Effectiveness of conservative non-pharmacological interventions in people with muscular dystrophies: a systematic review and meta-analysis.

INTRODUCTION: Management of muscular dystrophies (MD) relies on conservative non-pharmacological treatments, but evidence of their effectiveness is limited and inconclusive. OBJECTIVE: To investigate the effectiveness of conservative non-pharmacological interventions for MD physical management. METHODS: This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched Medline, CINHAL, Embase, AMED and Cochrane Central Register of Controlled Trial (inception to August 2022). Effect size (ES) and 95% Confidence Interval (CI) quantified treatment effect. RESULTS: Of 31,285 identified articles, 39 studies (957 participants), mostly at high risk of bias, were included. For children with Duchenne muscular dystrophy (DMD), trunk-oriented strength exercises and usual care were more effective than usual care alone in improving distal upper-limb function, sitting and dynamic reaching balance (ES range: 0.87 to 2.29). For adults with Facioscapulohumeral dystrophy (FSHD), vibratory proprioceptive assistance and neuromuscular electrical stimulation respectively improved maximum voluntary isometric contraction and reduced pain intensity (ES range: 1.58 to 2.33). For adults with FSHD, Limb-girdle muscular dystrophy (LGMD) and Becker muscular dystrophy (BMD), strength-training improved dynamic balance (sit-to-stand ability) and self-perceived physical condition (ES range: 0.83 to 1.00). A multicomponent programme improved perceived exertion rate and gait in adults with Myotonic dystrophy type 1 (DM1) (ES range: 0.92 to 3.83). CONCLUSIONS: Low-quality evidence suggests that strength training, with or without other exercise interventions, may improve perceived exertion, distal upper limb function, static and dynamic balance, gait and well-being in MD. Although more robust and larger studies are needed, current evidence supports the inclusion of strength training in MD treatment, as it was found to be safe.

Behavior Change Following Pain Neuroscience Education in Middle Schools: A Public Health Trial.

Chronic pain and the opioid epidemic need early, upstream interventions to aim at meaningful downstream behavioral changes. A recent pain neuroscience education (PNE) program was developed and tested for middle-school students to increase pain knowledge and promote healthier beliefs regarding pain. In this study, 668 seventh-grade middle-school students either received a PNE lecture (n = 220); usual curriculum school pain education (UC) (n = 198) or PNE followed by two booster (PNEBoost) sessions (n = 250). Prior to, immediately after and at six-month follow-up, pain knowledge and fear of physical activity was measured. Six months after the initial intervention school, physical education, recess and sports attendance/participation as well as healthcare choices for pain (doctor visits, rehabilitation visits and pain medication use) were measured. Students receiving PNEBoost used 30.6% less pain medication in the last 6 months compared to UC (p = 0.024). PNEBoost was superior to PNE for rehabilitation visits in students experiencing pain (p = 0.01) and UC for attending school in students who have experienced pain > 3 months (p = 0.004). In conclusion, PNEBoost yielded more positive behavioral results in middle school children at six-month follow-up than PNE and UC, including significant reduction in pain medication use.

Using quality improvement strategies to strengthen regional systems for Aboriginal and Torres Strait Islander eye health in the Northern Territory.

PROBLEM: In the Katherine region, Northern Territory, barriers to eye care for Aboriginal and Torres Strait Islander people include unclear eye care referral processes, challenges coordinating patient eye care between various providers, complex socioeconomic determinants and a lengthy outpatient ophthalmology waiting list. DESIGN: Mixed methods participatory approach using a regional needs analysis, clinical file audit and stakeholder survey, to develop, implement and monitor quality improvement strategies. SETTING: Collaboration with Aboriginal Community Controlled Health Services and regional eye care stakeholders in the Katherine region. KEY MEASURES FOR IMPROVEMENT: Clinical audit data captured frequency and rates of primary eye checks, ophthalmology referrals and spectacle prescriptions. A survey was developed and applied to assess stakeholder perspectives of regional eye care systems. STRATEGY FOR CHANGE: Quality improvement strategies informed by regional data (clinical audits and survey) included increasing service delivery to match eye care needs, primary eye care training for Aboriginal Community Controlled Health Services staff, updating Aboriginal Community Controlled Health Services primary care templates and forming a regional eye care coalition group. EFFECTS OF CHANGE: Post-implementation, rates and frequency of recorded optometry examinations, number of spectacles prescribed and rates of annual dilated fundus examinations for patients with diabetes increased. There was a decrease in the number of patients with diabetes who had never had an eye examination. Eye care stakeholders perceived a marked improvement in the effectiveness of the regional eye care system. LESSONS LEARNT: Our findings highlight the importance of engaging services and stakeholders to ensure a systems approach that is evidence-informed, contextually appropriate and reflects commitment to improved eye health outcomes.

