The effect of manual therapy on ankle dorsiflexion range of motion: A pilot crossover randomized trial.

INTRODUCTION: Restricted ankle dorsiflexion is common after lower limb injury. The aim of this pilot study was to investigate the effect of passive ankle joint mobilization and calf muscle massage on ankle dorsiflexion range of motion in adults with residual restricted dorsiflexion. The secondary aim was to assess the methodology of the pilot study to inform a larger clinical trial. METHOD: The study design was a randomized crossover trial with assessor blinding. Twenty-five healthy participants with a history of lower limb injury were included in the study. Ankle joint mobilization and calf muscle massage were applied for 5 min in a random order, one to two weeks apart. Ankle dorsiflexion was measured by using the weight-bearing lunge pre- and post-intervention (cm). Paired t-tests were used to analyze the effect of the manual therapy interventions on restricted ankles. A minimal detectable difference 95% (MMD95) was calculated. The pilot study was analyzed for suitability of inclusion criteria, blinding of assessors and the manual therapist, and the washout period. RESULTS: A significant increase in dorsiflexion was demonstrated for ankle joint mobilization (change score = 0.51 ± 0.76, p = 0.003) and calf muscle soft tissue massage (change score = 0.91 ± 1.07, p < 0.001). There was no difference in change scores between manual therapy techniques (mobilization 0.51 ± 0.76, massage 0.91 ± 1.07, p = 0.12). Evaluation of the pilot study revealed limitations to be modified in future studies. CONCLUSION: These preliminary data indicate ankle joint mobilization and calf muscle soft tissue massage had similar effects on increasing ankle dorsiflexion range of motion in ankles with residual dorsiflexion restriction.

University staff perspectives on determinants of high-quality health professions student placements in regional, rural and remote Australia: protocol for a mixed-method study.

INTRODUCTION: In rural areas, work-integrated learning in the form of health student placements has several potential benefits, including contributing to student learning, enhancing rural health service capacity and attracting future rural health workforce. Understanding what constitutes a high-quality rural placement experience is important for enhancing these outcomes. There is no current standardised definition of quality in the context of rural health placements, nor is there understanding of how this can be achieved across different rural contexts. This study is guided by one broad research question: what do university staff believe are the determinants of high-quality health professions student placements in regional, rural and remote Australia? METHODS AND ANALYSIS: This study will adopt a convergent mixed-method design with two components. Component A will use explanatory sequential mixed methods. The first phase of component A will use a survey to explore determinants that contribute to the development of high-quality health student placements from the perspective of university staff who are not employed in University Departments of Rural Health and are involved in the delivery of health student education. The second phase will use semistructured interviews with the same stakeholder group (non-University Department of Rural Health university staff) to identify the determinants of high-quality health student placements. Component B will use a case study Employing COnceptUal schema for policy and Translation Engagement in Research mind mapping method to capture determinants that contribute to the development of high-quality health student placements from the perspective of University Department of Rural Health university staff. ETHICS AND DISSEMINATION: The University of Melbourne Human Ethics Committee approved the study (2022-23201-33373-5). Following this, seven other Australian university human research ethics committees provided external approval to conduct the study. The results of the study will be presented in several peer-review publications and summary reports to key stakeholder groups.

Global Equity in Clinical Trials: An ASCO Policy Statement.

ASCO is a global professional society representing more than 50,000 physicians, other health care professionals, and advocates in over 100 countries specializing in cancer treatment, diagnosis, prevention, and advocacy. ASCO strives, through research, education, and promotion of the highest quality of patient care, to create a world where cancer is prevented or cured, and every survivor is healthy. In this pursuit, health equity remains the guiding institutional principle that applies to all its activities across the cancer care continuum. This ASCO policy statement emphasizes the urgent need for global equity in clinical trials, aiming to enhance access and representation in cancer research as it not only improves cancer outcomes but also upholds principles of fairness and justice in health care.

The immediate and lasting balance outcomes of clinical falls-prevention programs: A non-randomised study.

