Baseline Range of Motion, Strength, Motor Function, and Participation in Youth with Hutchinson-Gilford Progeria Syndrome.

AIMS: Limited information is available on impairments, activity limitations and participation restrictions in youth with Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic premature aging disease. The purposes were to: (1) describe range of motion (ROM), grip, pinch and quadriceps strength, functional balance, walking endurance, and gross motor limitations and participation restrictions; (2) evaluate the association between ROM impairments and age; and (3) evaluate the association between the Gross Motor Function Measure-88 (GMFM) scores and lower extremity (LE) ROM, quadriceps strength, and age. METHODS: Upper and LE ROM, grip, pinch and quadriceps strength, Timed Up and Go (TUG), Six Minute Walk Test, GMFM-88, and Canadian Occupational Performance Measure data were recorded for 38 participants with HGPS. RESULTS: All youth exhibited ROM impairments and most displayed decreased grip and pinch strength, walking endurance, and gross motor skills when compared to same-aged peers. However, the majority had good functional balance with TUG scores in the normal range. Participation restrictions included difficulty keeping up with peers when walking and difficulty completing activities of daily living. Some ROM measurements were negatively associated with age indicating that older participants had more extensive ROM limitation than younger participants. CONCLUSIONS: Physical and occupational therapists can use this information when evaluating youth with HGPS, designing a plan of care, and providing treatment interventions.

Rasch analysis of the Pediatric Evaluation of Disability Inventory-computer adaptive test (PEDI-CAT) item bank for children and young adults with spinal muscular atrophy.

INTRODUCTION: In this study we evaluated the suitability of a caregiver-reported functional measure, the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT), for children and young adults with spinal muscular atrophy (SMA). METHODS: PEDI-CAT Mobility and Daily Activities domain item banks were administered to 58 caregivers of children and young adults with SMA. Rasch analysis was used to evaluate test properties across SMA types. RESULTS: Unidimensional content for each domain was confirmed. The PEDI-CAT was most informative for type III SMA, with ability levels distributed close to 0.0 logits in both domains. It was less informative for types I and II SMA, especially for mobility skills. Item and person abilities were not distributed evenly across all types. CONCLUSIONS: The PEDI-CAT may be used to measure functional performance in SMA, but additional items are needed to identify small changes in function and best represent the abilities of all types of SMA. Muscle Nerve 54: 1097-1107, 2016.

Spinal muscular atrophy functional composite score: A functional measure in spinal muscular atrophy.

INTRODUCTION: With clinical trials underway, our objective was to construct a composite score of global function that could discriminate among people with spinal muscular atrophy (SMA). METHODS: Data were collected from 126 participants with SMA types 2 and 3. Scores from the Hammersmith Functional Motor Scale-Expanded and Upper Limb Module were expressed as a percentage of the maximum score and 6-minute walk test as percent of predicted normal distance. A principal component analysis was performed on the correlation matrix for the 3 percentage scores. RESULTS: The first principal component yielded a composite score with approximately equal weighting of the 3 components and accounted for 82% of the total variability. The SMA functional composite score, an unweighted average of the 3 individual percentage scores, correlated almost perfectly with the first principal component. CONCLUSIONS: This combination of measures broadens the spectrum of ability that can be quantified in type 2 and 3 SMA patients.

Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA that produces the farnesylated aberrant lamin A protein, progerin. This multisystem disorder causes failure to thrive and accelerated atherosclerosis leading to early death. Farnesyltransferase inhibitors have ameliorated disease phenotypes in preclinical studies. Twenty-five patients with HGPS received the farnesyltransferase inhibitor lonafarnib for a minimum of 2 y. Primary outcome success was predefined as a 50% increase over pretherapy in estimated annual rate of weight gain, or change from pretherapy weight loss to statistically significant on-study weight gain. Nine patients experienced a ≥50% increase, six experienced a ≥50% decrease, and 10 remained stable with respect to rate of weight gain. Secondary outcomes included decreases in arterial pulse wave velocity and carotid artery echodensity and increases in skeletal rigidity and sensorineural hearing within patient subgroups. All patients improved in one or more of these outcomes. Results from this clinical treatment trial for children with HGPS provide preliminary evidence that lonafarnib may improve vascular stiffness, bone structure, and audiological status.

