A new and simplified comprehensive ultrasound protocol of haemophilic joints: the Universal Simplified Ultrasound (US-US) protocol.

AIM: To present a new protocol to optimise ultrasound (US) assessment of haemophilic arthropathy. MATERIALS AND METHODS: Ultrasound of haemophilic arthropathy joints was performed using three different ultrasound protocols, namely, the Toronto-Vellore Comprehensive Ultrasound (TVC-US) protocol, the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US), and the newly developed Universal Simplified Ultrasound (US-US) protocol. Synovial hypertrophy, haemosiderin deposition, effusion, erosion, and cartilage loss were evaluated in 20 joints. The reliability and diagnostic efficiency of these protocols was compared using magnetic resonance imaging (MRI). RESULTS: The correlation between the TVC-US and US-US protocols for synovial hypertrophy was excellent: kappa significance (KS) was 1, but was substantial (KS=0.65) with the HEAD-US protocol. For effusion, both the TVC-US and the HEAD-US protocols had substantial correlation with the US-US protocol (KS=0.7 and 0.6 respectively). The correlation for erosion and cartilage loss was excellent between the TVC-US and the US-US with MRI (KS=1), but poor (KS=0) with the HEAD-US protocol. The US-US protocol also had good interobserver agreement (KS=1). CONCLUSION: The accuracy of the US-US protocol is comparable to the TVC-US protocol and MRI and is superior to the HEAD-US protocol in the assessment of haemophilic arthropathy.

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

INTRODUCTION: 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. AIMS: 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. METHODS: 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. RESULTS AND CONCLUSION: 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.

Episodic replacement of clotting factor concentrates does not prevent bleeding or musculoskeletal damage - the MUSFIH study.

PATIENTS AND METHODS: A longitudinal study was carried out in 255 children from 10 centres in nine developing countries over 5 years to assess the musculoskeletal outcome of children on episodic factor replacement. Outcome was documented by assessment of the annual joint bleeding rate (AJBR), WFH clinical and Pettersson radiological joint scores as well as the FISH score for activities. Of the 203 patients for whom data was available at the end of 5 years, 164 who had received only episodic treatment are included in this report. RESULTS: The median age at the beginning of the study was 10 years (IQR 7-12). The median clotting factor concentrate (CFC) usage was 662 IU kg-1 year-1 (IQ range: 280-1437). The median AJBR was 10 (IQ range: 5-17). The median AJBR was higher in the older children with the median being 5 for the 5 year old child, while it was 9 for the 10 year old and 11 for children older than 15. Given the episodic nature of the replacement therapy, those with a higher AJBR used significantly greater annual CFC doses (P < 0.001); The median change in WFH clinical score and Pettersson radiological score over the 5 years was 0.4/year for each, while the FISH deteriorated at a rate of 0.2/year with poor correlation of these changes with CFC dose. WFH and FISH scores were significantly worse in those with an AJBR of >3 per year (P = 0.001). The change in the Pettersson score was significantly more in those with an AJBR of >5 per year (P = 0.020). Significant changes in FISH scores were only noted after 10 years of age. CONCLUSION: Episodic CFC replacement over a large range of doses does not alter the natural course of bleeding in haemophilia or the musculoskeletal deterioration and should not be recommended as a long term option for treatment. Prophylaxis is the only way to preserve musculoskeletal function in haemophilia.

Correlating clinical and radiological assessment of joints in haemophilia: results of a cross sectional study.

OBJECTIVES: This study was undertaken to determine the correlation between the radiological changes in haemophilic arthropathy [X-ray, Ultrasound (US) and MRI] and clinical assessment as determined by the Hemophilia Joint Health Score (HJHS); and to document the US and MRI changes in joints that appear normal on plain X-ray and clinical evaluation. MATERIALS AND METHODS: Of 55 study joints (22 knees and 33 ankles) in 51 patients with haemophilia/von Willebrand disease, with a median age of 15 years (range: 5-17) were assessed using X-rays (Pettersson score) and clinical examination (HJHS) at two centres (Toronto, Canada; Vellore, India). MRI and ultrasonographic scoring was done through a consensus assessment by imagers at both centres using the IPSG MRI and US scores. RESULTS: The HJHS had a good correlation with the Pettersson score (rs = 0.66). Though the HJHS had moderate correlation with the osteochondral component of the MRI and US scores (rs 0.51, 0.45 respectively), its correlation with the soft tissue component was poor (rs 0.19; 0.26 respectively). Of the 18 joints with a Pettersson score of zero, 88.9% had changes that were detected clinically by the HJHS. Osteochondral abnormalities were identified in 38.9% of these joints by the MRI, while US images of the same joints were deemed abnormal in 83.3% by the current criteria. US identified haemosiderin and other soft tissue changes in all of the joints, while the same changes were noted in 94.4% of these joints on MRI. There were four joints with a HJHS of zero, all of which had soft tissue changes on MRI (score 1-7) and US (score 2-7). Osteochondral changes were detected in three of these joints by US and in 2 by MRI. There were four joints with an MRI score of 0-1 that had significant US scores (3-5) and HJHS scores (0-6). CONCLUSION: US and MRI are able to identify pathological changes in joints with normal X-ray imaging and clinical examination. However, further studies are required to be able to differentiate early abnormalities from normal. Clinical (HJHS) and radiological assessment (US/MRI) provide complimentary information and should be considered conjointly in the assessment of early joint arthropathy.

