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Background: Private hospitals in Australia manage 11% of acute and 48% of rehabilitation stroke admissions, yet little is known about implementation of stroke clinical guidelines in this setting. Clinical guidelines recommend that acute stroke patients be co-located in a stroke unit in a geographically defined area, rather than dispersed across the hospital., Objective: To investigate post-intervention adherence to clinical guidelines for stroke management, and to explore staff barriers and facilitators to guideline implementation., Methods: Observational study before-and-after local implementation of Australian stroke clinical guidelines. The primary outcome was a change in the proportion of patients who were physically co-located in an acute stroke unit. Secondary outcomes included changes in adherence to additional acute and rehabilitation guideline criteria, and staff identification of barriers and facilitators to guide implementation. Data were collected from medical record audits, health service information and staff surveys., Results: Co-location in an acute stroke unit did not change significantly after guideline implementation (49% adherence pre-intervention and 54% post-intervention). Across acute and rehabilitation wards, 15% (11/72) of guideline criteria improved (p < .05). These related to assessments of swallowing and neglect, presence of a stroke care co-ordinator and occupational therapist, post-discharge care plan, provision of patient education and return to driving. Facilitators to guideline implementation included staff education, collaboration, and dissemination of user-friendly stroke policies., Conclusion: Stroke clinical guideline implementation led to a favorable uptake of some criteria, yet not all. Implementation was assisted by staff education, user-friendly stroke policies and multidisciplinary team collaboration., Trial Registration: ANZCTR: registration number ACTRN12616000646448 (http://www.ANZCTR.org.au/ACTRN12616000646448.aspx).

Background: People living with Parkinson's disease (PD) have a high risk for falls., Objective: To examine gaps in falls prevention targeting people with PD as part of the Task Force on Global Guidelines for Falls in Older Adults., Methods: A Delphi consensus process was used to identify specific recommendations for falls in PD. The current narrative review was conducted as educational background with a view to identifying gaps in fall prevention., Results: A recent Cochrane review recommended exercises and structured physical activities for PD; however, the types of exercises and activities to recommend and PD subgroups likely to benefit require further consideration. Freezing of gait, reduced gait speed, and a prior history of falls are risk factors for falls in PD and should be incorporated in assessments to identify fall risk and target interventions. Multimodal and multi-domain fall prevention interventions may be beneficial. With advanced or complex PD, balance and strength training should be administered under supervision. Medications, particularly cholinesterase inhibitors, show promise for falls prevention. Identifying how to engage people with PD, their families, and health professionals in falls education and implementation remains a challenge. Barriers to the prevention of falls occur at individual, environmental, policy, and health system levels., Conclusion: Effective mitigation of fall risk requires specific targeting and strategies to reduce this debilitating and common problem in PD. While exercise is recommended, the types and modalities of exercise and how to combine them as interventions for different PD subgroups (cognitive impairment, freezing, advanced disease) need further study., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Prostate cancer progression to the lethal metastatic castration-resistant phenotype (mCRPC) is driven by αv integrins and is associated with Golgi disorganization and activation of the ATF6 branch of unfolded protein response (UPR). Overexpression of integrins requires N-acetylglucosaminyltransferase-V (MGAT5)-mediated glycosylation and subsequent cluster formation with Galectin-3 (Gal-3). However, the mechanism underlying this altered glycosylation is missing. For the first time, using HALO analysis of IHC, we found a strong association of integrin αv and Gal-3 at the plasma membrane (PM) in primary prostate cancer and mCRPC samples. We discovered that MGAT5 activation is caused by Golgi fragmentation and mislocalization of its competitor, N-acetylglucosaminyltransferase-III, MGAT3, from Golgi to the endoplasmic reticulum (ER). This was validated in an ethanol-induced model of ER stress, where alcohol treatment in androgen-refractory PC-3 and DU145 cells or alcohol consumption in patient with prostate cancer samples aggravates Golgi scattering, activates MGAT5, and enhances integrin expression at PM. This explains known link between alcohol consumption and prostate cancer mortality. ATF6 depletion significantly blocks UPR and reduces the number of Golgi fragments in both PC-3 and DU145 cells. Inhibition of autophagy by hydroxychloroquine (HCQ) restores compact Golgi, rescues MGAT3 intra-Golgi localization, blocks glycan modification via MGAT5, and abrogates delivery of Gal-3 to the cell surface. Importantly, the loss of Gal-3 leads to reduced integrins at PM and their accelerated internalization. ATF6 depletion and HCQ treatment synergistically decrease integrin αv and Gal-3 expression and temper orthotopic tumor growth and metastasis., Implications: Combined ablation of ATF6 and autophagy can serve as new mCRPC therapeutic., (©2023 American Association for Cancer Research.)

Low back pain is prevalent in the community and associated with deficits in core muscle strength and activation. Pilates is argued to improve movement and reduce pain, yet there is a limited understanding of the specific effects of Pilates training on core muscle strength or activity. A systematic search of databases (CINAHL, Embase, Ovid MEDLINE) used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methods to evaluate randomised controlled trials (RCTs) on the effects of Pilates to improve core muscle activation. Methodological quality was assessed using the Physiotherapy Evidence Database scale (PEDro). The certainty of findings was determined using the Grading of Recommendations Assessment, Development and Evaluation tool. Of the initial yield of 563 articles, eight RCTs met the inclusion criteria. A diverse range of Pilates interventions and outcome measures were utilised to assess effects on core muscle activation and strength. The main finding was that Pilates is not inferior to equivalently dosed exercises, and can be superior to non-equivalent or no exercise, for improving core muscle strength as indicated by muscle thickness. There was emerging evidence that Pilates positively impacts core muscle strength and can be an effective intervention for people living with chronic low back pain.

There is a need to ensure that healthcare organisations enable their workforces to use digital methods in service delivery. This study aimed to evaluate the current level of digital understanding and ability in nursing, midwifery, and allied health workforces and identify some of the training requirements to improve digital literacy in these health professionals. Representatives from eight healthcare organizations in Victoria, Australia participated in focus groups. Three digital frameworks informed the focus group topic guide that sought to examine the barriers and enablers to adopting digital healthcare along with training requirements to improve digital literacy. Twenty-three participants self-rated digital knowledge and skills using Likert scales and attended the focus groups. Mid-range scores were given for digital ability in nursing, midwifery, and allied health professionals. Focus group participants expressed concern over the gap between their organizations' adoption of digital methods relative to their digital ability, and there were concerns about cyber security. Participants also saw a need for the inclusion of consumers in digital design. Given the widening gap between digital innovation and health workforce digital capability, there is a need to accelerate digital literacy by rapidly deploying education and training and policies and procedures for digital service delivery.

Background: Dancing is an engaging physical activity for people living with Parkinson's disease (PD). We conducted a process evaluation for a PD trial on online dancing. Methods: "ParkinDANCE Online" was co-produced by people with PD, healthcare professionals, dance instructors, and a PD organisation. The evaluation mapped the following inputs: (i) stakeholder steering group to oversee program design, processes, and outcomes; (ii) co-design of online classes, based on a research evidence synthesis, expert advice, and stakeholder recommendations; (iii) trial fidelity. The key activities were (i) the co-design of classes and instruction manuals, (ii) the education of dance teachers, (iii) fidelity checking, (iv) online surveys, (v) and post-trial focus groups and interviews with participants. The outputs pertained to: (i) recruitment, (ii) retention, (iii) adverse events, (iv) fidelity, (v) protocol variations, and (vi) participant feedback. Results: Twelve people with PD, four dance instructors and two physiotherapists, participated in a 6-week online dance program. There was no attrition, nor were there any adverse events. Program fidelity was strong with few protocol variations. Classes were delivered as planned, with 100% attendance. Dancers valued skills mastery. Dance teachers found digital delivery to be engaging and practical. The safety of online testing was facilitated by careful screening and a home safety checklist. Conclusions: It is feasible to deliver online dancing to people with early PD.

