Sarcopenia.

Sarcopenia is the accelerated loss of skeletal muscle mass and function commonly, but not exclusively, associated with advancing age. It is observed across many species including humans in whom it can lead to decline in physical function and mobility as well as to increased risk of adverse outcomes including falls, fractures and premature mortality. Although prevalence estimates vary because sarcopenia has been defined in different ways, even using a conservative approach, the prevalence is between 5% and 10% in the general population. A life course framework has been proposed for understanding not only the occurrence of sarcopenia in later life but also influences operating at earlier life stages with potentially important implications for preventive strategies. Harnessing progress in understanding the hallmarks of ageing has been key to understanding sarcopenia pathophysiology. Considerable convergence in approaches to diagnosis of sarcopenia has occurred over the last 10 years, with a growing emphasis on the central importance of muscle strength. Resistance exercise is currently the mainstay of treatment; however, it is not suitable for all. Hence, adjunctive and alternative treatments to improve quality of life are needed. An internationally agreed approach to definition and diagnosis will enable a step change in the field and is likely to be available in the near future through the Global Leadership Initiative in Sarcopenia.

Association between the regular use of vaginal dilators and/or sexual activity and vaginal morbidity in locally advanced cervical cancer survivors - An EMBRACE-I study report.

PURPOSE: To provide risk estimations for vaginal morbidity with regard to vaginal dilation (summarizing the use of dilators and/or sexual activity) in locally advanced cervical cancer patients (LACC) treated with definitive radiochemotherapy and image-guided adaptive brachytherapy (IGABT) within the prospective, multi-institutional EMBRACE-I study. MATERIAL/METHODS: Physician-assessed vaginal morbidity (CTCAEv3.0), use of vaginal dilators and patient-reported sexual activity (EORTC-CX24) were prospectively assessed at baseline and during regular follow-up. Frequency analysis for vaginal dilation was performed in a sub-cohort of patients with ≥3 follow-ups. Regular dilation was defined if reported in ≥50% of follow-ups, no/infrequent dilation if reported in <50%. Actuarial estimates were calculated with Kaplan-Meier method; comparisons evaluated with the log-rank test. Univariate and multivariable Cox proportional hazard regression were used to evaluate risk factors for vaginal stenosis G≥2. RESULTS: The EMBRACE-I study included a total of 1416 patients (2008-2015); 882 were evaluated in the present report with a median follow-up of 60 months. Of those, 565 (64%) reported regular dilation. This was associated with a significantly lower 5-year risk of vaginal stenosis G≥2 compared to no/infrequent dilation (23% vs. 37%, p≤0.001). This univariate finding was confirmed by multivariable analysis, after adjusting for other risk factors (HR=0.630, p=0.001). Regular vaginal dilation was also associated with a significantly higher risk for vaginal dryness G≥1 (72% vs. 67%, p=0.028) and bleeding G≥1 (61% vs. 34%, p≤0.001). CONCLUSION: Vaginal stenosis represents irreversible fibrotic changes that can cause pain during gynecological examination and dyspareunia in LACC survivors. Regular vaginal dilation (defined as the use of dilators and/or sexual activity) is associated with a significantly lower risk for G≥2 vaginal stenosis, suggesting a potential improvement of vaginal patency. It is also associated with a significantly higher risk for mild G≥1 dryness and bleeding (no higher risk for G≥2), which both can be clinically managed.

Identifying combinations of long-term conditions associated with sarcopenia: a cross-sectional decision tree analysis in the UK Biobank study.