Assessments of outcome in haemophilia - what is the added value of QoL tools?

INTRODUCTION: Access to treatment and especially to long-term regular replacement treatment with clotting factor concentrates (prophylaxis) have caused dramatic contrasts in the clinical picture between haemophilia populations. An individual patient with severe haemophilia age 20 years can have normal joints or can be severely crippled and unable to work. Assessment of outcome in a standardized way has therefore become essential. AIM: Discuss the relevance and utility of the different outcome assessment tools in patient groups with different access to treatment. METHODS: In the last decade new outcome assessment tools specific for haemophilia have been developed that measure all aspects of health according to the International Classification of Functioning, Disability and Health (ICF) model. These tools are directed at assessing the clinical and radiological status of joints as well as overall functioning, such as participation and psychosocial aspects, evaluating overall health-related quality of life (HRQOL). For deciding which tools to use in clinical practice or research, one needs to consider the specific context with regard to disease burden, healthcare environment and socioeconomic background of the patients being evaluated. CONCLUSION: Prospective systematic assessment of outcome in haemophilia and related bleeding disorders is important. Based upon recent literature a critical appraisal of outcome tools is described.

Ultrasound and magnetic resonance imaging of healthy paediatric ankles and knees: a baseline for comparison with haemophilic joints.

The study was undertaken to document cartilage and soft tissue changes/findings in ankles and knees of normal children of different age groups to be used for comparison in the assessment of children with haemophilia. Cartilage thickness and soft tissue changes were recorded at predetermined sites of ankles/knees on both US and MRI in healthy boys in three age groups: 7-9; 10-14; and 15-18 years. To assess the validity of the ultrasound and MRI measurements, an ex vivo study was done using agar phantoms with techniques and scanners similar to those applied in vivo. Twenty (48%) knees and 22 (52%) ankles of 42 boys, were evaluated. There was a reduction in the thickness of joint cartilage with age. A difference in cartilage measurements was noted in most sites between the age groups on both US and MRI (P < 0.05 each), but such difference was not noted for joint fluid in ankles or knees (P = 0.20, P = 0.68 or P = 0.75, P = 0.63 for US, MRI, respectively). Although cartilage measurements were smaller on US than on MRI for both ankles and knees (P < 0.05 each), this observation was not recorded for fluid in knees (P = 0.02). For diminutive measurements (2 mm) mean US measurements were smaller than corresponding phantom's measurements, P = 0.02. Age-related measurements were noted for cartilage thickness on US and MRI in ankles and knees. US measurements were smaller than corresponding MRI measurements at most joint sites, which were supported by results on small-diameter phantoms.

A patient-prioritized ability assessment in haemophilia: the Canadian Occupational Performance Measure.

Assessment of musculoskeletal function in individuals with haemophilia has been attempted with clinimetric instruments, which use predetermined domains for assessing the same. This study introduces the application of an instrument, the Canadian Occupational Performance Measure (COPM), which is an open-ended questionnaire that allows patients to prioritize their needs and rate their performance in different tasks of daily living as well as their satisfaction in performing them. To study the utility of COPM in evaluating the musculoskeletal functional status of patients with haemophilia and to assess its effectiveness in planning individualized management plans for them. COPM was administered to 67 individuals with haemophilia aged 10-55 years and the data were compared with functional deficits identified through FISH (Functional Independence Score for Haemophilia). A total of 31 performance difficulties in the areas of self-care (62%), productivity (21%) and leisure (17%) were identified by COPM. All eight domains of FISH were identified in COPM as problems in self-care. In addition to these, COPM identified problems in the areas of productivity and leisure. In 78% of the responses on COPM, there was concordance between the performance and satisfaction scores. However, there was discordance between the two in the remaining 22% of responses. COPM is a useful tool for assessment of musculoskeletal dysfunction in haemophilia. It provides a greater insight into the needs of each patient and helps in planning individualized intervention strategies.