Background and Objectives: Internal neurofibromas, including plexiform neurofibromas (PNF), can cause significant morbidity in patients with neurofibromatosis type 1 (NF1). PNF growth is most pronounced in children and young adults, with more rapid growth thought to occur in a subset of PNF termed distinct nodular lesions (DNL). Growth behavior of internal neurofibromas and DNL in older adults is not well documented; yet knowledge thereof is important for patient risk stratification and clinical trial design. The primary objective of this study was to evaluate the long-term growth behavior of internal neurofibromas in adults with NF1. Secondary objectives were to correlate tumor growth behavior with patient-specific, tumor-specific, and patient-reported variables., Methods: In this prospective cohort study, internal neurofibromas were identified on coronal short TI inversion recovery sequences on baseline and follow-up whole-body MRIs (WBMRIs). Tumor growth and shrinkage were defined as a volume change ≥20%. The association between tumor growth and patient-specific (baseline age, sex, and genotype), tumor-specific (morphology, location, DNL presence on baseline WBMRI, and maximum standardized uptake value on baseline PET imaging), and patient-reported variables (endogenous and exogenous hormone exposure, pain intensity, and quality of life) was assessed using the Spearman correlation coefficient and Kruskal-Wallis test., Results: Of 106 patients with a baseline WBMRI obtained as part of a previous research study, 44 had a follow-up WBMRI. Three additional patients with WBMRIs acquired for clinical care were included, generating 47 adults for this study. The median age during baseline WBMRI was 42 years (range 18-70). The median time between WBMRIs was 10.4 years. Among 324 internal neurofibromas, 62.8% (56% of PNF and 62.1% of DNL) shrank spontaneously without treatment and 17.1% (17.9% of PNF and 13.8% of DNL) grew. Growth patterns were heterogeneous within participants. Patient-specific, tumor-specific, and patient-reported variables (including endogenous and exogenous hormone exposure) were not strong predictors of tumor growth., Discussion: Internal neurofibroma growth behavior in older adults differs fundamentally from that in children and young adults, with most tumors, including DNL, demonstrating spontaneous shrinkage. Better growth models are needed to understand factors that influence tumor growth. These results will inform clinical trial design for internal neurofibromas., (© 2022 American Academy of Neurology.)

Despite the understanding that renal clearance is pivotal for driving the pharmacokinetics of numerous therapeutic proteins and peptides, the specific processes that occur following glomerular filtration remain poorly defined. For instance, sites of catabolism within the proximal tubule can occur at the brush border, within lysosomes following endocytosis, or even within the tubule lumen itself. The objective of the current study was to address these limitations and develop methodology to study the kidney disposition of a model therapeutic protein. Exenatide is a peptide used to treat type 2 diabetes mellitus. Glomerular filtration and ensuing renal catabolism have been shown to be its principal clearance pathway. Here, we designed and validated a Förster resonance energy transfer-quenched exenatide derivative to provide critical information on the renal handling of exenatide. A combination of in vitro techniques was used to confirm substantial fluorescence quenching of intact peptide that was released upon proteolytic cleavage. This evaluation was then followed by an assessment of the in vivo disposition of quenched exenatide directly within kidneys of living rats via intravital two-photon microscopy. Live imaging demonstrated rapid glomerular filtration and identified exenatide metabolism occurred within the subapical regions of the proximal tubule epithelia, with subsequent intracellular trafficking of cleaved fragments. These results provide a novel examination into the real-time, intravital disposition of a protein therapeutic within the kidney and offer a platform to build upon for future work.

Aim: The aim of this study was to design, deliver and evaluate an interprofessional education programme for healthcare professionals on how to implement a modified version of the safe recovery programme to prevent falls in hospitalized patients., Design: Mixed methods design incorporating pre- and post education surveys and individual semi-structured interviews., Methods: Thirty-four health professional participants attended a 1-h face-to-face or Zoom® interprofessional education session to learn how to deliver an evidence-based patient falls prevention education strategy, the modified Safe Recovery Programme., Results: A 1-hour education session was insufficient to build full confidence to deliver the Safe Recovery Programme. There was no statistically significant change in participant views on interprofessional collaboration. Participants recommended prior consultation and preparation before delivery of IPE, with additional opportunities for discussion and feedback during implementation with patients. The findings highlight the importance of interprofessional education for evidence-based interventions in hospitals. Health professionals value education that is timely, interactive, realistic and engaging., (© 2022 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

This publication represents the first to report global information on characteristics and requirements of doctoral programs in the pharmaceutical sciences in schools/colleges of Pharmacy. Survey responses (140 responses) were received from doctoral programs in 23 countries, with the greatest number of responses obtained from Japan, followed by India and the United States. Program characteristics and requirements, and student and faculty information, including graduate placement, in programs in Asia, North America, Europe, Africa and Australia were compared. Survey responses indicated differences in entrance requirements for doctoral programs with minimum requirements being a bachelor's degree, pharmacy degree or master's degree, including a M.Phil. degree. Programs differed widely in size in all geographical areas, but there was a similar emphasis on core educational learning outcomes (core competencies) and Ph.D. graduation requirements including qualifying examinations, thesis defense with internal and external reviewers and requirements for peer-reviewed publications. Additionally, three-quarters of programs indicated that there was external review of their programs every 2-4 or 5-7 years. Female students and female faculty mentors represented about 50% of students/faculty in programs in most geographical areas. Placement of students after graduation indicated that the highest percentage went into the pharmaceutical industry in Asia (predominantly India) and North America, with a lower percentage in Europe, Africa and Australia., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Information on master's programs in the pharmaceutical sciences is lacking; this manuscript addresses this gap in the literature, by reporting on the results of an international survey performed in 2021 of master's programs in the pharmaceutical sciences offered at Schools/Colleges of Pharmacy. Ninety-six responses were received from universities from 23 countries, with the greatest number of responses obtained from India, followed by the United States and Japan. Master's programs in the pharmaceutical sciences are generally full time and 2 years in duration. Only 3% of programs were reported to be examination-based, while the remaining 97% had a research component with 70% of programs having a thesis defense with external and/or internal examiners. Master's programs tended to be larger in Asia and Europe than in North America; as well, programs in North America tended to have more international students. Didactic coursework was included in 96% of master's programs in North America, but only in 38% of Asian and 58% of European programs. The predominant placement of graduates from master's programs in Asia was in the pharmaceutical industry (70%); this contrasted with programs in Europe, Africa and North America where 28-36% enter careers in the pharmaceutical industry and higher percentages enter Ph.D. programs. The major challenge identified by programs was funding of faculty and of graduate students, although decreasing career opportunities was identified as a challenge in Asia and Africa., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare no conflict of interest., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Codesign strengthens partnerships between healthcare workers and patients. It also facilitates collaborations supporting the development, design and delivery of healthcare services. Prior rehabilitation reviews have focused mainly on the clinical and organisational outcomes of codesign with less focus on the lived experience of rehabilitation patients., Objective: To explore patient experiences of codesigned hospital rehabilitation interventions., Design: Rapid review and evidence synthesis of the literature., Data Sources: CINAHL, MEDLINE, Embase and Cochrane were searched from 1 January 2000 to 25 April 2022., Study Selection: Studies reporting patient experiences of codesigned rehabilitation interventions in hospitals., Results: 4156 studies were screened, and 38 full-text studies were assessed for eligibility. Seven studies were included in the final rapid review. Five out of the seven studies involved neurological rehabilitation. All eligible studies used qualitative research methods. The main barriers to codesign were related to staffing and dedicated time allocated to face-to-face patient-therapist interactions. High-quality relationships between patients and their therapists were a facilitator of codesign. Thematic synthesis revealed that codesigned rehabilitation interventions can enable a meaningful experience for patients and facilitate tailoring of treatments to align with individual needs. Personalised rehabilitation increases patient involvement in rehabilitation planning, delivery and decision-making. It also promotes positive feelings of empowerment and hope., Conclusion: This rapid review supports the implementation of codesigned rehabilitation interventions to improve patient experiences in hospitals., Prospero Registration Number: CRD42021264547., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Traumatic brain injuries (TBI) represent a significant percentage of critical injuries in military conflicts. Following injury, wounded warfighters are often subjected to multiple aeromedical evacuations (AE) and associated hypobaria, yet the impact in TBI patients remains to be characterized. This study evaluated the impact of two consecutive simulated AEs in a fluid-percussion TBI model in swine to characterize these effects., Methods: Following instrumentation, anesthetized Yorkshire swine underwent a frontal TBI via fluid-percussion. A hypobaric chamber was then used to simulate AE at simulated cabin pressure equivalent to 8000ft (hypobaria) in a 6 h initial flight on day 3, followed by a 9 h flight on day 6, and were monitored for 14 days. Animals in the normobaria group were subjected to the same steps at sea level while Sham animals in both groups were instrumented but not injured. Parameters measured included physiologic response, intracranial pressure (ICP), hematology, chemistry, and serum cytokines. Histopathology of brain, lung, intestine, and kidney was performed, as well as fluorojade staining to evaluate neurodegeneration. All animals were divided into sub-groups by block randomization utilizing a 2-way ANOVA to analyze independent variables., Results: Survival was 100% in all groups. Physiologic parameters were largely similar across groups as well during both 6 and 9 h AE. Animals exposed to hypobaria in both the TBI and Sham groups had elevated heart rate (HR) during the 6 h flight (p<0.05). Three animals in the TBI hypo group demonstrated leukocytosis with histologic evidence of meningeal inflammatory response. Expression of serum cytokines was low across all groups. No significant neuronal degeneration was identified in areas away from the site of injury., Conclusion: Aeromedical evacuation in swine was not associated with significant differences in physiologic measures, cytokine expression or levels of neuronal degeneration. Histological examination revealed higher risk of meningeal inflammatory response and leucocytosis in swine exposed to hypobaria., Competing Interests: Declaration of Competing Interests None of the authors have any commercial associations that might create a conflict of interest nor do any of the authors have any financial interests or personal relationships with other people or organizations that would represent a conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Megalin and cubilin, endocytic proteins present in the proximal tubule of the kidney, are responsible for reabsorbing filtered proteins from urine. Our hypothesis was that potential substrates of megalin/cubilin could be identified by examining urinary protein differences between control (WT) mice and kidney-specific megalin knockdown (KD) mice. Using the IonStar proteomics approach, 877 potential megalin/cubilin substrates were discovered, with 23 of these compounds representing known megalin/cubilin substrates. Some of the proteins with the largest fold changes in the urine between KD and WT included the known megalin substrates retinol-binding protein and vitamin D-binding protein. Of the total proteins identified as novel substrates, about three-quarters of compounds had molecular weights (MWs) below 69 kDa, the MW of albumin, and the remaining had higher MWs, with about 5% of the proteins having MWs greater than 150 kDa. Sex differences in the number of identified substrates occurred, but this may be due to differences in kidney megalin expression between both male and female megalin KD and WT animals, with the ratio of megalin between WT and KD being 2.76 and 2.14 for female and male mice, respectively. The top three ingenuity canonical pathways based on the urinary proteins in both female and male KD mice were acute phase response signaling, liver X receptor/retinoid X receptor activation, and intrinsic prothrombin activation pathways. In conclusion, analysis of urine samples from kidney-specific megalin KD and WT mice was found to be useful for the identification of potential endogenous substrates for megalin and cubilin., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The estrous cycle is regulated by rhythmic endocrine interactions of the nervous and reproductive systems, which coordinate the hormonal and ovulatory functions of the ovary. Folliculogenesis and follicle progression require the orchestrated response of a variety of cell types to allow the maturation of the follicle and its sequela, ovulation, corpus luteum formation, and ovulatory wound repair. Little is known about the cell state dynamics of the ovary during the estrous cycle and the paracrine factors that help coordinate this process. Herein, we used single-cell RNA sequencing to evaluate the transcriptome of >34,000 cells of the adult mouse ovary and describe the transcriptional changes that occur across the normal estrous cycle and other reproductive states to build a comprehensive dynamic atlas of murine ovarian cell types and states., Competing Interests: MM, MM, MC, HS, AK, NS, NN, SY, RS, MH, PD, BS, DP No competing interests declared, (© 2022, Morris, Meinsohn et al.)

