“We Live on an Island:” Perspectives on Rural Family Caregiving for Adults with Alzheimer’s Disease and Related Dementias in the United States

As the United States’ aging population grows, there will be increased prevalence of individuals living with Alzheimer’s Disease and related dementias (ADRD), who largely rely on the support of their family caregivers. Family caregivers residing in rural areas face additional challenges with managing caregiving responsibilities and navigating support services. The purpose of this multilevel phenomenological qualitative study was to explore the assets, unique needs, and resources of rural-residing ADRD caregivers from the caregiver, provider, and policy influencers’ perspectives. The study took place between 2019 through 2021 in northern Arizona, a largely rural and geographically vast area home to caregivers from diverse backgrounds. Twenty-seven caregivers to a loved one with ADRD participated in focus groups. Twelve health and social services providers and twelve policy influencers, those involved in leadership positions for aging programs or advocacy groups, completed individual interviews. Caregivers demonstrate many assets which contribute to their ability to manage and cope with their caregiving role. However, caregivers face a series of issues related to their caregiving role and need early and ongoing education regarding ADRD. There is a lack of resources available in rural areas, in particular providers, making it challenging to obtain needed resources necessary to support their loved one with ADRD. Furthermore, there is a need for more providers trained in working with aging adults and those experiencing ADRD, and a need for more culturally relevant resources

Musculoskeletal pain and loneliness, social support and social engagement among older adults : analysis of the Oxford Pain, Activity and Lifestyle Cohort

Background: Musculoskeletal (MSK) pain is common in older adults. Physical and psychological consequences of MSK pain have been established, but it is also important to consider the social impact. We aimed to estimate the association between MSK pain and loneliness, social support and social engagement. Methods: We used baseline data from the Oxford Pain, Activity and Lifestyle study. Participants were community‐dwelling adults aged 65 years or older from across England. Participants reported demographic information, MSK pain by body site, loneliness, social support and social engagement. We categorised pain by body regions affected (upper limb, lower limb and spinal). Widespread pain was defined as pain in all three regions. We used logistic regression models to estimate associations between distribution of pain and social factors, controlling for covariates. Results: Of the 4977 participants analysed, 4193 (84.2%) reported any MSK pain, and one‐quarter (n = 1298) reported widespread pain. Individuals reporting any pain were more likely to report loneliness (OR [odds ratio]: 1.62; 95% CI [confidence interval]: 1.32–1.97) or insufficient social support (OR: 1.54; 95% CI: 1.08–2.19) compared to those reporting no pain. Widespread pain had the strongest association with loneliness (OR: 1.94; 95% CI: 1.53–2.46) and insufficient social support (OR: 1.71; 95% CI: 1.14–2.54). Pain was not associated with social engagement. Conclusions: Older adults commonly report MSK pain, which is associated with loneliness and perceived insufficiency of social support. This finding highlights to clinicians and researchers the need to consider social implications of MSK pain in addition to physical and psychological consequences

Risk Factors for Mobility Decline in Community-Dwelling Older Adults: A Systematic Literature Review

Mobility is essential to maintaining independence for older adults. This systematic review aimed to summarize evidence about self-reported risk factors for self-reported mobility decline; and to provide an overview of published prognostic models for self-reported mobility decline among community-dwelling older adults. Databases were searched from inception to June 2, 2020. Studies were screened by two independent reviewers who extracted data and assessed study quality. Sixty-one studies (45,187 participants) were included, providing information on 107 risk factors. High-quality evidence and moderate/large effect sizes for the association with mobility decline were found for older age beyond 75 years, the presence of widespread pain, and mobility modifications. Moderate-high quality evidence and small effect sizes were found for a further 21 factors. Three model development studies demonstrated acceptable model performance, limited by high risk of bias. These findings should be considered in intervention development, and in developing a prediction instrument for practical application

Current physical therapy care of patients undergoing breast reconstruction for breast cancer: a survey of practice in the United Kingdom and Brazil

