Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study

Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p ≤ 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731

Findings from the Longitudinal CINRG Becker Natural History Study

BACKGROUND: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype. OBJECTIVE: A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials. METHODS: A cohort of 83 patients with Becker muscular dystrophy (5-75 years at baseline) were followed for up to 3 years with annual assessments. Muscle and pulmonary function outcomes were analyzed herein. Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data to characterize these clinical outcomes. RESULTS: Deletion mutations of dystrophin exons 45-47 or 45-48 were most common. Subgroup analysis showed greater pairwise association between motor outcomes at baseline than association between these outcomes and age. Stronger correlations between outcomes for adults than for those under 18 years were also observed. Using cross-sectional binning analysis, a ceiling effect was seen for North Star Ambulatory Assessment but not for other functional outcomes. Longitudinal analysis showed a decline in percentage predicted forced vital capacity over the life span. There was relative stability or improved median function for motor functional outcomes through childhood and adolescence and decreasing function with age thereafter. CONCLUSIONS: There is variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype of Becker muscular dystrophy. Disease progression is largely manifest in adulthood. There are implications for clinical trial design revealed by this longitudinal analysis of a Becker natural history dataset

Simultaneous bilateral total ankle replacement using a 3-component prosthesis: Outcome in 26 patients followed for 2–10 years

Total ankle replacement is an established surgical procedure in patients with end-stage ankle osteoarthritis. We analyzed complications and medium-term results in patients with simultaneous bilateral total ankle replacement

Characterization of pulmonary function in 10â18 year old patients with Duchenne muscular dystrophy

Pulmonary function loss in patients with Duchenne muscular dystrophy (DMD) is progressive and leads to pulmonary insufficiency. The purpose of this study in 10â18 year old patients with DMD is the assessment of the inter-correlation between pulmonary function tests (PFTs), their reliability and the association with the general disease stage measured by the Brooke score. Dynamic PFTs (peak expiratory flow [PEF], forced vital capacity [FVC], forced expiratory volume in one second [FEV1]) and maximum static airway pressures (MIP, MEP) were prospectively collected from 64 DMD patients enrolled in the DELOS trial (ClinicalTrials.gov, number NCT01027884). Baseline PEF percent predicted (PEF%p) was <80% and patients had stopped taking glucocorticoids at least 12 months prior to study start. At baseline PEF%p, FVC%p and FEV1%p correlated well with each other (Spearman's rho: PEF%pâFVC%p: 0.54; PEF%pâFEV1%p: 0.72; FVC%pâFEV1%p: 0.91). MIP%p and MEP%p correlated well with one another (MIP%pâMEP%p: 0.71) but less well with PEF%p (MIP%pâPEF%p: 0.40; MEP%pâPEF%p: 0.41) and slightly better with FVC%p (MIP%pâFVC%p: 0.59; MEP%pâFVC%p: 0.74). The within-subject coefficients of variation (CV) for successive measures were 6.97% for PEF%p, 6.69% for FVC%p and 11.11% for FEV1%p, indicating that these parameters could be more reliably assessed compared to maximum static airway pressures (CV for MIP%p: 18.00%; MEP%p: 15.73%). Yearly rates of PFT decline (placebo group) were larger in dynamic parameters (PEF%p: â8.9% [SD 2.0]; FVC%p: â8.7% [SD 1.1]; FEV1%p: â10.2% [SD 2.0]) than static airway pressures (MIP%p: â4.5 [SD 1.3]; MEP%p: â2.8 [SD 1.1]). A considerable drop in dynamic pulmonary function parameters was associated with loss of upper limb function (transition from Brooke score category 4 to category 5). In conclusion, these findings expand the understanding of the reliability, correlation and evolution of different pulmonary function measures in DMD patients who are in the pulmonary function decline phase

Less Anterior Knee Pain with a Mobile-bearing Prosthesis Compared with a Fixed-bearing Prosthesis

