment compliance such as ambivalence and misperceptions about medication. Time to the first drink, time to first relapse, drinks per drinking day and cumulative abstinence. In intention-to-treat analyses, there were no differences between groups on outcome measures of drinking, craving or biochemical markers. Similarly, analyses of the 94 subjects that completed the study in full and demonstrated 80% compliance, revealed no significant treatment effects. Differential treatment effects were identified after stratification according to scores on the Alcohol Dependence Scale (ADS) and Depression Anxiety and Stress Scale (DASS). A significant beneficial treatment effect on time to first relapse was revealed for subjects with 'no depression' allocated to naltrexone (n = 56; P < 0.01). In addition, a significant beneficial treatment effect was revealed in subjects with 'low dependence' allocated to naltrexone (n = 34; P < 0.05). The results of this study support the efficacy of naltrexone in the relapse prevention of alcoholism amongst those with low levels of clinical depression and alcohol dependence severity. No effect of acamprosate was found in our sample.

An organisational change intervention for increasing the delivery of smoking cessation support in addiction treatment centres: study protocol for a randomized controlled trial.

PubMed

Bonevski, Billie; Guillaumier, Ashleigh; Shakeshaft, Anthony; Farrell, Michael; Tzelepis, Flora; Walsberger, Scott; D'Este, Catherine; Paul, Chris; Dunlop, Adrian; Searles, Andrew; Kelly, Peter; Fry, Rae; Stirling, Robert; Fowlie, Carrie; Skelton, Eliza

2016-06-14

The provision of smoking cessation support in Australian drug and alcohol treatment services is sub-optimal. This study examines the cost-effectiveness of an organisational change intervention to reduce smoking amongst clients attending drug and alcohol treatment services. A cluster-randomised controlled trial will be conducted with drug and alcohol treatment centres as the unit of randomisation. Biochemically verified (carbon monoxide by breath analysis) client 7-day-point prevalence of smoking cessation at 6 weeks will be the primary outcome measure. The study will be conducted in 33 drug and alcohol treatment services in four mainland states and territories of Australia: New South Wales, Australian Capital Territory, Queensland, and South Australia. Eligible services are those with ongoing client contact and that include pharmacotherapy services, withdrawal management services, residential rehabilitation, counselling services, and case management services. Eligible clients are those aged over 16 years who are attending their first of a number of expected visits, are self-reported current smokers, proficient in the English language, and do not have severe untreated mental illness as identified by the service staff. Control services will continue to provide usual care to the clients. Intervention group services will receive an organisational change intervention, including assistance in developing smoke-free policies, nomination of champions, staff training and educational client and service resources, and free nicotine replacement therapy in order to integrate smoking cessation support as part of usual client care. If effective, the organisational change intervention has clear potential for implementation as part of the standard care in drug and alcohol treatment centres. Australian and New Zealand Clinical Trials Registry, ACTRN12615000204549 . Registered on 3 March 2015.

Preventing work-related stress among staff working in children's cancer Principal Treatment Centres in the UK: a brief survey of staff support systems and practices.

PubMed

Beresford, B; Gibson, F; Bayliss, J; Mukherjee, S

2018-03-01

Growing evidence of the association between health professionals' well-being and patient and organisational outcomes points to the need for effective staff support. This paper reports a brief survey of the UK's children's cancer Principal Treatment Centres (PTCs) regarding staff support systems and practices. A short on-line questionnaire, administered in 2012-2013, collected information about the availability of staff support interventions which seek to prevent work-related stress among different members of the multi-disciplinary team (MDT). It was completed by a member of staff with, where required, assistance from colleagues. All PTCs (n = 19) participated. Debriefs following a patient death was the most frequently reported staff support practice. Support groups were infrequently mentioned. There was wide variability between PTCs, and between professional groups, regarding the number and type of interventions available. Doctors appear to be least likely to have access to support. A few Centres routinely addressed work-related stress in wider staff management strategies. Two Centres had developed a bespoke intervention. Very few Centres were reported to actively raise awareness of support available from their hospital's Occupational Health department. A minority of PTCs had expert input regarding staff support from clinical psychology/liaison psychiatry. © 2016 The Authors. European Journal of Cancer Care Published by John Wiley & Sons Ltd.

Expansion of antiretroviral treatment to rural health centre level by a mobile service in Mumbwa district, Zambia

PubMed Central

Dube, Christopher; Hayakawa, Tadao; Kakimoto, Kazuhiro; Yamada, Norio; Simpungwe, James B

2010-01-01

Abstract Problem Despite the Government’s effort to expand services to district level, it is still hard for people living with HIV to access antiretroviral treatment (ART) in rural Zambia. Strong demands for expanding ART services at the rural health centre level face challenges of resource shortages. Approach The Mumbwa district health management team introduced mobile ART services using human resources and technical support from district hospitals, and community involvement at four rural health centres in the first quarter of 2007. This paper discusses the uptake of the mobile ART services in rural Mumbwa. Local setting Mumbwa is a rural district with an area of 23 000 km2 and a population of 167 000. Before the introduction of mobile services, ART services were provided only at Mumbwa District Hospital. Relevant changes The mobile services improved accessibility to ART, especially for clients in better functional status, i.e. still able to work. In addition, these mobile services may reduce the number of cases “lost to follow-up”. This might be due to the closer involvement of the community and the better support offered by these services to rural clients. Lessons learnt These mobile ART services helped expand services to rural health facilities where resources are limited, bringing them as close as possible to where clients live. PMID:20931065

Going private: clinicians' experience of working in UK independent sector treatment centres.