PURPOSE: Exercise-based falls-prevention programs are cost-effective population-based approaches to reduce the risk of falling for older adults. The aim was to evaluate the short-term and long-term efficacy of three existing falls-prevention programs. METHODS: A non-randomized study design was used to compare the immediate-post and long-term physical outcome measures for three falls prevention programs; one high-level land-based program, one low-level land-based program and a water-based Ai Chi program. Timed-up-and-go (TUG), five-times sit-to-stand (5xSTS), six-minute walk test (6MWT) and six-meter walk test were assessed at baseline, post-program, and at six-months follow-up. Linear mixed models were used to analyze between- and within- group differences, with the high-level land-based program used as the comparator. RESULTS: Thirty-two participants completed post-program assessment and 26 returned for follow-up. There was a difference in the age (years) of participants between programs (p = 0.049). The intercept for TUG and six-meter walk test time was 47.70% (23.37, 76.83) and 32.31s (10.52, 58.41), slower for the low-level group and 40.49% (17.35, 69.89) and 36.34s (12.75, 64.87), slower for the Ai Chi group (p < 0.01), compared with the high-level group. Mean time taken to complete the TUG was less both immediately post-program and at 6-month follow-up (p = 0.05). Walking speed for the six-meter walk test was only faster at six-months (p < 0.05). The 5xSTS duration was significantly reduced only at post-intervention (p < 0.05). CONCLUSION: These results indicate land-based and water-based falls-prevention programs improve physical outcome measures associated with falls-risk and many improvements are maintained for six months after the completion of the program. (Retrospective trial registration: ACTRN1262300119069).

Effectiveness of exercise intervention on physical and health outcomes in patients admitted to an acute medical ward: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of inpatient medical ward exercise on physical and health outcomes in adults compared with usual care. DATA SOURCES: Medline, CINAHL and EMBASE were searched from inception to 20 April 2023. REVIEW METHODS: Randomised-controlled trials in English that reported physical and health outcomes of adults who received an exercise intervention on an acute medical ward were included. Two reviewers independently extracted data. Methodological quality was assessed using the PEDro and TESTEX scales. The GRADE rating assessed the quality of evidence to evaluate the certainty of effect. Meta-analyses were performed where possible. RESULTS: Thirteen studies were included, with 1273 unique participants (mean [SD] age, 75.5 [11] years), which compared exercise intervention with usual care. Low quality evidence demonstrated a significant improvement in aerobic capacity ([MD], 1.39 m [95% CI, 0.23, 2.55], p = 0.02) and maximum isometric strength ([MD], 2.3 kg [95% CI, 2.2, 2.4], p < 0.001) for the exercise intervention compared with usual care. Low quality evidence demonstrated no difference for in-hospital falls count ([OR], 1.93 [95% CI, 0.61, 6.12] p = 0.27) or mortality ([OR], 0.77 [95% CI, 0.48, 1.23], p = 0.27). Moderate quality evidence demonstrated no difference for length of stay ([MD], -0.10 days [95% CI, -0.31, 0.11] p = 0.36). CONCLUSION: Exercise prescribed during an acute medical ward stay improves aerobic capacity and maximum isometric strength but may not reduce length of stay, in-hospital falls or mortality.

Echocardiographic image collection and evaluation in infants with CHD: lessons learned from the imaging core lab for the Residual Lesion Score study.

Many factors affect patient outcome after congenital heart surgery, including the complexity of the heart disease, pre-operative status, patient specific factors (prematurity, nutritional status and/or presence of comorbid conditions or genetic syndromes), and post-operative residual lesions. The Residual Lesion Score is a novel tool for assessing whether specific residual cardiac lesions after surgery have a measurable impact on outcome. The goal is to understand which residual lesions can be tolerated and which should be addressed prior to leaving the operating room. The Residual Lesion Score study is a large multicentre prospective study designed to evaluate the association of Residual Lesion Score to outcomes in infants undergoing surgery for CHD. This Pediatric Heart Network and National Heart, Lung, and Blood Institute-funded study prospectively enrolled 1,149 infants undergoing 5 different congenital cardiac surgical repairs at 17 surgical centres. Given the contribution of echocardiographic measurements in assigning the Residual Lesion Score, the Residual Lesion Score study made use of a centralised core lab in addition to site review of all data. The data collection plan was designed with the added goal of collecting image quality information in a way that would permit us to improve our understanding of the reproducibility, variability, and feasibility of the echocardiographic measurements being made. There were significant challenges along the way, including the coordination, de-identification, storage, and interpretation of very large quantities of imaging data. This necessitated the development of new infrastructure and technology, as well as use of novel statistical methods. The study was successfully completed, but the size and complexity of the population being studied and the data being extracted required more technologic and human resources than expected which impacted the length and cost of conducting the study. This paper outlines the process of designing and executing this complex protocol, some of the barriers to implementation and lessons to be considered in the design of future studies.

Indigenizing Cardiac Rehabilitation - The Role for Cultural Adaptation.