Subtrochanteric femoral shortening for hip centre restoration in complex total hip arthroplasty with functional outcome.

AIMS: Complex total hip arthroplasty (THA) with subtrochanteric shortening osteotomy is necessary in conditions other than developmental dysplasia of the hip (DDH) and septic arthritis sequelae with significant proximal femur migration. Our aim was to evaluate the hip centre restoration with THAs in these hips. METHODS: In all, 27 THAs in 25 patients requiring THA with femoral shortening between 2012 and 2019 were assessed. Bilateral shortening was required in two patients. Subtrochanteric shortening was required in 14 out of 27 hips (51.9%) with aetiology other than DDH or septic arthritis. Vertical centre of rotation (VCOR), horizontal centre of rotation, offset, and functional outcome was calculated. The mean followup was 24.4 months (5 to 92 months). RESULTS: The mean VCOR was 17.43 mm (9.5 to 27 mm) and horizontal centre of rotation (HCOR) was 24.79 mm (17.2 to 37.6 mm). Dislocation at three months following acetabulum reconstruction required femoral shortening for offset correction and hip centre restoration in one hip. Mean horizontal offset was 39.72 (32.7 to 48.2 mm) compared to 42.89 (26.7 to 50.6 mm) on the normal side. Mean Harris Hip Score (HHS) of 22.64 (14 to 35) improved to 79.43 (68 to 92). Mean pre-operative shortening was 3.95 cm (2 to 8 cm). Residual limb length discrepancy was 1.5 cm (0 to 2 cm). Sciatic neuropraxia in two patients recovered by six months, and femoral neuropraxia in one hip recovered by 12 months. Mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was 13.92 (9 to 19). Mean 12-item short form survey (SF-12) physical scores of 50.6 and mental of 60.12 were obtained. CONCLUSION: THA with subtrochanteric shortening is valuable in complex hips with high dislocation. The restoration of the hip centre of rotation and offset is important in these hips. LEVEL OF EVIDENCE IV: Femoral shortening useful in conditions other than DDH and septic sequelae.Restoration of hip centre combined with offset to be planned and ensured.

Polymorphism in factor VII gene modifies phenotype of severe haemophilia.

The basis for 10-15% of patients with severe haemophilia having clinically mild disease is not fully understood. We hypothesized that polymorphisms in various coagulant factors may affect frequency of bleeding while functionally significant polymorphisms in inflammatory and immunoregulatory genes may also contribute to variations in the extent of joint damage. These variables were studied in patients with severe haemophilia, who were categorized as 'mild' (<5 bleeds in the preceding year, <10 World Federation of Haemophilia clinical and <10 Pettersson scores, n = 14) or 'severe' (all others, n = 100). A total of 53 parameters were studied in each individual for their association with the clinical severity. Age, F8:c activity and the incidence of thrombotic markers were comparable between the groups while the median number of bleeds, number of affected joints, clinical, radiological and functional joint scores (P < or = 0.001) and life-time clotting factor use (P < or = 0.007) were different. Patients with severe molecular defects had a 4.1-fold increased risk for a severe phenotype (95% CI: 1.18-14.42, P = 0.026) compared with other mutations. Of the polymorphisms studied, the FVII353Q (RR = 3.5, 95% CI: 1.04-12.05, P = 0.044) allele was associated with a severe phenotype. This data shows that apart from the F8/F9 genotype, functional polymorphisms in FVII gene affect the phenotype of patients with severe haemophilia.

Drug resistant Skeletal Tuberculosis in a tertiary care centre in South India.

BACK GROUND: Drug resistant tuberculosis is alarmingly on the rise especially in developing countries. Skeletal tuberculosis accounts up to 10% of all extra pulmonary tuberculosis. World Health Organisation (WHO) has not formulated guidelines for the management of Multi-drug resistant skeletal tuberculosis. RESULTS: A retrospective analysis of patients treated for musculoskeletal tuberculosis was done, to study drug resistance patterns. The outcome was assessed both clinically and radiologically.898 patients were treated for skeletal tuberculosis during the period of 2006-2013 (96 months). 478 (53.2%) patients were treated for tubercular spondylitis and 420 (46.8%) for extra-spinal skeletal tuberculosis. Ninety two patients (10.2%) had documented resistance to the anti-tubercular drugs. There were 42 mono resistant tuberculosis cases (4.7%), 13 poly resistant cases (1.4%), 33 multi-drug resistant cases (MDR TB) (3.7%) and 4 (0.4%) extremely drug resistant tuberculosis cases (XDR). All the patients were treated medically as per drug susceptibility patterns and protocols. Surgery was performed when indicated in 59 (66%) cases. 85% completed their course of treatment and were successfully healed as per pre-set clinical, biochemical and radiological criteria. The remaining were lost to follow up. One patient died as a result of post op respiratory infection. CONCLUSIONS: The prevalence of Multi-drug resistant tuberculosis patients in our centre was 3.7% and that of Extremely drug resistant tuberculosis cases was 0.4%. A Multi-disciplinary approach with drug susceptibility tests, sensitive drugs, and surgery if required is essential. Health education is essential to improve awareness among health care professionals about the danger of drug resistance in tuberculosis.