Background and Purpose: Exercise interventions can improve physical recovery and reduce falls in older adults following hospitalization. The aim of the study was to identify factors associated with exercise engagement after hospital discharge., Methods: This study was a secondary analysis of data collected as part of a randomized controlled trial. Participants were 60 years and older, discharged from 3 rehabilitation hospitals in Australia, and followed for 6 months after discharge. The primary outcome was level of engagement in exercise after discharge, measured using setting, type, frequency, and time. A secondary outcome was self-efficacy for exercise at 6-month follow-up. Data were gathered at baseline in hospital and at 6 months after discharge by telephone using structured surveys. Associations between exercise and participant characteristics were evaluated using logistic regression models., Results and Discussion: Participants' (n = 292) mean age was 78 (SD 8) years and 63% were female. There were 146 (50%) who exercised after hospitalization for a median (interquartile range) time of 60 (60-75) minutes per week. Characteristics that were significantly associated with post-discharge engagement in exercise were having higher levels of functional ability at discharge (adjusted odds ratio [AOR] 1.2, 95% CI 1.0, 1.4), living with a partner (AOR 2.9, 95% CI 1.7, 4.9), and engagement in exercise prior to hospital admission (AOR 1.7, 95% CI 1.0, 2.8). The mean self-efficacy for exercise score at 6 months post-discharge was 58.5/90 (SD 24.5). Characteristics that were significantly predictive of a higher mean self-efficacy score at 6 months after hospitalization were having a college or university education (adjusted β-coefficient [Adj β] 11.5, 95% CI 3.8, 19.0), exercise prior to hospital admission (Adj β 12.3, 95% CI 5.1, 19.5), living with a partner at discharge (Adj β 14.5, 95% CI 7.1, 21.9), and higher functional ability at discharge (Adj β 4.0, 95% CI 1.9, 6.1)., Conclusion: Older adults have low levels of engagement in exercise that might impact their recovery after hospitalization. During exercise prescription, clinicians should prioritize older adults who live alone, who have lower functional ability, and no previous habit of exercising., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 APTA Geriatrics, An Academy of the American Physical Therapy Association.)

Objective: To investigate the feasibility and preliminary effects of Pilates exercises in primigravida women., Design: Single-blind randomized controlled feasibility trial., Setting: Community Pilates classes., Participants: Low-risk pregnant women., Interventions: Pregnant women were randomly assigned to Pilates exercises (experimental) group for 6 consecutive weeks or usual antenatal care, the control group., Main Outcomes: The primary outcome was feasibility of Pilates classes. Secondary outcomes included quality of life, pain, and mobility., Results: 21 women were recruited to the trial. Eleven were randomly allocated to the experimental group and 10 to the control group. Retention of participants was excellent for the Pilates group (100%) compared to 70% in the control group. There were no adverse events. The Pilates group showed greater gains in quality of life on the SF-12 from the pre-test (M = 81.0, SD = 11.8) to the post-test (M = 83.3, SD = 8.52) compared to the control group (pre-test M = 69.78, SD = 15.9) (post-test M = 68.1, SD = 16.05) (Wald Chi-Square = 5.597, p = 0.018). Although the duration of labour was shorter in the Pilates group (Mdn = 215, IQR: 279 min) than usual care (Mdn = 458.5, IQR: 305 min), the difference was not statistically significant. There were no significant differences between groups for pain, mobility, abdominal separation, urinary continence, analgesia, or the mode of birth., Conclusions: Modified Pilates appears feasible and safe for low-risk pregnant women. Further research is needed in on this topic., Competing Interests: Declaration of competing interest, (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Questions: In people recovering from traumatic brain injury, is a 3-month ballistic resistance training program targeting three lower limb muscle groups more effective than non-ballistic exercise rehabilitation for improving mobility, strength and balance? Does improved mobility translate to better health-related quality of life?, Design: A prospective, multicentre, randomised trial with concealed allocation, intention-to-treat analysis and blinded measurement., Participants: A total of 144 people with a neurological movement disorder affecting mobility as a result of traumatic brain injury., Intervention: For 3 months, the experimental group had three 60-minute sessions of non-ballistic exercise rehabilitation per week replaced by ballistic resistance training. The control group had non-ballistic exercise rehabilitation of equivalent time. The non-ballistic exercise rehabilitation consisted of balance exercises, lower limb stretching, conventional strengthening exercises, cardiovascular fitness training and gait training., Outcome Measures: The primary outcome was mobility measured using the High-Level Mobility Assessment Tool (HiMAT). Secondary outcomes were walking speed, strength, balance and quality of life. They were measured at baseline (0 months), after completion of the 3-month intervention (3 months) and 3 months after cessation of intervention (6 months)., Results: After 3 months of ballistic resistance training, the experimental group scored 3 points (95% CI 0 to 6) higher on the 54-point HiMAT than the control group and remained 3 points (95% CI -1 to 6) higher at 6 months. Although there was a transient decrement in balance at 3 months in the experimental group, the interventions had similar effects on all secondary outcomes by 6 months. Participants with a baseline HiMAT < 27 gained greater benefit from ballistic training: 6 points (1 to 10) on the HiMAT., Conclusion: This randomised trial shows that ballistic resistance training has a similar or better effect on mobility than non-ballistic training in people with traumatic brain injury. It may be better targeted towards those with more severe mobility limitations., Trial Registration: ACTRN12611001098921., (Copyright © 2022 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.)

Objective Implementing the routine collection of patient reported outcome measures (PROMs) is key to improving healthcare quality and patient satisfaction. The implementation process can be strengthened through staff and patient co-design. The aim of this project was to develop a set of Australian PROM implementation recommendations ('AusPROM') to guide rapid translation into practice. Methods Staff working across 29 Australian private hospitals participated in the project. The hospitals provided elective surgery and spanned each state and territory of Australia. Staff engaged in a Delphi technique to develop the AusPROM, which involved three iterative focus groups. To ensure full disclosure, staff were also provided with additional project-related data sources throughout the Delphi technique. This included data from a patient focus group (patient co-design), patient survey, technical feasibility testing, 3 months of pilot testing (four sites), 3 months of national implementation (29 sites) and global evidence. This process ensured that staff and patient feedback was used to co-design the three iterations of the AusPROM recommendations until the final agreed version was established. Results A total of 22 AusPROM recommendations were included in the final iteration. The recommendations covered the domains of PROM characteristics, healthcare organisation characteristics, external influences, staff and patient characteristics, and facilitators to implementing AusPROMS in routine practice. Conclusion The AusPROM recommendations offer practical considerations for the implementation of PROMs in hospitals. The iterative nature of the Delphi technique ensured that staff and patient co-design were central to the development of the AusPROM recommendations.