Cardiac rehabilitation (CR) is an integral component of cardiovascular care, which reduces morbidity and mortality and improves quality of life. Largely as a result of Canada's colonial history, Indigenous communities face higher rates of cardiovascular morbidity and mortality. Indigenous Peoples in Canada have a unique cultural, historical, and geographic context that limits access to high-quality cardiovascular care, including CR, which has traditionally been delivered in an urban, hospital-based setting. Culturally-adapted, holistic exercise/diet programs and CR programs have been successful in Canada, Australia, and New Zealand, demonstrating acceptability to the community, safety, and improvements in cardiovascular risk factors. Key components of a successful culturally-adapted CR program include program leadership and development by Indigenous community members and key partners, cultural sensitivity training for healthcare providers and financial/geographic accessibility. Encouragement of traditional practices, including healthy traditional dietary practices and recognizing land-based activities as exercise have also proved important in the successful delivery of CR in Indigenous communities. This review summarizes the current evidence for culturally-adapted CR programming for Indigenous patients, including strategies to engage communities in education on cardiovascular risk factor optimization and to promote guideline-based exercise and diet through an Indigenous lens.

Reduction of Financial Health Incentives and Changes in Physical Activity.

Importance: Governments and others continue to use financial incentives to influence citizen health behaviors like physical activity. However, when delivered on a population scale they can be prohibitively costly, suggesting more sustainable models are needed. Objectives: To evaluate the association of incomplete financial incentive withdrawal ("schedule thinning") with physical activity after more than a year of incentive intervention and to explore whether participant characteristics (eg, app engagement and physical activity) are associated with withdrawal outcomes. Design, Setting, and Participants: This case-control study with a pre-post quasi-experimental design included users of a government-funded health app focused on financial incentives. Eligible participants were residents in 3 Canadian provinces over 25 weeks in 2018 and 2019. Data were analyzed from July 2021 to December 2022. Exposure: Due to fiscal constraints, financial incentives for daily physical activity goals were withdrawn in Ontario in December 2018 (case)-representing a 90% reduction in incentive earnings-but not in British Columbia or Newfoundland and Labrador (controls). Main Outcome and Measures: The primary outcome was objectively assessed weekly mean daily step count. Linear regression models were used to compare pre-post changes in daily step counts between provinces (a difference-in-differences approach). Separate models were developed to examine factors associated with changes in daily step count (eg, app engagement and physical activity). Clinically meaningful initial effect sizes were previously reported (approximately 900 steps/d overall and 1800 steps/d among the physically inactive). Results: In total there were 584 760 study participants (mean [SD] age, 34.3 [15.5] years; 220 388 women [63.5%]), including 438 731 from Ontario, 124 101 from British Columbia, and 21 928 from Newfoundland and Labrador. Significant physical activity declines were observed when comparing pre-post changes in Ontario to British Columbia (-198 steps/d; 95% CI, -224 to -172 steps/d) and Newfoundland and Labrador (-274 steps/d; 95% CI, -323 to -225 steps/d). The decrease was most pronounced for highly engaged Ontario users (-328 steps/d; 95% CI, -343 to -313 steps/d). Among physically inactive Ontario users, physical activity did not decline following withdrawal (107 steps/d; 95% CI, 90 to 124 steps/d). Conclusions and Relevance: In this case-control study of incomplete financial incentive withdrawal, statistically significant daily step count reductions were observed in Ontario; however, these declines were modest and not clinically meaningful. Amidst substantial program savings, the physical activity reductions observed here may be acceptable to decision-makers working within finite budgets.

Ki67 and breast cancer mortality in women with invasive breast cancer.