Chronic rupture of the extensor apparatus of the knee joint.

Chronic ruptures of the extensor mechanism of the knee are uncommon injuries, and previously reported literature assumes the presence of an intact patella for repair. We present a case of chronic rupture following patellectomy done twelve years previously. The defect in the extensor apparatus was extensive (18cm), and this was bridged using a large fascia lata graft from the opposite thigh, with reasonably successful results.

Proprioceptive changes in the contralateral knee joint following anterior cruciate injury.

Loss of proprioception following an anterior cruciate ligament (ACL) injury has been well documented. We evaluated proprioception in both the injured and the uninjured limb in 25 patients with ACL injury and in 25 healthy controls, as assessed by joint position sense (JPS), the threshold for the detection of passive movement (TDPM) and postural sway during single-limb stance on a force plate. There were significant proprioceptive deficits in both ACL-deficient and uninjured knees compared with control knees, as assessed by the angle reproduction test (on JPS) and postural sway on single limb stance. The degree of loss of proprioception in the ACL-deficient knee and the unaffected contralateral knee joint in the same patient was similar. The TDPM in the injured knee was significantly higher than that of controls at 30° and 70° of flexion. The TDPM of the contralateral knee joint was not significantly different from that in controls. Based on these findings, the effect of proprioceptive training of the contralateral uninjured knee should be explored.

The "dot-in-circle" sign -- a characteristic MRI finding in mycetoma foot: a report of three cases.

Three patients referred for MRI of the foot were found to have imaging features characteristic of mycetoma. Two patients presented with recurrent soft tissue masses, which were operated on several times and not suspected to be of infective aetiology. The third patient had typical clinical features with a history of blackish granule discharge. In all three patients, MRI showed conglomerate areas of small round discrete T(2) weighted hyperintense lesions, representing granulation tissue surrounded by a low-signal-intensity rim representing intervening fibrous septa. Within many of these hyperintense lesions, there was a central low-signal-intensity dot, which gives rise to the "dot-in-circle" sign that has been very rarely described in the literature. This sign is an easily recognisable and unique appearance that is highly suggestive of mycetoma.

Psychometric analysis of the Functional Independence Score in Haemophilia (FISH).

Joint morbidity in haemophilia has traditionally been measured using clinical and radiological scores. There have been no reliable, validated tools for the assessment of functional independence in persons with haemophilia till recently. The Functional Independence Score in Haemophilia (FISH) has been developed as a performance based assessment tool to address this need. The FISH is designed to measure the patient's independence in performing activities of daily living (grooming and eating, bathing and dressing), transfers (chair and floor), and mobility (walking, step climbing and running). On assessment of its psychometric properties in 63 patients with haemophilia (mean age 14 years), FISH was found to have good internal consistency (Cronbach's alpha of 0.85). It had moderate correlation with the World Federation of Hemophilia clinical score (r = -0.61), and a correlation with the Pettersson score of -0.38. It had good correlation with other self-rated functional scores, such as the Stanford Health Assessment Questionnaire (r = -0.75); the Western Ontario and McMaster Universities Osteoarthritis Index (r = -0.66) and the Haemophilia Activities List (HAL) (r = -0.66). It had good reliability with a pooled intra class correlation of 0.98. On assessing responsiveness following treatment of flexion deformities of the knee in 12 patients, the FISH showed significant changes in the score with a standardized responsiveness mean of -1.93. In conclusion, the FISH was found to be a reliable and valid tool with good internal consistency and responsiveness to therapy, for the assessment of functional independence in persons with haemophilia.

Recent developments in clinimetric instruments.

