Can motor proficiency testing predict sports injuries and sports-induced bleeds in people with haemophilia?

INTRODUCTION: Predicting the risk of sports injuries and sports-induced bleeds (SIBs) in people with haemophilia (PWH) may support clinical counselling. AIM: To assess the association between motor proficiency testing and sports injuries and SIBs and to identify a specific set of tests for predicting injury risk in PWH. METHODS: In a single centre, prospective study male PWH aged 6-49 playing sports ≥1x/week were tested for running speed and agility, balance, strength and endurance. Test results below -2Z were considered poor. Sports injuries and SIBs were collected for 12 months while 7 days of physical activity (PA) for each season was registered with accelerometers. Injury risk was analysed according to test results and type of physical activity (%time walking, cycling, running). Predictive values for sports injuries and SIBs were determined. RESULTS: Data from 125 PWH (mean [± SD] age: 25 [± 12], 90% haemophilia A; 48% severe, 95% on prophylaxis, median factor level: 2.5 [IQR 0-15]IU/dl) were included. Few participants (n = 19, 15%) had poor scores. Eighty-seven sports injuries and 26 SIBs were reported. Poor scoring participants reported 11/87 sports injuries and 5/26 SIBs. The current tests were poor predictors of sports injuries (Range PPV: 0%-40%), or SIBs (PPV: 0%-20%). PA type was not associated with season (activity seasonal p values > .20) and type of PA was not associated with sports injuries or SIBs (Spearman's rho < .15). CONCLUSION: These motor proficiency- and endurance tests were unable to predict sports injuries or SIBs in PWH, potentially due to few PWH with poor results and low numbers of sports injuries and SIBs.

Clotting factor activity levels and bleeding risk in people with haemophilia playing sports.

BACKGROUND: Improved treatment options for people with haemophilia (PWH) have increased the possibilities for sports participation, but the risk of sports-induced bleeding (SIB) is still considered considerable by many. AIM: To assess sports associated injury- and bleeding risk in PWH and to assess clotting levels associated with safe sports participation. METHODS: Sports injuries and SIBs were prospectively collected for 12 months in PWH aged 6-49 without inhibitors playing sports at least once weekly. Injuries were compared according to factor levels, severity, joint health, sports risk category and sports intensity. Factor activity at the time of injury was estimated using a pharmacokinetic model. RESULTS: 125 participants aged 6-49 (41 children, 90% haemophilia A; 48% severe, 95% severe on prophylaxis) were included. Sports injuries were reported by 51 participants (41%). Most participants (62%) reported no bleeds at all and only 16% reported SIBs. SIBs were associated with factor levels at time of injury (OR: 0.93/%factor level (CI 0.88-0.99); p = .02), but not with haemophilia severity (OR: 0.62 (CI 0.20-1.89); p = .40), joint health, sports risk category or sports intensity. PWH with factor levels <10% during sports injury had a bleeding risk of 41% versus 20% in those with higher (>10%) factor levels. CONCLUSION: The results of this study emphasize the importance of clotting factor levels in prevention of bleeds. This information is vital for patient counselling and tailoring prophylactic treatment with clotting factors and non-replacement therapy.

Validation of the pedHALshort and HALshort in Dutch children and adults with haemophilia.