Background: falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present., Objectives: to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders; (ii) gaps in previous guidelines; (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries., Methods: a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting., Recommendations: all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations., Conclusions: the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To explore the opinions of people living with Parkinson's disease about access to and participation in community aquatic therapy., Methods: Focus groups and individual interviews were conducted with people living with Parkinson's disease in Ireland ( n  = 24) and Australia ( n  = 10). All discussions were audio-recorded, transcribed verbatim, and thematically analysed., Results: Four main themes were identified. Primarily, participants were optimistic about their reasons for choosing aquatic therapy and found it beneficial to their health and well-being. Optimal components of aquatic therapy identified were access to individually tailored aquatic programs, completed as a minimum once a week, at a moderate to high-intensity level, and guided by a credentialed instructor. Fear was a significant barrier for a small proportion of participants and was linked to water competence, past experiences, and fall risk associated with the aquatic environment. Participants identified a strong need for education and increased awareness about aquatic therapy benefits to promote greater engagement., Conclusion: Aquatic therapy is a popular exercise choice for people with Parkinson's disease, especially in the early to middle disease stages. Considering the views of people living with Parkinson's disease can aid the design and implementation of interventions and future aquatic research internationally.Implications for RehabilitationAquatic therapy is emerging as an effective physiotherapy approach for managing motor and non-motor symptoms in Parkinson's disease.Little is known regarding community-based aquatic therapy programs from the perspectives of people living with Parkinson's disease internationally.People with Parkinson's disease may benefit from timely information about the unique benefits, prerequisites, and local aquatic therapy facilities to promote greater uptake of aquatic programs.Tailored aquatic therapy interventions delivered within a group setting by a credentialed healthcare professional may increase long-term adherence.

Patient education is key to preventing hospital falls yet is inconsistently implemented by health professionals. A mixed methods study was conducted involving a ward-based evaluation of patients receiving education from health professionals using a scripted conversation guide with a falls prevention brochure, followed by semi-structured qualitative interviews with a purposive sample of health professionals involved in delivering the intervention. Over five weeks, 37 patients consented to surveys (intervention n = 27; control n = 10). The quantitative evaluation showed that falls prevention education was not systematically implemented in the trial ward. Seven individual interviews were conducted with health professionals to understand the reasons why implementation failed. Perceived barriers included time constraints, limited interprofessional collaboration, and a lack of staff input into designing the research project and patient interventions. Perceived enablers included support from senior staff, consistent reinforcement of falls education by health professionals, and fostering patient empowerment and engagement. Recommended strategies to enhance implementation included ensuring processes were in place supporting health professional accountability, the inclusion of stakeholder input in designing the falls intervention and implementation processes, as well as leadership engagement in falls prevention education. Although health professionals play a key role in delivering evidence-based falls prevention education in hospitals, implementation can be compromised by staff capacity, capability, and opportunities for co-design with patients and researchers. Organisational buy-in to practice change facilitates the implementation of evidence-based falls prevention activities.

Background: Patient reported outcome measures (PROMs) engage patients in co-evaluation of their health and wellbeing outcomes. This study aimed to determine the feasibility, response rate, degree of recovery and patient acceptability of a PROM survey for elective surgery., Methods: We sampled patients with a broad range of elective surgeries from four major Australian hospitals to evaluate (1) feasibility of the technology used to implement the PROMs across geographically dispersed sites, (2) response rates for automated short message service (SMS) versus email survey delivery formats, (3) the degree of recovery at one and four weeks post-surgery as measured by the Quality of Recovery 15 Item PROM (QoR-15), and (4) patient acceptability of PROMS based on survey and focus group results. Feasibility and acceptability recommendations were then co-designed with stakeholders, based on the data., Results: Over three months there were 5985 surveys responses from 20,052 surveys (30% response rate). Feasibility testing revealed minor and infrequent technical difficulties in automated email and SMS administration of PROMs prior to surgery. The response rate for the QoR-15 was 34.8% (n = 3108/8919) for SMS and 25.8% (n = 2877/11,133) for email. Mean QoR-15 scores were 122.1 (SD 25.2; n = 1021); 113.1 (SD 27.7; n = 1906) and 123.4 (SD 26.84; n = 1051) for pre-surgery and one and four weeks post-surgery, respectively. One week after surgery, 825 of the 1906 responses (43%) exceeded 122.6 (pre-surgery average), and at four weeks post-surgery, 676 of the 1051 responses (64%) exceeded 122.6 (pre-surgery average). The PROM survey was highly acceptable with 76% (n = 2830/3739) of patients rating 8/10 or above for acceptability. Fourteen patient driven recommendations were then co-developed., Conclusion: Administering PROMS electronically for elective surgery hospital patients was feasible, acceptable and discriminated changes in surgical recovery over time. Patient co-design and involvement provided innovative and practical solutions to implementation and new recommendations for implementation. Trial Registration and Ethical Approval ACTRN12621000298819 (Phase I and II) and ACTRN12621000969864 (Phase III). Ethics approval has been obtained from La Trobe University (Australia) Human Research Ethics Committee (HEC20479)., Key Points: Patient reported outcome measures (PROMs) help to engage patients in understanding their health and wellbeing outcomes. This study aimed to determine how patients feel about completing a PROM survey before and after elective surgery, and to develop a set of recommendations on how to roll out the survey, based on patient feedback. We found that implementing an electronic PROM survey before and after elective surgery was relatively easy to do and was well accepted by patients. Consumer feedback throughout the project enabled co-design of innovative and practical solutions to PROM survey administration., (© 2022. The Author(s).)

Virtual communities of practice consist of individuals who use a common online platform to share professional expertise and experiences. In healthcare settings a virtual community of practice (VCoP) can optimise knowledge, skills, and the implementation of evidence-based practice. To ensure effective knowledge synthesis and translation into practice, it is essential to clarify the best methods for designing and implementing VCoPs within healthcare organisations. This scoping review aimed to identify the methods used to establish and facilitate online or digitally enabled communities of practice within healthcare organisations across the globe. Six online databases identified papers published from January 2010 to October 2020. Papers were independently screened by two reviewers using Covidence. Data were captured and analysed using a data extraction chart in Covidence. Twenty-four publications that detail methods for establishing a VCoP in healthcare were included. Few studies used a framework to establish a VCoP. It was difficult to identify details regarding methods of development and key elements such as roles, how they were coordinated, and types of technology used. Healthcare organisations can benefit from using a standardised framework for the establishment, implementation and evaluation of VCoPs to improve practice, staff engagement, and knowledge sharing.

Background: During the COVID-19 pandemic, cardiovascular patients were found to be presenting to hospitals with myocardial infarctions and cerebrovascular accidents at progressed disease states. We noticed a parallel in acute limb ischemia (ALI) patients presenting during Massachusetts' COVID-19 State of Emergency declaration. We question whether patients developed a hesitancy to seek medical attention at hospitals due to fear of COVID-19. Our objective was to compare acuity of ALI, interventions, and limb survival in patients presenting before, during, and after a state of emergency., Methods: Four timeframes were set to compare patients presenting peri-2020 COVID-19 State of Emergency and patients presenting during a pre-pandemic era at a tertiary, academic institution. A reference period from 2019, Pre-State of Emergency period, State of Emergency period, and Post-State of Emergency period were designated. Patient characteristics, interventions, and outcomes data were collected. Unpaired t-test, ANOVA, and Chi-square statistical analyses were used., Results: A total of 95 patients presenting with ALI were identified. Compared to Reference group, state of emergency group had more patients presenting with Rutherford Class III, 12.9% vs 35%, and less patient presenting with Class I, 45.1% vs 0%, P = .02. State of emergency group had more delayed presentations with ≥6 hours after symptom onset, 45% vs 85%, P = .01. Above-knee amputations were performed in 20% of patients during state of emergency and 31.6% for Post-State of Emergency, vs 6.5% in the Reference group; P = .03. There was no difference in intensive care unit admission, length of stay, or mortality between patients from different groups., Conclusion: During a state of emergency, ALI patients were noted to present later from symptom onset, have greater disease severity, and more likely to undergo amputations. We suspect delay in presentation and limb lost to be attributed to reluctance to seek immediate medical attention.

