A person-centred consultation intervention to improve shared decision-making about, and uptake of, osteoporosis medicines (iFraP): a pragmatic, parallel-group, individual randomised controlled trial protocol.

Background: Good quality shared decision-making (SDM) conversations involve people with, or at risk of osteoporosis and clinicians collaborating to decide, where appropriate, which evidence-based medicines best fit the person's life, beliefs, and values. We developed the improving uptake of Fracture Prevention drug treatments (iFraP) intervention comprising a computerised Decision Support Tool (DST), clinician training package and information resources, for use in UK Fracture Liaison Service consultations.Two primary objectives to determine (1) the effect of the iFraP intervention on patient-reported ease in decision-making about osteoporosis medicines, and (2) cost-effectiveness of iFraP intervention compared to usual NHS care. Secondary objectives are to determine the iFraP intervention effect on patient reported outcome and experience measures, clinical effectiveness (osteoporosis medicine adherence), and to explore intervention acceptability, mechanisms, and processes underlying observed effects, and intervention implementation. Methods: The iFraP trial is a pragmatic, parallel-group, individual randomised controlled trial in patients referred to a Fracture Liaison Service, with nested mixed methods process evaluation and health economic analysis. Participants aged ≥50 years (n=380) are randomised (1:1 ratio) to one of two arms: (1) iFraP intervention (iFraP-i) or (2) comparator usual NHS care (iFraP-u) and are followed up at 2-weeks and 3-months. The primary outcome is ease of decision-making assessed 2 weeks after the consultation using the Decisional Conflict Scale (DCS). The primary objectives will be addressed by comparing the mean DCS score in each trial arm (using analysis of covariance) for patients given an osteoporosis medicine recommendation, alongside a within-trial cost-effectiveness and value of information (VoI) analysis. Process evaluation data collection includes consultation recordings, semi-structured interviews, and DST analytics. Discussion: The iFraP trial will answer important questions about the effectiveness of the new 'iFraP' osteoporosis DST, coupled with clinician training, on SDM and informed initiation of osteoporosis medicines. Trial registration ISRCTN: 10606407, 21/11/2022 https://doi.org/10.1186/ISRCTN10606407.

Background: For people with osteoporosis, broken bones (called 'fragility fractures') can occur from low or no trauma and cause significant disability. Medicines can strengthen bone and lower the chance of fragility fractures. However, many people who experience a fragility fracture do not start or continue taking osteoporosis medicines. People commonly choose not to take osteoporosis medicines because they are unsure what medicines are for, confused about fracture 'risk' and/or worried about side-effects. To address this, we developed the 'iFraP intervention': 1. The iFraP 'decision-support tool': to support patients and healthcare professionals talk together to make decisions about medicines2. iFraP training for healthcare professionals to:a. use the tool in appointments with patientsb. give understandable, clear and consistent information c. listen to and address patient concerns This trial investigates whether the iFraP intervention makes decision-making about osteoporosis medicines easier, and whether it is cost-effective, acceptable and practical to deliver. Methods: 380 patients will take part who will be 50 years and older and referred to a fracture prevention service, because they have broken a bone. Patients taking part will be allocated to receive either a usual NHS appointment or an appointment using the iFraP intervention. Patients will complete a questionnaire before their appointment, and 2 weeks and 3 months afterwards. Some patients will be asked if they consent to have their appointment recorded and/or be interviewed, to understand how the decision-support tool is being used, and patient's views of the iFraP intervention. Outputs: If successful, the iFraP intervention will benefit patients and the NHS by helping patients make decisions about osteoporosis medicine. If the iFraP intervention increases the number of people with osteoporosis that start and continue taking osteoporosis medicines, iFraP will lower the number of future fractures, and reduce the negative outcomes that result from fractures (e.g. significant disability).