Evaluation for learning and improvement at the right time: an example from the field.

Evaluation expertise to assist with identifying improvements, sourcing relevant literature and facilitating learning from project implementation is not routinely available or accessible to not-for-profit organisations. The right information, at the right time and in an appropriate format, is not routinely available to program managers. Program management team members who were implementing The Fred Hollows Foundation's Indigenous Australia Program's Trachoma Elimination Program required information about what was working well and what required improvement. This article describes a way of working where the program management team and an external evaluation consultancy collaboratively designed and implemented an utilisation-focused evaluation, informed by a developmental evaluation approach. Additionally, principles of knowledge translation were embedded in this process, thereby supporting the evaluation to translate knowledge into practice. The lessons learned were that combining external information and practice-based knowledge with local knowledge and experience is invaluable; it is useful to incorporate evaluative information from inception and for the duration of a program; a collaborative working relationship can result in higher quality information being produced and it is important to communicate findings to different audiences in different formats.

Pathways to becoming an internal evaluator: Perspectives from the Australian non-government sector.

There is a lack of clarity around intra-organisational evaluation roles and pathways into these roles in non-government organisations (NGOs). This article presents three auto-narratives from the authors who are working as internal evaluators in the NGO sector. We examine this phenomenon of role ambiguity by exploring our evaluation journeys and struggles to find identities in the formal evaluation community. Findings from the auto-narratives identify implications for the evaluation field regarding professionalisation. This article explores how aspects of professionalisation, such as clarification of roles and tasks of internal evaluators, could facilitate their recruitment, assess credibility and guide career trajectory. Elucidating internal evaluation career pathways contributes to the evaluation discipline by providing information relevant for evaluation capacity building, evaluator training, and the professionalisation movement.

The prevalence, distribution, and functional importance of lower limb somatosensory impairments in chronic stroke survivors: a cross sectional observational study.

Purpose: To investigate the prevalence and distribution of lower limb somatosensory impairments in community dwelling chronic stroke survivors and examine the association between somatosensory impairments and walking, balance, and falls. Methods: Using a cross sectional observational design, measures of somatosensation (Erasmus MC modifications to the (revised) Nottingham Sensory Assessment), walking ability (10 m walk test, Walking Impact Scale, Timed "Get up and go"), balance (Functional Reach Test and Centre of Force velocity), and falls (reported incidence and Falls Efficacy Scale-International), were obtained. Results: Complete somatosensory data was obtained for 163 ambulatory chronic stroke survivors with a mean (SD) age 67(12) years and mean (SD) time since stroke 29 (46) months. Overall, 56% (n = 92/163) were impaired in the most affected lower limb in one or more sensory modality; 18% (n = 30/163) had impairment of exteroceptive sensation (light touch, pressure, and pin-prick), 55% (n = 90/163) had impairment of sharp-blunt discrimination, and 19% (n = 31/163) proprioceptive impairment. Distal regions of toes and foot were more frequently impaired than proximal regions (shin and thigh). Distal proprioception was significantly correlated with falls incidence (r = 0.25; p < 0.01), and centre of force velocity (r = 0.22, p < 0.01). The Walking Impact Scale was the only variable that significantly contributed to a predictive model of falls accounting for 15-20% of the variance. Conclusion: Lower limb somatosensory impairments are present in the majority of chronic stroke survivors and differ widely across modalities. Deficits of foot and ankle proprioception are most strongly associated with, but not predictive, of reported falls. The relative contribution of lower limb somatosensory impairments to mobility in chronic stroke survivors appears limited. Further investigation, particularly with regard to community mobility and falls, is warranted. Implications for Rehabilitation Somatosensory impairments in the lower limb were present in approximately half of this cohort of chronic stroke survivors. Tactile discrimination is commonly impaired; clinicians should include an assessment of discriminative ability. Deficits of foot and ankle proprioception are most strongly associated with reported falls. Understanding post-stroke lower limb somatosensory impairments may help inform therapeutic strategies that aim to maximise long-term participation, minimise disability, and reduce falls.

Strengthening food systems with remote Indigenous Australians: stakeholders' perspectives.

