Clinician Perspectives of Gene Therapy as a Treatment Option for Duchenne Muscular Dystrophy.

Background: Duchenne muscular dystrophy (DMD) is a progressive, life-limiting, neuromuscular disorder. Clinicians play an important role in informing families about therapy options, including approved gene therapies and clinical trials of unapproved therapies.

Objective: This study aimed to understand the perspectives of clinicians about gene therapy for DMD, which has not previously been studied.

Mpox Diagnosis, Behavioral Risk Modification, and Vaccination Uptake among Gay, Bisexual, and Other Men Who Have Sex with Men, United Kingdom, 2022.

During the 2022 multicountry mpox outbreak, the United Kingdom identified cases beginning in May. UK cases increased in June, peaked in July, then rapidly declined after September 2022. Public health responses included community-supported messaging and targeted mpox vaccination among eligible gay, bisexual, and other men who have sex with men (GBMSM).

Long-term Retinal Morphology and Functional Associations in Treated Neovascular Age-Related Macular Degeneration: Findings from the Inhibition of VEGF in Age-Related Choroidal Neovascularisation Trial.

Purpose: To describe the frequency of long-term morphologic features and their relationships with visual function in participants who exited the Inhibition of VEGF in Age-Related Choroidal Neovascularisation (IVAN; ISRCTN92166560) trial.

Design: Multicenter cohort study up to 7 years after enrollment.

Participants: Patients enrolled in the IVAN trial, excluding participants who died or withdrew during the trial.

Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): defining and measuring functional impacts in pediatric patients.

Background: Research about pediatric patients' perspective on mucopolysaccharidosis type VI (MPS VI) and its impact on daily life is limited. We aimed to identify the disease concepts of interest that most impact function and day-to-day life of pediatric patients with MPS VI, and to consider clinical outcome assessments (COAs) that may potentially measure meaningful improvements in these concepts.

Methods: Potential focus group participants were identified by the National MPS Society (USA) and invited to participate if they self-reported a clinician-provided diagnosis of MPS VI and were 4 to 18 years, receiving enzyme replacement therapy (ERT), and available to attend a 1-day focus group with their caregiver in Dallas, TX, USA.

Long-term outcomes of patients with mucopolysaccharidosis VI treated with galsulfase enzyme replacement therapy since infancy.

Objective: Long-term outcomes of patients with mucopolysaccharidosis (MPS) VI treated with galsulfase enzyme replacement therapy (ERT) since infancy were evaluated.

Methods: The study was a multicenter, prospective evaluation using data from infants with MPS VI generated during a phase 4 study (ASB-008; Clinicaltrials.govNCT00299000) and clinical data collected ≥5 years after completion of the study.

Use of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) in X-Linked Myotubular Myopathy: Content Validity and Psychometric Performance.

X-linked myotubular myopathy (XLMTM) is a life-threatening, congenital myopathy characterized by extreme hypotonia, weakness, delayed motor milestones, and respiratory failure, often resulting in pediatric mortality. This study evaluated the content validity and psychometric performance of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders as a measure of neuromuscular functioning in children with X-linked myotubular myopathy. This study was conducted in two phases.

Measuring What Matters to Individuals with Angelman Syndrome and Their Families: Development of a Patient-Centered Disease Concept Model.

Angelman syndrome (AS) is a complex, heterogeneous, and life-long neurodevelopmental disorder. Despite the considerable impact on individuals and caregivers, no disease-modifying treatments are available. To support holistic clinical management and the development of AS-specific outcome measures for clinical studies, we conducted primary and secondary research identifying the impact of symptoms on individuals with AS and their unmet need.

Long-term Visual Outcomes after Release from Protocol in Patients who Participated in the Inhibition of VEGF in Age-related Choroidal Neovascularisation (IVAN) Trial.

Purpose: To describe visual outcomes, frequency of treatment and monitoring visits, and anti-vascular endothelial growth factor drugs used in usual care in participants who exited a trial in which treatment for neovascular age-related macular degeneration (nAMD) was initiated with bevacizumab or ranibizumab.

Design: Multicenter cohort study up to 7 years after trial exit.

Participants: Patients enrolled in the Inhibition of VEGF in Age-related choroidal Neovascularisation (IVAN) trial; after excluding participants from 2 sites and who died or withdrew during the trial, 537 were included in this follow-up cohort.

The OMACS-PIL study: a randomised controlled trial within the OMACS observational study.

Background: There has been little research to investigate whether the appearance of paper patient information leaflets (PILs) used to describe research studies to potential participants influences their decision to take part. Embedding a study within a trial (SWAT) is an efficient way of answering this type of methodological question. We included a randomised SWAT within a large cohort study, Outcome Monitoring after Cardiac Surgery (OMACS), to address this question.

Reliability and Validity of the 6-Minute Walk Test in Hypophosphatasia.

This investigation evaluated the reliability and validity of the 6-Minute Walk Test (6MWT) in patients with pediatric hypophosphatasia (HPP). Children (aged 6 to 12 years;  = 11), adolescents (13 to 17 years;  = 4), and adults (18 to 65 years;  = 9) completed the 6MWT at screening and baseline in two clinical studies of asfotase alfa. Test-retest reliability of the 6MWT, evaluated with Pearson's correlation coefficients () for screening versus baseline, was high for children ( = 0.

