ABSTRACT
INTRODUCTION: Contemporary haemophilia care demands Patient-Reported Outcomes. SO-FIT is a UK multi-centre study, assessing self-reported function, health-related quality of life (HRQoL) and joint health in boys with severe haemophilia. METHODS: Subjective physical function (PedHAL, HEP-Test-Q) and HRQoL (Haemo-QoL Short Form [SF]) were assessed alongside joint health using the objective Haemophilia Joint Health Score (HJHS v2.1). Demographic and clinical data were collected. RESULTS: Data from 127 boys mean age 12.38 ± 2.5 (range 8-17) treated at 16 sites were analysed. One-hundred-and-thirteen had haemophilia A, 25/9 past/current inhibitor, 124 were treated prophylactically (46.8% primary) and three on-demand. In the preceding 6 months, boys reported median 0 joint bleeds (range 0-8) with a median HJHS score of 1 (range 0-30). Boys reported good physical functioning; HEP-Test-Q (M = 80.32 ± 16.1) showed the highest impairments in the domain "endurance" (72.53 ± 19.1), in PedHAL (M = 85.44 ± 18.9) highest impairments were in the domains "leisure activities & sports" (M = 82.43 ± 23.4) and "lying/sitting/kneeling/standing" (M = 83.22 ± 20.3). Boys reported generally good HRQoL in Haemo-QoL SF SF (M = 22.81 ± 15.0) with highest impairments in the domains "friends" (M = 28.81 ± 30.5) and "sports & school" (M = 26.14 ± 25.1). HJHS revealed low correlations with the Haemo-QoL SF (r = .251, P < .006), the PedHAL (r = -.397, P < .0001) and the HEP-Test-Q (r = -.323, P < .0001). A moderate correlation was seen between HEP-Test-Q and Haemo-QoL SF of r = -.575 (P < .0001) and between PedHAL and Haemo-QoL SFr = -.561 (P < .0001) implying that good perceived physical function is related to good HRQoL. CONCLUSIONS: The SO-FIT study has demonstrated that children with severe haemophilia in the UK report good HRQoL and have good joint health as reflected in low HJHS scores.
Subject(s)
Health Status , Health Surveys/statistics & numerical data , Hemophilia A/physiopathology , Hemorrhage/physiopathology , Quality of Life , Adolescent , Child , Health Surveys/methods , Hemophilia A/drug therapy , Hemorrhage/prevention & control , Humans , Joints/physiopathology , Male , Self Report , United KingdomABSTRACT
INTRODUCTION: 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. AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Subject(s)
Gait/genetics , Hemophilia A/complications , Child , Hemophilia A/physiopathology , Humans , Male , Muscle Strength/physiology , Muscle, Skeletal/physiologyABSTRACT
INTRODUCTION: Intracranial haemorrhage (ICH) is the most serious bleeding event for patients with inherited bleeding disorders (IBD). The risks and long-term consequences remain unknown. AIM: This single-centre service evaluation aimed to identify the incidence, risks and long-term outcomes following ICH in patients with IBD. METHODS: The IBD database and medical notes between 1987 and 2013 were reviewed. Children without apparent neurological deficit following ICH completed standardized assessments and supplementary information sheets. RESULTS: ICH was confirmed in 38/1111 children with IBD. The overall risk of ICH amongst children with IBD was 3.4% (95% CI: 2.5, 4.7%). However, 27/38 had an ICH in the first year of life, 18 of which were in the neonatal period. In children with IBD who had an ICH, the risks of ICH in the neonatal period or first year of life were 18/38 (47%) (95% CI: 32, 63%) and 27/38 (71%) (95% CI: 55, 83%) respectively. Mortality risk from ICH in children with an IBD was 5/38 (13%) (95% CI: 5.8, 27.3 %). Ten of 32 survivors had known neurological sequelae including motor disorder deficits (MDD) while 22 had no documented evidence of neurological impairment or MDD. Re-evaluation was possible in 17/22 children, 8 of whom demonstrated evidence of MDD. After re-evaluation, the risk of significant neurological MDD from ICH increased from 31% CI (95% CI: 18, 49%) to 56% CI (95% CI: 39, 72%). CONCLUSION: Risks and consequences of ICH in IBD were highest within the neonatal period and first year of life. MDD after ICH was not reliably identified in early life and ongoing monitoring in the first decade of life will facilitate educational support or physical rehabilitation.