It is well accepted that actions to enhance food security and nutrition outcomes in remote Indigenous Australian communities have limited success when focusing on single factors and could far better be addressed by working across the whole food system. The formation of multi-sector groups to collectively work towards improved food security could facilitate this approach. This study sought to elicit the perceptions of a range of stakeholders on the enablers, barriers and perceived benefits of a multi-sector participatory approach that was developed and trialled with four communities to improve food security. Semi-structured interviews were used to collect data from 60 persons and transcripts were examined using thematic analysis. Findings revealed that there is support in engaging a diverse range of stakeholders in a process of community-led action to support incremental improvement. The employment and support of local community co-ordinators, the multi-sectoral and structured approach, the use of participatory tools, and the facilitation approach were identified as key enablers. Main barriers cited were competing demands and time restraints while a slowing in momentum and lack of timely communication of actions for follow-up were areas needing improvement. Perceived changes in the availability and accessibility of healthy food and improvements in retail practice were believed by participants to derive from (i) creating a supportive environment; (ii) bringing people together; and, (iii) increasing knowledge and capacity. This study offers insight into understanding where the opportunities are in supporting a multi-sectoral approach to improving food security in remote Indigenous Australia.

A training, assessment and feedback package for the trainee shoulder sonographer.

Diagnostic ultrasound of the shoulder is recognised as being one of the most technically challenging aspects of musculoskeletal ultrasound to master. It has a steep learning curve and makes gaining competency a time-intensive training process for both the trainee and their trainer. This article describes a training, assessment and feedback package developed within the framework of a Consortium for the Accreditation of Sonographic Education approved post-graduate ultrasound course. The package comprises: (i) a shoulder diagnostic ultrasound scan protocol with definition of findings, differential diagnosis and pro forma for recording scan findings, (ii) an assessment form for performance of shoulder diagnostic ultrasound scans with assessment criteria and (iii) a combined performance assessment and scan findings form, for each tissue being imaged. The package has been developed using medical education principles and provides a mechanism for trainees to follow an internationally recognised protocol. Supplementary information includes the differential diagnostic process used by an expert practitioner, which can otherwise be difficult to elicit. The package supports the trainee with recording their findings quickly and consistently and helps the trainee and trainer to explicitly recognise the challenges of scanning different patients or pathologies. It provides a mechanism for trainers to quantify and trainees to evidence their emerging competency. The package detailed in this article is therefore proposed for use in shoulder ultrasound training and its principles could be adapted for other musculoskeletal regions or other ultrasound disciplines.

Development of the good food planning tool: A food system approach to food security in indigenous Australian remote communities.

Few frameworks exist to assist food system planning, especially for Indigenous Australian remote communities. We developed a Good Food Planning Tool to support stakeholders to collectively plan and take action for local food system improvement. Development occurred over a four-year period through an evolving four phase participatory process that included literature review, several meetings with representatives of various organisations and communities and application of the Tool with multi-sector groups in each of four Indigenous Australian remote communities. A diverse range of 148 stakeholders, 78 of whom were Indigenous, had input to its development. Five food system domains: (i) Leadership and partnerships; (ii) Traditional food and local food production; (iii) Food businesses; (iv) Buildings, public places and transport; (v) Community and services and 28 activity areas form the framework of the Tool. The Good Food Planning Tool provides a useful framework to facilitate collective appraisal of the food system and to identify opportunities for food system improvement in Indigenous Australian remote communities, with potential for adaptation for wider application.

The dimerization of glucagon-like peptide-2 MIMETIBODY™ is linked to leucine-17 in the glucagon-like peptide-2 region.

Glucagon-like peptide-2 (GLP-2) is a member of the glucagon multigene family that is produced by intestinal enteroendocrine cells in response to food intake. GLP-2 stimulates growth of the intestinal epithelium, enhances its barrier functions, and increases nutrient uptake. Therefore, a GLP-2 agonist may be efficacious in human diseases characterized by malabsorption or injury to the gastrointestinal epithelium. MIMETIBODY™ refers to a proprietary scaffold developed to extend the half-life of rapidly cleared peptides. It consists of a peptide linked to a scaffold that contains sequence elements from a human immunoglobulin G including those that allow recycling through the FcRn. The GLP-2 sequence was engineered into the MIMETIBODY™ scaffold. The primary state of both GLP-2 and the GLP-2 MIMETIBODY™ in DPBS was a noncovalently associated dimer indicative of self-interaction. The increased heterogeneity and the decreased lot-to-lot reproducibility caused by the self-interaction of therapeutic proteins are a challenge to drug development. A similar protein, GLP-1 MIMETIBODY™, contains the related GLP-1 peptide and does not form a dimer under similar conditions. Therefore, to minimize or abrogate dimerization, several variants were made by substituting GLP-2 amino acids with the corresponding amino acids from GLP-1. Molecular weight and secondary structure analyses reveal that substituting leucine for glutamine at position 17 (L17Q) reduces dimerization and α-helix content yet retains bioactivity.

Geographic and outcome variation among black men diagnosed with prostate cancer.