PubMed

Waring, Justin; Bishop, Simon

2012-02-01

With increased possibility that public healthcare services in the UK will be outsourced to the private sector, this study investigates how clinicians working in Independent Sector Treatment Centres perceive the differences between public and private sectors. Qualitative interviews with 35 clinicians recruited from two ISTCs. All participants were transferred to the independent sector from the public National Health Service. Interview data were analysed to identify shared experience about the variable organisation and delivery of services. Clinicians perceived differences between public and independent sectors in the areas of 'environment and facilities', 'management', 'work organisation and care delivery', and 'patient experience'. The independent sector was described as offering a positive alternative to public services in regard to service environment and patient experience, but there were concerns about management priorities and the reconfiguration of work. Clinicians' experience of moving between sectors reveals mixed experiences. Although some improvements might legitimise the growing role of the independent sector, there remain doubts about the commercialisation of services, the motives of managers and the impact of clinical roles and capabilities. With policies looking to expand the mixed economy of public healthcare services, the study suggests clinicians will not automatically embrace a move between sectors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The oral food desensitization in the Italian allergy centres.

PubMed

Meglio, P; Caminiti, L; Pajno, G B; Dello Iacono, I; Tripodi, S; Verga, M C; Martelli, A

2015-05-01

Attempts aimed at inducing food tolerance through oral food desensitization (OFD) for the treatment of IgE-mediated food allergies are increasing. In Italy, a number of allergy centres offer this procedure. To collect information on how these centres are organized, how patients are selected, the methods used to administer OFD and how adverse reactions are managed. A questionnaire was e-mailed to all the Italian allergy centres offering OFD. The survey shows a high degree of variability between centres. A correct diagnosis of food allergy is crucial for selecting patients for OFD. In the Italian allergy centres, oral food challenges are mostly open label (84%), but in 16% of cases they are single-blind (8%) or double-blind (8%). A high proportion of allergy centres (83%) offer OFD to children presenting forms of anaphylaxis triggered by traces--or very low doses--of food allergen. The majority of allergy centres (76%) enroll patients over 3 years of age, with 44% enrolling patients above the age of 5. Not-controlled asthma, unreliability of parents in the management of OFD and/or risk of adverse events, are the main reasons for exclusion from the procedure. Although OFD may sometimes be successful and may be considered a valid alternative to an elimination diet, further randomized controlled trials are needed, in order to clarify some controversial points, such as the characteristics of the child undergoing OFD, and the methods of food preparation and administration. Moreover, further studies should further investigate OFD safety, efficacy and costs.

Headache service quality: evaluation of quality indicators in 14 specialist-care centres.

PubMed

Schramm, Sara; Uluduz, Derya; Gouveia, Raquel Gil; Jensen, Rigmor; Siva, Aksel; Uygunoglu, Ugur; Gvantsa, Giorgadze; Mania, Maka; Braschinsky, Mark; Filatova, Elena; Latysheva, Nina; Osipova, Vera; Skorobogatykh, Kirill; Azimova, Julia; Straube, Andreas; Eren, Ozan Emre; Martelletti, Paolo; De Angelis, Valerio; Negro, Andrea; Linde, Mattias; Hagen, Knut; Radojicic, Aleksandra; Zidverc-Trajkovic, Jasna; Podgorac, Ana; Paemeleire, Koen; De Pue, Annelien; Lampl, Christian; Steiner, Timothy J; Katsarava, Zaza

2016-12-01

The study was a collaboration between Lifting The Burden (LTB) and the European Headache Federation (EHF). Its aim was to evaluate the implementation of quality indicators for headache care Europe-wide in specialist headache centres (level-3 according to the EHF/LTB standard). Employing previously-developed instruments in 14 such centres, we made enquiries, in each, of health-care providers (doctors, nurses, psychologists, physiotherapists) and 50 patients, and analysed the medical records of 50 other patients. Enquiries were in 9 domains: diagnostic accuracy, individualized management, referral pathways, patient's education and reassurance, convenience and comfort, patient's satisfaction, equity and efficiency of the headache care, outcome assessment and safety. Our study showed that highly experienced headache centres treated their patients in general very well. The centres were content with their work and their patients were content with their treatment. Including disability and quality-of-life evaluations in clinical assessments, and protocols regarding safety, proved problematic: better standards for these are needed. Some centres had problems with follow-up: many specialised centres operated in one-touch systems, without possibility of controlling long-term management or the success of treatments dependent on this. This first Europe-wide quality study showed that the quality indicators were workable in specialist care. They demonstrated common trends, producing evidence of what is majority practice. They also uncovered deficits that might be remedied in order to improve quality. They offer the means of setting benchmarks against which service quality may be judged. The next step is to take the evaluation process into non-specialist care (EHF/LTB levels 1 and 2).

Physician-staffed emergency helicopter reduces transportation time from alarm call to highly specialized centre.