Asfotase alfa for infants and young children with hypophosphatasia: 7 year outcomes of a single-arm, open-label, phase 2 extension trial.

Background: Our previous phase 2, open-label study of 11 infants and young children with life-threatening perinatal or infantile hypophosphatasia showed 1 year safety and efficacy of asfotase alfa, an enzyme replacement therapy. We aimed to report the long-term outcomes over approximately 7 years of treatment.

Methods: We did a prespecified, end of study, 7 year follow-up of our single-arm, open-label, phase 2 trial in which children aged 3 years or younger with life-threatening perinatal or infantile hypophosphatasia were recruited from ten hospitals (six in the USA, two in the UK, one in Canada, and one in the United Arab Emirates).

Development and validation of a modified performance-oriented mobility assessment tool for assessing mobility in children with hypophosphatasia.

Purpose: To modify the Performance-Oriented Mobility Assessment-Gait (POMA-G) subtest and validate this modified POMA-G (mPOMA-G) in children with hypophosphatasia (HPP), a rare metabolic disorder that can manifest with musculoskeletal symptoms that impair mobility and ambulation.

Methods: Based on feedback from an expert panel, the POMA-G was modified by removing gait initiation/path assessments and expanding the rating scale for step length/continuity to capture aspects of observational gait analysis relevant to children with HPP. Three trained physical therapists used the mPOMA-G for video-based assessments of gait in 14 children with childhood HPP who participated in a clinical study of asfotase alfa or in a natural history study.

Clinical Outcome Assessments: Use of Normative Data in a Pediatric Rare Disease.

Pediatric rare diseases present unique challenges in clinical trial design and in selection of clinical outcome assessments (COAs) used to support claims in medical product labeling. COAs that discriminate level of function relative to a normative sample are particularly important in the pediatric rare disease setting because the literature is often void of natural history data. Pediatric rare disease clinical trials will often include a wide age distribution.

Service Evaluation of an Exercise on Referral Scheme for Adults with Existing Health Conditions in the United Kingdom.

Purpose: This paper outlines a service evaluation of an exercise referral scheme for adults suffering from a variety of physical or mental health conditions or who were deemed are at risk of developing such conditions. The evaluation aimed to assess the impact of the scheme at increasing physical activity and at reducing BMI and waist circumference.

Method: This was a retrospective evaluation looking at levels of physical activity and changes to anthropometric measures over a period of 6 months.

Asfotase alfa therapy for children with hypophosphatasia.

Hypophosphatasia (HPP) is caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Consequently, cell-surface deficiency of TNSALP phosphohydrolase activity leads to extracellular accumulation of inorganic pyrophosphate, a natural substrate of TNSALP and inhibitor of mineralization. Children with HPP can manifest rickets, skeletal pain, deformity, fracture, muscle weakness, and premature deciduous tooth loss.

Physical therapy management of infants and children with hypophosphatasia.

Hypophosphatasia (HPP) is a rare inborn error of metabolism resulting in undermineralization of bone and subsequent skeletal abnormalities. The natural history of HPP is characterized by rickets and osteomalacia, increased propensity for bone fracture, early loss of teeth in childhood, and muscle weakness. There is a wide heterogeneity in disease presentation, and the functional impact of the disease can vary from perinatal death to gait abnormalities.

Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease.

Emerging phenotypes in long-term survivors with Pompe disease on standard enzyme replacement therapy (ERT) (alglucosidase alfa 20 mg/kg/2 weeks) can include patients with worsening motor function. Whether higher doses of ERT improve skeletal function in these patients has not been systematically studied. This exploratory, randomized, open-label, 52-week study examined the safety and efficacy of 2 ERT regimens of alglucosidase alfa (20 mg/kg/week or 40 mg/kg/2 weeks) in 13 patients with Pompe disease and clinical decline or a lack of improvement on standard ERT: late-onset (n = 4), infantile-onset (n = 9).

Evidence-informed person-centered healthcare part I: do 'cognitive biases plus' at organizational levels influence quality of evidence?

Introduction: There is increasing concern about the unreliability of much of health care evidence, especially in its application to individuals.

Hypothesis: Cognitive biases, financial and non-financial conflicts of interest, and ethical violations (which, together with fallacies, we collectively refer to as 'cognitive biases plus') at the levels of individuals and organizations involved in health care undermine the evidence that informs person-centred care.

Methods: This study used qualitative review of the pertinent literature from basic, medical and social sciences, ethics, philosophy, law etc.

Does brief telephone support improve engagement with a web-based weight management intervention? Randomized controlled trial.

Background: Recent reviews suggest Web-based interventions are promising approaches for weight management but they identify difficulties with suboptimal usage. The literature suggests that offering some degree of human support to website users may boost usage and outcomes.

Objective: We disseminated the POWeR ("Positive Online Weight Reduction") Web-based weight management intervention in a community setting.