INTRODUCTION: The Haemophilia Activities List (HAL) and paediatric HAL assess self-reported limitations in various daily activities. To reduce patient burden, shorter versions of the pedHAL (22 items) and HAL (18 items) have been developed. AIM: This study aimed to determine the agreement between the pedHAL/HALfull and pedHAL/HALshort and construct validity and internal consistency of the pedHAL/ HALshort in persons with haemophilia (PWH). METHODS: A cross-sectional secondary analysis of the Hemophilia in the Netherlands-6 national survey was performed. Adult and paediatric PWH completed the original pedHAL/HALfull , from which pedHAL/ HALshort were derived. Score differences between the original and short versions were calculated. Construct validity was studied by testing hypotheses regarding the relationship of the pedHAL/HALshort with the pedHAL/HALfull , Haemophilia & Exercise Project Test-Questionnaire (HEP-Test-Q), Canadian Haemophilia Outcomes-Kids' Life Assessment Tool (CHO-KLAT) and RAND 36-item Health Survey (RAND-36) (convergent/discriminant validity) as well as its ability to discriminate between subgroups (known-group validity). Internal consistency was assessed with Cronbach's α. RESULTS: We included 113 children (median 10y [range 4-17], 53% severe haemophilia) and 691 adults (median 51y [range 18-88], 35% severe). Scores of the pedHAL/HALfull and pedHAL/HALshort were similar with high correlations (>0.9). Construct validity was confirmed for the pedHAL/HALshort . The HALshort was able to discriminate between different disease severities and ages. Cronbach's α of the pedHAL/HALshort was 0.95-0.97. CONCLUSION: This study confirmed the agreement between the pedHAL/HALfull and the pedHAL/HALshort and the construct validity of the pedHAL/HALshort . The next step is to study construct validity of the pedHAL/HALshort when administered as short forms.

Early motor outcomes in infants with critical congenital heart disease are related to neonatal brain development and brain injury.

AIM: To assess the relationship between neonatal brain development and injury with early motor outcomes in infants with critical congenital heart disease (CCHD). METHOD: Neonatal brain magnetic resonance imaging was performed after open-heart surgery with cardiopulmonary bypass. Cortical grey matter (CGM), unmyelinated white matter, and cerebellar volumes, as well as white matter motor tract fractional anisotropy and mean diffusivity were assessed. White matter injury (WMI) and arterial ischaemic stroke (AIS) with corticospinal tract (CST) involvement were scored. Associations with motor outcomes at 3, 9, and 18 months were corrected for repeated cardiac surgery. RESULTS: Fifty-one infants (31 males, 20 females) were included prospectively. Median age at neonatal surgery and postoperative brain magnetic resonance imaging was 7 days (interquartile range [IQR] 5-11d) and 15 days (IQR 12-21d) respectively. Smaller CGM and cerebellar volumes were associated with lower fine motor scores at 9 months (CGM regression coefficient=0.51, 95% confidence interval [CI]=0.15-0.86; cerebellum regression coefficient=3.08, 95% CI=1.07-5.09) and 18 months (cerebellum regression coefficient=2.08, 95% CI=0.47-5.12). The fractional anisotropy and mean diffusivity of white matter motor tracts were not related with motor scores. WMI was related to lower gross motor scores at 9 months (mean difference -0.8SD, 95% CI=-1.5 to -0.2). AIS with CST involvement increased the risk of gross motor problems and muscle tone abnormalities. Cerebral palsy (n=3) was preceded by severe ischaemic brain injury. INTERPRETATION: Neonatal brain development and injury are associated with fewer favourable early motor outcomes in infants with CCHD.

Assessing the test-retest reliability and smallest detectable change of the Haemophilia Activities List.

INTRODUCTION: The Haemophilia Activities List (HAL) is a preferred instrument to measure self-reported limitations in activities in persons with haemophilia (PWH). Information on reliability and interpretability of HAL scores is lacking. AIM: To examine the test-retest reliability and smallest detectable change (SDC) of the HAL in adult PWH. METHODS: Fifty adult (≥18 years) persons with mild to severe haemophilia completed the HAL (42 items, 7 domains, optimum 100) at baseline (T0) and 3-4 weeks later (T1). The intraclass correlation coefficient (ICC) and SDC were calculated for sum and component scores. RESULTS: Fifty persons with haemophilia were included (median age 49 years; 92% haemophilia A; 70% severe haemophilia). The median (interquartile ranges) HAL sum score was 77 (62 to 99) at T0 and 81 (64 to 98) at T1. Reliability was good with ICCs for sum and component scores >0.9. The SDC for the sum score was 10.2, for the upper extremity component score 9.2, for the basic lower extremity component score 16.7 and for the complex lower extremity component score 13.4. CONCLUSION: The HAL has a good reliability for the sum and component scores. Score changes of the normalized sum HAL score greater than the SDC 10.2 indicate that the change was not a result of measurement error.