PubMed

Fjaeldstad, Alexander; Kirk, Morten Hasager; Knudsen, Lars; Bjerring, Jesper; Christensen, Erika F

2013-07-01

Since 2007, the number of Danish emergency departments has decreased from 44 to 21. Longer distances to specialized treatment have increased the demand for advanced prehospital treatment. A Danish 24/7 Helicopter Emergency Medical System (HEMS) project in western Denmark was initiated on 6 January 2011. The HEMS provides prehospital care delivered by a specialized anaesthesiologist. This study evaluated the effect of HEMS on the time to treatment by a physician (time-to-doctor) and the time from a 112 emergency call to arrival at the highly specialized centre (time-to-centre) for patients with ST-elevation myocardial infarction (STEMI) or severe injury (Injury Severity Score > 15). In this prospective study with a matched historical control group, the time-to-doctor and the time-to-centre for patients with STEMI or severe injury transported by HEMS were compared with geographically matched patients with the same diagnoses and who were transported by ambulance. Time-to-centre was reduced from 102 to 84 min. for STEMI and from 322 to 97 min. for severely injured patients after HEMS implementation. HEMS did not substantially reduce time-to-doctor, mainly because of increased availability of physician-staffed cars. In 56% of cases, HEMS was dispatched secondarily more than 30 min. after the ambulance had been dispatched. Using HEMS reduced time to arrival at a highly specialized centre for patients with STEMI or severe injury. Simultaneous dispatch of an ambulance and HEMS shows potential for further reduction in the time-to-centre and the time-to-doctor. not relevant. The trial is registered at the Danish Data Protection Agency.

Development and validation of a new questionnaire for the assessment of subjective physical performance in adult patients with haemophilia--the HEP-Test-Q.

PubMed

von Mackensen, S; Czepa, D; Herbsleb, M; Hilberg, T

2010-01-01

Specific research studies for the investigation of physical performance in haemophilic patients are rare. However, these instruments become increasingly more important to evaluate therapeutic treatments. Within the frame of the Haemophilia & Exercise Project (HEP), a new questionnaire, namely HEP-Test-Q, has been developed for the assessment of subjective physical performance in haemophilic adults. In this article, the development and validation of the HEP-Test-Q is described. The development consisted of different phases including item collection, pilot testing and field testing. The preliminary version was pilot-tested in 24 German HEP-participants. Following evaluation and preliminary psychometric analysis, the HEP-Test-Q was revised. The final version consists of 25 items pertaining to the domains 'mobility', 'strength & coordination', 'endurance' and 'body perception', which was administered to 43 German haemophilic patients (43.8 +/- 11.2 years). Psychometric analysis included reliability and validity testing. Convergent validity was tested correlating the HEP-Test-Q with SF-36, Haem-A-QoL, HAL and the Orthopaedic Joint Score. Discriminant validity tested different clinical subgroups. Patients accepted the questionnaire and found it easy to fill in. Psychometric testing revealed good values for reliability in terms of internal consistency (Cronbach's alpha = 0.96) and test-retest reliability (r = 0.90) as well as for convergent validity correlating highly with Haem-A-QoL, HAL and SF-36. Discriminant validity testing showed significant differences for age, hepatitis A and hepatitis B and the number of target joints. HEP-Test-Q is a short and well-accepted questionnaire, assessing subjective physical performance of haemophiliacs, which might be combined with objective assessments to reveal aspects, which cannot be measured objectively, such as body perception.

A close insight to factor VIII inhibitor in the congenital hemophilia A.

PubMed

Tabriznia-Tabrizi, Shamsoreza; Gholampour, Marzie; Mansouritorghabeh, Hassan

2016-09-01

Hemophilia A (HA) has an X-linked pattern of inheritance and is the most common of the hemorrhagic disorders. HA is caused by a decreased or deficiency of the functional clotting factor VIII (FVIII) and effects 1 in 5000-10,000 male births. The common treatment for hemophilia is replacement therapy by plasma-derived or recombinant FVIII. Approximately 20-30% of people with a severe type of HA develop an inhibitor and this phenomenon is the main challenge in the management of these patients. Genetic factors and environmental determinants contribute to inhibitor development. Here, the roles of various genetic and environmental factors such as the type of FVIII concentrate used, the number of exposure days, and peak treatment time will be discussed in detail. It seems this information is helpful for hematologists. A literature review was done in January 2016 on PubMed and Scopus using the following keywords:' h(a)emophilia A & factor VIII inhibitor', 'h(a)emophilia A & factor VIII alloantibody', 'h(a)emophilia A & inhibitor'. There was no time limitation; however, there was an English language limitation placed on the articles selected. Expert commentary: Influential genetic and environmental factors in developing inhibitors have been discussed. Most of the risk factors are related to previously untreated patients with hemophili.

RTEMS Centre - Support and Maintenance Centre to RTEMS Operating System

NASA Astrophysics Data System (ADS)

Silva, H.; Constantino, A.; Freitas, D.; Coutinho, M.; Faustino, S.; Mota, M.; Colaço, P.; Sousa, J.; Dias, L.; Damjanovic, B.; Zulianello, M.; Rufino, J.