Background In both the United Kingdom (UK) and Brazil, women undergoing mastectomy should be offered breast reconstruction. Patients may benefit from physical therapy to prevent and treat muscular deficits. However, there are uncertainties regarding which physical therapy program to recommend. Objective The aim was to investigate the clinical practice of physical therapists for patients undergoing breast reconstruction for breast cancer. A secondary aim was to compare physical therapy practice between UK and Brazil. Methods Online survey with physical therapists in both countries. We asked about physical therapists’ clinical practice. Results 181 physical therapists completed the survey, the majority were from Brazil (77%). Respondents reported that only half of women having breast reconstruction were routinely referred to physical therapy postoperatively. Contact with patients varied widely between countries, the mean number of postoperative sessions was 5.7 in the UK and 15.1 in Brazil. The exercise programs were similar for different reconstruction operations. Therapists described a progressive loading structure over time: range of motion (ROM) was restricted to 90° of arm elevation in the first two postoperative weeks; by 2–4 weeks ROM was unrestricted; at 1–3 months muscle strengthening was initiated, and after three months the focus was on sports-specific activities. Conclusion Only half of patients having a breast reconstruction are routinely referred to physical therapy. Patients in Brazil have more intensive follow-up, with up to three times more face-to-face contact with a physical therapist than in the UK. Current practice broadly follows programs for mastectomy care rather than being specific to reconstruction surgery

Prevention of Shoulder Problems trial (PROSPER) : Physiotherapist Manual [intervention manual and related materials]

This Physiotherapist Manual contains the relevant information to prepare physiotherapists for delivering the PROSPER exercise programme. The main concepts from each chapter will be covered in detail during your PROSPER training. This is your own reference manual with the relevant background information about trial processes and procedures. The trial is run by the Warwick Clinical Trials Unit based at the University of Warwick and is funded by the National Institute for Health Research (NIHR) under the Health Technology Assessment (HTA) funding stream. The purpose of the trial is to investigate whether postoperative exercise can improve function and quality of life in women at high risk of developing shoulder problems after breast cancer treatment. Some physiotherapists will have considerable experience of treating women with breast cancer or treating patients with musculoskeletal shoulder problems. However, not everyone will have the same skill and experience level, therefore this manual has been written to account for differences in background training, skill and clinical expertise. The aims of this Physiotherapist Manual are: - To explain the trial design; - To describe common side effects from breast cancer treatment; - To provide the research evidence for the PROSPER exercise intervention; - To describe procedures for the assessment and treatment of PROSPER study participants; - To describe trial documentation and reporting procedures. This manual has been produced to ‘standardise’ treatment and to reduce the risk of differences between physiotherapists and centres providing care. For all trial participants referred to your service, we ask that you adhere to the manual. This does not affect the care of non-trial participants, please treat your other patients in your usual way. You may even decide to use some of the approaches within the manual for non-trial patients. Thank you again for taking part in PROSPER. We hope you enjoy reading the manual and we very much look forward to working with you

Better Outcomes for Older people with Spinal Trouble (BOOST) Trial: a randomised controlled trial of a combined physical and psychological intervention for older adults with neurogenic claudication, a protocol

Introduction Neurogenic claudication due to spinal stenosis is common in older adults. The effectiveness of conservative interventions is not known. The aim of the study is to estimate the clinical and cost-effectiveness of a physiotherapist-delivered, combined physical and psychological intervention. Methods and analysis This is a pragmatic, multicentred, randomised controlled trial. Participants are randomised to a combined physical and psychological intervention (Better Outcomes for Older people with Spinal Trouble (BOOST) programme) or best practice advice (control). Community-dwelling adults, 65 years and over, with neurogenic claudication are identified from community and secondary care services. Recruitment is supplemented using a primary care-based cohort. Participants are registered prospectively and randomised in a 2:1 ratio (intervention:control) using a web-based service to ensure allocation concealment. The target sample size is a minimum of 402. The BOOST programme consists of an individual assessment and twelve 90 min classes, including education and discussion underpinned by cognitive behavioural techniques, exercises and walking circuit. During and after the classes, participants undertake home exercises and there are two support telephone calls to promote adherence with the exercises. Best practice advice is delivered in one to three individual sessions with a physiotherapist. The primary outcome is the Oswestry Disability Index at 12 months. Secondary outcomes include the 6 Minute Walk Test, Short Physical Performance Battery, Fear Avoidance Beliefs Questionnaire and Gait Self-Efficacy Scale. Outcomes are measured at 6 and 12 months by researchers who are masked to treatment allocation. The primary statistical analysis will be by ‘intention to treat’. There is a parallel health economic evaluation and qualitative study