Shortening the Haemophilia Activities List (HAL) from 42 items to 18 items.

INTRODUCTION: The Haemophilia Activities List (HAL) was developed to measure activities and participation in persons with haemophilia (PWH). Shortening the questionnaire may facilitate use of the HAL. AIM: The aim of this study was to determine which items of the HAL are redundant, to construct a shorter version of the HAL, and to determine the construct validity of the HALshort . METHODS: A secondary analysis was performed on pooled data of two published studies using the HAL (seven domains, 42 items, optimum score: 100) in adults with haemophilia A/B. Data were divided into a derivation (62%) and a validation set (38%). Redundant items were identified by evaluation of: floor and ceiling effects, proportions of missing and 'not applicable' responses, inter-item correlations, component loadings in an exploratory factor analysis, internal consistency, and item-total correlations. Correlations with the SF-36 and EQ-5D-5L were used to determine construct validity of the HALshort . RESULTS: Data on 680 PWH were evaluated. In the derivation dataset (n = 420), median age was 30 years (range 18-80), 43% had severe haemophilia and 61% received prophylaxis. Median (IQR) HAL sum score was 65.0 (55.7-88.8). The stepwise procedure resulted in a HALshort of 18 items with a median sum score of 63.3 (54.4-86.7). Construct validity was similar for the HAL and HALshort in the validation dataset (n = 260). CONCLUSION: This clinimetric study resulted in a >50% shortening of the HAL. The 18-item HALshort reduces patient burden and is expected to capture the information on activities and participation. The HALshort needs further validation.

Shortening the paediatric Haemophilia Activities List (pedHAL) based on pooled data from international studies.

INTRODUCTION: The paediatric Haemophilia Activities List (pedHAL) was developed to measure activities and participation in children and youth with haemophilia. Results from international studies provide an opportunity to determine which items are universally important. AIM: The aim of this study was to determine which items of the pedHAL are redundant to construct a shorter version of the pedHAL. METHODS: This study is a cross-sectional multicentre secondary analysis on pooled data of published studies using the pedHAL (7 domains, 53 items, optimum score: 100) in children with haemophilia A/B aged 4-18 years. To identify redundant items, the following aspects were evaluated: floor and ceiling effects, proportions of missing and 'not applicable' responses, inter-item correlations, component loadings in an exploratory factor analysis, internal consistency and item-total correlations. RESULTS: Data on 315 patients with haemophilia from 6 studies were evaluated. Median age was 12.2 years) (range 4.0-18.0), 87.3% had severe haemophilia and 80.3% received prophylaxis. Median (IQR) pedHAL sum score was 96.7 (88.0-100). After a stepwise procedure, 31 items were removed, resulting in a pedHALshort of 22 items, representing all original 7 domains. Most remaining items belonged to the domains 'sitting/kneeling/standing' and 'functions of the legs'. The pedHALshort sum score was similar to the original pedHAL sum score, with small differences in 5 domains. CONCLUSION: This clinimetric study resulted in >50% reduction of the length of the pedHAL. The 22-item pedHALshort reduces patient burden and is expected to capture the information on activities and participation. The pedHALshort needs validation in other populations.

Similar sports participation as the general population in Dutch persons with haemophilia; results from a nationwide study.