Monocarboxylate transporter 6 (MCT6; SLC16A5) is an orphan transporter protein with expression in multiple tissues. The endogenous function of MCT6 related to human health and disease remains unknown. Our previous transcriptomic and proteomic analyses in Mct6 knockout (KO) mice suggested that MCT6 may play a role in lipid and glucose homeostasis, but additional evidence is required. Thus, the objective of this study was to further explore the impact of MCT6 on metabolic function using untargeted metabolomic analysis in Mct6 KO mice. The plasma from male and female mice and livers from male mice were submitted for global metabolomics analysis to assess the relative changes in endogenous small molecules across the liver and systemic circulation associated with absence of Mct6. More than 782 compounds were detected with 101 and 51 metabolites significantly changed in plasma of male and female mice, respectively, and 100 metabolites significantly changed in the livers of male mice (p < .05). Significant perturbations in lipid metabolism were annotated in the plasma and liver metabolome, with additional alterations in the amino acid metabolism pathway in plasma samples from male and female mice. Elevated lipid diacylglycerol and altered fatty acid metabolite concentrations were found in liver and plasma samples of male Mct6 KO mice. Significant reduction of N-terminal acetylated amino acids was found in plasma samples of male and female Mct6 KO mice. In summary, the present study confirmed the significant role of MCT6 in lipid and amino acid homeostasis, suggesting its contribution in metabolic diseases., (© 2022 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Obtaining pre-surgery PROM measures is not always feasible. The aim of this study was to examine if self-reports of change following elective surgery correlate with change scores from a validated PROM (15-item Quality of Recovery (QoR-15)). This cross-sectional study across 29 hospitals enrolled elective surgery patients. PROMs were collected one-week pre-surgery, as well as one- and four-weeks post-surgery via an electronic survey. We examined associations between patient “judgement of change” at one and four-weeks after surgery and the actual pre-to post-surgery PROM change scores. A total of 4177 surveys were received. The correlation between patient judgement of change, and the actual change score was moderately strong at one-week (n = 247, rs = 0.512, p < 0.001), yet low at four-weeks (n = 241, rs = 0.340, p < 0.001). Patient judgement was aligned to the direction of the PROM change score from pre- to post-surgery. We also examined the correlation between the QoR-15 (quality of recovery) and the EQ-5D-5L (QOL). There was a moderately strong positive correlation between the two PROMs (n = 356, rs = 0.666, p < 0.001), indicating that change in quality of recovery was related to change in QOL. These findings support the use of a single “judgement of change” recall question post-surgery.

High doses of the partial agonist of the GABA B receptor, γ-hydroxybutyric acid (GHB), causes respiratory depression that can lead to death. Previously, it has been shown that GABA B- receptor antagonism is able to prevent respiratory depression and sedation when inhibitors are pre-administered. In order to treat GHB overdoses, safety and efficacy of a treatment strategy at various times after GHB administration is necessary, in order to more closely replicate a true overdose situation. Preliminary studies developed an assay for SGS742 and determined its pharmacokinetics in rats. The effects of SGS742 on GHB-induced respiratory depression were evaluated when SGS742 administration was delayed 1 and 2 hours after intravenous or oral administration of GHB or γ-butyrolactone, a GHB prodrug. SGS742 reversed GHB-induced respiratory depression in a dose-dependent manner at both time points tested, with no effects on its toxicokinetics. However, some of the dosing paradigms resulted in toxicity in the form of tremors, seizures or abnormal movements. The tremors/seizures occurred in a manner that was dependent on both the dose and timing of SGS742 administration, and were not altered with pretreatment with gabazine, a GABA A receptor inhibitor, and only partially reduced with pretreatment with NCS382, a selective GHB receptor antagonist. Additional studies with a second GABA B antagonist SCH50911 demonstrated similar effects, producing reversal of respiratory depression but producing tremors and abnormal movements. Further studies are necessary in order to identify the potential use of GABA B antagonism as a treatment strategy for GHB overdoses. Significance Statement There is no current treatment for overdoses of the drug of abuse γ-hydroxybutyric acid (GHB). Since the toxicodynamic effects of GHB, including respiratory depression and lethality, are mediated through GABA B receptor agonism, GABA B receptor antagonists may represent a therapeutic strategy to treat overdoses. This study demonstrates that while GABA B receptor antagonists are effective as a pretreatment, they are less effective when administered at times after GHB administration and their administration is also associated with time- and dose-associated toxicity., (Copyright © 2020 American Society for Pharmacology and Experimental Therapeutics.)

Background: Falls remain a common and debilitating problem in hospitals worldwide. The aim of this study was to investigate the effects of falls prevention interventions on falls rates and the risk of falling in hospital., Design: Systematic review and meta-analysis., Participants: Hospitalised adults., Intervention: Prevention methods included staff and patient education, environmental modifications, assistive devices, policies and systems, rehabilitation, medication management and management of cognitive impairment. We evaluated single and multi-factorial approaches., Outcome Measures: Falls rate ratios (rate ratio: RaR) and falls risk, as defined by the odds of being a faller in the intervention compared to control group (odds ratio: OR)., Results: There were 43 studies that satisfied the systematic review criteria and 23 were included in meta-analyses. There was marked heterogeneity in intervention methods and study designs. The only intervention that yielded a significant result in the meta-analysis was education, with a reduction in falls rates (RaR = 0.70 [0.51-0.96], P = 0.03) and the odds of falling (OR = 0.62 [0.47-0.83], P = 0.001). The patient and staff education studies in the meta-analysis were of high quality on the GRADE tool. Individual trials in the systematic review showed evidence for clinician education, some multi-factorial interventions, select rehabilitation therapies, and systems, with low to moderate risk of bias., Conclusion: Patient and staff education can reduce hospital falls. Multi-factorial interventions had a tendency towards producing a positive impact. Chair alarms, bed alarms, wearable sensors and use of scored risk assessment tools were not associated with significant fall reductions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In hospitals, patient falls prevention education is frequently delivered by nurses and allied health professionals. Hospital falls rates remain high globally, despite the many systems and approaches that attempt to mitigate falling. The aim of this study was to investigate health professional views on the enablers and barriers to providing patient falls education in hospitals. Four focus groups with 23 nursing and allied health professionals were conducted at 3 hospitals. Three researchers independently coded the data and findings were analysed thematically with a descriptive qualitative approach to identify and develop themes according to barriers and enablers. Barriers included (i) limited interprofessional communication about patient falls; (ii) sub-optimal systems for falls education for patients and health professionals, and (iii) perceived patient-related barriers to falls education. Enablers to providing patient falls education included: (i) implementing strategies to increase patient empowerment; (ii) ensuring that health professionals had access to effective modes of patient education; and (iii) facilitating interprofessional collaboration. Health professionals identified the need to overcome organisational, patient and clinician-related barriers to falls education. Fostering collective responsibility amongst health professionals for evidence-based falls prevention was also highlighted., Competing Interests: The authors have declared that no competing interests exist.