Pain Reduction With Oral Methotrexate in Knee Osteoarthritis : A Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Treatments for osteoarthritis (OA) are limited. Previous small studies suggest that the antirheumatic drug methotrexate may be a potential treatment for OA pain. OBJECTIVE: To assess symptomatic benefits of methotrexate in knee OA (KOA). DESIGN: A multicenter, randomized, double-blind, placebo-controlled trial done between 13 June 2014 and 13 October 2017. (ISRCTN77854383; EudraCT: 2013-001689-41). SETTING: 15 secondary care musculoskeletal clinics in the United Kingdom. PARTICIPANTS: A total of 207 participants with symptomatic, radiographic KOA and knee pain (severity ≥4 out of 10) on most days in the past 3 months with inadequate response to current medication were approached for inclusion. INTERVENTION: Participants were randomly assigned 1:1 to oral methotrexate once weekly (6-week escalation 10 to 25 mg) or matched placebo over 12 months and continued usual analgesia. MEASUREMENTS: The primary end point was average knee pain (numerical rating scale [NRS] 0 to 10) at 6 months, with 12-month follow-up to assess longer-term response. Secondary end points included knee stiffness and function outcomes and adverse events (AEs). RESULTS: A total of 155 participants (64% women; mean age, 60.9 years; 50% Kellgren-Lawrence grade 3 to 4) were randomly assigned to methotrexate (n = 77) or placebo (n = 78). Follow-up was 86% (n = 134; methotrexate: 66, placebo: 68) at 6 months. Mean knee pain decreased from 6.4 (SD, 1.80) at baseline to 5.1 (SD, 2.32) at 6 months in the methotrexate group and from 6.8 (SD, 1.62) to 6.2 (SD, 2.30) in the placebo group. The primary intention-to-treat analysis showed a statistically significant pain reduction of 0.79 NRS points in favor of methotrexate (95% CI, 0.08 to 1.51; P = 0.030). There were also statistically significant treatment group differences in favor of methotrexate at 6 months for Western Ontario and McMaster Universities Osteoarthritis Index stiffness (0.60 points [CI, 0.01 to 1.18]; P = 0.045) and function (5.01 points [CI, 1.29 to 8.74]; P = 0.008). Treatment adherence analysis supported a dose-response effect. Four unrelated serious AEs were reported (methotrexate: 2, placebo: 2). LIMITATION: Not permitting oral methotrexate to be changed to subcutaneous delivery for intolerance. CONCLUSION: Oral methotrexate added to usual medications demonstrated statistically significant reduction in KOA pain, stiffness, and function at 6 months. PRIMARY FUNDING SOURCE: Versus Arthritis.

Postoperative opioids administered to inpatients with major or orthopaedic surgery: A retrospective cohort study using data from hospital electronic prescribing systems.

BACKGROUND: Opioids administered in hospital during the immediate postoperative period are likely to influence post-surgical outcomes, but inpatient prescribing during the admission is challenging to access. Modified-release(MR) preparations have been especially associated with harm, whilst certain populations such as the elderly or those with renal impairment may be vulnerable to complications. This study aimed to assess postoperative opioid utilisation patterns during hospital stay for people admitted for major/orthopaedic surgery. METHODS: Patients admitted to a teaching hospital in the North-West of England between 2010-2021 for major/orthopaedic surgery with an admission for ≥1 day were included. We examined opioid administrations in the first seven days post-surgery in hospital, and "first 48 hours" were defined as the initial period. Proportions of MR opioids, initial immediate-release(IR) oxycodone and initial morphine milligram equivalents (MME)/day were calculated and summarised by calendar year. We also assessed the proportion of patients prescribed an opioid at discharge. RESULTS: Among patients admitted for major/orthopaedic surgery, 71.1% of patients administered opioids during their hospitalisation. In total 50,496 patients with 60,167 hospital admissions were evaluated. Between 2010-2017 MR opioids increased from 8.7% to 16.1% and dropped to 11.6% in 2021. Initial use of oxycodone IR among younger patients (≤70 years) rose from 8.3% to 25.5% (2010-2017) and dropped to 17.2% in 2021. The proportion of patients on ≥50MME/day ranged from 13% (2021) to 22.9% (2010). Of the patients administered an opioid in hospital, 26,920 (53.3%) patients were discharged on an opioid. CONCLUSIONS: In patients hospitalised with major/orthopaedic surgery, 4 in 6 patients were administered an opioid. We observed a high frequency of administered MR opioids in adult patients and initial oxycodone IR in the ≤70 age group. Patients prescribed with ≥50MME/day ranged between 13-22.9%. This is the first published study evaluating UK inpatient opioid use, which highlights opportunities for improving safer prescribing in line with latest recommendations.

Exploring practice and perspectives on shared decision-making about osteoporosis medicines in Fracture Liaison Services: the iFraP development qualitative study.

Interviews and focus groups with patients, FLS clinicians, and GPs identified challenges relating to clinical and shared decision-making about bone health and osteoporosis medicines. Findings will inform the development of the multicomponent iFraP intervention to address identified training needs and barriers to implementation to facilitate SDM about osteoporosis medicines. PURPOSE: The iFraP (improving uptake of Fracture Prevention treatments) study aimed to develop a multicomponent intervention, including an osteoporosis decision support tool (DST), to support shared decision-making (SDM) about osteoporosis medicines. To inform iFraP intervention development, this qualitative study explored current practice in relation to communication about bone health and osteoporosis medicines, anticipated barriers to, and facilitators of, an osteoporosis DST, and perceived training needs. METHODS: Patients attending an FLS consultation (n = 8), FLS clinicians (n = 9), and general practitioners (GPs; n = 7) were purposively sampled to participate in a focus group and/or telephone interview. Data were transcribed, inductively coded, and then mapped to the Theoretical Domains Framework (TDF) as a deductive framework to systematically identify possible barriers to, and facilitators of, implementing a DST. RESULTS: Inductive codes were deductively mapped to 12 TDF domains. FLS clinicians were perceived to have specialist expertise (knowledge). However, clinicians described aspects of clinical decision-making and risk communication as difficult (cognitive skills). Patients reflected on decisional uncertainty about medicines (decision processes). Discussions about current practice and the proposed DST indicated opportunities to facilitate SDM, if identified training needs are met. Potential individual and system-level barriers to implementation were identified, such as differences in FLS configuration and a move to remote consulting (environmental context and resources). CONCLUSIONS: Understanding of current practice revealed unmet training needs, indicating that using a DST in isolation would be unlikely to produce a sustained shift to SDM. Findings will shape iFraP intervention development to address unmet needs.