INTRODUCTION: Although sports participation is advocated in people with haemophilia (PWH), detailed data concerning sports participation in Dutch PWH is lacking. AIM: to assess sports participation in Dutch PWH (6-65 years) compared to the Dutch general population (GP). METHODS: Data from a nationwide, cross-sectional study in PWH were analysed. Sports participation (type, duration, frequency) was assessed by the Modifiable Activities Questionnaire (MAQ), limitations in activities using the (Paediatric) Haemophilia Activities List ((Ped)HAL). Sports in the two highest categories according to the National Hemophilia Foundation classification were considered high-risk sports. Groups were compared using Chi-square testing. RESULTS: A total of 524 Adult PWH (median age: 45 (IQR: 30-55); 37% severe) and 126 paediatric PWH (median age: 11 (IQR: 8-14); 52% severe) were included. Sports participation was higher in adults (70%) than the GP (58%) and similar to the GP in children (PWH: 68%, GP: 72%). High-risk sports participation decreased with age in PWH: from 65% (6-12 years) to 17% (50-65 years), which was also observed in the GP. Sports participation in children was independent of severity (non-severe: 67% vs. severe: 65%; P = 0.97), but not in adults (non-severe: 75%, severe: 62%; P < 0.01). Non-severe PWH played more high-risk sports than severe PWH: children at 65% vs. 48% (P = 0.05), adults at 25% vs. 15% (P = 0.07). DISCUSSION: These results suggest that sports participation in PWH was comparable to the GP. Sports participation was dependent of haemophilia severity in adults. Children were more involved in high-risk sports than adults. More studies on sports-related injury-risk are needed for adequate counselling.

Motor Developmental Delay After Cardiac Surgery in Children With a Critical Congenital Heart Defect: A Systematic Literature Review and Meta-analysis.

PURPOSE: To systematically review evidence regarding the severity and prevalence of motor development in children with a critical congenital heart defect (CCHD) without underlying genetic anomalies. SUMMARY OF KEY POINTS: Twelve percent of all included studies reported abnormal mean motor developmental scores, and 38% reported below average motor scores. Children with single-ventricle physiology, especially those with hypoplastic left heart syndrome, had the highest severity and prevalence of motor delay, particularly at 0 to 12 months. Most included studies did not differentiate between gross and fine motor development, yet gross motor development was more affected. RECOMMENDATIONS FOR CLINICAL PRACTICE: We recommend clinicians differentiate between the type of heart defect, fine and gross motor development, and the presence of genetic anomalies. Furthermore, increased knowledge about severity and prevalence will enable clinicians to tailor their interventions to prevent motor development delays in CCHD.

Parents' experiences of VOICE: A novel support programme in the NICU.

BACKGROUND: Admission of an infant to a neonatal intensive care unit (NICU) is often a stressful experience for parents and can be associated with feelings of inadequacy to fulfil the desirable parental role. The values, opportunities, integration, control, and evaluation (VOICE) programme was developed to engage parents in care, to decrease stress, and to increase empowerment. AIM: To explore the experiences of parents regarding involvement in the VOICE programme during admission of their infant to the NICU. DESIGN: The VOICE programme includes at least five personal structured meetings between parents, nurses, and other health care professionals throughout the pathway from birth, NICU, and follow up. A qualitative design was adopted using semi-structured interviews. Interviews with 13 parents of 11 infants born at <27 weeks' gestational age were conducted: nine mothers and two couples of father and mother. Thematic analysis was deployed. RESULTS: The findings have been described in one overarching theme: "parental empowerment." Parents felt strengthened and were empowered in the development of their role as primary caretaker by the VOICE programme. The parental empowerment theme emerged from four related interpretive themes that were derived: (a) involvement in care, (b) personalized information and communication, (c) transition to a parental role, and (d) emotional support. CONCLUSION: The VOICE programme can be a structured approach used to implement family support in a NICU to empower parents to become a partner in the care of their infant and feel confident. RELEVANCE TO CLINICAL PRACTICE: This study encourages health care professionals to provide parental support through a structured intervention programme, which contributes to the empowerment of parents in the NICU and encouraged them to participate in care and decision-making.

Evaluating international Haemophilia Joint Health Score (HJHS) results combined with expert opinion: Options for a shorter HJHS.