OBJECTIVES: This study aims to determine whether machine learning can identify specific combinations of long-term conditions (LTC) associated with increased sarcopenia risk and hence address an important evidence gap-people with multiple LTC (MLTC) have increased risk of sarcopenia but it has not yet been established whether this is driven by specific combinations of LTC. DESIGN: Decision trees were used to identify combinations of LTC associated with increased sarcopenia risk. Participants were classified as being at risk of sarcopenia based on maximum grip strength of <32 kg for men and <19 kg for women. The combinations identified were triangulated with logistic regression. SETTING: UK Biobank. PARTICIPANTS: UK Biobank participants with MLTC (two or more LTC) at baseline. RESULTS: Of 140 001 participants with MLTC (55.3% women, median age 61 years), 21.0% were at risk of sarcopenia. Decision trees identified several LTC combinations associated with an increased risk of sarcopenia. These included drug/alcohol misuse and osteoarthritis, and connective tissue disease and osteoporosis in men, which showed the relative excess risk of interaction of 3.91 (95% CI 1.71 to 7.51) and 2.27 (95% CI 0.02 to 5.91), respectively, in age-adjusted models. CONCLUSION: Knowledge of LTC combinations associated with increased sarcopenia risk could aid the identification of individuals for targeted interventions, recruitment of participants to sarcopenia studies and contribute to the understanding of the aetiology of sarcopenia.

The use of natural language processing for the identification of ageing syndromes including sarcopenia, frailty and falls in electronic healthcare records: a systematic review.

BACKGROUND: Recording and coding of ageing syndromes in hospital records is known to be suboptimal. Natural Language Processing algorithms may be useful to identify diagnoses in electronic healthcare records to improve the recording and coding of these ageing syndromes, but the feasibility and diagnostic accuracy of such algorithms are unclear. METHODS: We conducted a systematic review according to a predefined protocol and in line with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Searches were run from the inception of each database to the end of September 2023 in PubMed, Medline, Embase, CINAHL, ACM digital library, IEEE Xplore and Scopus. Eligible studies were identified via independent review of search results by two coauthors and data extracted from each study to identify the computational method, source of text, testing strategy and performance metrics. Data were synthesised narratively by ageing syndrome and computational method in line with the Studies Without Meta-analysis guidelines. RESULTS: From 1030 titles screened, 22 studies were eligible for inclusion. One study focussed on identifying sarcopenia, one frailty, twelve falls, five delirium, five dementia and four incontinence. Sensitivity (57.1%-100%) of algorithms compared with a reference standard was reported in 20 studies, and specificity (84.0%-100%) was reported in only 12 studies. Study design quality was variable with results relevant to diagnostic accuracy not always reported, and few studies undertaking external validation of algorithms. CONCLUSIONS: Current evidence suggests that Natural Language Processing algorithms can identify ageing syndromes in electronic health records. However, algorithms require testing in rigorously designed diagnostic accuracy studies with appropriate metrics reported.

EBV T-cell immunotherapy generated by peptide selection has enhanced effector functionality compared to LCL stimulation.

Adoptive immunotherapy with Epstein-Barr virus (EBV)-specific T cells is an effective treatment for relapsed or refractory EBV-induced post-transplant lymphoproliferative disorders (PTLD) with overall survival rates of up to 69%. EBV-specific T cells have been conventionally made by repeated stimulation with EBV-transformed lymphoblastoid cell lines (LCL), which act as antigen-presenting cells. However, this process is expensive, takes many months, and has practical risks associated with live virus. We have developed a peptide-based, virus-free, serum-free closed system to manufacture a bank of virus-specific T cells (VST) for clinical use. We compared these with standard LCL-derived VST using comprehensive characterization and potency assays to determine differences that might influence clinical benefits. Multi-parameter flow cytometry revealed that peptide-derived VST had an expanded central memory population and less exhaustion marker expression than LCL-derived VST. A quantitative HLA-matched allogeneic cytotoxicity assay demonstrated similar specific killing of EBV-infected targets, though peptide-derived EBV T cells had a significantly higher expression of antiviral cytokines and degranulation markers after antigen recall. High-throughput T cell receptor-beta (TCRß) sequencing demonstrated oligoclonal repertoires, with more matches to known EBV-binding complementary determining region 3 (CDR3) sequences in peptide-derived EBV T cells. Peptide-derived products showed broader and enhanced specificities to EBV nuclear antigens (EBNAs) in both CD8 and CD4 compartments, which may improve the targeting of highly expressed latency antigens in PTLD. Importantly, peptide-based isolation and expansion allows rapid manufacture and significantly increased product yield over conventional LCL-based approaches.

Dose escalation of tolinapant (ASTX660) in combination with standard radical chemoradiotherapy in cervical cancer : a study protocol for a phase 1b TiTE-CRM clinical trial (CRAIN) in UK secondary care centres.