Assessment of impairment and function is essential in order to monitor joint status and evaluate therapeutic interventions in patients with haemophilia. The improvements in the treatment of haemophilia have required the development of more sensitive tools to detect the more minor dysfunctions that may now be apparent. This paper outlines some of the recent developments in this field. The Haemophilia Joint Health Score (HJHS) provides a systematic and robust measure of joint impairment. The MRI Scoring System has been designed to provide a comprehensive scoring system combining both progressive and additive scales. The Functional Independence Score for Haemophilia (FISH) has been developed to assess performance of functional activities and can be used in conjunction with the Haemophilia Activities List (HAL) which provides a self report measure of function. It is recommended that both measures are evaluated as these tools measure different constructs. Further refinement and testing of the psychometric properties of all of these tools is in progress. More widespread use of these tools will enable the sharing of data across the world so promoting best practice and ultimately enhancing patient care.

Functional Independence Score in Haemophilia: a new performance-based instrument to measure disability.

Morbidity in haemophilia has been described predominantly in terms of musculoskeletal dysfunction and assessed by the clinical and radiological joint scores. These scores document changes in a particular joint, but do not reflect the impact of these changes on the individual in terms of his overall musculoskeletal function. Several self-assessment instruments have been used to measure musculoskeletal function but none have been specifically validated for use in haemophilia. In order to objectively assess musculoskeletal function of patients with haemophilia, we developed Functional Independence Score in Hemophilia (FISH), a performance-based instrument. FISH measures the patient's independence in performing seven activities under three categories: self-care (grooming and eating, bathing and dressing), transfers (chair and floor) and mobility (walking and step climbing). Each function is graded from 1 to 4 depending on the amount of assistance needed in performing the function. We evaluated 35 patients who were over 10 years old and had had at least three major bleeds per year. All subjects were scored for clinical (World Federation of Hemophilia, WFH score) and radiological changes (Pettersson's score). Functional independence of the patient was assessed using the Stanford Health Assessment Questionnaire (HAQ) and the FISH. Correlation of the FISH score was modest with both the WFH clinical score (r = -0.68) and the radiological score (r = -0.44). While there was good correlation between FISH and HAQ (r = -0.90), FISH had better internal consistency than HAQ (Cronbach's alpha 0.83 vs. 0.66). FISH appears to be a promising disease-specific instrument for assessing overall musculoskeletal function in haemophilia. It requires evaluation in different patient populations.

A comparison of heparin/warfarin and enoxaparin thromboprophylaxis in spinal cord injury: the Sheffield experience.

OBJECTIVES: To compare the safety and effectiveness of two different thromboprophylactic protocols in the management of patients with spinal cord injury - one using heparin/warfarin and the other using enoxaparin. STUDY DESIGN: Retrospective. SETTING: Princess Royal Spinal Injuries Unit, Sheffield, UK. METHODS: Retrospective review of two cohorts of patients with acute spinal injury admitted to a supra-regional spinal injuries centre and treated with different pharmacological agents. One group received heparin/warfarin in combination with antiembolism stockings and mechanical measures for thromboprophylaxis whereas the second group received enoxaparin in combination with the other measures. Patients who developed clinical symptoms suggestive of deep vein thrombosis or pulmonary embolism were investigated as appropriate. RESULTS: Four of the 101 patients on heparin/warfarin developed symptoms of venous thromboembolism compared to 13 of the 72 who were on enoxaparin. Of the 13, three had been on 40 mg of enoxaparin daily and 10 on 20 mg enoxaparin daily. Six patients on enoxaparin and one patient on warfarin developed thromboembolic complications after they had been mobilised and the anticoagulant discontinued. Eight patients on warfarin prophylaxis and three patients on enoxaparin developed haemorrhagic complications necessitating cessation of therapy. CONCLUSION: This study suggests that the traditional protocol of warfarin/heparin for thromboprophylaxis in spinal cord injury patients remains a safer option than enoxaparin.

Dose and outcome of care in haemophilia--how do we define cost-effectiveness?

Severe haemophilia (factor [F]VIII/FIX activity < 0.01 IU mL(-1)) is characterized by repeated haemarthroses resulting in severe arthropathy in adulthood. In 1958, Professor Nilsson in Sweden introduced prophylactic infusions with clotting factor concentrates at regular intervals in order to maintain clotting factor levels above 0.01 IU mL(-1) and to prevent bleeding. Since then, evidence of the long-term beneficial effects of prophylactic treatment for severe haemophilia has been increasing and it has become the recommended treatment strategy for children with severe haemophilia by both the World Health Organization and the US National Hemophilia Foundation Medical and Scientific Advisory Committee. However, the implementation of this recommendation has been hampered by issues of cost and venous access. The high costs of prophylaxis have largely prevented its use in major parts of the world. The question therefore is whether the current models of replacement of clotting factor concentrates, while certainly being effective, are also optimal. Can the data on outcome at different levels of factor replacement be used to assess their cost-effectiveness?