Validation of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND).

PURPOSE: Preliminary validation of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) for motor skill assessment in spinal muscular atrophy type I. METHODS: A total of 27 subjects 3 to 260 months old (mean = 49, SD = 69) with spinal muscular atrophy-I were evaluated with the CHOP INTEND. Subjects were evaluated as part of a multicenter natural history study. RESULTS: CHOP INTEND scores and age were significantly correlated (r = -0.51, P = .007; 2 survival of the motor neuron [SMN] 2 gene copies, n = 16, r = -0.60, 3 SMN2 gene copies, n = 9, r = -0.83). Respiratory support and CHOP INTEND scores were correlated (r = -0.74, P < .0001, n = 26). The CHOP INTEND and age regression in patients with 2 copies versus 3 copies of SMN2 approached significance (P = .0711, n = 25). Subjects who required respiratory support scored significantly lower (mean = 15.5, SD = 10.2 vs mean = 31.2, SD = 4.2, P < .0001, n = 27). Correlation with motor unit number estimation and combined motor unit activation were not significant. CONCLUSION: The CHOP INTEND reflects measures of disease severity and supports continued exploration of the CHOP INTEND.

Psychometric properties of the PEDI-CAT for children and youth with spinal muscular atrophy.

PURPOSE: The purpose of this study was to examine the psychometric properties of the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT) in children and youth with Spinal Muscular Atrophy (SMA). METHODS: In this prospective cross-sectional study, caregivers of children and youth with SMA completed the PEDI-CAT Daily Activities and Mobility domains. A subset of caregivers completed a questionnaire about the measure. RESULTS: Mean ranks of scaled scores for Daily Activities (n = 96) and Mobility (n = 95) domains were significantly different across the three SMA types and across the three motor classifications. Normative scores indicated that 85 participants (89.5%) had limitations in Mobility and 51 in Daily Activities (53.1%). Floor effects were observed in≤10.4% of the sample for Daily Activities and Mobility. On average, caregivers completed the Mobility domain in 5.4 minutes and the Daily Activities domain in 3.3 minutes. Most caregivers reported that they provided meaningful information (92.1%), were willing to use the PEDI-CAT format again (79%), and suggested adding content including power wheelchair mobility items. CONCLUSION: Convergent validity was demonstrated for the Daily Activities and Mobility domains. Normative scores detected limitations in Mobility and Daily Activity performance for most participants with SMA. The PEDI-CATwas feasible to administer and caregivers expressed willingness to complete the PEDI-CAT in the future.

The buddy group - peer support for the bereaved.

We describe in this paper the story of the 'Buddy Groups' for bereaved people that were set up at Weston Hospicecare in 2008 and have endured ever since. The group have helped bereaved people to find meaning and value despite their grief. We observed that, through the strength of the relationships formed, people were able to recover well. Group members reported back to us the significant value they placed on being in a Buddy Group.

Effect of FePd alloy composition on the dynamics of artificial spin ice.

Artificial spin ices (ASI) are arrays of single domain nano-magnetic islands, arranged in geometries that give rise to frustrated magnetostatic interactions. It is possible to reach their ground state via thermal annealing. We have made square ASI using different FePd alloys to vary the magnetization via co-sputtering. From a polarized state the samples were incrementally heated and we measured the vertex population as a function of temperature using magnetic force microscopy. For the higher magnetization FePd sample, we report an onset of dynamics at T = 493 K, with a rapid collapse into >90% ground state vertices. In contrast, the low magnetization sample started to fluctuate at lower temperatures, T = 393 K and over a wider temperature range but only reached a maximum of 25% of ground state vertices. These results indicate that the interaction strength, dynamic temperature range and pathways can be finely tuned using a simple co-sputtering process. In addition we have compared our experimental values of the blocking temperature to those predicted using the simple Néel-Brown two-state model and find a large discrepancy which we attribute to activation volumes much smaller than the island volume.