BACKGROUND: Cervical cancer is the fourth most common cancer in women, with an estimated 342,000 deaths worldwide in 2020. Current standard of care in the UK for locally advanced cervical cancer is concurrent chemoradiotherapy with weekly cisplatin, yet 5-year overall survival rates are only 65% with a distant relapse rate of 50%. Inhibitors of Apoptosis Proteins (IAPs) are often overexpressed in cancer cells and associated with tumour progression and resistance to treatment. Tolinapant, developed by Astex Pharmaceuticals, is an IAP antagonist with an additional mechanism of action via down-regulation of NF-kB, an important regulator in cervical cancer. Preclinical studies performed using tolinapant in combination with cisplatin and radiotherapy showed inhibition of tumour growth and enhanced survival. There is therefore a strong rationale to combine tolinapant with chemoradiotherapy (CRT). METHODS: CRAIN is a phase Ib open-label, dose escalation study to characterise the safety, tolerability and initial evidence for clinical activity of tolinapant when administered in combination with cisplatin based CRT. Up to 42 patients with newly diagnosed cervix cancer will be recruited from six UK secondary care sites. The number of participants and the duration of the trial will depend on toxicities observed and dose escalation decisions, utilising a TiTE-CRM statistical design. Treatment will constist of standard of care CRT with 45 Gy external beam radiotherapy given in 25 daily fractions over 5 weeks with weekly cisplatin 40mg/m2. This is followed by brachytherapy for which common schedules will be 28 Gy in 4 fractions high-dose-rate or 34 Gy in 2 fractions pulsed-dose-rate. Tolinapant will be administered in fixed dose capsules taken orally daily for seven consecutive days as an outpatient on alternate weeks (weeks 1, 3, 5) during chemoradiation. Dose levels for tolinapant which will be assessed are: 60 mg; 90 mg (starting level); 120 mg; 150 mg; 180 mg. Escalation will be guided by emerging safety data and decisions by the Safety Review Committee. DISCUSSION: If this trial determines a recommended phase II dose and shows tolinapant to be safe and effective in combination with CRT, it would warrant future phase trials. Ultimately, we hope to provide a synergistic treatment option for these patients to improve outcome. TRIAL REGISTRATIONS: EudraCT Number: 2021-006555-34 (issued 30th November 2021); ISRCTN18574865 (registered 30th August 2022).

Palliative psychiatry: research, clinical, and educational priorities.

BACKGROUND: Palliative psychiatry has been proposed as a new clinical construct within mental health care and aims to improve quality of life (QoL) for individuals experiencing severe and persistent mental illness (SPMI). To date, explorations of palliative psychiatry have been largely theoretical, and more work is needed to develop its approaches into tangible clinical practice. METHODS: In this paper, we synthesize existing literature with discussions held at a one-day knowledge user meeting titled "A Community of Practice for Palliative Psychiatry" to generate priorities for research, clinical practice, and education that will help advance the development of palliative psychiatry. RESULTS: Palliative psychiatry will benefit from research that is co-produced by people with lived experience (PWLE) of mental illness, that clarifies contested concepts within mental health care and wider medicine, and that adapts existing interventions that have the potential to improve the QoL of individuals experiencing SPMI into the mental health care context. Specific methods and tools might be developed for use in clinical spaces taking a palliative psychiatry approach. More work must be done to understand the populations that might benefit from palliative psychiatry, and to mitigate mental health care providers' (MHCPs') anxieties about using these approaches in their work. As palliative psychiatry is developed, current MHCPs, trainees, individuals experiencing SPMI, and their loved ones will all require education about and orientation to this novel approach within mental health care. CONCLUSIONS: There are several priorities in research, clinical practice, and education that can help advance the development of palliative psychiatry. All future work must be considered through a human rights-based, anti-oppressive lens. Research projects, clinical models, and educational initiatives should all be developed in co-production with PWLE to mitigate the epistemic injustices common in mental health care.

Socioeconomic gradients in 24-hour movement patterns across weekends and weekdays in a working-age sample: evidence from the 1970 British Cohort Study.

