Model of multidisciplinary teamwork in hip fracture care: a qualitative interview study.

OBJECTIVES: Hip fractures are common injuries in older age with high mortality requiring multidisciplinary clinical care. Despite guidance, there is considerable variation in hip fracture services and patient outcomes; furthermore, little is known about how successful multidisciplinary working can be enabled. This study aimed to characterise professionals' views about the core components of multidisciplinary teamwork in hip fracture care. DESIGN: The study comprised qualitative interviews with healthcare professionals delivering hip fracture care. Interviews were audio recorded, transcribed and analysed abductively: material was coded inductively and grouped into higher level concepts informed by theories and frameworks relating to teamwork. SETTING: Four hospitals in England. PARTICIPANTS: Participants were 40 healthcare professionals including orthopaedic surgeons, orthogeriatricians, physiotherapists and service managers. RESULTS: Results identified four components of successful multidisciplinary teamwork: (1) defined roles and responsibilities, (2) information transfer processes, (3) shared goals and (4) collaborative leadership. These were underpinned by a single concept: shared responsibility. Defined roles and responsibilities were promoted through formal care pathways, reinforced through induction and training with clear job plans outlining tasks. Information transfer processes facilitated timely information exchange to appropriate individuals. Well-defined common purpose was hindered by complex interdisciplinary professional relationships, particularly between orthogeriatric and orthopaedic staff, and encouraged through multidisciplinary team meetings and training. Clinical service leads were integral to bridging interdisciplinary boundaries. Mutual trust and respect were based on recognition of the value of different professional groups. Teamwork depended on formal clinical leads with facilitative and motivational roles, and on hospital leadership that created an environment supporting collaboration. Shared responsibility for patients was encouraged by joint orthopaedic and orthogeriatric care models. Staff shared responsibility by assisting colleagues when needed. CONCLUSIONS: Shared responsibility across the multidisciplinary team is fundamental to delivery of hip fracture care. Findings will inform development of clinical practice recommendations and training to build teamworking competencies.

Evaluation of a comprehensive health check offered to frontline health workers in Zimbabwe.

Health workers are essential for a functioning healthcare system, and their own health is often not addressed. During the COVID-19 pandemic health workers were at high risk of SARS-CoV-2 infection whilst coping with increased healthcare demand. Here we report the development, implementation, and uptake of an integrated health check combining SARS-CoV-2 testing with screening for other communicable and non-communicable diseases for health workers in Zimbabwe during the COVID-19 pandemic. Health checks were offered to health workers in public and private health facilities from July 2020 to June 2022. Data on the number of health workers accessing the service and yield of screening was collected. Workshops and in-depth interviews were conducted to explore the perceptions and experiences of clients and service providers. 6598 health workers across 48 health facilities accessed the service. Among those reached, 5215 (79%) were women, the median age was 37 (IQR: 29-44) years and the largest proportion were nurses (n = 2092, 32%). 149 (2.3%) healthcare workers tested positive for SARS-CoV-2. Uptake of screening services was almost 100% for all screened conditions except HIV. The most common conditions detected through screening were elevated blood pressure (n = 1249; 19%), elevated HbA1c (n = 428; 7.7%) and common mental disorder (n = 645; 9.8%). Process evaluation showed high acceptability of the service. Key enablers for health workers accessing the service included free and comprehensive service provision, and availability of reliable point-of-care screening methods. Implementation of a comprehensive health check for health workers was feasible, acceptable, and effective, even during a pandemic. Conventional occupational health programmes focus on infectious diseases. In a society where even health workers cannot afford health care, free comprehensive occupational health services may address unmet needs in prevention, diagnosis, and treatment for chronic non-communicable conditions.

Perinatal HIV infection is associated with deficits in muscle function in children and adolescents in Zimbabwe.