2009-05-01

RTEMS CENTRE - Support and Maintenance Centre to RTEMS Operating System is a joint ESA/Portuguese Task Force initiative to develop a support and maintenance centre to the Real-Time Executive for Multiprocessor Systems (RTEMS). This paper gives a high level visibility of the progress, the results obtained and the future work in the RTEMS CENTRE [6] and in the RTEMS Improvement [7] projects. RTEMS CENTRE started officially in November 2006, with the RTEMS 4.6.99.2 version. A full analysis of RTEMS operating system was produced. The architecture was analysed in terms of conceptual, organizational and operational concepts. The original objectives [1] of the centre were primarily to create and maintain technical expertise and competences in this RTOS, to develop a website to provide the European Space Community an entry point for obtaining support (http://rtemscentre.edisoft.pt), to design, develop, maintain and integrate some RTEMS support tools (Timeline Tool, Configuration and Management Tools), to maintain flight libraries and Board Support Packages, to develop a strong relationship with the World RTEMS Community and finally to produce some considerations in ARINC-653, DO-178B and ECSS E-40 standards. RTEMS Improvement is the continuation of the RTEMS CENTRE. Currently the RTEMS, version 4.8.0, is being facilitated for a future qualification. In this work, the validation material is being produced following the Galileo Software Standards Development Assurance Level B [5]. RTEMS is being completely tested, errors analysed, dead and deactivated code removed and tests produced to achieve 100% statement and decision coverage of source code [2]. The SW to exploit the LEON Memory Management Unit (MMU) hardware will be also added. A brief description of the expected implementations will be given.

[Medical waste management in healthcare centres in the occupied Palestinian territory].

PubMed

Al-Khatib, Issam A

2007-01-01

Medical waste management in primary and secondary healthcare centres in the occupied Palestinian territory was assessed. The overall monthly quantity of solid healthcare waste was estimated to be 512.6 tons. Only 10.8% of the centres completely segregated the different kinds of healthcare waste and only 15.7% treated their medical waste. In the centres that treated waste, open burning was the main method of treatment. The results indicate that Palestinians are exposed to health and environmental risks because of improper disposal of medical waste and steps are needed to improve the situation through the establishment and enforcement of laws, provision of the necessary infrastructure for proper waste management and training of healthcare workers and cleaners.

Community mental health centres initiated by the South-Eastern Europe Stability Pact: evaluation in seven countries.

PubMed

Priebe, Stefan; Matanov, Aleksandra; Demi, Neli; Blagovcanin Simic, Joka; Jovanovic, Sandra; Gajic, Milena; Radonic, Elizabeta; Bajraktarov, Stojan; Boderscova, Larisa; Konatar, Monika; Nica, Raluca; Muijen, Matthijs

2012-06-01

Eight community mental health care centres (initiated by the South-Eastern Europe Stability Pact) in Albania, Bosnia-Herzegovina, Croatia, Macedonia, Moldova, Montenegro and Romania were evaluated. Characteristics of patients, patient reported outcomes and patient views of care were assessed in 305 psychiatric patients. Patient characteristics varied across centres, with most patients having long term psychotic disorders. Treatment satisfaction and therapeutic relationships were rated favourably. Subjective quality of life mean scores were rather low, with higher satisfaction with health and dissatisfaction with the financial and employment situation. Being unemployed was the only factor associated with poor quality of life and lower treatment satisfaction. Most developing centres target patients with persistent psychotic disorders. Care appears highly valued by the patients. The findings encourage establishing more centres in the region and call for employment schemes for people with mental illnesses.

Community Rehabilitation: "Home versus Centre" Guidelines for Choosing the Optimal Treatment Location

ERIC Educational Resources Information Center

Barker, Lauren N.; Ziino, Carlo

2010-01-01

This study aimed to produce indicators and guidelines for clinician use in determining whether individual therapy sessions for community rehabilitation services should be delivered in a home/community-based setting or centre-based setting within a flexible service delivery model. Concept mapping techniques as described by Tochrim and Kane (2005)…

Prevalence and treatment of cancer pain in Italian oncological wards centres: a cross-sectional survey.

PubMed

Mercadante, Sebastiano; Roila, Fausto; Berretto, Oscar; Labianca, Roberto; Casilini, Stefania

2008-11-01

The aim of this national cross-sectional survey was to draw information on pain prevalence and intensity from a large sample of patients who were admitted to oncologic centres for different reasons and to evaluate the pain treatment and possible influencing factors. A total of 2,655 patients completed the study. Nine hundred and one patients (34%) reported pain. Higher pain levels were observed in inpatients, in the presence of bone metastases, and with low levels of Eastern Cooperative Oncology Group status. The number of patients receiving strong opioids increased with the highest levels of pain. However, a significant part of patients with moderate-severe pain were not receiving appropriate medication, patients being predominantly administered non-opioid drugs. General practitioners' attitudes did not negatively influence the opioid prescription. The results of this survey indicate a need for continuing educational and informative program in pain management for oncologists and more generally for any physician dealing with cancer patients.

Motivational and behavioural models of change: A longitudinal analysis of change among men with chronic haemophilia-related joint pain.