BACKGROUND: Socioeconomic differences in movement behaviours may contribute to health inequalities. The aim of this descriptive study was to investigate socioeconomic patterns in device-measured 24-hour movement and assess whether patterns differ between weekdays and weekends. METHODS: 4894 individuals aged 46 years from the 1970 British Cohort Study were included. Participants wore thigh-worn accelerometers for 7 days. Movement behaviours were classified in two 24-hour compositions based on intensity and posture, respectively: (1) sleep, sedentary behaviour, light-intensity activity and moderate-vigorous activity; and (2) sleep, lying, sitting, standing, light movement, walking and combined exercise-like activity. Four socioeconomic measures were explored: education, occupation, income and deprivation index. Movement behaviours were considered compositional means on a 24-hour scale; isometric log ratios expressed per cent differences in daily time in each activity compared with the sample mean. RESULTS: Associations were consistent across all socioeconomic measures. For example, those with a degree spent more time in exercise-like activities across weekdays (10.8%, 95% CI 7.3 to 14.7; ref: sample mean) and weekends (21.9%, 95% CI 17.2 to 26.9). Other patterns differed markedly by the day of the week. Those with no formal qualifications spent more time standing (5.1%, 95% CI 2.3 to 7.1), moving (10.8%, 95% CI 8.6 to 13.1) and walking(4.0%, 95% CI 2.2 to 6.1) during weekdays, with no differences on weekends. Conversely, those with no formal qualifications spent less time sitting during weekdays (-6.6%, 95% CI -7.8 to -4.8), yet more time lying on both weekends (8.8%, 95% CI 4.9 to 12.2) and weekdays (7.5%, 95% CI 4.0 to 11.5). CONCLUSIONS: There were strong socioeconomic gradients in 24-hour movement behaviours, with notable differences between weekdays/weekends and behaviour type/posture. These findings emphasise the need to consider socioeconomic position, behaviour type/posture and the day of the week when researching or designing interventions targeting working-age adults.

Associations between life course longitudinal growth and hip shapes at ages 60-64 years: evidence from the MRC National Survey of Health and Development.

OBJECTIVE: We sought to examine associations between height gain across childhood and adolescence with hip shape in individuals aged 60-64 years from the Medical Research Council National Survey of Health and Development, a nationally representative British birth cohort. METHODS: Height was measured at ages 2, 4, 6, 7, 11 and 15 years, and self-reported at age 20 years. 10 modes of variation in hip shape (HM1-10), described by statistical shape models, were previously ascertained from DXA images taken at ages 60-64 years. Associations between (1) height at each age; (2) Super-Imposition by Translation And Rotation (SITAR) growth curve variables of height size, tempo and velocity; and (3) height gain during specific periods of childhood and adolescence, and HM1-10 were tested. RESULTS: Faster growth velocity was associated with a wider, flatter femoral head and neck, as described by positive scores for HM6 (regression coefficient 0.014; 95% CI 0.08 to 0.019; p<0.001) and HM7 (regression coefficient 0.07; 95% CI 0.002 to 0.013; p=0.009), and negative scores for HM10 (regression coefficient -0.006; 95% CI -0.011 to 0.00, p=0.04) and HM2 (males only, regression coefficient -0.017; 95% CI -0.026 to -0.09; p<0.001). Similar associations were observed with greater height size and later height tempo. Examination of height gains during specific periods of childhood and adolescence identified those during the adolescence period as being most consistently associated. CONCLUSION: Our analyses suggest that individual growth patterns, particularly in the adolescent period, are associated with modest variations in hip shape at 60-64 years, which are consistent with features seen in osteoarthritis.

Improving care for patients with multiple long-term conditions admitted to hospital: challenges and potential solutions.

Increasing numbers of people live with multiple long-term conditions. These people are more likely to be admitted to hospital, experience adverse outcomes and receive poorer quality care than those with a single condition. Hospitals remain organised around a model of single-organ, disease-specific care which is not equipped to meet the needs of people living with multiple long-term conditions. This article considers these challenges and explores potential solutions. These include different service models to provide holistic, multidisciplinary inpatient and outpatient care across specialty boundaries, training a workforce to deliver high-quality hospital care for people living with multiple long-term conditions, and developing technological, financial and cultural enablers of change. Considerably more research is required to fully appreciate the shared risk factors, underlying mechanisms, patterns and consequences of multiple long-term conditions. This is essential to design and deliver better structures and processes of hospital care for people living with multiple long-term conditions.