Evidence-based definition of hypoprolactinemia in European men aged 40-86 years: the European male ageing study.

Empirical evidence for a low normal or reference interval for serum prolactin (PRL) is lacking for men, while the implications of very low PRL levels for human health have never been studied. A clinical state of "PRL deficiency" has not been defined except in relation to lactation. Using data from the European Male Ageing Study (EMAS), we analyzed the distribution of PRL in 3,369 community-dwelling European men, aged 40-80 years at phase-1 and free from acute illnesses. In total, 2,948 and 2,644 PRL samples were collected during phase-1 and phase-2 (3 to 5.7 years later). All samples were analysed in the same centre with the same assay. After excluding individuals with known pituitary diseases, PRL ≥ 35 ng/ml, and PRL-altering drugs including antipsychotic agents, selective serotonin reuptake inhibitors, or dopamine agonists, 5,086 data points (2,845 in phase-1 and 2,241 in phase-2) were available for analysis. The results showed that PRL declined minimally with age (slope = -0.02) and did not correlate with BMI. The positively skewed PRL distribution was log-transformed to a symmetrical distribution (skewness reduced from 13.3 to 0.015). Using two-sigma empirical rule (2[]SD about the mean), a threshold at 2.5% of the lower end of the distribution was shown to correspond to a PRL value of 2.98ng/ml. With reference to individuals with PRL levels of 5-34.9 ng/ml (event rate = 6.3%), the adjusted risk of developing type 2 diabetes increased progressively in those with PRL levels of 3-4.9 ng/ml: event rate = 9.3%, OR (95% CI) 1.59 (0.93-2.71), and more so with PRL levels of 0.3-2.9 ng/ml: event rate = 22.7%, OR 5.45 (1.78-16.62). There was also an increasing trend in prediabetes and diabetes based on fasting blood glucose levels was observed with lower categories of PRL. However, PRL levels were not associated with cancer, cardiovascular diseases, depressive symptoms or mortality. Our findings suggest that a PRL level below 3 ng/ml (64 mlU/l) significantly identifies European men with a clinically-important outcome (of type 2 diabetes), offering a lower reference-value for research and clinical practice.

Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men : Individual Participant Data Meta-analyses.

BACKGROUND: Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial. PURPOSE: To clarify associations of sex hormones with these outcomes. DATA SOURCES: Systematic literature review to July 2019, with bridge searches to March 2024. STUDY SELECTION: Prospective cohort studies of community-dwelling men with sex steroids measured using mass spectrometry and at least 5 years of follow-up. DATA EXTRACTION: Independent variables were testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol concentrations. Primary outcomes were all-cause mortality, CVD death, and incident CVD events. Covariates included age, body mass index, marital status, alcohol consumption, smoking, physical activity, hypertension, diabetes, creatinine concentration, ratio of total to high-density lipoprotein cholesterol, and lipid medication use. DATA SYNTHESIS: Nine studies provided individual participant data (IPD) (255 830 participant-years). Eleven studies provided summary estimates (n = 24 109). Two-stage random-effects IPD meta-analyses found that men with baseline testosterone concentrations below 7.4 nmol/L (<213 ng/dL), LH concentrations above 10 IU/L, or estradiol concentrations below 5.1 pmol/L had higher all-cause mortality, and those with testosterone concentrations below 5.3 nmol/L (<153 ng/dL) had higher CVD mortality risk. Lower SHBG concentration was associated with lower all-cause mortality (median for quintile 1 [Q1] vs. Q5, 20.6 vs. 68.3 nmol/L; adjusted hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.95]) and lower CVD mortality (adjusted HR, 0.81 [CI, 0.65 to 1.00]). Men with lower baseline DHT concentrations had higher risk for all-cause mortality (median for Q1 vs. Q5, 0.69 vs. 2.45 nmol/L; adjusted HR, 1.19 [CI, 1.08 to 1.30]) and CVD mortality (adjusted HR, 1.29 [CI, 1.03 to 1.61]), and risk also increased with DHT concentrations above 2.45 nmol/L. Men with DHT concentrations below 0.59 nmol/L had increased risk for incident CVD events. LIMITATIONS: Observational study design, heterogeneity among studies, and imputation of missing data. CONCLUSION: Men with low testosterone, high LH, or very low estradiol concentrations had increased all-cause mortality. SHBG concentration was positively associated and DHT concentration was nonlinearly associated with all-cause and CVD mortality. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

Insulin-like peptide 3 (INSL3) as an indicator of leydig cell insufficiency (LCI) in Middle-aged and older men with hypogonadism: reference range and threshold.

Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential primary hypogonadism. Using results from large cohort studies we explore sources of biological and technical variance, and establish a reference range for adult men. It is constitutively secreted with little within-individual variation and reflects testicular capacity to produce testosterone. The main INSL3 assays available indicate good concordance with low technical variance; there is no effect of ethnicity. INSL3 declines with age from 35 years at about 15% per decade. Like low calculated free testosterone, and to a lesser extent low total testosterone, reduced INSL3 is significantly associated with increasing age-related morbidity, including lower overall sexual function, reflecting LCI. Consequently, low INSL3 (≤0.4 ng/ml; ca. <2 SD from the population mean) might serve as an additional biochemical marker in the assessment of functional hypogonadism (late-onset hypogonadism, LOH) where testosterone is in the borderline low range. Excluding individuals with low LCI (INSL3 ≤ 0.4 ng/ml) leads to an age-independent (> 35 years) reference range (serum) for INSL3 in the eugonadal population of 0.4 - 2.3 ng/ml, with low INSL3 prospectively identifying individuals at risk of increased future morbidity.

Experiences of postmenopausal osteoporosis: a narrative review.

PURPOSE: A narrative review was conducted to identify, critically appraise, and synthesise primary research on the lived experiences of postmenopausal women with osteoporosis. MATERIALS AND METHODS: A systematic search of qualitative studies published between January 1960 and August 2021 was conducted across seven databases. The selected qualitative studies reported the lived experiences of postmenopausal women with osteoporosis, both with and without a history of fragility fractures. RESULTS: A total of 17 publications (n = 334) were identified. These results suggest that osteoporosis and fragility fractures significantly affected postmenopausal women's lives. They reported difficulties in carrying out daily activities due to pain and change in their routines to cope with health problems. Some women were satisfied with the information provided by healthcare professionals. Their medicine adherence was also determined by their belief in the importance of their scheduled treatment for osteoporosis. CONCLUSION: Qualitative studies that explored the lived experiences of postmenopausal women with osteoporosis can provide important insights into the impact of the disease on women's lives and potential pathways for improving care and management.Implications for rehabilitationOsteoporosis and fragility fractures affect the quality of life of postmenopausal women worldwide.The provision of targeted and tailored health information for postmenopausal women with osteoporosis is paramount in improving their health literacy and aiding in the long-term management of their bone health.What is already knownOsteoporosis and related fragility fractures are common, affecting more than 200 million people worldwide, including three million people in the UK.Osteoporotic fractures have significant clinical and public health impacts.What this study addsOsteoporosis, particularly fragility fractures, has a significant impact on the lives of postmenopausal women, including pain and functional impairment.Women's belief in the importance of their scheduled treatment plays a significant role in their concordance with the prescribed medications for osteoporosis.Provision of targeted health information for postmenopausal women with osteoporosis is key to their involvement in decision-making and disease management.

Does testosterone influence the association between sleep and frailty in men: results from the European Male Aging Study.

BACKGROUND: Previous studies have suggested an association between sleep disturbance and frailty. The mechanism is unknown, although it has been suggested that hormonal factors may play a role. METHODS: The aim was to determine the association between sleep duration, sleep quality and frailty, and to determine whether testosterone influenced this association. Males aged 40-79 years were recruited from eight European centres to the European Male Aging Study (EMAS). Subjects completed an interviewer-assisted questionnaire including questions regarding sleep quality and duration. Sleep quality was scored 0-20 and categorised as 0-4, 5-9, 10-14, and 15-20, with higher scores indicating poorer quality. A 39-component frailty index (FI) was constructed. Total testosterone levels were measured. The association between sleep duration, sleep quality and the FI was assessed using negative binomial regression, with adjustment for putative confounders including testosterone level. RESULTS: Two thousand three hundred ninety-three participants contributed data to the analysis. The mean age was 63.3 years and mean sleep duration was 7.01 h. The mean frailty index was 0.15. Mean testosterone levels declined with decreasing sleep quality. After adjustment, compared to those with a sleep score of 0-4, the FI was 57% (95% CI 38%, 78%) higher among those with a sleep score of 15-20. After adjustment compared to those with normal sleep duration (6-9 h), those with a short (< 6 h) and long (≥ 9 h) sleep duration had a 16% (95% CI 6%, 28%) and 11% (95% CI 0%, 23%) higher FI, respectively. Adjustment for testosterone did not influence the strength of either association. CONCLUSION: Frailty is associated with impaired sleep quality and sleep duration. The association cannot, however, be explained by variation in testosterone levels.

Variation in UK fracture liaison service consultation conduct and content before and during the COVID pandemic: results from the iFraP-D UK survey.