PubMed

Elander, J; Richardson, C; Morris, J; Robinson, G; Schofield, M B

2017-09-01

Motivational and behavioural models of adjustment to chronic pain make different predictions about change processes, which can be tested in longitudinal analyses. We examined changes in motivation, coping and acceptance among 78 men with chronic haemophilia-related joint pain. Using cross-lagged regression analyses of changes from baseline to 6 months as predictors of changes from 6 to 12 months, with supplementary structural equation modelling, we tested two models in which motivational changes influence behavioural changes, and one in which behavioural changes influence motivational changes. Changes in motivation to self-manage pain influenced later changes in pain coping, consistent with the motivational model of pain self-management, and also influenced later changes in activity engagement, the behavioural component of pain acceptance. Changes in activity engagement influenced later changes in pain willingness, consistent with the behavioural model of pain acceptance. Based on the findings, a combined model of changes in pain self-management and acceptance is proposed, which could guide combined interventions based on theories of motivation, coping and acceptance in chronic pain. This study adds longitudinal evidence about sequential change processes; a test of the motivational model of pain self-management; and tests of behavioural versus motivational models of pain acceptance. © 2017 European Pain Federation - EFIC®.

Birth centre confinement at the Queen Victoria Medical Centre. I. Obstetric and neonatal outcome.

PubMed

Campbell, J; Hudson, H; Lumley, J; Morris, N; Rao, J; Spensley, J

1981-10-03

A review of hte first 175 confinements at the Queen Victoria Medical Centre Birth Centre is presented. The design, structure and function of hte Birth Centre is described and the safety of the programme demonstrated. Seventy-four pregnancies (42%) accepted for Birth Centre confinement required transfer because of antepartum or intrapartum complications. There were satisfactory obstetric and neonatal outcomes in all pregnancies. The first year's experience has allowed a reassessment of the risk factors, which will permit greater use of the Birth Centre without any increases risk to mothers or babies.

Differences in the quality of diabetes care caused by social inequalities disappear after treatment and education in a tertiary care centre.

PubMed

Bäz, L; Müller, N; Beluchin, E; Kloos, C; Lehmann, T; Wolf, G; Müller, U A

2012-05-01

To assess the relationship between social status and quality of diabetes care in a tertiary care centre in Germany. Social status was assessed in 940 consecutive patients in a university outpatient department by a questionnaire. The assessment comprised three components: education, highest professional position and household net income (total score 3-21). Quality of diabetes care was measured by HbA(1c) , blood pressure and BMI. The influence of social status on quality measures was analysed at entry and last visit by fitting linear mixed models. At the entry visit, patients with lower social status had a higher HbA(1c) compared with patients with higher status (0.06% per each point of social score difference). After a mean follow- up of 6.0 years (Type 2 diabetes) and 9.4 years (Type 1 diabetes) no significant differences in HbA(1c) could be found. However, difference in BMI (-0.41 kg/m² per each point of social score) persisted at last observation. Blood pressure was only negligibly affected by the care programme. Low social status is associated with worse quality of diabetes care at entry in a tertiary care centre. The differences in HbA(1c) disappeared after treatment and structured education, whereas the difference in BMI persisted. There was no significant influence of social status or treatment on blood pressure. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Antimicrobial resistance pattern of Neisseria gonorrhoeae isolates from peripheral health centres and STD clinic attendees of a tertiary care centre in India.

PubMed

Bala, M; Ray, K; Gupta, S M

2008-06-01

The aim of the study was to compare the antimicrobial resistance pattern of Neisseria gonorrhoeae isolates from urban and rural peripheral health centres and from sexually transmitted disease (STD) clinic attendees. Antimicrobial susceptibility testing of 191 N. gonorrhoeae isolates (165 isolates from STD clinic attendees and 26 from peripheral health centres) was carried out in Delhi, India, using the calibrated dichotomous sensitivity technique for penicillin, tetracycline, ceftriaxone, ciprofloxacin, spectinomycin and nalidixic acid, and minimum inhibitory concentrations were determined using E-test. Penicillin-resistant, ciprofloxacin-resistant, penicillinase-producing N. gonorrhoeae and tetracycline-resistant N. gonorrhoeae strains were higher in STD clinic attendees than in peripheral health centres, probably because of less antibiotic pressure in the peripheral areas. High-level resistance to ciprofloxacin and multiresistant strains were also higher in STD clinic attendees. The present study emphasizes the importance of surveillance of antimicrobial resistance of N. gonorrhoeae in different population subgroups in order to monitor the spread of multiresistant strains and to update the national treatment recommendations.

The Search for Centre

ERIC Educational Resources Information Center

Nunes, April

2006-01-01

This paper acknowledges the importance of a dancer's centre but likewise highlights the problematic nature of the communication of this concept from dance teacher to student. After a brief introduction of orthodox approaches in finding centre, this paper suggests a method of locating centre through the ancient somatic technique.

Do Independent Sector Treatment Centres (ISTC) impact on specialist registrar training in primary hip and knee arthroplasty?