Previous work from our laboratories has identified multiple defects in endocytosis, protein trafficking, and secretion, along with altered Golgi function after alcohol administration. Manifestation of alcohol-associated liver disease (ALD) is associated with an aberrant function of several hepatic proteins, including asialoglycoprotein receptor (ASGP-R), their atypical distribution at the plasma membrane (PM), and secretion of their abnormally glycosylated forms into the bloodstream, but trafficking mechanism is unknown. Here we report that a small GTPase, Rab3D, known to be involved in exocytosis, secretion, and vesicle trafficking, shows ethanol (EtOH)-impaired function, which plays an important role in Golgi disorganization. We used multiple approaches and cellular/animal models of ALD, along with Rab3D knockout (KO) mice and human tissue from patients with ALD. We found that Rab3D resides primarily in trans- and cis-faces of Golgi; however, EtOH treatment results in Rab3D redistribution from trans-Golgi to cis-medial-Golgi. Cells lacking Rab3D demonstrate enlargement of Golgi, especially its distal compartments. We identified that Rab3D is required for coat protein I (COPI) vesiculation in Golgi, and conversely, COPI is critical for intra-Golgi distribution of Rab3D. Rab3D/COPI association was altered not only in the liver of patients with ALD but also in the donors consuming alcohol without steatosis. In Rab3D KO mice, hepatocytes experience endoplasmic reticulum (ER) stress, and EtOH administration activates apoptosis. Notably, in these cells, ASGP-R, despite incomplete glycosylation, can still reach cell surface through ER-PM junctions. This mimics the effects seen with EtOH-induced liver injury. Conclusion: We revealed that down-regulation of Rab3D contributes significantly to EtOH-induced Golgi disorganization, and abnormally glycosylated ASGP-R is excreted through ER-PM connections, bypassing canonical (ER→Golgi→PM) anterograde transportation. This suggests that ER-PM sites may be a therapeutic target for ALD., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Introduction: Patient-centred care can be facilitated by co-design, which refers to collaboration between healthcare professionals and consumers in producing and implementing healthcare. Systematic reviews on co-design have mainly focused on the effectiveness of co-produced healthcare interventions. Less attention has been directed towards the experiences of patients in co-designed interventions. This rapid review aims to explore patient experiences of co-designed rehabilitation interventions and inform rehabilitation decision-making., Methods and Analysis: A rapid review will expedite timely information on co-design experiences for stakeholders. Four electronic databases, including Cochrane CENTRAL, MEDLINE, Embase and CINAHL, will be searched for papers published from 1 January 2000 to 1 January 2022. The Cochrane Risk of Bias tool will be used for randomised trials. Critical appraisal checklists from The Joanna Briggs Institute shall evaluate the risk of bias of non-randomised trials and qualitative studies. A narrative synthesis will be provided for the quantitative studies. Thematic synthesis will be conducted on qualitative findings. The overall strength of the evidence will be measured using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for quantitative investigations and the GRADE-Confidence in Evidence from Reviews of Qualitative Research for qualitative studies. The results will be presented using narrative summaries, identified themes, summary tables, flow charts and quantitative statistical analyses., Ethics and Dissemination: Ethics approval is not required for the review. The protocol and rapid review will be submitted to an online, open access and peer-reviewed journal for publication. The review findings will be rapidly translated to consumers, clinicians, healthcare leaders, organisations, researchers and policy makers via publications, evidence summaries, conferences, workshops, websites, social media and online events., Prospero Registration Number: CRD42021264547., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To test the feasibility, safety and effectiveness of the My Therapy programme for inpatients with mild-moderate cognitive impairment., Design: Observational pilot study., Patients: Rehabilitation inpatients with mild-moderate cognitive impairment., Methods: During their inpatient admission, participants received My Therapy, a programme that can increase the dose of rehabilitation through independent self-practice of exercises, outside of supervised therapy. Outcomes included My Therapy participation, falls, Functional Independence Measure (FIM) and 10-m walk test. Outcomes were compared with those of participants without cognitive impairment from the original My Therapy study ( n = 116) using χ 2 and independent t -tests., Results: Eight participants with mild-moderate cognitive impairment (mean (standard deviation (SD)) age 89.6 years (4.8); 3 women) were included. All participants completed the My Therapy programme on at least one day of their admission, with no associated falls. Participants had an 8.4 s (SD 5.1) reduction in their 10-m walk test and a 21.5 point (SD 11.1) improvement on FIM scores from admission to discharge. There were no significant between-group differences in feasibility, safety or effectiveness for participants with and without cognitive impairment., Conclusion: This pilot study has shown that including exercise self-management as part of inpatient rehabilitation is feasible, safe and effective for patients with cognitive impairment., Competing Interests: The authors have no conflicts of interest to declare., (Journal Compilation © 2022 Foundation of Rehabilitation Information.)

Background: Aquatic therapy is one therapy option for people living with Parkinson's disease (PD). However, the optimal prescription, dosage, and delivery remain unclear., Objective: i) To generate consensus statements, ii) to establish evidence-based clinical practice aquatic therapy guidelines for PD., Methods: Seventy-three international experts were invited to participate in a 3-step modified Delphi study. Gaps in the aquatic therapy evidence, patient preferences, and stakeholder engagement were considered when developing the initial list of 43-statements identified by the research development group. Practice experts rated each statement on an 11-point Likert scale. Consensus for inclusion was set at a priori of ≥70% of respondents scoring an item ≥7. Two rounds of Delphi questionnaires were completed online, and the expert comments were analyzed using content analysis. An online consensus meeting with an expert subgroup (n = 10) then advised on the guideline's acceptability and debated items until consensus for inclusion was reached., Results: Fifty experts participated in the Delphi round one (83% response rate) and 45 in round two (90% response rate), representing 15 countries. In round one, 35 statements met the criteria for consensus. Content analysis informed the revised statements in round two, where 12 of the remaining 16 statements met consensus. The final agreed aquatic therapy guidelines include key information about dosage, content, safety, contraindications, and the optimal aquatic therapy delivery throughout the disease course., Conclusion: Stakeholders, including international practice experts, informed a rigorous evidence-based approach to integrate the best available evidence, patient preferences, and practice expertise to inform these guidelines.

Introduction: Parkinson's disease can be associated with speech deterioration and low communication confidence which in turn compromises social interaction. Therapeutic singing is an engaging method for combatting speech decline; however, face-to-face delivery can limit access to group singing. The aim of this study is to test the feasibility and acceptability of an online mode of delivery for a Parkinson's singing intervention (ParkinSong) as well as remote data collection procedures., Methods and Analysis: This ParkinSong Online feasibility trial is a single-arm, pre-post study of online singing delivery and remote data collection for 30 people living with Parkinson's. The primary outcome measure is feasibility: recruitment, retention, attendance, safety, intervention fidelity, acceptability and associated costs. Secondary outcomes are speech (loudness, intelligibility, quality, communication-related quality of life) and wellbeing (apathy, depression, anxiety, stress, health-related quality of life). This mode of delivery aims to increase the accessibility of singing interventions., Ethics and Dissemination: Ethics approval was obtained from The University of Melbourne Human Research Ethics Committee (2021-14465-16053-3) and the trial has been prospectively registered. Results will be presented at national and international conferences, published in a peer-reviewed journal, and disseminated to the Parkinson's community, researchers and policymakers., Trial Registration Number: ACTRN12621000940875., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/. Drs Tamplin, Baker, Sousa, Haines and Vogel receive institutional support from The University of Melbourne. Dr Tamplin is the current President of the Australian Music Therapy Association. Prof. Morris has a joint appointment with Healthscope and La Trobe University. Prof. Vogel is the chief science officer of Redenlab who provided the remote speech data collection software. Mrs Tull is employed by Fight Parkinson’s who are co-funding this research., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: While the challenges for psychological well-being for Australian healthcare workers have been documented, there has been a dearth of qualitative research on the sources of resilience that sustained workers during the COVID-19 pandemic. This study identified sources of resilience that clinicians used to cope with frontline challenges during the COVID-19 pandemic., Methods: Semi-structured interviews were conducted with 20 frontline health professionals, across five Australian hospitals, between October 2020 and April 2021. The interviews were recorded and transcribed, and the results were analysed using thematic analysis based on a phenomenological approach., Results: Three sources of resilience were identified by respondents: personal, relational, and organisational. A positive mindset, sense of purpose, and self-care behaviours emerged as key sources of personal resilience. Teamwork, altruism, and social support from family and friends contributed to relational resilience. Leadership, effective communication, and effective implementation of COVID-19 policies were associated with resilience at the organisational level. Frontline healthcare workers also voiced the need for the implementation of further strategies to support personal resilience whilst nurturing resilience within clinical teams and across entire healthcare organisations., Conclusions: Trust in healthcare systems, organisation leaders, colleagues, and personal support teams was an overarching theme supporting resilience.

Background: Therapeutic dancing can be beneficial for people living with Parkinson's disease (PD), yet community-based classes can be difficult to access., Objective: To evaluate the feasibility and impact of online therapeutic dancing classes for people in the early to mid-stages of PD., Methods: Co-produced with people living with PD, physiotherapists, dance teachers and the local PD association, the 'ParkinDANCE' program was adapted to enable online delivery during the COVID-19 pandemic. Participants completed 8 one-hour sessions of online therapeutic dancing. Each person was assigned their own dance teacher and together they selected music for the classes. A mixed-methods design enabled analysis of feasibility and impact. Feasibility was quantified by attendance and adverse events. Impact was determined from individual narratives pertaining to consumer experiences and engagement, analysed with qualitative methods through a phenomenological lens., Results: Attendance was high, with people attending 100% sessions. There were no adverse events. Impact was illustrated by the key themes from the in-depth interviews: (i) a sense of achievement, enjoyment and mastery occurred with online dance; (ii) project co-design facilitated participant engagement; (iii) dance instructor capabilities, knowledge and skills facilitated positive outcomes; (iv) music choices were key; and (v) participants were able to quickly adapt to online delivery with support and resources., Conclusions: Online dance therapy was safe, feasible and perceived to be of benefit in this sample of early adopters. During the pandemic, it was a viable form of structured physical activity. For the future, online dance may afford benefits to health, well-being and social engagement.