We conducted a survey of FLSs' consultation conduct and content which identified marked variation in whether FLS HCPs discussed osteoporosis medicine with patients. A review of service pro formas showed more content related to 'investigating' and 'intervening' than to 'informing'. We propose an expanded FLS typology and model FLS pro forma. PURPOSE: To investigate the nature of direct patient contact in fracture liaison service (FLS) delivery, examine the use and content of pro formas to guide information eliciting and sharing in FLS consultations, and determine service changes which were implemented as a result of the COVID-19 pandemic. METHODS: An electronic survey of UK FLS healthcare practitioners (HCPs) was distributed through clinical networks, social media, and other professional networks. Participants were asked to upload service pro formas used to guide consultation content. Documentary analysis findings were mapped to UK FLS clinical standards. RESULTS: Forty-seven HCPs responded, providing data on 39 UK FLSs, over half of all 74 FLSs reporting to FLS-database. Results showed variation in which HCP made clinical decisions, whether medicines were discussed with patients or not, and in prescribing practice. Services were variably affected by COVID, with most reporting a move to more remote consulting. The documentary analysis of eight service pro formas showed that these contained more content related to 'investigating' and 'intervening', with fewer pro formas prompting the clinician to offer information and support (e.g., about coping with pain). Based on our findings we propose an expanded FLS typology and have developed a model FLS pro forma. CONCLUSION: There is marked variation in the delivery of services and content of consultations in UK FLSs including discussion about osteoporosis medications. Clinical standards for FLSs should clarify the roles of primary and secondary HCPs and the importance of holistic approaches to patient care.

Number of CAG repeats and mortality in middle aged and older men.

DESIGN: The androgen receptor (AR) mediates peripheral effects of testosterone. Previous data suggests an association between the number of CAG repeats in exon-1 of the AR gene and AR transcriptional activity. The aim of this analysis was to determine the association between the number of AR CAG repeats and all-cause mortality in men and the influence of testosterone level on the association. PATIENTS AND MEASUREMENTS: Follow-up data to 27 January 2018 were available for men aged 40-79 years recruited across six countries of the European Male Aging Study between 2003 and 2005. Cox proportional hazards modelling was used to determine the association between CAG repeat number/mortality. Results were expressed as hazard ratios (HR)/95% confidence intervals (CI). RESULTS: One thousand nine hundred and seventy-seven men were followed up. Mean baseline age was 60 ± 11.1 years. Mean duration of follow-up was 12.2 years. At follow up 25.1% of men had died. CAG repeat length ranged from 6 to 39, with the highest proportion of CAG repeat number at 21 repeats (16.4%). In a multivariable model, compared to men with 22-23 AR CAG repeats: for men with <22 and >23 AR CAG HR, 95% CI for mortality were, <22 CAG repeats 1.17 (0.93-1.49) and >23 CAG repeats 1.14 (0.88-1.47). In a post-hoc analysis, the association was significant for men in the lowest tertile of baseline testosterone (<14.2 nmol/L) with >23 CAG repeats: in the adjusted model for <22 and >23 CAG repeats, respectively, 1.49 (0.97-2.27) and 1.68 (1.06-2.67) versus 22-23 repeats. CONCLUSIONS: Our European-wide cohort data overall found no association of androgen receptor CAG repeat number and mortality in men. However, post hoc analysis suggested that an association might be present in men with lower baseline testosterone concentrations, which merits further investigation.

Factors Associated With Circulating Sex Hormones in Men : Individual Participant Data Meta-analyses.

BACKGROUND: Various factors modulate circulating testosterone in men, affecting interpretation of testosterone measurements. PURPOSE: To clarify factors associated with variations in sex hormone concentrations. DATA SOURCES: Systematic literature searches (to July 2019). STUDY SELECTION: Prospective cohort studies of community-dwelling men with total testosterone measured using mass spectrometry. DATA EXTRACTION: Individual participant data (IPD) (9 studies; n = 21 074) and aggregate data (2 studies; n = 4075). Sociodemographic, lifestyle, and health factors and concentrations of total testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone, and estradiol were extracted. DATA SYNTHESIS: Two-stage random-effects IPD meta-analyses found a nonlinear association of testosterone with age, with negligible change among men aged 17 to 70 years (change per SD increase about the midpoint, -0.27 nmol/L [-7.8 ng/dL] [CI, -0.71 to 0.18 nmol/L {-20.5 to 5.2 ng/dL}]) and decreasing testosterone levels with age for men older than 70 years (-1.55 nmol/L [-44.7 ng/dL] [CI, -2.05 to -1.06 nmol/L {-59.1 to -30.6 ng/dL}]). Testosterone was inversely associated with body mass index (BMI) (change per SD increase, -2.42 nmol/L [-69.7 ng/dL] [CI, -2.70 to -2.13 nmol/L {-77.8 to -61.4 ng/dL}]). Testosterone concentrations were lower for men who were married (mean difference, -0.57 nmol/L [-16.4 ng/dL] [CI, -0.89 to -0.26 nmol/L {-25.6 to -7.5 ng/dL}]); undertook at most 75 minutes of vigorous physical activity per week (-0.51 nmol/L [-14.7 ng/dL] [CI, -0.90 to -0.13 nmol/L {-25.9 to -3.7 ng/dL}]); were former smokers (-0.34 nmol/L [-9.8 ng/dL] [CI, -0.55 to -0.12 nmol/L {-15.9 to -3.5 ng/dL}]); or had hypertension (-0.53 nmol/L [-15.3 ng/dL] [CI, -0.82 to -0.24 nmol/L {-23.6 to -6.9 ng/dL}]), cardiovascular disease (-0.35 nmol/L [-10.1 ng/dL] [CI, -0.55 to -0.15 nmol/L {-15.9 to -4.3 ng/dL}]), cancer (-1.39 nmol/L [-40.1 ng/dL] [CI, -1.79 to -0.99 nmol/L {-51.6 to -28.5 ng/dL}]), or diabetes (-1.43 nmol/L [-41.2 ng/dL] [CI, -1.65 to -1.22 nmol/L {-47.6 to -35.2 ng/dL}]). Sex hormone-binding globulin was directly associated with age and inversely associated with BMI. Luteinizing hormone was directly associated with age in men older than 70 years. LIMITATION: Cross-sectional analysis, heterogeneity between studies and in timing of blood sampling, and imputation for missing data. CONCLUSION: Multiple factors are associated with variation in male testosterone, SHBG, and LH concentrations. Reduced testosterone and increased LH concentrations may indicate impaired testicular function after age 70 years. Interpretation of individual testosterone measurements should account particularly for age older than 70 years, obesity, diabetes, and cancer. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