Subject(s)
Blood Coagulation Disorders, Inherited/complications , Intracranial Hemorrhages/etiology , Adolescent , Blood Coagulation Disorders, Inherited/pathology , Child , Child, Preschool , Databases, Factual , Humans , Incidence , Intracranial Hemorrhages/epidemiology , Retrospective Studies , Risk Factors , Surveys and Questionnaires , Young AdultABSTRACT
INTRODUCTION: Haemophilia Joint Health Score (HJHS) is the most sensitive validated score for physical examination of joint health in haemophilia. HJHS performed at regular intervals can be used for clinical monitoring as well as for comparative outcomes research. AIM: To determine whether routinely collected HJHS could be used to compare outcome of three different prophylactic regimens in children with severe haemophilia A (primary) and which parameters caused variability in HJHS (secondary). METHODS: International retrospective observational multi-centre study comparing routine HJHS in 127 children with severe haemophilia A born from 1995 to 2009, from London, Stockholm and Utrecht centres. Patient and treatment data were collected from the European Paediatric Network for Haemophilia Management registry and patient files. The independent effects of regimens, physiotherapists, age and inhibitor status on HJHS were explored, using multivariable regression analysis. RESULTS: Prophylaxis varied across participating centres, with differences in initial frequency of infusions (1× per week vs. 3× per week), age at reaching infusions ≥3× per week, and dose kg(-1) week(-1) at HJHS assessment. Evaluation at median age of 11 years showed an illogical association of HJHS with treatment regimen: the least intensive regimen had the lowest HJHS. The HJHS increased with age and history of inhibitor, as expected (internal validity). But the comparison of prophylactic regimens was obscured by systematic differences in assessment between physiotherapists, both within and between centres. CONCLUSION: Inter-physiotherapist discrepancies in routine HJHS hamper comparison of scores between treatment regimens. For multi-centre research, additional inter-observer standardization for HJHS scoring is needed.
Subject(s)
Hemophilia A/diagnosis , Internationality , Joints , Physical Examination/standards , Adolescent , Child , Hemophilia A/drug therapy , Humans , Reference Standards , Retrospective StudiesABSTRACT
Joint damage from bleeding episodes leads to physical or functional limitations in people with haemophilia. Various factors may influence the frequency and severity of joint damage. This study examined whether age, prophylaxis, history of high-titre inhibitors (HTI) and bleeding events influenced the Haemophilia Joint Health Score (HJHS) in children. Medical and physiotherapy notes of boys with severe haemophilia, aged 4-18 years, were reviewed to identify factors associated with increased HJHS. The HJHS of 83 boys (median age: 11) ranged from 0 to 25, with 44/83 (53%) having a score of zero. The median HJHS was 0 (mean 2.6). In the non-HTI group, the HJHS for boys on late prophylaxis was 2.68 times higher than those who started early and the HJHS was on average 10% higher for every additional recent bleed. In this group the odds of having a zero score fell by 30% for every year increase in age. Boys with a history of HTI had higher HJHS scores than the non-HTI group, and age, number of recent bleeds and tolerized status were positively associated with HJHS. The score rose on average by 28% for every year of age and by 76% for non-tolerized boys. This study provides further evidence supporting early prophylaxis use and the importance of immune tolerance therapy. The HJHS is a useful tool for identifying and tracking changes in joint health with respect to therapy or disease progression. With improvements in haemophilia treatment, the disproportionate number of zero scores will continue to make interpretation of the HJHS challenging.
Subject(s)
Hemophilia A/pathology , Joints/pathology , Adolescent , Age Distribution , Child , Child, Preschool , Hemorrhage/pathology , Humans , Logistic Models , Male , Risk FactorsABSTRACT
Treatment studies in haemophilia focus on joint bleeds; however, some 10-25% of bleeds occur in muscles. This review addresses management of muscle haematoma in severe haemophilia, defines gaps in the published evidence, and presents a combined clinician and physiotherapist perspective of treatment modalities. The following grade 2C recommendations were synthesized: (i) Sport and activity should be based on individual factor levels, bleeding history and physical characteristics, (ii) Musculoskeletal review aids the management of children and adults, (iii) 'Time to full recovery' should be realistic and based on known timelines from the healthy population, (iv) Diagnosis should be carried out by both a clinician and physiotherapist, (v) Severe muscle bleeds should be treated similarly to surgical patients: a 50% trough for 10-14 days followed by high-level prophylaxis, (vi) Protection, rest, ice, compression and elevation should be implemented in the acute stage, and (vii) Physiotherapy and rehabilitation should be divided into: control of haemorrhage (phase 1); restoration of Range of Movement (ROM) and strength (phase 2); functional rehabilitation and return to normal living (phase 3). Recommendations specifically for inhibitor patients include: (i) Minor to moderate bleeds should be managed by home-treatment within 1 h of bleed onset using either one injection of rFVIIa 270 µg kg(-1), or two to three injections of rFVIIa 90 µg kg(-1) (2-3 h intervals), or FEIBA 50-100 U kg(-1) (repeated at 12-hourly intervals, if necessary) and (ii) Severe muscle bleeds should be supervised by the treatment centre and include bypassing agents until clinical improvement is observed.
