Non-surgical correction of knee flexion deformity in persons with haemophilia: A staged multidisciplinary approach.

INTRODUCTION: Flexion deformity of the knee is a common complication following recurrent haemarthrosis in persons with haemophilia (PWH) on episodic factor replacement therapy, restricting independent mobility. There is limited literature on the comprehensive management of this condition. This report provides the outcome of a staged multidisciplinary approach for the correction of knee flexion deformity (KFD) even in limited resource settings. PATIENTS AND METHODS: The data of 49 consecutive PWH who were treated for KFD were analysed. The approach included graded physical therapy (PT), followed by serial casting and/or mobilisation under anaesthesia (MUA). MUA was done in carefully selected knees. Surgical correction was opted when non-surgical methods failed. RESULTS: Of the 49 patients (55 knees), with a median KFD of 40 degrees (range: 10-90), 26/55 (47%) were corrected by graded PT. With serial casting, 9/19 (47%) knees had their KFD corrected. MUA was done for 11 knees of which five achieved correction (45%). Surgical correction was required for only seven knees (12.7%). Following this approach, KFD improved from 40 degrees (range: 10-90) to 15 degrees (range: 0-40), with only minor loss of flexion from 105 (range: 60-155) to 90 degrees (range: 30-150). Out of 55 KFD, 46 (83.6%) KFD were corrected; non-surgical, 39 (70.9%) and surgery, seven (12.7%). The remaining patients (nine KFD; 16.4%) were able to achieve their functional goal despite not meeting the correction criteria. CONCLUSION: This study shows that in PWH, functionally significant KFD correction can be achieved in about 71%, through non-surgical methods, even without prophylactic factor replacement.

Mobilization under anaesthesia for correction of knee flexion deformity in haemophilia.

INTRODUCTION: Haemophilia patients not treated with primary or secondary prophylaxis, often present with recurrent haemarthrosis. Knee is the most frequently involved joint leading to disabling knee flexion deformity (KFD). Here, we present a retrospective study of our experience on the role of mobilization under general anaesthesia in the correction of KFD. AIM: To study the effectiveness of mobilization under anaesthesia (MUA) for correction of knee flexion deformity (KFD) in persons with haemophilia (PWH). METHODS: Outcome of all patients managed with MUA in our multidisciplinary haemophilia clinic from 2008 to 2019 were included for analysis. PWH with KFD > 20 degree who underwent MUA were included in the study. Under general anaesthesia and cover of clotting factor replacement, gentle joint mobilization was done to achieve maximal correction in flexion deformity, followed by above knee casting in this position. The outcome measures assessed were reduction in knee flexion deformity following MUA and complications, if any. RESULTS: Thirty patients (34 knees) with knee flexion deformity were included in the study. Mean age of the study population was 14.23 years ± 8.3. Study population was analysed in two groups, Group 1 included patients who underwent single MUA and Group 2, patients who underwent two or more MUA. There was significant improvement in KFD correction in both groups. [Group 1; Mean difference: 22 ± 13.7, p value -0.01, 95% CI (16.4-27.5) and Group 2; Mean difference 48.8 ± 19.8, p value -0.00, 95% CI (34.2-64.5)]. CONCLUSION: MUA can be effective in the short-term correction of KFD in PWH particularly those below 15 years of age. It should be done judiciously when target correction is not achieved with other physical methods.

Role of Ultrasonography in Upper Airway Assessment for Decannulating Tracheostomy in Acquired Brain Injury-A Pilot Study.

OBJECTIVE: To compare the findings of ultrasonography of the upper airway with flexible fiberoptic laryngoscopy and determine the efficacy of transcutaneous laryngeal ultrasonography for decannulation. DESIGN: Prospective cross-sectional study. SETTING: Tertiary care referral center in South India. PARTICIPANTS: Twenty-four patients with acquired brain injury (N=24). MAIN OUTCOME MEASURES: Participants underwent an airway assessment by ultrasonography followed by assessment of airway by flexible laryngoscopy done within the next 72 hours. RESULTS: Vocal cord assessment by ultrasonography revealed a sensitivity of 81.2% and specificity of 87.5%. A statistically significant association between vocal cord mobility as assessed by ultrasonography and decannulation was observed (sensitivity of 81.25%, specificity of 87.5%, P=.002). Although aspiration was not assessed by ultrasonography, a statistically significant association was observed between vocal cord mobility on ultrasonography and aspiration as assessed by laryngoscopy (sensitivity of 81.25%, specificity of 87.5%, P=.011). CONCLUSION: Laryngeal ultrasonography is an emerging diagnostic modality with a potential role for assessing vocal cord mobility and airway prior to decannulation in centers that lack the expertise and the infrastructure to perform a flexible laryngoscopy.

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.

Body composition and metabolic parameters in men with chronic traumatic paraplegia - A pilot study from India.