Impact of postmenopausal osteoporosis on the lives of Omani women and the use of cultural and religious practises to relieve pain: A hermeneutic phenomenological study.

INTRODUCTION: Osteoporosis is a significant clinical and public health concern worldwide. Despite the impact of this condition on women's lives, most studies have focused on its clinical manifestations, drug efficacy, and medical treatment. Furthermore, most studies have been conducted in the West. This study aimed to uncover the personal experiences of postmenopausal Omani women living with osteoporosis. METHODS: In this interpretive phenomenological study, a purposive sample of 15 postmenopausal Omani women with osteoporosis was recruited from primary and secondary care facilities in Muscat, Oman. Semi-structured one-to-one interviews were conducted via Zoom and telephone because of coronavirus disease 2019 restrictions. The interviews were audio-recorded, and the Ajjawi and Higgs framework was used to analyse the data thematically. RESULTS: The following key themes were constructed from the interviews: the impact of osteoporosis on religious practices, cultural and social life, and financial status, and the benefits derived from religious and cultural practices and rituals, including Muslim prayer, recitation of Quranic verses, and herbal remedies to cope with osteoporosis-related pain and suffering. CONCLUSION: Osteoporosis and fragility fractures have a significant impact on the religious, cultural, and financial lives of postmenopausal Omani women with osteoporosis. Muslim prayers, recitation of Quranic verses, and herbal remedies are coping strategies for pain in this population. PATIENT OR PUBLIC CONTRIBUTION: Postmenopausal Omani women with osteoporosis participated in this study through interviews and contributed their lived experiences. Orthopaedic doctors helped recruit patients with postmenopausal osteoporosis.

Sarcopenia-defining parameters, but not sarcopenia, are associated with cognitive domains in middle-aged and older European men.

BACKGROUND: Previous research suggests that sarcopenia is associated with lower cognitive functioning. Evidence on the longitudinal relationship between cognition and sarcopenia, according to the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2), is scarce. This study aimed to investigate both cross-sectional and longitudinal associations between sarcopenia and its defining parameters (muscle strength, muscle mass and physical performance) and cognitive performance in middle-aged and older men. METHODS: This was a secondary analysis of data from the European Male Ageing Study (EMAS), a multicentre cohort study of men aged 40-79 years, recruited from population registers in eight European centres. Cognitive functioning was assessed by using a battery of three neuropsychological tests, measuring fluid intelligence: Rey-Osterrieth Complex Figure (ROCF-Copy and ROCF-Recall), Camden Topographical Recognition Memory (CTRM) and Digit Symbol Substitution Test (DSST). Sarcopenia-defining parameters appendicular lean mass (aLM), gait speed (GS), chair stand test (CST) and handgrip strength (HGS) were measured. Sarcopenia was diagnosed according to the criteria of the EWGSOP2. All measurements were performed at baseline and after a follow-up of 4.3 years. Cross-sectional associations between cognition, sarcopenia-defining parameters and prevalent sarcopenia (EWGSOP2) were analysed. Longitudinally, the predictive value of baseline cognition on decline in sarcopenia-defining parameters, onset of new sarcopenia and vice versa was examined. Linear and logistic regression were used and adjusted for putative confounders. RESULTS: In the whole cohort (n = 3233), ROCF-Copy (ß = 0.016; P < 0.05), ROCF-Recall (ß = 0.010; P < 0.05), CTRM (ß = 0.015; P < 0.05), DSST score (ß = 0.032; P < 0.05) and fluid cognition (ß = 0.036; P < 0.05) were significantly and independently associated with GS at baseline. In the Leuven + Manchester subcohorts (n = 456), ROCF-Copy (ß = 1.008; P < 0.05), ROCF-Recall (ß = 0.908; P < 0.05) and fluid cognition (ß = 1.482; P < 0.05) were associated with HGS. ROCF-Copy (ß = 0.394; P < 0.05), ROCF-Recall (ß = 0.316; P < 0.05), DSST (ß = 0.393; P < 0.05) and fluid cognition (ß = 0.765; P < 0.05) were associated with aLM. The prevalence of sarcopenia in this population was 17.8%. No associations were detected between cognition and prevalent or incident sarcopenia. Longitudinal analysis showed that low ROCF-Copy score at baseline was associated with an increase in CST in men ≥70 years (ß = -0.599; P < 0.05). In addition, a decrease in ROCF-Recall was associated with a decrease in GS, and a decrease in DSST was associated with an increase in CST (ß = 0.155; P < 0.0001, ß = -0.595; P < 0.001, respectively) in persons with the highest change in both cognition and muscle function. CONCLUSIONS: Sarcopenia was not associated with cognitive performance in this population, whereas several components of sarcopenia were associated with domain-specific cognitive performance. Longitudinally, baseline and change in subdomains of cognition predicted change in muscle function in specific subgroups.