An expanded version of the Hammersmith Functional Motor Scale for SMA II and III patients.

PURPOSE: To develop and evaluate an expanded version of the Hammersmith Functional Motor Scale allowing for evaluation of ambulatory SMA patients. PROCEDURES: Thirty-eight patients with SMA type II or III were evaluated using the Gross Motor Function Measure and the Hammersmith Functional Motor Scale. Based on statistical and clinical criteria, we selected 13 Gross Motor Function Measure items to develop an expanded HFMS. The expanded Hammersmith Functional Motor Scale was validated by comparison with the Gross Motor Function Measure minus the 13 items (GMFM-75) and an assessment of clinical function. The reliability of the expanded Hammersmith Functional Motor Scale in 36 patients was established. FINDINGS: The expanded Hammersmith Functional Motor Scale was highly correlated with the GMFM-75 and the clinical function assessment (p=0.97, and p=0.90). The expanded Hammersmith Functional Motor Scale showed excellent test-retest reliability (International Coordinating Committee = 0.99). CONCLUSIONS: The expanded Hammersmith Functional Motor Scale allows assessment of high functioning SMA type II and III patients. Ease of administration and correlation with established motor function measures justify use in future SMA clinical trials.

An investigation of the photo-clastogenic potential of ultrafine titanium dioxide particles.

Ultrafine titanium dioxide is widely used in a number of commercial products including sunscreens and cosmetics. There is extensive evidence on the safety of ultrafine titanium dioxide. However, there are some published studies indicating that some forms at least may be photogenotoxic, photocatalytic and/or carcinogenic. In order to clarify the conflicting opinions on the safety of ultrafine titanium dioxide particles, the current studies were performed to investigate the photo-clastogenic potential of eight different classes of ultrafine titanium dioxide particles. The photo-clastogenicity of titanium dioxide was measured in Chinese hamster ovary (CHO) cells in the absence and presence of UV light at a dose of 750 mJ/cm(2). The treatments were short (3 h) followed by a 17-h recovery and achieved concentrations that either induced approximately 50% cytotoxicity or reached 5000 microg/ml if non-cytotoxic. None of the titanium dioxide particles tested induced any increase in chromosomal aberration frequencies either in the absence or presence of UV. These studies show that ultrafine titanium dioxide particles do not exhibit photochemical genotoxicity in the model system used.

Physical therapy services received by individuals with spinal muscular atrophy (SMA).

PURPOSE: The consensus statement for standard of care in SMA recommends multidisciplinary medical care including physical therapy (PT) services. To date there are no reports regarding the implementation of these recommendations and the type of care or services received by individuals with SMA. The purpose of this study is to describe the PT services received by individuals with SMA. METHODS: Interviews were conducted with patients or their caregivers at the Pediatric Neuromuscular Clinical Research (PNCR) Network sites from October 2011 to September 2012. Questions included information about clinical status of the patient, sociodemographic profile of the patient or caregiver, and PT services received in the past year, including the setting, frequency, duration and type of PT, and therapies administered by caregivers. RESULTS: Eighty-six percent of 105 participants reported receiving PT services, some in multiple settings: 62% in the neuromuscular clinic, 38% at school, 34% at home, and 13% in an outpatient clinic. Greater frequency of PT services received was associated with younger age and inability to walk, but not SMA type. CONCLUSION: This is the first multicenter study documenting PT services received by patients with SMA. Further research is needed to better understand the impact of PT services on the natural history of SMA.

Strength retention of 70:30 poly(L-lactide-co-D,L-lactide) following real-time aging.