Purpose: There is limited understanding of the characteristics and evaluation of more affected hand dexterity loss in Parkinson's disease. We described 9-Hole Peg Test performance for the more affected hand and examined the construct validity of these pegboard scores in mild to severe Parkinson's disease. Methods: This observational study analysed baseline data from a cluster-randomised controlled trial.Participants ( n  = 582) completed the pegboard with their more affected hand, the Patient-Specific Index-Parkinson's Disease and Self-assessment Parkinson's Disease Disability Scale. Mean pegboard performance was summarised at each disease stage. To investigate known groups validity, we explored differences in pegboard scores between participants identifying upper limb problems in their 'top three' functional limitations, and those prioritising other limitations. Convergent validity investigated correlations between pegboard performance and self-reported hand function., Results: Pegboard performance was reduced compared with normative values, and problems with hand activities were reported at each disease stage. Significant differences in pegboard performance between the two functional limitation priority groups ( p  < 0.05), and moderate correlations between pegboard dexterity and hand function (Self-assessment Parkinson's Disease Disability Scale) provided evidence for construct validity., Conclusions: People with mild to severely disabling Parkinson's disease have reduced dexterity and problems with hand function. Evidence supported the construct validity of 9-Hole Peg Test more affected hand performance.IMPLICATIONS FOR REHABILITATIONPeople with mild to severely disabling PD experience dexterity loss and problems with hand function.It is important for clinicians to assess dexterity and hand function in people with this movement disorder.Evidence supports the construct validity of 9-Hole Peg Test for measuring more affected hand performance in Parkinson's disease.

Background: Implementing evidence into clinical practice is a key focus of healthcare improvements to reduce unwarranted variation. Dissemination of evidence-based recommendations and knowledge brokering have emerged as potential strategies to achieve evidence implementation by influencing resource allocation decisions. The aim of this study was to determine the effectiveness of these two research implementation strategies to facilitate evidence-informed healthcare management decisions for the provision of inpatient weekend allied health services., Methods and Findings: This multicentre, single-blinded (data collection and analysis), three-group parallel cluster randomised controlled trial with concealed allocation was conducted in Australian and New Zealand hospitals between February 2018 and January 2020. Clustering and randomisation took place at the organisation level where weekend allied health staffing decisions were made (e.g., network of hospitals or single hospital). Hospital wards were nested within these decision-making structures. Three conditions were compared over a 12-month period: (1) usual practice waitlist control; (2) dissemination of written evidence-based practice recommendations; and (3) access to a webinar-based knowledge broker in addition to the recommendations. The primary outcome was the alignment of weekend allied health provision with practice recommendations at the cluster and ward levels, addressing the adoption, penetration, and fidelity to the recommendations. The secondary outcome was mean hospital length of stay at the ward level. Outcomes were collected at baseline and 12 months later. A total of 45 clusters (n = 833 wards) were randomised to either control (n = 15), recommendation (n = 16), or knowledge broker (n = 14) conditions. Four (9%) did not provide follow-up data, and no adverse events were recorded. No significant effect was found with either implementation strategy for the primary outcome at the cluster level (recommendation versus control β 18.11 [95% CI -8,721.81 to 8,758.02] p = 0.997; knowledge broker versus control β 1.24 [95% CI -6,992.60 to 6,995.07] p = 1.000; recommendation versus knowledge broker β -9.12 [95% CI -3,878.39 to 3,860.16] p = 0.996) or ward level (recommendation versus control β 0.01 [95% CI 0.74 to 0.75] p = 0.983; knowledge broker versus control β -0.12 [95% CI -0.54 to 0.30] p = 0.581; recommendation versus knowledge broker β -0.19 [-1.04 to 0.65] p = 0.651). There was no significant effect between strategies for the secondary outcome at ward level (recommendation versus control β 2.19 [95% CI -1.36 to 5.74] p = 0.219; knowledge broker versus control β -0.55 [95% CI -1.16 to 0.06] p = 0.075; recommendation versus knowledge broker β -3.75 [95% CI -8.33 to 0.82] p = 0.102). None of the control or knowledge broker clusters transitioned to partial or full alignment with the recommendations. Three (20%) of the clusters who only received the written recommendations transitioned from nonalignment to partial alignment. Limitations include underpowering at the cluster level sample due to the grouping of multiple geographically distinct hospitals to avoid contamination., Conclusions: Owing to a lack of power at the cluster level, this trial was unable to identify a difference between the knowledge broker strategy and dissemination of recommendations compared with usual practice for the promotion of evidence-informed resource allocation to inpatient weekend allied health services. Future research is needed to determine the interactions between different implementation strategies and healthcare contexts when translating evidence into healthcare practice., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12618000029291., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the outcomes of face-to-face, digital, and virtual modes of dancing for people living with Parkinson's disease (PD)., Design: Systematic review informed by Cochrane and PRIMSA guidelines. Data Sources. Seven electronic databases were searched: AMED, Cochrane, PEDro, CINHAL, PsycINFO, EMBASE, and MEDLINE., Methods: Eligible studies were randomised controlled trials (RCT) and other trials with quantitative data. The PEDro scale evaluated risk of bias for RCTs. Joanna Briggs Institute instruments were used to critically appraise non-RCTs. The primary outcome was the feasibility of dance interventions, and the secondary outcomes included gait, balance, quality of life, and disability., Results: The search yielded 8,327 articles after duplicates were removed and 38 met the inclusion criteria. Seven were at high risk of bias, 20 had moderate risk of bias, and 11 had low risk of bias. There was moderately strong evidence that dance therapy was beneficial for balance, gait, quality of life, and disability. There was good adherence to digital delivery of dance interventions and, for people with PD, online dance was easy to access., Conclusion: Dancing is an accessible form of exercise that can benefit mobility and quality of life in people with PD. The COVID-19 pandemic and this review have drawn attention to the benefits of access to digital modes of physical activity for people living with chronic neurological conditions., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Sara Emmanouilidis et al.)

Introduction: Incorporating patient-reported outcome measures (PROMs) into usual care in hospitals can improve safety and quality. Gaps exist in electronic PROM (ePROM) implementation recommendations, including for elective surgery. The aims are to: (1) understand barriers and enablers to ePROM implementation in hospitals and develop Australian ePROM implementation recommendations (AusPROM); (2) test the feasibility and acceptability of the Quality of Recovery 15 item short-form (QoR-15) PROM for elective surgery patients applying the AusPROM and (3) establish if the QoR-15 PROM has concurrent validity with the EQ-5D-5L., Methods and Analysis: Phase I will identify staff barriers and facilitators for the implementation of the AusPROM recommendations using a Delphi technique. Phase II will determine QoR-15 acceptability for elective surgery patients across four pilot hospitals, using the AusPROM recommendations. For phase II, in addition to a consumer focus group, patients will complete brief acceptability surveys, incorporating the QoR-15, in the week prior to surgery, in the week following surgery and 4 weeks postsurgery. The primary endpoint will be 4 weeks postsurgery. Phase III will be the national implementation of the AusPROM (29 hospitals) and the concurrent validity of the QoR-15 and generic EQ-5D-5L. This protocol adopts the Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trials Protocols guidelines., Ethics and Dissemination: The results will be disseminated via public forums, conferences and peer-reviewed journals. Ethics approval: La Trobe University (HEC20479)., Trial Registration Number: ACTRN12621000298819 (Phase I and II) and ACTRN12621000969864 (Phase III)., Competing Interests: Competing interests: The funding source will have no influence over the study design; collection, management, analysis and interpretation of data; writing of the report and the decision to submit the report for publication. NB (Alpha Crucis Group) was funded by Healthscope as a consultant for this study. MEM has a joint appointment between La Trobe University and Healthscope. VA, JW, AH and DL are employees at Healthscope., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The development of persistent endoplasmic reticulum (ER) stress is one of the cornerstones of prostate carcinogenesis; however, the mechanism is missing. Also, alcohol is a physiological ER stress inducer, and the link between alcoholism and progression of prostate cancer (PCa) is well documented but not well characterized. According to the canonical model, the mediator of ER stress, ATF6, is cleaved sequentially in the Golgi by S1P and S2P proteases; thereafter, the genes responsible for unfolded protein response (UPR) undergo transactivation., Methods: Cell lines used were non-malignant prostate epithelial RWPE-1 cells, androgen-responsive LNCaP, and 22RV1 cells, as well as androgen-refractory PC-3 cells. We also utilized PCa tissue sections from patients with different Gleason scores and alcohol consumption backgrounds. Several sophisticated approaches were employed, including Structured illumination superresolution microscopy, Proximity ligation assay, Atomic force microscopy, and Nuclear magnetic resonance spectroscopy., Results: Herein, we identified the trans-Golgi matrix dimeric protein GCC185 as a Golgi retention partner for both S1P and S2P, and in cells lacking GCC185, these enzymes lose intra-Golgi situation. Progression of prostate cancer (PCa) is associated with overproduction of S1P and S2P but monomerization of GCC185 and its downregulation. Utilizing different ER stress models, including ethanol administration, we found that PCa cells employ an elegant mechanism that auto-activates ER stress by fragmentation of Golgi, translocation of S1P and S2P from Golgi to ER, followed by intra-ER cleavage of ATF6, accelerated UPR, and cell proliferation. The segregation of S1P and S2P from Golgi and activation of ATF6 are positively correlated with androgen receptor signaling, different disease stages, and alcohol consumption. Finally, depletion of ATF6 significantly retarded the growth of xenograft prostate tumors and blocks production of pro-metastatic metabolites., Conclusions: We found that progression of PCa associates with translocation of S1P and S2P proteases to the ER and subsequent ATF6 cleavage. This obviates the need for ATF6 transport to the Golgi and enhances UPR and cell proliferation. Thus, we provide the novel mechanistic model of ATF6 activation and ER stress implication in the progression of PCa, suggesting ATF6 is a novel promising target for prostate cancer therapy., (© 2021. The Author(s).)