OBJECTIVES: To determine how muscle strength, power, mass, and density (i.e. quality) differ between children living with HIV (CWH) and those uninfected, and whether antiretroviral therapy (ART) regime is associated with muscle quality. DESIGN: A cross-sectional study in Harare, Zimbabwe. METHODS: The study recruited CWH aged 8-16 years, taking ART for at least 2 years, from HIV clinics, and HIV-uninfected children from local schools. Muscle outcomes comprised grip strength measured by hand-held Jamar dynamometer, lower limb power measured by standing long-jump distance, lean mass measured by dual-energy X-ray absorptiometry, and muscle density (reflecting intramuscular fat) by peripheral quantitative computed tomography. Linear regression calculated adjusted mean differences (aMD) by HIV status. RESULTS: Overall, 303 CWH and 306 without HIV, had mean (SD) age 12.5 (2.5) years, BMI 17.5 (2.8), with 50% girls. Height and fat mass were lower in CWH, mean differences (SE) 7.4 (1.1) cm and 2.7 (0.4)kgs, respectively. Male CWH had lower grip strength [aMD 2.5 (1.1-3.9) kg, P  < 0.001], long-jump distance [7.1 (1.8-12.5) cm, P  = 0.006], muscle density [0.58 (0.12-1.05) mg/cm 3 , P  = 0.018, but not lean mass 0.06 (-1.08 to 1.21) kg, P  = 0.891) versus boys without HIV; differences were consistent but smaller in girls. Mediation analysis suggested the negative effect of HIV on jumping power in boys was partially mediated by muscle density ( P  = 0.032). CWH taking tenofovir disoproxil fumarate (TDF) had lower muscle density [0.56 (0.00-1.13)mg/cm 3 , P  = 0.049] independent of fat mass, than CWH on other ART. CONCLUSION: Perinatally acquired HIV is associated, particularly in male individuals, with reduced upper and lower limb muscle function, not mass. Intra-muscular fat (poorer muscle quality) partially explained reductions in lower limb function. TDF is a novel risk factor for impaired muscle quality.

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.

BACKGROUND: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia. METHODS: We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial. RESULTS: Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone. CONCLUSION: These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.

Growth Profiles of Children and Adolescents Living with and without Perinatal HIV Infection in Southern Africa: A Secondary Analysis of Cohort Data.

Impaired linear growth and slower pubertal growth can be associated with perinatal HIV infection. We characterised growth relative to population norms, among the full adolescent period in southern Africa to better understand processes leading to morbidity in adulthood. We conducted a secondary analysis of 945 adolescents aged 8-20 years from urban Malawi and Zimbabwe; we included children with HIV (CWH), an uninfected comparison group from a cohort study, and CWH with co-morbid chronic lung disease (CLD) from a randomised controlled trial. We used latent class analysis of anthropometric Z-scores generated from British 1990 reference equations at two annual time-points, to identify growth trajectory profiles and used multinomial logistic regression to identify factors associated with growth profiles. Growth faltering (one or more of weight-for-age, height-for-age, or BMI-for-age Z-scores < -2) occurred in 38% (116/303) of CWH from the cohort study, 62% (209/336) of CWH with CLD, and 14% (44/306) of HIV-uninfected participants. We identified seven different growth profiles, defined, relatively, as (1) average growth, (2) tall not thin, (3) short not thin, (4) stunted not thin, (5) thin not stunted, (6) thin and stunted and (7) very thin and stunted. Females in profile 3 exhibited the highest body fat percentage, which increased over 1 year. Males at older age and CWH especially those with CLD were more likely to fall into growth profiles 4-7. Improvements in height-for-age Z-scores were observed in profiles 6-7 over 1 year. Interventions to target those with the worst growth faltering and longer-term follow-up to assess the impact on adult health are warranted.

Adjusting expected deaths for mortality displacement during the COVID-19 pandemic: a model based counterfactual approach at the level of individuals.