This study evaluated the in vitro strength retention and polymer characteristics of plates and screws made from commercially available 70:30 poly(L-lactide-co-D,L-lactide) over a 2-year time period. Test samples included three routine manufacturing lots each of plates (1.2 mm thick, 41.70 mm long, with 2.5-mm holes), which were machined from compression-molded sheets, and screws (2.4-mm major diameter and 1.86-mm minor diameter), which were manufactured by injection molding. All samples were sterilized by e-beam irradiation prior to in vitro aging following a standard methodology. Mechanical testing and polymer analysis was performed after 0, 6, 13, 26, 39, 52, 65, 78, and 104 weeks. The initial (time zero) tensile strength of the plates averaged 33.2+/-1.9 MPa; the plates retained 100% of this strength at 6 weeks, 84% at 13 weeks, and 34% at 39 weeks. The screws had an initial (time zero) shear strength of 29.8+/-4.2 MPa, and maintained 97% of this strength at 26 weeks and 73% of this strength at 39 weeks. The inherent viscosity and molecular weight (M(w)) at time zero averaged approximately 1.4 dL/g and 165,000 g/mol, respectively, and decreased at similar rates for both the plates and screws. These results demonstrate excellent strength retention of devices fabricated from 70:30 poly(L-lactide-co-D,L-lactide) over time periods exceeding those associated with normal bone healing.

OA36†The buddy group.

BACKGROUND: In September 2008 a training course called Sharing the Journey was offered at Weston Hospicecare. During the six week course, a number of participants were bereaved. Because of the strong relationships developed between them they wanted to continue meeting after the six weeks. This highlighted that friendships can develop between strangers who are in a similar caring role but also sharing the experiences helps bereaved get back into the social networks. Having been in a long relationship or a caring role for several years some people struggle going out alone. AIM: The aim of The Buddy Group is to support bereaved "carer givers" to share their experience and get back into the social network. METHOD: The Buddy Group meet on a monthly basis within the Hospice environment, and plan their social events together and see it as a safe environment to express their emotions. As the groups have moved forward, two carers have assumed the role of facilitating the more recent groups and arranging the events. The Hospice is utilised for a venue and for support for the carers facilitating the group. RESULTS: The Buddy Group was an off shoot from the Sharing the Journey course and meet monthly for arranging social activities and supporting their bereavement journey. To date 120 people since September 2008 have benefitted from the Buddy Group and we are now on Buddy Group 5. Buddy Group 1 and 2 don't attend the Hospice but meet outside of the Hospice venue for social networking. Currently, the Hospice are operating three groups at the same time and are receiving facilitated assistance from two carers that had attended both Sharing the Journey and The Buddy Groups. They see themselves as the concept of "caring for the carers". CONCLUSION: The development of a Buddy Group may need facilitated support from a Hospice professional staff member initially, but after some time can become sustained by group members who have experienced the carers role. The bereavement journey is supported by fellow group members which results in members getting back into the social networks, preventing isolation and loneliness. The feedback from group members is extremely positive.

A three-dimensional osteochondral composite scaffold for articular cartilage repair.

There is a recognized and urgent need for improved treatment of articular cartilage defects. Tissue engineering of cartilage using a cell-scaffold approach has demonstrated potential to offer an alternative and effective method for treating articular defects. We have developed a unique, heterogeneous, osteochondral scaffold using the TheriForm three-dimensional printing process. The material composition, porosity, macroarchitecture, and mechanical properties varied throughout the scaffold structure. The upper, cartilage region was 90% porous and composed of D,L-PLGA/L-PLA, with macroscopic staggered channels to facilitate homogenous cell seeding. The lower, cloverleaf-shaped bone portion was 55% porous and consisted of a L-PLGA/TCP composite, designed to maximize bone ingrowth while maintaining critical mechanical properties. The transition region between these two sections contained a gradient of materials and porosity to prevent delamination. Chondrocytes preferentially attached to the cartilage portion of the device, and biochemical and histological analyses showed that cartilage formed during a 6-week in vitro culture period. The tensile strength of the bone region was similar in magnitude to fresh cancellous human bone, suggesting that these scaffolds have desirable mechanical properties for in vivo applications, including full joint replacement.

Self-discrepancy in body dysmorphic disorder.