INTRODUCTION: The Hemophilia Joint Health Score (HJHS) was developed to detect early changes in joint health in children and adolescents with haemophilia. The HJHS is considered by some to be too time consuming for clinical use and this may limit broad adoption. AIM: This study was a first step to develop a shorter and/or more convenient version of the HJHS for the measurement of joint function in children and young adults with haemophilia, by combining real-life data and expert opinion. METHODS: A cross-sectional multicenter secondary analysis on pooled data of published studies using the HJHS (0-124, optimum score 0) in persons with haemophilia A/B aged 4-30 was performed. Least informative items, scoring options and/or joints were identified. An expert group of 19 international multidisciplinary experts evaluated the results and voted on suggestions for adaptations in a structured meeting (consensus set at ≥ 80%). RESULTS: Original data on 499 persons with haemophilia from 7 studies were evaluated. Median age was 15.0 years [range 4.0-29.9], 83.2% had severe haemophilia and 61.5% received prophylaxis. Median (IQR) HJHS total was 6.0 (1.0-17.0). The items 'duration swelling' and 'crepitus' were identified as clinically less informative and appointed as candidates for reduction. CONCLUSION: Analysis of 499 children and young adults with haemophilia showed that the HJHS is able to discriminate between children and adults and different treatment regimens. Reduction of the items 'duration swelling' and 'crepitus' resulted in the HJHSshort , which had the same discriminative ability. Additional steps are needed to achieve a substantially shorter HJHS assessment.

Sports participation and sports injuries in Dutch boys with haemophilia.

INTRODUCTION: Sports participation in children with hemophilia is generally considered to be associated with increased injury risk, which is generally considered highest in severe hemophilia. AIM: To assess sports participation according to age and severity in children with hemophilia and its association with sports injuries. METHODS: In a retrospective single-center study, sports participation, injuries, and bleeding data from three consecutive annual clinic visits were collected for young patients with hemophilia (PWH, aged 6-18). Sports in categories 2.5 and 3 of 3 according to the National Hemophilia Foundation classification were considered high-risk. Groups were compared using chi-square testing. RESULTS: 105 PWH (median age: 13(IQR 10-14); 53% severe; bleeding rate: 1/y) were identified; three were unable to perform sports and were excluded. The majority of PWH (77%) played sports weekly, of which 80% high-risk sports. Sports participation (median 3.0x/wk), and the proportion of injured PWH was similar in severe (42%) and non-severe (33%) PWH. Sports injuries were rare (65% no injuries in 3 years, median 0/y (IQR 0-1)). Annually, PWH did not report more injuries (15%) than age-matched boys (28%). Sports injuries were not associated with frequency and type of sports. DISCUSSION: This retrospective study showed high sports participation (including high-risk sports) and low injury rates. Sports participation was similar across severities and injury rates were not higher than among the general population. Injuries were not associated with frequency or type of sports. A prospective study with objective assessment of sports participation and injuries is warranted to confirm these findings and avoid recall bias.

The Paediatric Haemophilia Activities List (pedHAL) in routine assessment: changes over time, child-parent agreement and informative domains.

INTRODUCTION: The Paediatric Haemophilia Activities List (pedHAL) assesses self-reported limitations in activities and participation in children with haemophilia. AIM: To assess longitudinal changes, child-parent agreement and to identify which pedHAL domains yielded most information in boys with access to early prophylaxis. METHODS: The pedHAL (53 items, 7 domains, optimum 100) was completed annually at the Van Creveldkliniek by boys aged 4-18 years with moderate/severe haemophilia and their parents. Development of the pedHAL in relation to bleeds, changes per domain over 3-5 years, child-parent agreement (% difference child-parent≤|5|) per domain and domain scores (limitations defined as ≤ 95) were determined. RESULTS: Seventy-three patients and their parents (92% severe haemophilia, median age 13.1 years [range 5.4;18.0]) completed ≥1 pedHAL. Median (IQR) pedHAL sum score was 99.5 (95.2;100.0) for children and 99.6 (95.8;100.0) for parents. If patients scored >95 and had no joint and/or muscle bleed, 90.9% of the patients scored >95 at the next assessment. The median change in sum score was 0.0 for both the 3- and 5-year interval. Child-parent agreement varied between domains from 92% ('self-care') to 71% ('sitting/kneeling/standing'). Most limitations were reported in the domains 'sitting/kneeling/standing', 'functions of the legs' and 'leisure activities and sports.' CONCLUSION: In routine clinical practice in Dutch children on prophylaxis, pedHAL scores were high and remained stable in 3-5 years at group level. In individual patients without joint and/or muscle bleeds, pedHAL scores remained high after 1 year. Child-parent agreement was not optimal which indicated that both child report and parent proxy should be reported.