Subject(s)
Hematoma/rehabilitation , Hemophilia A/complications , Hemophilia B/complications , Muscular Diseases/rehabilitation , Athletic Injuries/etiology , Athletic Injuries/rehabilitation , Blood Coagulation Factors/therapeutic use , Coagulants/therapeutic use , Evidence-Based Medicine , Hematoma/drug therapy , Hematoma/etiology , Hematoma/prevention & control , Hemophilia A/drug therapy , Hemophilia B/drug therapy , Humans , Muscular Diseases/drug therapy , Muscular Diseases/etiology , Muscular Diseases/prevention & control , Physical Therapy ModalitiesABSTRACT
Intracranial haemorrhages (ICH) in children with haemophilia are rare, and the outcome is variable, ranging from no apparent impairment to death. The aim of this investigation was to identify if children with haemophilia and ICH, have any long-term problems with motor function, visual motor integration or strengths and difficulties compared with a control group. A review of the Haemophilia Database at Great Ormond Street Hospital for Children NHS Trust was undertaken to identify boys with haemophilia and a history of ICH, as well as a control group of peers with no such history. Boys were born between January 1994 and December 2002. All boys were assessed using the movement Assessment Battery for Children, the Developmental Test of Visual Motor Integration and The Strengths and Difficulties Questionnaire as standardized assessments of motor competence, visual motor integration and behavioural difficulties. Six boys with haemophilia and ICH and 11 controls (mean age: 7 years; range: 4-12 years) were assessed. Children with ICH were significantly more likely to have problems with motor function and visual motor integration (Fisher's exact: P < 0.05). In addition, they had a tendency towards more problems with strengths and difficulties than their peer group (Fisher's exact: P = 0.06). Five of the six boys who had sustained an ICH were in mainstream schools; four requiring assistance with their education. The results of this small study suggest that ICH may signify long-term consequences for boys with haemophilia. The multidisciplinary team need to be aware of the rare but potentially important impact on motor function, visual motor integration and behaviour, which may inhibit the child from functioning optimally. An agreed comprehensive battery of assessments in collaboration with schools and healthcare workers is required to identify impairments to enable prompt interventions to be co-ordinated.
Subject(s)
Hemophilia A/complications , Hemophilia B/complications , Intracranial Hemorrhages/etiology , Child , Child, Preschool , Developmental Disabilities/etiology , Education, Special , Form Perception , Hemophilia A/psychology , Hemophilia B/psychology , Humans , Intracranial Hemorrhages/psychology , Male , Motor Skills Disorders/etiology , Psychomotor Disorders/etiologyABSTRACT
Development of haemophilic arthropathy has long-term implications for functional mobility in people with haemophilia, but early manifestations are often asymptomatic and difficult to identify. Earlier identification of joint damage may improve outcomes. The aim of this case note review was to determine whether the GAITRite system (electronic pressure sensitive walkway) could identify early changes in gait patterns in boys with haemophilia compared with their peers. Clinic data from medical and physiotherapy notes of boys with severe haemophilia were compared with data from age and leg length-matched controls. Data from two consecutive walks at preferred speed were collected on all participants using the GAITRite system. Clinic assessment notes from 26 boys (aged 7-17 years) with severe haemophilia were identified. Of these, 20 boys had no evidence of joint pathology on assessment and six boys had radiographic evidence of arthropathy. When these data were compared with normal controls, there were statistically significant increases in swing time, stance time, single support and double support in the asymptomatic group (P < 0.01) suggesting subtle early compensatory changes in gait pattern. The children with arthropathy had additional significant differences in their gait compared with matched controls. These differences included normalized velocity, step length, stride length, step time and base of support (P < 0.01). The GAITRite system appears sensitive enough to identify early subtle changes in gait and differentiate between asymptomatic boys with haemophilia and those with arthropathy in comparison with a matched control group. The electronic walkway is an accessible and portable means of providing quantitative gait analysis in the clinical environment. This is an important finding as early identification of gait changes may provide clinicians with the opportunity to intervene with the aim of arresting progression of joint damage.