OBJECTIVES: According to self-discrepancy theory (SDT), depression, social anxiety, eating disorders and paranoia result from different types of conflicting self-beliefs. Body dysmorphic disorder (BDD) consists of a preoccupation with imagined or slight defects in one's appearance, which is often associated with a depressed mood and social anxiety. SDT was therefore applied to BDD patients to further understand their beliefs about their appearance. DESIGN: Using a comparative group design, BDD patients were compared against a non-patient control group. METHOD: A sample of 149 participants, consisting of three groups - BDD (72), BDD preoccupied with their weight and shape (35), and controls (42) - completed a modified version of the Selves Questionnaire (Higgins, Bond, Klein, & Strauman, 1986) requiring them to list and rate physical characteristics according to the following standpoints: (a) self-actual; (b) self-ideal; (c) self-should; (d) other-actual; and (e) other-ideal. RESULTS: BDD patients displayed significant discrepancies between their self-actual and both their self-ideal and self-should. However, there were no significant discrepancies in BDD patients between their self-actual and other-actual or other-ideal domains. Analysis of variance using depression and social anxiety scores as covariates revealed a significant difference for both the self-ideal and self-should discrepancy. CONCLUSION: The results suggest that BDD patients have an unrealistic ideal or demand as to how they should look. BDD patients are more like depressed patients (rather than social phobics or bulimics), being more concerned with a failure to achieve their own aesthetic standard than with the perceived ideals of others.

Observational study of spinal muscular atrophy type I and implications for clinical trials.

OBJECTIVES: Prospective cohort study to characterize the clinical features and course of spinal muscular atrophy type I (SMA-I). METHODS: Patients were enrolled at 3 study sites and followed for up to 36 months with serial clinical, motor function, laboratory, and electrophysiologic outcome assessments. Intervention was determined by published standard of care guidelines. Palliative care options were offered. RESULTS: Thirty-four of 54 eligible subjects with SMA-I (63%) enrolled and 50% of these completed at least 12 months of follow-up. The median age at reaching the combined endpoint of death or requiring at least 16 hours/day of ventilation support was 13.5 months (interquartile range 8.1-22.0 months). Requirement for nutritional support preceded that for ventilation support. The distribution of age at reaching the combined endpoint was similar for subjects with SMA-I who had symptom onset before 3 months and after 3 months of age (p=0.58). Having 2 SMN2 copies was associated with greater morbidity and mortality than having 3 copies. Baseline electrophysiologic measures indicated substantial motor neuron loss. By comparison, subjects with SMA-II who lost sitting ability (n=10) had higher motor function, motor unit number estimate and compound motor action potential, longer survival, and later age when feeding or ventilation support was required. The mean rate of decline in The Children's Hospital of Philadelphia Infant Test for Neuromuscular Disorders motor function scale was 1.27 points/year (95% confidence interval 0.21-2.33, p=0.02). CONCLUSIONS: Infants with SMA-I can be effectively enrolled and retained in a 12-month natural history study until a majority reach the combined endpoint. These outcome data can be used for clinical trial design.

Improving diabetes outcomes by an innovative group visit model: a pilot study.

PURPOSE: To develop a group visit model that improves A1C, blood pressure, lipids, depression, and satisfaction among patients with diabetes that can be used in primary care practice settings. DATA SOURCES: Using a pre/post-test descriptive design, data were collected from 22 adult patients of a private family practice office. All patients had a diagnosis of diabetes and A1C of 7.5 or above. The participants consisted of over 70% of persons aged 50 or older who reported having diabetes for over 5 years. Eighty percent were female and 32% were African American. A1C, blood pressure, weight, lipids, depression, and satisfaction surveys were measured before and after the group visit series. CONCLUSIONS: The mean reduction in A1C was 1.1 points (p = .009). Weight decreased by a mean of 3.01 pounds (p = .001), diastolic blood pressure improved by a mean of 5.76 mmHg (p = .002). The Beck Depression Inventory showed significant improvement (p = .045) in depression scores. The Seattle Outpatient Satisfaction Questionnaire showed improvement (p = .028). IMPLICATIONS FOR PRACTICE: This model of care needs further testing, but preliminary data show it to be effective in improving clinical outcomes of patients with diabetes and realistic for nurse practitioner's to implement.