BACKGROUND: Near-real time surveillance of excess mortality has been an essential tool during the COVID-19 pandemic. It remains critical for monitoring mortality as the pandemic wanes, to detect fluctuations in the death rate associated both with the longer-term impact of the pandemic (e.g. infection, containment measures and reduced service provision by the health and other systems) and the responses that followed (e.g. curtailment of containment measures, vaccination and the response of health and other systems to backlogs). Following the relaxing of social distancing regimes and reduction in the availability of testing, across many countries, it becomes critical to measure the impact of COVID-19 infection. However, prolonged periods of mortality in excess of the expected across entire populations has raised doubts over the validity of using unadjusted historic estimates of mortality to calculate the expected numbers of deaths that form the baseline for computing numbers of excess deaths because many individuals died earlier than they would otherwise have done: i.e. their mortality was displaced earlier in time to occur during the pandemic rather than when historic rates predicted. This is also often termed "harvesting" in the literature. METHODS: We present a novel Cox-regression-based methodology using time-dependent covariates to estimate the profile of the increased risk of death across time in individuals who contracted COVID-19 among a population of hip fracture patients in England (N = 98,365). We use these hazards to simulate a distribution of survival times, in the presence of a COVID-19 positive test, and then calculate survival times based on hazard rates without a positive test and use the difference between the medians of these distributions to estimate the number of days a death has been displaced. This methodology is applied at the individual level, rather than the population level to provide a better understanding of the impact of a positive COVID-19 test on the mortality of groups with different vulnerabilities conferred by sociodemographic and health characteristics. Finally, we apply the mortality displacement estimates to adjust estimates of excess mortality using a "ball and urn" model. RESULTS: Among the exemplar population we present an end-to-end application of our methodology to estimate the extent of mortality displacement. A greater proportion of older, male and frailer individuals were subject to significant displacement while the magnitude of displacement was higher in younger females and in individuals with lower frailty: groups who, in the absence of COVID-19, should have had a substantial life expectancy. CONCLUSION: Our results indicate that calculating the expected number of deaths following the first wave of the pandemic in England based solely on historical trends results in an overestimate, and excess mortality will therefore be underestimated. Our findings, using this exemplar dataset are conditional on having experienced a hip fracture, which is not generalisable to the general population. Fractures that impede mobility in the weeks that follow the accident/surgery considerably shorten life expectancy and are in themselves markers of significant frailty. It is therefore important to apply these novel methods to the general population, among whom we anticipate strong patterns in mortality displacement - both in its length and prevalence - by age, sex, frailty and types of comorbidities. This counterfactual method may also be used to investigate a wider range of disruptive population health events. This has important implications for public health monitoring and the interpretation of public health data in England and globally.

ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

BACKGROUND: Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result. Polymorphic variation in the ACE promoter (I/D alleles) has been associated with differences in ACE activity and muscle physiology in a range of clinical conditions. This aim of this analysis was to determine whether I/D polymorphic variation is associated with muscle mass, strength, in sarcopenia or contributed to the lack of response to treatment in the LACE study. METHODS: Sarcopenic individuals were recruited into a 2x2 factorial multicentre double-blind study of the effects of perindopril and/or leucine versus placebo on physical performance and muscle mass. DNA extracted from blood samples (n = 130 72 women and 58 men) was genotyped by PCR for the ACE I/D polymorphism. Genotypes were then compared with body composition measured by DXA, hand grip and quadriceps strength before and after 12 months' treatment with leucine and/or perindopril in a cross-sectional analysis of the influence of genotype on these variables. RESULTS: Allele frequencies for the normal UK population were extracted from 13 previous studies (I = 0.473, D = 0.527). In the LACE cohort the D allele was over-represented (I = 0.412, D = 0.588, p = 0.046). This over-representation was present in men (I = 0.353, D = 0.647, p = 0.010) but not women (I = 0.458, D = 0.532, p = 0.708). In men but not women, individuals with the I allele had greater leg strength (II/ID = 18.00 kg (14.50, 21.60) vs DD = 13.20 kg (10.50, 15.90), p = 0.028). Over the 12 months individuals with the DD genotype increased in quadriceps strength but those with the II or ID genotype did not. Perindopril did not increase muscle strength or mass in any polymorphism group relative to placebo. CONCLUSION: Our results suggest that although ACE genotype was not associated with response to ACE inhibitor therapy in the LACE trial population, sarcopenic men with the ACE DD genotype may be weaker than those with the ACE I/D or II genotype.

Call to action: a five nations consensus on the use of intravenous zoledronate after hip fracture.