Are associations between physical activity and bone mineral density in adults sex- and age-dependent? An analysis of the UK Biobank study.

Although physical activity (PA) is recognized as a key bone mass determinant across life, athlete studies suggest that it may be less effective in women and older individuals. This has not been explored within the general population. We aimed to address this knowledge gap using data from the UK Biobank Study, a large population-based study of middle-aged and older adults. Free-living PA data collected at 100 Hz for 7 d using wrist-worn accelerometers were classified as sedentary behavior (0-29 milligravities [mg]), light (30-124 mg), or moderate-to-vigorous PA (125 + mg). LS and FN-BMD were assessed using DXA. The associations between PA and BMD were assessed using linear regression models, with formal assessments of sex and age interactions undertaken and adjustments made for accelerometer wear time, height, body mass index, education, ethnicity, disability, and (in women only) menopausal status. In total, 15 133 UK Biobank participants (52% women) had complete PA, bone, and covariate data. In this sample, greater overall and moderate-to-vigorous PA was associated with higher LS BMD. In women, these associations were typically weaker in older individuals, for example, regression coefficients in women aged 70 yr or older were ~50% lower than at 45-54 yr (age-by-PA interactions P < .01 in all models). Similar associations were observed in basic but not full models for FN BMD. Greater sedentary time was associated with lower LS BMD in men only, and greater light PA and sedentary time were associated with higher and lower FN BMD, respectively, in both sexes. These results suggest that associations between PA and bone health at clinically-relevant sites are weaker in older than younger women. That positive associations are evident between overall and moderate-vigorous PA and FN BMD even in women ≥70 yr suggests that PA for bone health should still be promoted in older women.

Rising to the challenge of defining and operationalising multimorbidity in a UK hospital setting: the ADMISSION research collaborative.

PURPOSE: Greater transparency and consistency when defining multimorbidity in different settings is needed. We aimed to: (1) adapt published principles that can guide the selection of long-term conditions for inclusion in research studies of multimorbidity in hospitals; (2) apply these principles and identify a list of long-term conditions; (3) operationalise this list by mapping it to International Classification of Diseases 10th revision (ICD-10) codes. METHODS: Review by independent assessors and ratification by an interdisciplinary programme management group. RESULTS: Agreement was reached that when defining multimorbidity in hospitals for research purposes all conditions must meet the following four criteria: (1) medical diagnosis; (2) typically present for ≥ 12 months; (3) at least one of currently active; permanent in effect; requiring current treatment, care or therapy; requiring surveillance; remitting-relapsing and requiring ongoing treatment or care, and; (4) lead to at least one of: significantly increased risk of death; significantly reduced quality of life; frailty or physical disability; significantly worsened mental health; significantly increased treatment burden (indicated by an increased risk of hospital admission or increased length of hospital stay). Application of these principles to two existing lists of conditions led to the selection of 60 conditions that can be used when defining multimorbidity for research focused on hospitalised patients. ICD-10 codes were identified for each of these conditions to ensure consistency in their operationalisation. CONCLUSIONS: This work contributes to achieving the goal of greater transparency and consistency in the approach to the study of multimorbidity, with a specific focus on the UK hospital setting.

Myoprotective whole foods, muscle health and sarcopenia in older adults.