PubMed

Clamp, Jonathan A; Baiju, Dean; Copas, David P; Hutchinson, James W; Rowles, John M

2008-09-01

The introduction of Modernising Medical Careers (MMC) is likely to reduce specialist registrar (SpR) operative experience during higher surgical training (HST). A further negative impact on training by local Independent Sector Treatment Centres (ISTCs) could reduce experience, and thus competence, in primary joint arthroplasty at completion of higher surgical training. Retrospective case note and radiograph analysis of patients receiving primary hip and knee arthroplasty in a teaching hospital, before and after the establishment of a local ISTC. Patients and operative details were recorded from the selected case notes. Corresponding radiographs were assessed and the severity of the disease process assessed. Fewer primary hip and knee replacements were performed by SpRs in the time period after the establishment of an ISTC. ISTCs may adversely affect SpR training in primary joint arthroplasty.

Self-referral psychological treatment centre for young adults: a 2-year observational evaluation of routine practice before and after treatment

PubMed Central

Halje, Karin; Timpka, Toomas; Tylestedt, Petra; Adler, Anna-Karin; Fröberg, Lena; Schyman, Tommy; Johansson, Kristoffer; Dahl, Katarina

2015-01-01

Objectives To examine a self-referral psychological service provided to young adults with regard to effects on anxiety, depression and psychological distress and to explore client factors predicting non-adherence and non-response. Design Observational study over a 2-year period. Setting Young Adults Centre providing psychological services by self-referral (preprimary care) to Linköping, Åtvidaberg, and Kinda municipalities (combined population 145 000) in Östergötland county, Sweden. Participants 607 young adults (16–25 years of age); 71% females (n=429). Intervention Individually scheduled cognitive behavioural therapy delivered in up to six 45 min sessions structured according to an assessment of the client's mental health problems: anxiety, depression, anxiety and depression combined, or decreased distress without specific anxiety or depression. Primary outcome measures Pre–post intervention changes in psychological distress (General Health Questionnaire-12, GHQ-12), Hospital Anxiety and Depression Scale Anxiety/Depression (HADS-A/D). Results 192 clients (32.5%) discontinued the intervention on their own initiative and 39 clients (6.6%) were referred to a psychiatric clinic during the course of the intervention. Intention-to-treat analyses including all clients showed a medium treatment effect size (d=0.64) with regard to psychological distress, and small effect sizes were observed with regard to anxiety (d=0.58) and depression (d=0.57). Restricting the analyses to clients who adhered to the agreed programme, a large effect size (d=1.26) was observed with regard to psychological distress, and medium effect sizes were observed with regard to anxiety (d=1.18) and depression (d=1.19). Lower age and a high initial HADS-A score were the strongest risk factors for non-adherence, and inability to concentrate and thinking of oneself as a worthless person increased the risk for discontinuation. Conclusions We conclude that provision of psychological

Recognising and Managing Refractory Coeliac Disease: A Tertiary Centre Experience.

PubMed

Nasr, Ikram; Nasr, Iman; Beyers, Carl; Chang, Fuju; Donnelly, Suzanne; Ciclitira, Paul J

2015-12-01

Refractory coeliac disease (RCD) is a rare complication of coeliac disease (CD) and involves malabsorption and villous atrophy despite adherence to a strict gluten-free diet (GFD) for at least 12 months in the absence of another cause. RCD is classified based on the T-cells in the intra-epithelial lymphocyte (IEL) morphology into type 1 with normal IEL and type 2 with aberrant IEL (clonal) by PCR (polymerase chain reaction) for T cell receptors (TCR) at the β/γ loci. RCD type 1 is managed with strict nutritional and pharmacological management. RCD type 2 can be complicated by ulcerative jejunitis or enteropathy associated lymphoma (EATL), the latter having a five-year mortality of 50%. Management options for RCD type 2 and response to treatment differs across centres and there have been debates over the best treatment option. Treatment options that have been used include azathioprine and steroids, methotrexate, cyclosporine, campath (an anti CD-52 monoclonal antibody), and cladribine or fluadribine with or without autologous stem cell transplantation. We present a tertiary centre's experience in the treatment of RCD type 2 where treatment with prednisolone and azathioprine was used, and our results show good response with histological recovery in 56.6% of treated individuals.

A pericentric inversion of chromosome X disrupting F8 and resulting in haemophilia A.

PubMed

Xin, Yu; Zhou, Jingyi; Ding, Qiulan; Chen, Changming; Wu, Xi; Wang, Xuefeng; Wang, Hongli; Jiang, Xiaofeng

2017-08-01

The frequency of X chromosome pericentric inversion is much less than that of autosome chromosome. We hereby characterise a pericentric inversion of X chromosome associated with severe factor VIII (FVIII) deficiency in a sporadic haemophilia A (HA) pedigree. PCR primer walking and genome walking strategies were adopted to identify the exact breakpoints of the inversion. Copy number variations (CNVs) of the F8 and the whole chromosomes were detected by AccuCopy and Affymetrix CytoScan High Definition (HD) assays, respectively. A karyotype analysis was performed by cytogenetic G banding technique. We identified a previously undescribed type of pericentric inversion of the X chromosome [inv(X)(p11.21q28)] in the proband with FVIII:C <1%. One breakpoint was located in the intron 7 of the F 8, which disrupted the transcription of the F8, and the other located in the upstream of the PFKFB1 of the X chromosome. The inversion segment was approximately 64.4% of the total chromosomal length. The karyotype analysis of the X chromosome confirmed the pericentric inversion of the X chromosome in the proband and his mother. A haplotype analysis traced the inversion to his maternal grandfather, who was not a somatic mosaic of the inversion. This finding indicated that the causative mutation may originate from his germ cells or a rare possibility of germ-cell mosaicism. The characterisation of pericentric inversion involving F8 extended the molecular mechanisms causing HA. The pericentric inversion rearrangement involves F8 by non-homologous end joining is responsible for pathogensis of severe HA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

[Frameless set-up with ExacTrac® system for stereotactic radiotherapy of brain metastasis: Descriptive study from five French centres].