The use of phylogeny to interpret cross-cultural patterns in plant use and guide medicinal plant discovery: an example from Pterocarpus (Leguminosae)

The study of traditional knowledge of medicinal plants has led to discoveries that have helped combat diseases and improve healthcare. However, the development of quantitative measures that can assist our quest for new medicinal plants has not greatly advanced in recent years. Phylogenetic tools have entered many scientific fields in the last two decades to provide explanatory power, but have been overlooked in ethnomedicinal studies. Several studies show that medicinal properties are not randomly distributed in plant phylogenies, suggesting that phylogeny shapes ethnobotanical use. Nevertheless, empirical studies that explicitly combine ethnobotanical and phylogenetic information are scarce.In this study, we borrowed tools from community ecology phylogenetics to quantify significance of phylogenetic signal in medicinal properties in plants and identify nodes on phylogenies with high bioscreening potential. To do this, we produced an ethnomedicinal review from extensive literature research and a multi-locus phylogenetic hypothesis for the pantropical genus Pterocarpus (Leguminosae: Papilionoideae). We demonstrate that species used to treat a certain conditions, such as malaria, are significantly phylogenetically clumped and we highlight nodes in the phylogeny that are significantly overabundant in species used to treat certain conditions. These cross-cultural patterns in ethnomedicinal usage in Pterocarpus are interpreted in the light of phylogenetic relationships.This study provides techniques that enable the application of phylogenies in bioscreening, but also sheds light on the processes that shape cross-cultural ethnomedicinal patterns. This community phylogenetic approach demonstrates that similar ethnobotanical uses can arise in parallel in different areas where related plants are available. With a vast amount of ethnomedicinal and phylogenetic information available, we predict that this field, after further refinement of the techniques, will expand into similar research areas, such as pest management or the search for bioactive plant-based compounds

Exercise to prevent shoulder problems after breast cancer surgery : the PROSPER RCT