PURPOSE OF REVIEW: Sarcopenia increases in prevalence at older ages and may be exacerbated by poor diet. Whole foods rich in specific nutrients may be myoprotective and mitigate the risk of sarcopenia. Here we review recent evidence published from observational and intervention studies regarding myoprotective foods and explore their benefit for the prevention and/or treatment of sarcopenia in older adults. RECENT FINDINGS: We found limited new evidence for the role of whole foods in sarcopenia and sarcopenia components (muscle mass, strength, physical performance). There was some evidence for higher consumption of protein-rich foods (milk and dairy) being beneficial for muscle strength in observational and intervention studies. Higher consumption of antioxidant-rich foods (fruit and vegetables) was associated with better physical performance and lower odds of sarcopenia in observational studies. Evidence for other protein- and antioxidant-rich foods were inconsistent or lacking. There remains a clear need for intervention studies designed to identify the role of whole foods for the treatment of sarcopenia. SUMMARY: Although evidence for myoprotective roles of dairy, fruit and vegetables is emerging from observational studies, higher level evidence from intervention studies is needed for these foods to be recommended in diets of older adults to prevent and/or treat sarcopenia.

Nicotine Vaping Expectancies: Organization and Activation in Memory Based on Vaping Use Patterns.

OBJECTIVE: The prevalence of smoking combustible cigarettes has decreased, but rates of nicotine vaping among adolescents and young adults have increased dramatically. Vaping is associated with acute health problems and exposes users to toxic metals with unknown long-term consequences. Research on factors influencing vaping is needed to inform the development of effective prevention and intervention methods. Nicotine vaping expectancies, or expected effects related to vaping, may be an important target as they can predict vaping behaviors. The purpose of this study was to examine nicotine expectancy activation patterns with corresponding nicotine vaping behaviors. METHOD: Using methods from alcohol expectancy research, we applied a memory model approach to identifying nicotine vaping expectancies and modeling organization and activation patterns concerning the frequency of nicotine vaping. We created a memory model-based nicotine expectancy measure based on information from 200 adolescents in 8th and 12th grades, and college students. Our expectancy measure was completed by a second sample of 862 college students. RESULTS: We mapped expectancies into network format using Individual Differences Scaling (INDSCAL) and we modeled likely paths of expectancy activation using Preference Mapping (PREFMAP). Nonusers primarily emphasized a positive-negative expectancy dimension and were more likely to activate expectancies of negative internal experiences about vaping. Students who vaped nicotine daily or almost daily primarily emphasized an external appearance-internal experience expectancy dimension and were more likely to activate expectancies of negative affect reduction and withdrawal relief. CONCLUSIONS: Our results identify specific targets for expectancy-based prevention and intervention methods that have the potential to be as effective as similar approaches to preventing and reducing alcohol use.

Prediction of Patient Outcomes in Locally Advanced Cervical Carcinoma Following Chemoradiotherapy-Comparative Effectiveness of Magnetic Resonance Imaging and 2-Deoxy-2-[18F]fluoro-D-glucose Imaging.

PURPOSE: To evaluate the utility and comparative effectiveness of three five-point qualitative scoring systems for assessing response on PET-CT and MRI imaging individually and in combination, following curative-intent chemoradiotherapy (CRT) in locally advanced cervical cancer (LACC). Their performance in the prediction of subsequent patient outcomes was also assessed; Methods: Ninety-seven patients with histologically confirmed LACC treated with CRT using standard institutional protocols at a single centre who underwent PET-CT and MRI at staging and post treatment were identified retrospectively from an institutional database. The post-CRT imaging studies were independently reviewed, and response assessed using five-point scoring tools for T2WI, DWI, and FDG PET-CT. Patient characteristics, staging, treatment, and follow-up details including progression-free survival (PFS) and overall survival (OS) outcomes were collected. To compare diagnostic performance metrics, a two-proportion z-test was employed. A Kaplan-Meier analysis (Mantel-Cox log-rank) was performed. RESULTS: The T2WI (p < 0.00001, p < 0.00001) and DWI response scores (p < 0.00001, p = 0.0002) had higher specificity and accuracy than the PET-CT. The T2WI score had the highest positive predictive value (PPV), while the negative predictive value (NPV) was consistent across modalities. The combined MR scores maintained high NPV, PPV, specificity, and sensitivity, and the PET/MR consensus scores showed superior diagnostic accuracy and specificity compared to the PET-CT score alone (p = 0.02926, p = 0.0083). The Kaplan-Meier analysis revealed significant differences in the PFS based on the T2WI (p < 0.001), DWI (p < 0.001), combined MR (p = 0.003), and PET-CT/MR consensus scores (p < 0.001) and in the OS for the T2WI (p < 0.001), DWI (p < 0.001), and combined MR scores (p = 0.031) between responders and non-responders. CONCLUSION: Post-CRT response assessment using qualitative MR scoring and/or consensus PET-CT and MRI scoring was a better predictor of outcome compared to PET-CT assessment alone. This requires validation in a larger prospective study but offers the potential to help stratify patient follow-up in the future.