BACKGROUND: The percentage of cells staining positive for Ki67 is sometimes used for decision-making in patients with early invasive breast cancer (IBC). However, there is uncertainty regarding the most appropriate Ki67 cut points and the influence of interlaboratory measurement variability. We examined the relationship between breast cancer mortality and Ki67 both before and after accounting for interlaboratory variability and 8 patient and tumor characteristics. METHODS: A multicenter cohort study of women with early IBC diagnosed during 2009-2016 in more than 20 NHS hospitals in England and followed until December 31, 2020. RESULTS: Ki67 was strongly prognostic of breast cancer mortality in 8212 women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early IBC (Ptrend < .001). This relationship remained strong after adjustment for patient and tumor characteristics (Ptrend < .001). Standardization for interlaboratory variability did little to alter these results. For women with Ki67 scores of 0%-5%, 6%-10%, 11%-19%, and 20%-29% the corresponding 8-year adjusted cumulative breast cancer mortality risks were 3.3% (95% confidence interval [CI] = 2.8% to 4.0%), 3.7% (95% CI = 3.0% to 4.4%), 3.4% (95% CI = 2.8% to 4.1%), and 3.4% (95% CI = 2.8% to 4.1%), whereas for women with Ki67 scores of 30%-39% and 40%-100%, these risks were higher, at 5.1% (95% CI = 4.3% to 6.2%) and 7.7% (95% CI = 6.6% to 9.1) (Ptrend < .001). Similar results were obtained when the adjusted analysis was repeated with omission of pathological information about tumor size and nodal involvement, which would not be available preoperatively for patients being considered for neoadjuvant therapy. CONCLUSION: Our findings confirm the prognostic value of Ki67 scores of 30% or more in women with ER-positive, HER2-negative early IBC, irrespective of interlaboratory variability. These results also suggest that Ki67 may be useful to aid decision-making in the neoadjuvant setting.

Temporal evolution of the heart failure phenotype in Barth syndrome and treatment with elamipretide.

Barth syndrome (BTHS) is a rare genetic disorder caused by pathogenic variants in TAFAZZIN leading to reduced remodeled cardiolipin (CL), a phospholipid essential to mitochondrial function and structure. Cardiomyopathy presents in most patients with BTHS, typically appearing as dilated cardiomyopathy (DCM) in infancy and evolving to hypertrophic cardiomyopathy (HCM) resembling heart failure (HF) with preserved ejection fraction (HFpEF) in some patients ≥12 years. Elamipretide localizes to the inner mitochondrial membrane where it associates with CL, improving mitochondrial function, structure and bioenergetics, including ATP synthesis. Numerous preclinical and clinical studies in BTHS and other forms of HF have demonstrated that elamipretide improves left ventricular relaxation by ameliorating mitochondrial dysfunction, making it well suited for therapeutic use in adolescent and adult patients with BTHS.

Breast cancer mortality in 500 000 women with early invasive breast cancer diagnosed in England, 1993-2015: population based observational cohort study.

OBJECTIVES: To describe long term breast cancer mortality among women with a diagnosis of breast cancer in the past and estimate absolute breast cancer mortality risks for groups of patients with a recent diagnosis. DESIGN: Population based observational cohort study. SETTING: Routinely collected data from the National Cancer Registration and Analysis Service. PARTICIPANTS: All 512 447 women registered with early invasive breast cancer (involving only breast and possibly axillary nodes) in England during January 1993 to December 2015, with follow-up to December 2020. MAIN OUTCOME MEASURES: Annual breast cancer mortality rates and cumulative risks by time since diagnosis, calendar period of diagnosis, and nine characteristics of patients and tumours. RESULTS: For women with a diagnosis made within each of the calendar periods 1993-99, 2000-04, 2005-09, and 2010-15, the crude annual breast cancer mortality rate was highest during the five years after diagnosis and then declined. For any given time since diagnosis, crude annual breast cancer mortality rates and risks decreased with increasing calendar period. Crude five year breast cancer mortality risk was 14.4% (95% confidence interval 14.2% to 14.6%) for women with a diagnosis made during 1993-99 and 4.9% (4.8% to 5.0%) for women with a diagnosis made during 2010-15. Adjusted annual breast cancer mortality rates also decreased with increasing calendar period in nearly every patient group, by a factor of about three in oestrogen receptor positive disease and about two in oestrogen receptor negative disease. Considering just the women with a diagnosis made during 2010-15, cumulative five year breast cancer mortality risk varied substantially between women with different characteristics: it was <3% for 62.8% (96 085/153 006) of women but ≥20% for 4.6% (6962/153 006) of women. CONCLUSIONS: These five year breast cancer mortality risks for patients with a recent diagnosis may be used to estimate breast cancer mortality risks for patients today. The prognosis for women with early invasive breast cancer has improved substantially since the 1990s. Most can expect to become long term cancer survivors, although for a few the risk remains appreciable.

Neurologic Manifestations of Long COVID Differ Based on Acute COVID-19 Severity.

OBJECTIVE: To characterize neurologic manifestations in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients. METHODS: Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro-COVID-19 clinic between 5/2020 and 8/2021. RESULTS: PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre-existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were "brain fog" (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T-score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients. INTERPRETATION: PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro-PASC in these populations warranting targeted interventions. ANN NEUROL 2023;94:146-159.