Background: Upper limb problems are common after breast cancer treatment. Objectives: To investigate the clinical effectiveness and cost-effectiveness of a structured exercise programme compared with usual care on upper limb function, health-related outcomes and costs in women undergoing breast cancer surgery. Design: This was a two-arm, pragmatic, randomised controlled trial with embedded qualitative research, process evaluation and parallel economic analysis; the unit of randomisation was the individual (allocated ratio 1 : 1). Setting: Breast cancer centres, secondary care. Participants: Women aged ≥ 18 years who had been diagnosed with breast cancer and were at higher risk of developing shoulder problems. Women were screened to identify their risk status. Interventions: All participants received usual-care information leaflets. Those randomised to exercise were referred to physiotherapy for an early, structured exercise programme (three to six face-to-face appointments that included strengthening, physical activity and behavioural change strategies). Main outcome measures: The primary outcome was upper limb function at 12 months as assessed using the Disabilities of Arm, Hand and Shoulder questionnaire. Secondary outcomes were function (Disabilities of Arm, Hand and Shoulder questionnaire subscales), pain, complications (e.g. wound- related complications, lymphoedema), health-related quality of life (e.g. EuroQol-5 Dimensions, five-level version; Short Form questionnaire-12 items), physical activity and health service resource use. The economic evaluation was expressed in terms of incremental cost per quality-adjusted life-year and incremental net monetary benefit gained from an NHS and Personal Social Services perspective. Participants and physiotherapists were not blinded to group assignment, but data collectors were blinded. Results: Between 2016 and 2017, we randomised 392 participants from 17 breast cancer centres across England: 196 (50%) to the usual-care group and 196 (50%) to the exercise group. Ten participants (10/392; 3%) were withdrawn at randomisation and 32 (8%) did not provide complete baseline data. A total of 175 participants (89%) from each treatment group provided baseline data. Participants’ mean age was 58.1 years (standard deviation 12.1 years; range 28–88 years). Most participants had undergone axillary node clearance surgery (327/392; 83%) and 317 (81%) had received radiotherapy. Uptake of the exercise treatment was high, with 181 out of 196 (92%) participants attending at least one physiotherapy appointment. Compliance with exercise was good: 143 out of 196 (73%) participants completed three or more physiotherapy sessions. At 12 months, 274 out of 392 (70%) participants returned questionnaires. Improvement in arm function was greater in the exercise group [mean Disabilities of Arm, Hand and Shoulder questionnaire score of 16.3 (standard deviation 17.6)] than in the usual-care group [mean Disabilities of Arm, Hand and Shoulder questionnaire score of 23.7 (standard deviation 22.9)] at 12 months for intention-to-treat (adjusted mean difference Disabilities of Arm, Hand and Shoulder questionnaire score of –7.81, 95% confidence interval –12.44 to –3.17; p = 0.001) and complier-average causal effect analyses (adjusted mean difference –8.74, 95% confidence interval –13.71 to –3.77; p ≤ 0.001). At 12 months, pain scores were lower and physical health-related quality of life was higher in the exercise group than in the usual-care group (Short Form questionnaire-12 items, mean difference 4.39, 95% confidence interval 1.74 to 7.04; p = 0.001). We found no differences in the rate of adverse events or lymphoedema over 12 months. The qualitative findings suggested that women found the exercise programme beneficial and enjoyable. Exercise accrued lower costs (–£387, 95% CI –£2491 to £1718) and generated more quality-adjusted life years (0.029, 95% CI 0.001 to 0.056) than usual care over 12 months. The cost-effectiveness analysis indicated that exercise was more cost-effective and that the results were robust to sensitivity analyses. Exercise was relatively cheap to implement (£129 per participant) and associated with lower health-care costs than usual care and improved health-related quality of life. Benefits may accrue beyond the end of the trial. Limitations: Postal follow-up was lower than estimated; however, the study was adequately powered. No serious adverse events directly related to the intervention were reported. Conclusions: This trial provided robust evidence that referral for early, supported exercise after breast cancer surgery improved shoulder function in those at risk of shoulder problems and was associated with lower health-care costs than usual care and improved health-related quality of life. Future work: Future work should focus on the implementation of exercise programmes in clinical practice for those at highest risk of shoulder problems. Trial registration: This trial is registered as ISRCTN35358984. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 15. See the NIHR Journals Library website for further project information

MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus

Deletions at chromosome 2p25.3 are associated with a syndrome consisting of intellectual disability and obesity. The smallest region of overlap for deletions at 2p25.3 contains PXDN and MYT1L. MYT1L is expressed only within the brain in humans. We hypothesized that single nucleotide variants (SNVs) in MYT1L would cause a phenotype resembling deletion at 2p25.3. To examine this we sought MYT1L SNVs in exome sequencing data from 4, 296 parent-child trios. Further variants were identified through a genematcher-facilitated collaboration. We report 9 patients with MYT1L SNVs (4 loss of function and 5 missense). The phenotype of SNV carriers overlapped with that of 2p25.3 deletion carriers. To identify the transcriptomic consequences of MYT1L loss of function we used CRISPR-Cas9 to create a knockout cell line. Gene Ontology analysis in knockout cells demonstrated altered expression of genes that regulate gene expression and that are localized to the nucleus. These differentially expressed genes were enriched for OMIM disease ontology terms “mental retardation”. To study the developmental effects of MYT1L loss of function we created a zebrafish knockdown using morpholinos. Knockdown zebrafish manifested loss of oxytocin expression in the preoptic neuroendocrine area. This study demonstrates that MYT1L variants are associated with syndromic obesity in humans. The mechanism is related to dysregulated expression of neurodevelopmental genes and altered development of the neuroendocrine hypothalamus