Experiences of hospital care for people with multiple long-term conditions: a scoping review of qualitative research.

BACKGROUND: Multiple long-term conditions-the co-existence of two or more chronic health conditions in an individual-present an increasing challenge to populations and healthcare systems worldwide. This challenge is keenly felt in hospital settings where care is oriented around specialist provision for single conditions. The aim of this scoping review was to identify and summarise published qualitative research on the experiences of hospital care for people living with multiple long-term conditions, their informal caregivers and healthcare professionals. METHODS: We undertook a scoping review, following established guidelines, of primary qualitative research on experiences of hospital care for people living with multiple long-term conditions published in peer-reviewed journals between Jan 2010 and June 2022. We conducted systematic electronic searches of MEDLINE, CINAHL, PsycInfo, Proquest Social Science Premium, Web of Science, Scopus and Embase, supplemented by citation tracking. Studies were selected for inclusion by two reviewers using an independent screening process. Data extraction included study populations, study design, findings and author conclusions. We took a narrative approach to reporting the findings. RESULTS: Of 8002 titles and abstracts screened, 54 papers reporting findings from 41 studies conducted in 14 countries were identified as eligible for inclusion. The perspectives of people living with multiple long-term conditions (21 studies), informal caregivers (n = 13) and healthcare professionals (n = 27) were represented, with 15 studies reporting experiences of more than one group. Findings included poor service integration and lack of person-centred care, limited confidence of healthcare professionals to treat conditions outside of their specialty, and time pressures leading to hurried care transitions. Few studies explored inequities in experiences of hospital care. CONCLUSIONS: Qualitative research evidence on the experiences of hospital care for multiple long-term conditions illuminates a tension between the desire to provide and receive person-centred care and time pressures inherent within a target-driven system focussed on increasing specialisation, reduced inpatient provision and accelerated journeys through the care system. A move towards more integrated models of care may enable the needs of people living with multiple long-term conditions to be better met. Future research should address how social circumstances shape experiences of care.

A Systematic Review of Criminal Justice Initiatives to Strengthen the Criminal Investigation and Prosecution of Sexual Violence in East Africa.

Sexual violence (SV) is a widespread public health and human rights problem, with countries in East Africa having higher rates than the global average. Prosecutions of SV in East Africa are rare, and survivors face many challenges accessing medico-legal justice and services. Developing initiatives that support survivors in navigating the criminal justice system is vital, yet there is limited research on efforts to improve the criminal justice system's management and treatment of survivors. We conducted a scoping review of research on initiatives to strengthen responses toward investigating and prosecuting cases. We identified 25 academic articles and reports through a search of electronic databases and gray literature that address these initiatives in East Africa. The results reveal that seven types of initiatives have been studied: one-stop centers (OSCs), multisectoral referral networks, gender desks, community interventions, mobile applications, and specialized police and prosecution units. Upon review, we found that barriers to success include a lack of resources and facilities, a lack of trained health care, police, and judicial personnel to perform services, weak medico-legal partnerships, and stigma and impunity restricting the uptake and fair distribution of services. Overall, limited systematic evidence on the effectiveness and adaptability of initiatives exists, showing that SV interventions in East Africa remain an under-researched and under-resourced area, and need greater scientific rigor to inform practice and coordinated advocacy. This review is a call to action for policy makers and service providers working in East Africa-and for international bodies working toward achieving Sustainable Development Goals 5-to improve criminal justice initiatives.

Comparison of devices used to measure blood pressure, grip strength and lung function: A randomised cross-over study.