PubMed

Ohnleiter, T; Mahé, M-A; Biau, J; Wdowczyk, D; Clavier, J-B; Antoni, D; Noël, G

2016-12-01

This study aimed to analyse the positioning protocols with the ExacTrac ® system, associated with a dedicated linear accelerator such as Novalis ® , for stereotactic treatment of brain metastases in several French centres. A survey, including three questions about the prescription of irradiation and twenty-one questions about how the ExacTrac ® system is used, was sent to nine French centres owning a dedicated Novalis ® accelerator. Five centres have accepted to participate in the study. All centres checked the positioning before each treatment's bow, with residual mismatch tolerances of 0.5 to 0.7mm for the translations and 0.5 to 1° for the rotations. All centres except one also realised orthogonal planar images of classic incidences to help operators ensure proper isocentre positioning. Prescribed doses were 20Gy in one fraction, 30Gy and 33Gy in three fractions or 34Gy in four fractions, mainly depending on the size of the lesion. Finally, a physician validated the images at the treatment station before starting the irradiation. The practices of the different centres concerning the positioning protocols were rather homogeneous, in agreement with the literature data on ExacTrac ® system's accuracy, as well as proposed fractionations. The systematic medical validation at the treatment station may, however, be questioned because of the waiting time between the doctor's call and validation itself and because of its usefulness; indeed, corrections by the radiation oncologist are very rare and in some centres, non-existent. Copyright © 2016. Published by Elsevier SAS.

Treatment referral system for tuberculosis patients in Dhaka, Bangladesh

PubMed Central

Hirayama, T.; Islam, A.; Ishikawa, N.; Afsana, K.

2015-01-01

Objective: To evaluate the referral system in an urban DOTS-based programme in Dhaka, Bangladesh, including the peri-urban area, and to identify opportunities to strengthen the system. Design: This was a retrospective cohort study in which diagnosed tuberculosis (TB) patients and health providers from DOTS centres were interviewed. Research tools included pre-tested structured questionnaires and the TB patients' referral records. Results: Of 4974 TB patients who were referred to the different treatment centres, only 1756 (35%) of the counterfoils of the referral slips were returned. Of 250 patients randomly selected for interview, 165 reported to a DOTS centre, 69 did not and 16 could not be traced. Variations in educational qualification, residence and the identification of DOTS centres after counselling were statistically significant (P < 0.05). Lower monthly income (RR = 7.84, RR = 5.03), distance from the centre (RR = 36.21) and those receiving treatment from pharmacies (RR = 3) or non-governmental organisations (RR = 28.48) have more risk of irregular treatment. Conclusion: A high proportion of referred patients were registered and initiated treatment, but many did not report to the referral treatment centre. Proper counselling and taking into account the patients' preferences during referral are essential to address access barriers to treatment adherence and improved treatment outcome. PMID:26767176

The benefits of exercise for patients with haemophilia and recommendations for safe and effective physical activity.

PubMed

Negrier, C; Seuser, A; Forsyth, A; Lobet, S; Llinas, A; Rosas, M; Heijnen, L

2013-07-01

Most health care professionals involved in the management of people with haemophilia (PWH) believe that exercise is beneficial and its practice is widely encouraged. This article aims to demonstrate that appropriate exercise (adapted to the special needs of the individual PWH) may be beneficial for all PWH through improved physical, psychosocial and medical status. Based on evidence gathered from the literature, many PWH, particularly those using long-term prophylaxis or exhibiting a mild/moderate bleeding phenotype, are as active as their healthy peers. PWH experience the same benefits of exercise as the general population, being physically healthier than if sedentary and enjoying a higher quality of life (QoL) through social inclusion and higher self-esteem. PWH can also gain physically from increased muscle strength, joint health, balance and flexibility achieved through physiotherapy, physical activity, exercise and sport. Conversely, very little data exist on activity levels of PWH in countries with limited resources. However, regarding specific exercise recommendations in PWH, there is a lack of randomized clinical trials, and consequently formal, evidence-based guidelines have not been produced. Based on published evidence from this review of the literature, together with the clinical experience of the authors, a series of recommendations for the safe participation of PWH in regular physical activities, exercises and sport are now proposed. In summary, we believe that appropriately modified programmes can potentially allow all PWH to experience the physical and psychosocial benefits of being physically active which may ultimately lead to an improved QoL. © 2013 John Wiley & Sons Ltd.

Decentralisation of directly observed treatment in a large African city: evaluation of the experience of Djibouti.