OBJECTIVE: To study body composition, measures of insulin resistance and dyslipidemia in Indian men with paraplegia as compared to age and body mass index (BMI) matched able-bodied men. DESIGN: Cross sectional study. SETTING: Departments of Physical Medicine and Rehabilitation and Endocrinology. PARTICIPANTS: Males aged 18-45 years with chronic traumatic paraplegia versus age and BMI-matched able-bodied men. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Measures of body composition such as total body fat, lean mass, regional adiposity using dual energy x-ray absorptiometry (DXA), metabolic profile and insulin resistance. RESULTS: Subjects with paraplegia (n = 43), compared to controls (n = 36), had higher %Fat mass (FM) (25.5 (21.2-28.9) vs 20.2 (15.9-22.2); P < 0.01), lower trunk to leg ratio (0.66 (0.51-0.73) vs 0.87 (0.72-0.94); P < 0.01), lower lean mass index (14.38 (2.57) vs 17.80 (2.34); P < 0.01) and lower appendicular lean mass index (5.81 ± 1.26 vs 8.17 ± 1.12; P < 0.01). Fasting blood glucose (mg/dl) was higher (89.0(81.5-96.5) vs 80.0 (74.5-88.2); P < 0.01), Homeostasis model assessment of insulin resistance was higher (1.33 (1.03-2.12) vs 0.94 (0.52-1.78); P = 0.02), Quantitative insulin sensitivity check index (QUICKI) was lower (0.36 ± 0.04 vs 0.38 ± 0.05; P = 0.02) and HDL-C was lower (33.00 (30.00-42.75) vs 38.50 (33.00-43.25); P < 0.02) in cases compared to controls. QUICKI correlated positively with HDL-C and negatively with %FM, estimated VAT volume and TG. Trunk to leg ratio correlated positively with TG even after controlling for %FM. CONCLUSION: Men with chronic paraplegia had lower lean mass, higher total and regional fat mass, increased insulin resistance and low HDL-C when compared with BMI-matched able-bodied controls. Both total and regional adiposity correlated with poor metabolic profile.

The Hemophilia Joint Health Score version 2.1 Validation in Adult Patients Study: A multicenter international study.

Background: The Hemophilia Joint Health Score (HJHS) was developed and validated to detect arthropathy in children. Additional evidence is required to show validity in adults. We studied the convergent and discriminant construct validity of the HJHS version 2.1(HJHSv2.1) in adults with hemophilia. A secondary aim was to define age-related normative adult HJHSv2.1 reference values. Methods: We studied 192 adults with hemophilia, and 120 healthy adults in four age-matched groups-18 to 29, 30 to 40, 41 to 50, and >50 years-at nine centers. Trained physiotherapists scored the HJHS and World Federation of Hemophilia (WFH) joint score. Health history, the Functional Independence Scale of Hemophilia (FISH), Hemophilia Activities List (HAL), and Short-Form McGill Pain Questionnaire (SF-MPQ) were also collected. Results: The median age was 35.0 years. Of participants with hemophilia, 68% had severe, 14% moderate, and 18% mild disease. The HJHS correlated strongly with WFH score (Spearman's rho [rs ] = .95, P < .001). Moderate correlations were seen between the FISH (rs  = .50, P < .001) and SF-MPQ Present Pain Intensity (rs  = .50, P < .001), while a modest correlation was found with the HAL (rs  = -.37, P < .001). The HJHS significantly differentiated between age groups (Kruskal-Wallis T = 35.02, P < .001) and disease severity in participants with hemophilia. The HJHS had high internal reliability (Cronbach's α = .88). We identified duration of swelling as a redundant item in the HJHS. Conclusions: The HJHS shows evidence of strong convergent and discriminant construct validity to detect arthropathy in adults with hemophilia and is well suited for use in this population.

Status dystonicus: Diagnosis and management of a rare and challenging entity.

We report the case of a six-year-old girl with Moyamoya disease who presented with bilateral internal carotid artery malignant infarct following encephaloduroarteriosynangiosis (EDAS). During her neurorehabilitation, she developed gradually worsening dystonic spasms with opisthotonic posturing, tachycardia, tachypnea and desaturation. This rare life threatening movement disorder was diagnosed as status dystonicus based on the history and clinical presentation. Status Dystonicus occurs commonly in children and the etiology is often diverse. It occurs in patients with preexisting dystonia or following an acute central nervous system insult of varied etiology. Status dystonicus is usually precipitated by one or more triggering factors. Rarity and lack of objective criteria for diagnosis often delays the management thereby increasing the risk of mortality and morbidity. Here, we discuss the challenges faced in the diagnosis and management of a child with denovo status dystonicus.

Recent CR1 non-LTR retrotransposon activity in coscoroba reveals an insertion site preference.