Anterior knee pain is one of the major short-term complaints after TKA. Since the introduction of the mobile-bearing TKA, numerous studies have attempted to confirm the theoretical advantages of a mobile-bearing TKA over a fixed-bearing TKA but most show little or no actual benefits. The concept of self-alignment for the mobile bearing suggests the posterior-stabilized mobile-bearing TKA would provide a lower incidence of anterior knee pain compared with a fixed-bearing TKA. We therefore asked whether the posterior-stabilized mobile-bearing knee would in fact reduce anterior knee pain. We randomized 103 patients scheduled for cemented three-component TKA for osteoarthrosis in a prospective, double-blind clinical trial. With a 1-year followup, more patients experienced persistent anterior knee pain in the posterior-stabilized fixed-bearing group (10 of 53, 18.9%) than in the posterior-stabilized mobile-bearing group (two of 47, 4.3%). No differences were observed for range of motion, visual analog scale for pain, Oxford 12-item questionnaire, SF-36, or the American Knee Society score. The posterior-stabilized mobile-bearing knee therefore seems to provide a short-term advantage compared with the posterior-stabilized fixed-bearing knee

Evidence of superficial knowledge regarding antibiotics and their use: Results of two cross-sectional surveys in an urban informal settlement in Kenya

<div><p>We assessed knowledge and practices related to antibiotic use in Kibera, an urban informal settlement in Kenya. Surveys was employed at the beginning (entry) and again at the end (exit) of a 5-month longitudinal study of AMR. Two-hundred households were interviewed at entry, of which 149 were also interviewed at exit. The majority (>65%) of respondents in both surveys could name at least one antibiotic, with amoxicillin and cotrimoxazole jointly accounting for 85% and 77% of antibiotics mentioned during entry and exit, respectively. More than 80% of respondents felt antibiotics should not be shared or discontinued following the alleviation of symptoms. Nevertheless, 66% and 74% of respondents considered antibiotics effective for treating colds and flu in the entry and exit surveys, respectively. There was a high (87%, entry; 70% exit) level of reported antibiotic use (past 12 months) mainly for colds/flu, coughs and fever, with >80% of respondents obtaining antibiotics from health facilities and pharmacies. Less than half of respondents remembered getting information on the correct use of antibiotics, although 100% of those who did reported improved attitudes towards antibiotic use. Clinicians and community pharmacists were highly trusted information sources. Paired household responses (n = 149) generally showed improved knowledge and attitudes by the exit survey although practices were largely unchanged. Weak agreement (κ = -0.003 to 0.22) between survey responses suggest both that unintended learning had not occurred, and that participant responses were not based on established knowledge or behaviors. Targeted public education regarding antibiotics is needed to address this gap.</p></div

An integrated mid-range theory of postpartum family development: a guide for research and practice.

AIM: This paper is a report of a study to identify parents' perceptions of postpartum family experiences. BACKGROUND: There is a growing worldwide emphasis on family support. Government policy in the United Kingdom advocates a family-centred approach in which a core universal postbirth service is offered to all families with additional support for parents of children with complex needs. Health visitors provide family postpartum care without an agreed theory directing or standardizing practice. There is a need to identify parental experiences to define family-centred care. METHOD: A qualitative, exploratory approach was undertaken using a purposive sample of 17 postpartum families. Data were collected in one region of Northern Ireland in 2001-2002. Participants' experiences and views were accessed during two focus groups with a total of seven participants, and six in-depth interviews. Thematic analysis was conducted. FINDINGS: One core theme, 'thriving and surviving', and three main themes, 'baby nurture', 'life changes', 'coping and adapting resources', were identified to describe how parents developed during the first 8-week postpartum. These were influenced by the physical, the psychosocial and the environmental factors. The identified themes were mapped together to form an Integrated Mid-Range Theory of Postpartum Parent Development. CONCLUSION: As parents need to negotiate successfully both present coping and future development during the postpartum period, there is a need for professionals to offer services that are orientated to holistic short- and long-term well-being. The findings, further to additional research, may be used by health visitors and other professionals to direct universal postpartum care