Aim: To produce a pelvic floor muscle training variation of the Consensus on Exercise Reporting Template (CERT-PFMT)., Methods: Qualitative methods were used to explore the perspectives of physiotherapists who have postgraduate continence and pelvic floor rehabilitation qualifications on using research evidence to implement pelvic floor muscle training for urinary incontinence. The same experienced facilitator guided the discussions with questions derived from systematic reviews and content experts. The face-to-face focus groups were audio-recorded and verbatim transcripts were thematically analysed. For each CERT item the authors collated participant quotations that identified required explanation or elaboration for the CERT-PFMT. Systematic reviews of pelvic floor muscle training for urinary incontinence were searched by the research team for examples of good reporting., Results: Twenty- nine continence physiotherapists participated in one of seven focus groups. Participants agreed that all key elements they needed for replicating pelvic floor muscle training interventions from a research report were provided in the published CERT checklist. CERT items 2 (qualifications), 6 (motivation), 7 (progression rules), 8 (exercise description), 13 (intervention description) and 15 (starting level) required additional explanations for pelvic floor muscle training. Clinicians reported that original CERT explanations for items 1, 3-5, 8-12, 14 and 16 could be used without modification., Conclusions: The CERT-PFMT reporting guideline has been designed with clinician input to inform how to document pelvic floor muscle training to enable replication in clinical practice. It can be used for research protocols, to construct manuscripts reporting pelvic floor muscle training for urinary incontinence and by journal editors and reviewers., (Copyright © 2021 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.)

Gamma hydroxybutyric acid (GHB) has been approved clinically to treat excessive daytime sleepiness and cataplexy in patients with narcolepsy, alcohol and opioid withdrawal, and as an anesthetic. The use of GHB clinically is limited due to its high abuse potential. The absorption, clearance and tissue uptake of GHB is mediated by proton-dependent and sodium-coupled monocarboxylate transporters (MCTs and SMCTs) and inhibition of these transporters may result in a change in GHB pharmacokinetics and pharmacodynamics. Previous studies have reported that non-steroidal anti-inflammatory drugs (NSAIDs) may inhibit these monocarboxylate transporters. Therefore, the purpose of this work was to analyze the interaction between GHB (at a dose of 600 mg/kg i. v.) and the NSAID, diclofenac, by examining the effects of this drug on the in vivo pharmacokinetics and pharmacodynamics in rat studies. The pharmacodynamic effect evaluated was respiratory depression, a measure of toxicity observed by GHB at this dose. There was an improvement in the respiratory rate with diclofenac administration suggesting an effect of diclofenac on GHB toxicity. In vitro studies with rat blood brain endothelial cells (RBE4) that express MCT1 indicated that diclofenac can inhibit GHB transport with an IC 50 of 10.6 μM at pH 7.4. In vivo studies found a decrease in brain GHB concentrations and a decrease in the brain-to-plasma concentration ratio following diclofenac treatment. With this study we can conclude that diclofenac and potentially other NSAIDs can inhibit the transport of GHB into the brain, therefore decreasing GHB's pharmacodynamic effects and toxicity., (© 2021 John Wiley & Sons Ltd.)

Background/objectives: We investigated the impact of ceasing routine falls risk assessment tool (FRAT) completion and instead used clinical reasoning to select fall mitigation strategies., Design: Two-group, multi-site cluster-randomized active-control non-inferiority trial., Setting: Hospital wards., Participants: Adult inpatients admitted to participating hospitals (n = 10 hospitals, 123,176 bed days)., Intervention: Hospitals were randomly assigned (1:1) to a usual care control group that continued to use a historical FRAT to assign falls risk scores and accompanying mitigation strategies, or an experimental group whereby clinicians did not assign risk scores and instead used clinical reasoning to select fall mitigation strategies using a decision support list., Measurements: The primary measure was between-group difference in mean fall rates (falls/1000 bed days). Falls were identified from incident reports supplemented by hand searches of medical records over three consecutive months at each hospital. The incidence rate ratio (IRR) of monthly falls rates in control versus experimental hospitals was also estimated., Results: The experimental clinical reasoning approach was non-inferior to the usual care FRAT that assigned fall risk ratings when compared to a-priori stakeholder derived and sensitivity non-inferiority margins. The mean fall rates were 3.84 falls/1000 bed days for the FRAT continuing sites and 3.11 falls/1000 bed days for experimental sites. After adjusting for historical fall rates at each hospital, the IRR (95%CI) was 0.78 (0.64, 0.95), where IRR < 1.00 indicated fewer falls among the experimental group. There were 4 and 3 serious events in the control and experimental groups, respectively., Conclusion: Replacing a FRAT scoring system with clinical reasoning did not lead to inferior fall outcomes in the short term and may even reduce fall incidence., (© 2021 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background: Ensuring patients receive an effective dose of therapeutic exercises and activities is a significant challenge for inpatient rehabilitation. My Therapy is a self-management program which encourages independent practice of occupational therapy and physiotherapy exercises and activities, outside of supervised therapy sessions., Methods: This implementation trial aims to determine both the clinical effectiveness of My Therapy on the outcomes of function and health-related quality of life, and cost-effectiveness per minimal clinically important difference (MCID) in functional independence achieved and per quality adjusted life year (QALY) gained, compared to usual care. Using a stepped-wedge cluster randomised design, My Therapy will be implemented across eight rehabilitation wards (inpatient and home-based) within two public and two private Australian health networks, over 54-weeks. We will include 2,160 patients aged 18 + years receiving rehabilitation for any diagnosis. Each ward will transition from the usual care condition (control group receiving usual care) to the experimental condition (intervention group receiving My Therapy in addition to usual care) sequentially at six-week intervals. The primary clinical outcome is achievement of a MCID in the Functional Independence Measure (FIM™) at discharge. Secondary outcomes include improvement in quality of life (EQ-5D-5L) at discharge, length of stay, 30-day re-admissions, discharge accommodation, follow-up rehabilitation services and adverse events (falls). The economic outcomes are the cost-effectiveness per MCID in functional independence (FIM™) achieved and per QALY gained, for My Therapy compared to usual care, from a health-care sector perspective. Cost of implementation will also be reported. Clinical outcomes will be analysed via mixed-effects linear or logistic regression models, and economic outcomes will be analysed via incremental cost-effectiveness ratios., Discussion: The My Therapy implementation trial will determine the effect of adding self-management within inpatient rehabilitation care. The results may influence health service models of rehabilitation including recommendations for systemic change to the inpatient rehabilitation model of care to include self-management. Findings have the potential to improve patient function and quality of life, and the ability to participate in self-management. Potential health service benefits include reduced hospital length of stay, improved access to rehabilitation and reduced health service costs., Trial Registration: This study was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12621000313831; registered 22/03/2021, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380828&isReview=true )., (© 2021. The Author(s).)

Recently hospitalized older people are at risk of falls and face barriers to undertaking fall prevention strategies after they return home from hospital. The authors examined the effects of tailored education delivered by physiotherapists on the knowledge (capability) and the motivation of older people to engage in fall prevention after hospital discharge. Utilizing data gathered from a recent trial, data was analyzed from 390 people who were 60 years and over without impaired cognition (>7/10 abbreviated mental test score) and discharged from three Australian hospitals. Motivation and capability were measured at baseline in the hospital and at 6-months after hospital discharge by blinded assistants using structured surveys. Bivariate analysis using generalized linear modeling explored the impact of education on the capability and motivation. Engagement in fall prevention strategies was entered as an independent variable during analysis to determine associations with capability and motivation. The education significantly improved capability [-0.4, 95% CI (-0.7, -0.2), p < 0.01] and motivation [-0.8, 95% CI (-1.1, -0.5), p < 0.01] compared with social-control at the time of hospital discharge. In contrast, social-control participants gained capability and motivation over the 6-months, and no significant differences were found between groups in capability [0.001, 95% CI (-0.2, 0.2), p = 0.9] and motivation [-0.01, 95% CI (-0.3, 0.3), p = 0.9] at follow-up. Tailored fall prevention education is recommended around hospital discharge. Participants still needed to overcome barriers to falls prevention engagement post hospitalization. Thus, tailored education along with direct clinical services such as physiotherapy and social supports is warranted for older people to avoid falls and regain function following hospitalization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Naseri, McPhail, Morris, Haines, Etherton-Beer, Shorr, Flicker, Bulsara, Lee, Francis-Coad, Waldron and Hill.)