BACKGROUND: Prostate cancer is the sixth leading cause of death from cancer among men worldwide. We have previously reported that prostate cancer survival rates for Caribbean-born males in the US was similar to survival rates of African-Americans and was higher than their counterparts diagnosed in the Caribbean. However, it is not clear whether differences in mortality could be attributed to differences in treatment. METHODS: This current analysis seeks to further explore reasons for the geographic variation of prostate cancer survival for Caribbean-born men. This analysis included 2,554 Black newly diagnosed prostate cancer cases (960 cases diagnosed in the US and 1,594 cases diagnosed in the Caribbean). Clinical data were extracted from the cancer registry and clinical charts. RESULTS: There were noted differences in the pattern of treatment for each place of birth category when stratified according to disease stage at diagnosis. Among the patients diagnosed with early-intermediate disease (stage I-III) the majority of US-born Brooklyn men were treated with surgery only (31%) and a similar pattern was observed for Caribbean-born Brooklyn men (35%). In contrast, the majority of Caribbean-born Trinidad & Tobago men were treated with hormone therapy (31%).Caribbean-born men diagnosed in the Caribbean had a significantly higher risk of death from prostate cancer (Adjusted Hazard [AdjHR]: 3.7, 95% Confidence Interval [CI]: 2.8-5.0) when compared with the risk of death for Caribbean-born males diagnosed in the US. This observation was consistent for each treatment group with the exception of the cases treated with hormone therapy only. For these cases, there was no difference in the risk of death between Caribbean-born males diagnosed in the Caribbean (AdjHR: 1.4, 95% CI: 0.8-2.6) compared to Caribbean-born males diagnosed in the US. CONCLUSIONS: In addition to difference in access and utilization of screening, differences in treatment strategy may also be a strong predictor of outcome for Caribbean-born males diagnosed with prostate cancer. Further studies are needed to confirm these findings. In addition, other environmental factors related to survival that was not considered in this analysis also need to be investigated.

Prostate cancer characteristics and survival in males of African Ancestry according to place of birth: data from Brooklyn-New York, Guyana, Tobago and Trinidad.

BACKGROUND: Prostate cancer mortality rates for African-Americans are much higher than Caucasians and a similar trend is observed for prostate cancer survival. Data on recently immigrated African-descent men are lacking. METHODS: Using cancer registry data from Brooklyn, NY and two countries in the Caribbean (Guyana and Trinidad and Tobago), survival rates were estimated. We also examined whether Black race or Caribbean birthplace predict prostate cancer survival among males living in the United States (US). RESULTS: The Caribbean cases were diagnosed at a later age than those in the US (Guyana: 74.5 years, Trinidad and Tobago: 72.4 years, Brooklyn: 65.8 years). Patients in the Caribbean had a worse 5-year survival rate compared to those in the US (41.6% vs. 84.4%) but for immigrant Caribbean-born males living in the US the 5-year survival rate was not significantly different from African-Americans (78.1%, 95% CI: 70.9-83.7% vs. 81.4%, 95% CI: 69.5-89.1%, P = 0.792). The risk of death for Caribbean-born was more than three times higher than US-born men (HR: 3.43, 95% CI: 2.17-5.44, adjusted for ethnicity, stage, and mean age of diagnosis). A mean age of diagnosis >65 years old and stage IV disease, but not ethnicity, were found to be independently associated with the risk of death. CONCLUSION: The survival disadvantage for Caribbean-born patients may be partly due to later diagnosis. Interventions focused on screening, education about the disease and early detection could potentially reduce cancer mortality in this population.

Noncanonical conformation of CDR L1 in the anti-IL-23 antibody CNTO4088.

CNTO4088 is a monoclonal antibody to human IL-23. The X-ray structure of the Fab fragment revealed an unusual noncanonical conformation of CDR L1. Most antibodies with the kappa light chain exhibit a canonical structure for CDR L1 in which residue 29 anchors the CDR loop to the framework. Analysis of the residues believed to define the conformation of CDR L1 did not explain why it should not adopt a canonical conformation in this antibody. This makes CNTO4088 a benchmark case for developing prediction methods and structure-modeling tools.

Disparities in uterine cancer survival in a Brooklyn cohort of black women.

AIM: The present study evaluates uterine cancer survival in a black cohort living in Brooklyn and determines whether foreign-born women have a health benefit over those born in the USA. MATERIALS & METHODS: De-identified cancer registry data were obtained for all black patients (n = 311) diagnosed with primary uterine cancer between 1993 and 2007. Survival rates were analyzed according to place of birth. RESULTS: The 5-year survival rate was slightly higher for US-born black patients; the predictors of overall survival were different for foreign-born black women compared with US-born black women. Age was a predictor of death in US-born women and type of treatment was a predictor in foreign-born women. CONCLUSION: This study demonstrates that grouping together US-born and foreign-born black patients may mask important differences within the black population. The observed differences between US-born and foreign-born black patients may be associated with variations in environmental and other lifestyle exposures that contribute to more aggressive histologic types.