Education mediating the associations between early life factors and frailty: a cross-sectional study of the UK Biobank.

OBJECTIVES: Exposures in utero and during infancy may impact the development of diseases later in life. They may be linked with development of frailty, although the mechanism is unclear. This study aims to determine the associations between early life risk factors and development of frailty among middle-aged and older adults as well as potential pathways via education, for any observed association. DESIGN: A cross-sectional study. SETTINGS: This study used data from UK Biobank, a large population-based cohort. PARTICIPANTS: 502 489 individuals aged 37-73 years were included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Early life factors in this study included being breast fed as a baby, maternal smoking, birth weight, the presence of perinatal diseases, birth month and birth place (in or outside the UK). We developed a frailty index comprising 49 deficits. We used generalised structural equation modelling to examine the associations between early life factors and development of frailty and whether any observed association was mediated via educational attainment. RESULTS: A history of breast feeding and normal birth weight were associated with a lower frailty index while maternal smoking, the occurrence of perinatal diseases and birth month with a longer day length were associated with a higher frailty index. Educational level mediated the relationship between these early life factors and frailty index. CONCLUSIONS: This study highlights that biological and social risk occurring at different stages of life are related to the variations in frailty index in later life and suggests opportunities for prevention across the life course.

Household wealth, neighbourhood deprivation and frailty amongst middle-aged and older adults in England: a longitudinal analysis over 15 years (2002-2017).

BACKGROUND: frailty is a condition of reduced function and health due to ageing processes and is associated with a higher risk of falls, hospitalisation, disability and mortality. OBJECTIVE: to determine the relationship between household wealth and neighbourhood deprivation with frailty status, independently of demographic factors, educational attainment and health behaviours. DESIGN: population-based cohort study. SETTING: communities in England. SUBJECTS: in total 17,438 adults aged 50+ from the English Longitudinal Study of Ageing. METHODS: multilevel mixed-effects ordered logistic regression was used in this study. Frailty was measured using a frailty index. We defined small geographic areas (neighbourhoods) using English Lower layer Super Output Areas. Neighbourhood deprivation was measured by the English Index of Multiple Deprivation, grouped into quintiles. Health behaviours included in this study are smoking and frequency of alcohol consumption. RESULTS: the proportion of respondents who were prefrail and frail were 33.8% [95% confidence interval (CI) 33.0-34.6%] and 11.7 (11.1-12.2)%, respectively. Participants in the lowest wealth quintile and living in the most deprived neighbourhood quintile had 1.3 (95% CI = 1.2-1.3) and 2.2 (95% CI = 2.1-2.4) times higher odds of being prefrail and frail, respectively, than the wealthiest participants living in the least deprived neighbourhoods Living in more deprived neighbourhood and poorer wealth was associated with an increased risk of becoming frail. Those inequalities did not change over time. CONCLUSIONS: in this population-based sample, living in a deprived area or having low wealth was associated with frailty in middle-aged and older adults. This relationship was independent of the effects of individual demographic characteristics and health behaviours.

Patient and healthcare provider experience and perceptions of a preoperative rehabilitation class for lumbar discectomy: A qualitative study.

BACKGROUND: Lumbar disc disease is a leading cause of low back pain. Lumbar discectomy (LD) may be indicated if symptoms are not managed conservatively. Rehabilitation has traditionally been delivered postoperatively; however, there is increasing delivery preoperatively. There are few data concerning perceptions and experiences of preoperative rehabilitation. Exploring experiences of preoperative rehabilitation may help in the development and delivery of effective care for patients. OBJECTIVES: To develop an understanding of patient and healthcare provider (HCP) experiences, perspectives and preferences of preoperative LD rehabilitation, including why patients do not attend. DESIGN: A qualitative interpretive approach using focus groups and individual interviews. METHODS: Data were collected from; a) patients listed for surgery and attended the preoperative rehabilitation (October 2019 to March 2020), b) patients listed for surgery but did not attend rehabilitation, and c) HCPs involved in the delivery of rehabilitation. Data were transcribed verbatim and analysed using thematic analysis. RESULTS/FINDINGS: Twenty participants were included, twelve patients and eight HCPs. The preoperative class was a valuable service for both patients and HCPs. It provided a solution to staffing and time pressures. It provided the required education and exercise content helping the patients along their surgery pathway. Travel distance, transportation links, parking difficulty and cost, lack of knowledge about the class aims, and previous negative experiences were barriers to patient attendance. CONCLUSIONS: For most patients and HCPs, the preoperative class was valuable. Addressing the challenges and barriers could improve attendance. Future research should focus on management of patient expectations and preferences preoperatively.