PubMed

Bernatas, J J; Ali, I M; Ismaël, H A; Matan, A B; Aboubakar, I H

2003-08-01

Decentralisation of directly observed treatment (DOT) for tuberculosis patients in three public centres in Djibouti city from April 2000. To evaluate decentralisation based on the success rate by site of treatment and according to certain critical variables. Comparative evaluation of the success rate of smear-positive patients followed in all treatment centres from 1 May 2000 to 31 March 2001. The success rate was 58% for the main centre, Centre Paul Faure, and 81% for all the peripheral centres together (P < 10.6). It was 80% for the three new centres and 85% for the established centres (P > 0.05). Age under 20 years, female sex and treatment centre were factors linked to success. After stratification, sex was shown to be the confounding variable. Multivariate analysis shows that non-Djibouti nationality is related to treatment success (P = 0.02). In the groups of established and new centres, there is an inverse linear relationship between success rate and workload, with greater capacity in the established centres. Urban decentralisation of DOT increases the chances of treatment success among smear-positive patients. Another centre for supervised treatment needs to be created in one of the public health centres in Djibouti city.

Relapse to opioid use in opioid-dependent individuals released from compulsory drug detention centres compared with those from voluntary methadone treatment centres in Malaysia: a two-arm, prospective observational study

PubMed Central

Wegman, Martin P; Altice, Frederick L; Kaur, Sangeeth; Rajandaran, Vanesa; Osornprasop, Sutayut; Wilson, David; Wilson, David P; Kamarulzaman, Adeeba

2017-01-01

Summary Background Detention of people who use drugs into compulsory drug detention centres (CDDCs) is common throughout East and Southeast Asia. Evidence-based pharmacological therapies for treating substance use disorders, such as opioid agonist treatments with methadone, are generally unavailable in these settings. We used a unique opportunity where CDDCs coexisted with voluntary drug treatment centres (VTCs) providing methadone in Malaysia to compare the timing and occurrence of opioid relapse (measured using urine drug testing) in individuals transitioning from CDDCs versus methadone maintenance in VTCs. Methods We did a parallel, two-arm, prospective observational study of opioid-dependent individuals aged 18 years and older who were treated in Malaysia in the Klang Valley in two settings: CDDCs and VTCs. We used sequential sampling to recruit individuals. Assessed individuals in CDDCs were required to participate in services such as counselling sessions and manual labour. Assessed individuals in VTCs could voluntarily access many of the components available in CDDCs, in addition to methadone therapy. We undertook urinary drug tests and behavioural interviews to assess individuals at baseline and at 1, 3, 6, 9, and 12 months post-release. The primary outcome was time to opioid relapse post-release in the community confirmed by urinary drug testing in individuals who had undergone baseline interviewing and at least one urine drug test (our analytic sample). Relapse rates between the groups were compared using time-to-event methods. This study is registered at ClinicalTrials.gov (NCT02698098). Findings Between July 17, 2012, and August 21, 2014, we screened 168 CDDC attendees and 113 VTC inpatients; of these, 89 from CDDCs and 95 from VTCs were included in our analytic sample. The baseline characteristics of the two groups were similar. In unadjusted analyses, CDDC participants had significantly more rapid relapse to opioid use post-release compared with VTC

Epidemiological data and costs of burn injuries in workers in Switzerland: an argument for immediate treatment in burn centres.

PubMed

de Roche, R; Lüscher, N J; Debrunner, H U; Fischer, R

1994-02-01

A complete statistical evaluation of epidemiological data and costs of burn injuries in 1984 with a follow-up for 5 years is presented, considering a collective of 1.77 million workers in Switzerland. The majority of burns are minor injuries; only about 5 per cent of the burn victims are admitted to a hospital, 0.2 per cent died. Burn injuries at work are rare, mainly owing to strict safety measures. Only one-fifth of the costs caused by burns are due to medical treatment. All other expenses result from continuation of payments of salaries and annuities. The treatment of the few severely burned patients in burn units produces effective costs which are higher than the tariff paid by the insurance. Even so, the predominant portion of the enormous costs is taken up by wages while off work and annuities. As our conclusion we stress the importance of primary care for all severe burns including all burns of the hands in a specialized centre. Any economic effort for primary burn treatment, however high it may be, is justified if the duration of rehabilitation and invalidity can be reduced.

Politics, policy and payment--facilitators or barriers to person-centred rehabilitation?

PubMed

Turner-Stokes, Lynne

This paper explores the tensions between politics and payment in providing affordable services that satisfy the public demand for patient-centred care. The two main approaches taken by the UK Government to curtail the spiralling costs of healthcare have been to focus development in priority areas and to cap spending through the introduction of a fixed-tariff episode-based funding system. The National Service Framework for Long Term Neurological Conditions embraces many laudable principles of person-centred management, but the 'one-size-fits all' approach to reimbursement potentially cuts right across these. A series of tools have been developed to determine complexity of rehabilitation needs that will support the development of banded tariffs. A practical approach is also offered to demonstrate the cost-efficiency of rehabilitation services for people with complex needs, and help to ensure that they are not excluded from treatment because of their higher treatment costs. Whilst responding to public demand for person-centred care, we must recognize the current financial pressure on healthcare systems. Clinicians will have greater credibility if they routinely collect and share outcomes that demonstrate the economic benefits of intervention, as well the impact on health, function and quality of life.