Motor and cognitive assessment of infants and young boys with Duchenne Muscular Dystrophy: results from the Muscular Dystrophy Association DMD Clinical Research Network.

Therapeutic trials in Duchenne Muscular Dystrophy (DMD) exclude young boys because traditional outcome measures rely on cooperation. The Bayley III Scales of Infant and Toddler Development (Bayley III) have been validated in developing children and those with developmental disorders but have not been studied in DMD. Expanded Hammersmith Functional Motor Scale (HFMSE) and North Star Ambulatory Assessment (NSAA) may also be useful in this young DMD population. Clinical evaluators from the MDA-DMD Clinical Research Network were trained in these assessment tools. Infants and boys with DMD (n = 24; 1.9 ± 0.7 years) were assessed. The mean Bayley III motor composite score was low (82.8 ± 8; p ≤ .0001) (normal = 100 ± 15). Mean gross motor and fine motor function scaled scores were low (both p ≤ .0001). The mean cognitive comprehensive (p=.0002), receptive language (p ≤ .0001), and expressive language (p = .0001) were also low compared to normal children. Age was negatively associated with Bayley III gross motor (r = -0.44; p = .02) but not with fine motor, cognitive, or language scores. HFMSE (n=23) showed a mean score of 31 ± 13. NSAA (n = 18 boys; 2.2 ± 0.4 years) showed a mean score of 12 ± 5. Outcome assessments of young boys with DMD are feasible and in this multicenter study were best demonstrated using the Bayley III.

Prospective cohort study of spinal muscular atrophy types 2 and 3.

OBJECTIVE: To characterize the natural history of spinal muscular atrophy type 2 and type 3 (SMA 2/3) beyond 1 year and to report data on clinical and biological outcomes for use in trial planning. METHODS: We conducted a prospective observational cohort study of 79 children and young adults with SMA 2/3 who participated in evaluations for up to 48 months. Clinically, we evaluated motor and pulmonary function, quality of life, and muscle strength. We also measured SMN2 copy number, hematologic and biochemical profiles, muscle mass by dual x-ray absorptiometry (DXA), and the compound motor action potential (CMAP) in a hand muscle. Data were analyzed for associations between clinical and biological/laboratory characteristics cross-sectionally, and for change over time in outcomes using all available data. RESULTS: In cross-sectional analyses, certain biological measures (specifically, CMAP, DXA fat-free mass index, and SMN2 copy number) and muscle strength measures were associated with motor function. Motor and pulmonary function declined over time, particularly at time points beyond 12 months of follow-up. CONCLUSION: The intermediate and mild phenotypes of SMA show slow functional declines when observation periods exceed 1 year. Whole body muscle mass, hand muscle compound motor action potentials, and muscle strength are associated with clinical measures of motor function. The data from this study will be useful for clinical trial planning and suggest that CMAP and DXA warrant further evaluation as potential biomarkers.

Validation of the Expanded Hammersmith Functional Motor Scale in spinal muscular atrophy type II and III.

The relationships between the Expanded Hammersmith Functional Motor Scale (HFMSE) and genotype and motor and respiratory outcomes were examined in patients with spinal muscular atrophy types II and III (n = 70). The correlation between the HFMSE and Gross Motor Function Measure was r = 0.98. Correlations between HFMSE and forced vital capacity (percentage of predicted normal) (n = 56) and a functional rating (n = 57) were r = 0.87 and r = 0.92, respectively. Correlations with strength were as follows: knee extension, r = 0.74 (n = 60); elbow flexion, r = 0.77 (n = 61); and knee flexion, r = 0.74 (n = 58). The HFMSE differentiated patients by SMN2 copy number (P = .0007); bi-level positive airway pressure use, <8 versus ≥8 hours/day (P < .0001); ambulatory status (P < .0001); and spinal muscular atrophy type (P < .0001). The HFMSE demonstrates significant associations with established measures of function, strength, and genotype, and discriminates patients based on function, diagnostic category, and bi-level positive airway pressure need. Time of administration averaged 12 minutes. The HFMSE is a valid, time-efficient outcome measure for clinical trials in spinal muscular atrophy types II and III.