Development, validation and performance of laboratory frailty indices: A scoping review.

INTRODUCTION: Frailty is a syndrome characterised by decline in functional ability and increasing vulnerability to disease and associated with adverse outcomes. Several established methods exist for assessing frailty. This scoping review aims to characterise the development and validation of frailty indices based on laboratory test results (FI-Lab) and to assess their utility. METHODS: Studies were included in the review if they included data concerning the development and/or testing an FI-Lab using the deficit accumulation method. Studies were identified using PubMed/MEDLINE, Embase (Elsevier), OpenGrey and Google Scholar from 2010 to 2021. Two reviewers independently screened all abstracts, and those that met the inclusion criteria were reviewed in detail. Data extracted included details about the study characteristics, number, type and coding of laboratory variables included, validation, and outcomes. A narrative synthesis of the available evidence was adopted. RESULTS: The search yielded 915 articles, of which 29 studies were included. In general, 89% of studies were conducted after 2016 and 51% in a hospital-based setting. The number of variables included in FI-Labs ranged from 13 to 77, and 51% included some non-laboratory variables in their indices, with pulse and blood pressure being the most frequent. The validity of FI-Lab was demonstrated through change with age, correlation with established frailty indices and association with adverse health outcomes. The most frequent outcome studied was mortality (79% of the studies), with FI-Lab associated with increased mortality in all but one. Other outcomes studied included self-reported health, institutionalisation, and activities of daily living. The effect of combining the FI-Lab with a non-laboratory-based FI was assessed in 7 studies with a marginal increase in predictive ability. CONCLUSION: Frailty indices constructed based on the assessment of laboratory variables, appear to be a valid measure of frailty and robust to the choice of variables included.

Day-to-day variability of knee pain and the relationship with physical activity in people with knee osteoarthritis: an observational, feasibility study using consumer smartwatches.

OBJECTIVE: To assess the feasibility of using smartwatches in people with knee osteoarthritis (OA) to determine the day-to-day variability of pain and the relationship between daily pain and step count. DESIGN: Observational, feasibility study. SETTING: In July 2017, the study was advertised in newspapers, magazines and, on social media. Participants had to be living/willing to travel to Manchester. Recruitment was in September 2017 and data collection was completed in January 2018. PARTICIPANTS: 26 participants aged>50 years with self-diagnosed symptomatic knee OA were recruited. OUTCOME MEASURES: Participants were provided with a consumer cellular smartwatch with a bespoke app that triggered a series of daily questions including two times per day questions about level of knee pain and one time per month question from the pain subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. The smartwatch also recorded daily step counts. RESULTS: Of the 25 participants, 13 were men and their mean age was 65 years (standard deviation (SD) 8 years). The smartwatch app was successful in simultaneously assessing and recording data on knee pain and step count in real time. Knee pain was categorised into sustained high/low or fluctuating levels, but there was considerable day-to-day variation within these categories. Levels of knee pain in general correlated with pain assessed by KOOS. Those with sustained high/low levels of pain had a similar daily step count average (mean 3754 (SD 2524)/4307 (SD 2992)), but those with fluctuating pain had much lower step count levels (mean 2064 (SD 1716)). CONCLUSIONS: Smartwatches can be used to assess pain and physical activity in knee OA. Larger studies may help inform a better understanding of causal links between physical activity patterns and pain. In time, this could inform development of personalised physical activity recommendations for people with knee OA.

A prospective analysis examining frailty remission and the association with future falls risk in older adults in England.

BACKGROUND: Previous research has shown older adults experience dynamic changes in frailty status. This study aimed to determine the occurrence of sustained frailty remission and how remission is associated with falls risk. METHODS: Participants who contributed data to the analysis were in the English Longitudinal Study of Ageing from Waves 1 to 8 (2002-2017). Frailty was defined across waves using the frailty index and categorised into robust, pre-frail and frail. We classified participants who improved their frailty category from Wave 1 (2002) to Wave 2 (2004) and sustained/improved category again into Wave 3 (2006) and compared them with those who were either robust or frail across Waves 1-3. Cox proportional hazard modelling was used to determine the risk of incident falls reported at Waves 4-8, with results expressed as hazard ratios and 95% confidence intervals. RESULTS: Of 2,564 participants, 389 (15·2%) improved frailty category and sustained this during Waves 2-3, 1,489 (58·1%) remained robust and 686 (26·8%) remained frail during Waves 1-3. During the 10-year period (Waves 4-8), a total of 549 participants reported a fall. Compared with those who remained frail during Waves 1-3, those who with sustained frailty remission had a lower risk of future falls (HR 0·41; 95% CI = 0·36-0·45). CONCLUSIONS: Frailty remission is possible and can be sustained across 5 years. There is a lower risk of future falls in those who sustain frailty remission compared with those who remain frail.