BACKGROUND: Chicken repeat 1 (CR1) is a taxonomically widespread non-LTR retrotransposon. Insertion site bias, or lack thereof, has not been demonstrated for CR1. Recent CR1 retrotranspositions were used to examine flanking regions for GC content and nucleotide bias at the insertion site. RESULTS: Elucidation of the exact octomer repeat sequence (TTCTGTGA) allowed for the identification of younger insertion events. The number of octomer repeats associated with a CR1 element increases after insertion with CR1s having one octomer being youngest. These young CR1s are flanked by regions of low GC content (38%). Furthermore, a bias for specific bases within the first four positions at the site of insertion was revealed. CONCLUSION: This study focused on those loci where the insertion event has been most recent, as this would tend to minimize noise introduced by post-integration mutational events. Our data suggest that CR1 is not inserting into regions of higher GC content within the coscoroba genome; but rather, preferentially inserting into regions of lower GC content. Furthermore, there appears to be a base preference (TTCT) for the insertion site. The results of this study increase the current level of understanding regarding the elusive CR1 non-LTR retrotransposon.

Rapid capture of DNA targets.

A rapid capture technique was developed to efficiently isolate specific DNA targets from a variety of genomes. The specificity can be easily adapted to any target for which partial sequence is known, allowing for the isolation of a wide set of target molecules from either characterized or uncharacterized genomes. These targets include but are not limited to transposable elements, microsatellites, repetitive sequences, and possibly unique sequences. Additionally, because the thermodynamics of nucleic acid hybridizations differ from processes such as PCR, a wider variety of targets with a range of mismatches to any customized probe can be isolated. Further this method allows sequences flanking known internal regions to be co-isolated, facilitating the development of flanking primers for downstream applications. Considerable reduction in the frequency of nonspecific binding between key components (background) obviates the need for subsequent screening steps. Rapid capture of DNA targets quickly provides information about target and flanking sequences.

Identification of novel CR1 subfamilies in an avian order with recently active elements.

Chicken repeat 1 (CR1) is a taxonomically widespread non-LTR retrotransposon. Recent CR1 retrotranspositions in waterfowl suggested that, unlike chicken at least one subfamily remains active. Based on sequence information from 143 CR1 loci, six distinct groups of CR1 within the waterfowl coscoroba each with unique 3' untranslated regions and distinct open reading frames are described. Through comparison to other previously described avian CR1 subfamilies, it is shown that five of the six coscoroba groups represent new subfamilies. At least one of these subfamilies is likely active and provides a target for future isolation of the first active member of this taxonomically widespread non-LTR family.

Wii-based interactive video games as a supplement to conventional therapy for rehabilitation of children with cerebral palsy: A pilot, randomized controlled trial.

OBJECTIVE: To assess the effect of interactive video gaming (IVG) with Nintendo Wii (Wii) supplemented to conventional therapy in rehabilitation of children with cerebral palsy (CP). DESIGN: Randomized, controlled, assessor-blinded study. PARTICIPANTS: Children with CP; 10 children each in the control and intervention groups. INTERVENTION: IVG using Wii, given as a supplement to conventional therapy, for 45 min per day, 6 days a week for 3 weeks. The children in the control group received conventional therapy alone. OUTCOME MEASURES: Posture control and balance, upper limb function, visual-perceptual skills, and functional mobility. RESULTS: Significant improvement in upper limb functions was seen in the intervention group but not in the control group. Improvements in balance, visual perception, and functional mobility were not significantly different between control and intervention groups. CONCLUSIONS: Wii-based IVG may be offered as an effective supplement to conventional therapy in the rehabilitation of children with CP.

Measurement of physical performance and objective fatigability in people with mild-to-moderate traumatic brain injury.

The aims of this study were to objectively measure the physical performance and physical endurance of patients with traumatic brain injury with minimization of cognitive and psychological fatigue, and to compare the physical performance of brain injured patients with that of healthy controls. This was a nonrandomized partially blinded controlled study. The study setting was the Outpatient Multidisciplinary Brain Injury Clinic in the Department of Physical Medicine and Rehabilitation of a tertiary care university teaching hospital. Participants included an experimental group that comprised independently ambulant men (age 18-55 years) with mild-to-moderate traumatic brain injury (n = 24) who complained of greater fatigue than before their injury and an age-matched and sex-matched control group (n = 24). The intervention included the Six-Minute Walk Test. The primary outcome measures were the Six-Minute Walk Distance, the Fatigue Severity Scale, Addenbrooke's Cognitive Examination, and the Fatigue Visual Numeric Scale; the secondary outcome measures were the Physiological Cost Index of Walking and the Borg Scale of Perceived Exertion. The Six-Minute Walk Distance of the experimental group (452.33+/-68.816) when compared with that of the control group (518.08+/-92.114) was reduced by 12.7 and 30.5%, respectively, when compared with the predicted Six-Minute Walking Distance (650.04+/-79.142) for the same age and sex. The mean Fatigue Severity Scale values were 2.51 and 1.62 for the experimental and control groups, respectively. The mean Addenbrooke's Cognitive Examination Score for the patients was 85.5+/-7.265. In conclusion, the Six-Minute Walk Test is useful in segregating physical fatigue from cognitive and psychological aspects of fatigue when cognitive and psychological dimensions are known. The Six-Minute Walk Test can be used as a tool for exercise intensity prescription in men with mild-to-moderate brain injury, to avoid the deleterious effects of fatigue.