Consensus-based recommendations for the management of juvenile dermatomyositis.

BACKGROUND: In 2012, a European initiative called Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile dermatomyositis (JDM) is a rare disease within the group of paediatric rheumatic diseases (PRDs) and can lead to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. Consequently, treatment regimens differ throughout Europe. OBJECTIVES: To provide recommendations for diagnosis and treatment of JDM. METHODS: Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was constituted, consisting of 19 experienced paediatric rheumatologists and 2 experts in paediatric exercise physiology and physical therapy, mainly from Europe. Recommendations derived from a validated systematic literature review were evaluated by an online survey and subsequently discussed at two consensus meetings using nominal group technique. Recommendations were accepted if >80% agreement was reached. RESULTS: In total, 7 overarching principles, 33 recommendations on diagnosis and 19 recommendations on therapy were accepted with >80% agreement among experts. Topics covered include assessment of skin, muscle and major organ involvement and suggested treatment pathways. CONCLUSIONS: The SHARE initiative aims to identify best practices for treatment of patients suffering from PRD. Within this remit, recommendations for the diagnosis and treatment of JDM have been formulated by an evidence-informed consensus process to produce a standard of care for patients with JDM throughout Europe.

2016 ACR-EULAR adult dermatomyositis and polymyositis and juvenile dermatomyositis response criteria-methodological aspects.

Objective: The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM. Methods: Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data. Results: Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference. Conclusion: Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis.

Validation of Accelerometer Prediction Equations in Children with Chronic Disease.

The purpose of this study was to assess the criterion validity of existing accelerometer-based energy expenditure (EE) prediction equations among children with chronic conditions, and to develop new prediction equations. Children with congenital heart disease (CHD), cystic fibrosis (CF), dermatomyositis (JDM), juvenile arthritis (JA), inherited muscle disease (IMD), and hemophilia (HE) completed 7 tasks while EE was measured using indirect calorimetry with counts determined by accelerometer. Agreement between predicted EE and measured EE was assessed. Disease-specific equations and cut points were developed and cross-validated. In total, 196 subjects participated. One participant dropped out before testing due to time constraints, while 15 CHD, 32 CF, 31 JDM, 31 JA, 30 IMD, 28 HE, and 29 healthy controls completed the study. Agreement between predicted and measured EE varied across disease group and ranged from (ICC) .13-.46. Disease-specific prediction equations exhibited a range of results (ICC .62-.88) (SE 0.45-0.78). In conclusion, poor agreement was demonstrated using current prediction equations in children with chronic conditions. Disease-specific equations and cut points were developed.

Musculoskeletal outcome in hemophilia: bleeds, joint structure and function, activity, and health-related fitness.

Treatment in hemophilia is designed to reduce bleed frequency, minimize joint damage, and maximize functional independence and quality of life. Therefore, success of a factor replacement protocol is usually gauged by its ability to produce near "normal joints"-without any significant pathology. The most commonly used outcome measurement tools are based on the radiological and clinical assessment of joint arthropathy. To improve the sensitivity to early changes, the clinical scores have been refined, and imaging based on magnetic resonance imaging and ultrasonography has been initiated. Although these scores are useful in assessing the structure and function of a joint, they do not consider the impact of arthropathy on overall musculoskeletal function. They are also not capable of assessing the efficacy of interventions on functional independence, participation in life activities, and quality of life. The development of functional scores such as the Functional Independence Score for Hemophilia, the pediatric Hemophilia Activities List, and some quality of life measurement tools have helped provide a more comprehensive assessment of health. This article describes the psychometric properties and limitations of the various clinimetric tools that are used to assess musculoskeletal outcome in hemophilia and suggests an algorithm for their use in clinical practice.