Subject(s)
Diagnosis, Computer-Assisted/instrumentation , Gait/physiology , Hemophilia A/physiopathology , Joint Diseases/etiology , Adolescent , Analysis of Variance , Child , Diagnosis, Computer-Assisted/methods , Hemophilia A/diagnosis , Humans , Joint Diseases/physiopathology , Male , Outcome Assessment, Health Care , Reproducibility of Results , Research Design , Sensitivity and SpecificityABSTRACT
AIMS: To assess the outcome of outpatient multidisciplinary rehabilitative treatment (graded activities/exercise programme, family sessions, and supportive care) compared with supportive care alone for children and adolescents with chronic fatigue syndrome (CFS/ME). METHODS: Fifty six young people (aged 9-17 years) with CFS/ME by standard criteria were followed up for 3-24 months. All subjects received supportive care. Families additionally opted to either enter the rehabilitation programme (supportive care plus graded activities/exercise programme and family sessions) or have no additional treatment. RESULTS: Twenty two (39%) subjects had supportive care alone and 26 (46%) entered the programme. Treatment groups were comparable at baseline in terms of age, severity and duration of illness, Wellness score, and school attendance. At end of follow up, those in the programme group had significantly higher Wellness score and school attendance than those having supportive care alone. The programme significantly reduced the overall severity of illness: after the programme, 43% had complete resolution of CFS/ME compared to only 4.5% of those having supportive care alone. The presence of depressed mood and family beliefs about the aetiology of CFS/ME were not significantly associated with outcomes. CONCLUSIONS: Outpatient rehabilitative treatment offers significant potential to improve the prognosis of CFS/ME in childhood and adolescence.
Subject(s)
Ambulatory Care/methods , Fatigue Syndrome, Chronic/rehabilitation , Adolescent , Child , Exercise Therapy/methods , Family , Female , Home Nursing/methods , Humans , Male , Patient Care Team , Schools , Severity of Illness Index , Treatment OutcomeABSTRACT
Methylation of a critical carboxyl group in guinea-pig left atrium with trimethoxonium ion leads to loss of excitability. The critical group(s) could be protected with a number of cationic drugs, so that on washout of the protecting drug and reaction products full excitability returned. Tetrodotoxin, edrophonium, cholinergic agonists and amantadine protected the preparation. During the recovery period readmission of these drugs led to the same pharmacological response as during the control period, suggesting protection of specific site(s). This thesis was confirmed in crossover experiments, in which the atrium was exposed to the methylating agent in the presence of one protecting drug, then exposed to another during recovery. The expected pharmacological responses were obtained. Assay of muscarinic receptors with [3H]-quinuclidinyl benzilate after methylation without protection or in the presence of tetrodotoxin or acetylcholine suggested that these receptors are not involved in the maintenance of excitability. It is postulated that the Na+ channel and the K+ channel are located in the same macromolecular membrane complex, and that the K+ channel has a cholinoreceptive sub-site.
Subject(s)
Heart/physiology , Ion Channels/physiology , Sodium/metabolism , Acetylcholine/pharmacology , Amantadine/pharmacology , Animals , Atrial Function , Guinea Pigs , Heart Atria/drug effects , In Vitro Techniques , Ion Channels/drug effects , Membrane Potentials/drug effects , Methylation , Microelectrodes , Tetrodotoxin/pharmacologyABSTRACT
The kinetic behaviour of three forms of acetylcholinesterase as a function of ionic strength of the medium was investigated. The forms of enzyme were that bound to human erythrocyte membranes, acetylcholinesterase solubilized from these by Triton X-100, and a commercial preparation of the enzyme from bovine erythrocytes. The properties investigated were hydrolysis of the substrate acetylthiocholine, decarbamylation of dimethylcarbamyl-acetylcholinesterase and ageing of isopropylmethylphosphonyl-acetylcholinesterase. The effect of 10(?5) M gallamine triethiodide on these properties was also examined as a function of ionic strength. Detailed results for the variation of kinetic behaviour with ionic strength and the presence of gallamine are presented. No unified theory to predict the influence of these variables on all three forms of the enzyme could be formulated. Thus, the enzyme conformation stabilized by gallamine at low ionic strength was not necessarily similar to that of the gallamine-free enzyme at physiological ionic strength. Nor was it useful to consider the free enzyme at low ionic strength to be a model of the membrane-bound enzyme in vivo (Crone, 1973). It was concluded that kinetic results for solubilized and partially or wholly purified acetylcholinesterase cannot be extrapolated to the membrane-bound enzyme. Prediction of the effect of drugs on the system in vivo requires the use of the membrane-bound enzyme.