BACKGROUND: Blood pressure, grip strength and lung function are frequently assessed in longitudinal population studies, but the measurement devices used differ between studies and within studies over time. We aimed to compare measurements ascertained from different commonly used devices. METHODS: We used a randomised cross-over study. Participants were 118 men and women aged 45-74 years whose blood pressure, grip strength and lung function were assessed using two sphygmomanometers (Omron 705-CP and Omron HEM-907), four handheld dynamometers (Jamar Hydraulic, Jamar Plus+ Digital, Nottingham Electronic and Smedley) and two spirometers (Micro Medical Plus turbine and ndd Easy on-PC ultrasonic flow-sensor) with multiple measurements taken on each device. Mean differences between pairs of devices were estimated along with limits of agreement from Bland-Altman plots. Sensitivity analyses were carried out using alternative exclusion criteria and summary measures, and using multilevel models to estimate mean differences. RESULTS: The mean difference between sphygmomanometers was 3.9mmHg for systolic blood pressure (95% Confidence Interval (CI):2.5,5.2) and 1.4mmHg for diastolic blood pressure (95% CI:0.3,2.4), with the Omron HEM-907 measuring higher. For maximum grip strength, the mean difference when either one of the electronic dynamometers was compared with either the hydraulic or spring-gauge device was 4-5kg, with the electronic devices measuring higher. The differences were small when comparing the two electronic devices (difference = 0.3kg, 95% CI:-0.9,1.4), and when comparing the hydraulic and spring-gauge devices (difference = 0.2kg, 95% CI:-0.8,1.3). In all cases limits of agreement were wide. The mean difference in FEV1 between spirometers was close to zero (95% CI:-0.03,0.03), limits of agreement were reasonably narrow, but a difference of 0.47l was observed for FVC (95% CI:0.53,0.42), with the ndd Easy on-PC measuring higher. CONCLUSION: Our study highlights potentially important differences in measurement of key functions when different devices are used. These differences need to be considered when interpreting results from modelling intra-individual changes in function and when carrying out cross-study comparisons, and sensitivity analyses using correction factors may be helpful.

Comparing associations of handgrip strength and chair stand performance with all-cause mortality-implications for defining probable sarcopenia: the Tromsø Study 2015-2020.

BACKGROUND: Widely adopted criteria suggest using either low handgrip strength or poor chair stand performance to identify probable sarcopenia. However, there are limited direct comparisons of these measures in relation to important clinical endpoints. We aimed to compare associations between these two measures of probable sarcopenia and all-cause mortality. METHODS: Analyses included 7838 community-dwelling participants (55% women) aged 40-84 years from the seventh survey of the Tromsø Study (2015-2016), with handgrip strength assessed using a Jamar + Digital Dynamometer and a five-repetition chair stand test (5-CST) also undertaken. We generated sex-specific T-scores and categorised these as "not low", "low", and "very low" handgrip strength or 5-CST performance. Cox Proportional Hazard regression models were used to investigate associations between these two categorised performance scores and time to death (up to November 2020 ascertained from the Norwegian Cause of Death registry), adjusted for potential confounders including lifestyle factors and specific diseases. RESULTS: A total of 233 deaths occurred (median follow-up 4.7 years) with 1- and 5-year mortality rates at 3.1 (95% confidence interval [CI] 2.1, 4.6) and 6.3 (95% CI 5.5, 7.2) per 1000 person-years, respectively. There was poor agreement between the handgrip strength and 5-CST categories for men (Cohen's kappa [κ] = 0.19) or women (κ = 0.20). Fully adjusted models including handgrip strength and 5-CST performance mutually adjusted for each other, showed higher mortality rates among participants with low (hazard ratio [HR] 1.22, 95% CI 0.87, 1.71) and very low (HR 1.68, 95% CI 1.02, 2.75) handgrip strength compared with the not low category. Similar associations, although stronger, were seen for low (HR 1.88, 95% CI 1.38, 2.56) and very low (HR 2.64, 95% CI 1.73, 4.03) 5-CST performance compared with the not low category. CONCLUSIONS: We found poor agreement between T-score categories for handgrip strength and 5-CST performance and independent associations with mortality. Our findings suggest that these tests identify different people at risk when case-finding probable sarcopenia. As discussions on an international consensus for sarcopenia definitions proceed, testing both handgrip strength and chair stand performance should be recommended rather than viewing these as interchangeable assessments.