Currently in the UK and Ireland, after a hip fracture most patients do not receive bone protection medication to reduce the risk of refracture. Yet randomised controlled trial data specifically examining patients with hip fracture have shown that intravenous zoledronate reduces refracture risk by a third. Despite this evidence, use of intravenous zoledronate is highly variable following a hip fracture; many hospitals are providing this treatment, whilst most are currently not. A range of clinical uncertainties, doubts over the evidence base and practical concerns are cited as reasons. This paper discusses these concerns and provides guidance from expert consensus, aiming to assist orthogeriatricians, pharmacists and health services managers establish local protocols to deliver this highly clinically and cost-effective treatment to patients before they leave hospital, in order to reduce costly re-fractures in this frail population.

Patients' recovery of mobility and return to original residence after hip fracture are associated with multiple modifiable components of hospital service organisation: the REDUCE record-linkage cohort study in England and Wales.

BACKGROUND: Hip fractures are devastating injuries causing disability, dependence, and institutionalisation, yet hospital care is highly variable. This study aimed to determine hospital organisational factors associated with recovery of mobility and change in patient residence after hip fracture. METHODS: A cohort of patients aged 60 + years in England and Wales, who sustained a hip fracture from 2016 to 2019 was examined. Patient-level Hospital Episodes Statistics, National Hip Fracture Database, and mortality records were linked to 101 factors derived from 18 hospital-level organisational metrics. After adjustment for patient case-mix, multilevel models were used to identify organisational factors associated with patient residence at discharge, and mobility and residence at 120 days after hip fracture. RESULTS: Across 172 hospitals, 165,350 patients survived to discharge, of whom 163,230 (99%) had post-hospital discharge destination recorded. 18,323 (11%) died within 120 days. Among 147,027 survivors, 58,344 (40%) across 143 hospitals had their residence recorded, and 56,959 (39%) across 140 hospitals had their mobility recorded, at 120 days. Nineteen organisational factors independently predicted residence on hospital discharge e.g., return to original residence was 31% (95% confidence interval, CI:17-43%) more likely if the anaesthetic lead for hip fracture had time allocated in their job plan, and 8-13% more likely if hip fracture service clinical governance meetings were attended by an orthopaedic surgeon, physiotherapist or anaesthetist. Seven organisational factors independently predicted residence at 120 days. Patients returning to their pre-fracture residence was 26% (95%CI:4-42%) more likely if hospitals had a dedicated hip fracture ward, and 20% (95%CI:8-30%) more likely if treatment plans were proactively discussed with patients and families on admission. Seventeen organisational factors predicted mobility at 120 days. More patients re-attained their pre-fracture mobility in hospitals where (i) care involved an orthogeriatrician (15% [95%CI:1-28%] improvement), (ii) general anaesthesia was usually accompanied by a nerve block (7% [95%CI:1-12%], and (iii) bedside haemoglobin testing was routine in theatre recovery (13% [95%CI:6-20%]). CONCLUSIONS: Multiple, potentially modifiable, organisational factors are associated with patient outcomes up to 120 days after a hip fracture, these factors if causal should be targeted by service improvement initiatives to reduce variability, improve hospital hip fracture care, and maximise patient independence.

Organisational factors associated with hospital costs and patient mortality in the 365 days following hip fracture in England and Wales (REDUCE): a record-linkage cohort study.

BACKGROUND: Hip fracture care delivery varies between hospitals, which might explain variations in patient outcomes and health costs. The aim of this study was to identify hospital-level organisational factors associated with long-term patient outcomes and costs after hip fracture. METHODS: REDUCE was a record-linkage cohort study in which national databases for all patients aged 60 years and older who sustained a hip fracture in England and Wales were linked with hospital metrics from 18 organisational data sources. Multilevel models identified organisational factors associated with the case-mix adjusted primary outcomes: cumulative all-cause mortality, days spent in hospital, and inpatient costs over 365 days after hip fracture. FINDINGS: Between April 1, 2016, and March 31, 2019, 178 757 patients with an index hip fracture were identified from 172 hospitals in England and Wales. 126 278 (70·6%) were female, 52 479 (29·4%) were male, and median age was 84 years (IQR 77-89) in England and 83 years (77-89) in Wales. 365 days after hip fracture, 50 354 (28·2%) patients had died. Patients spent a median 21 days (IQR 11-41) in hospital, incurring costs of £14 642 (95% CI 14 600-14 683) per patient, ranging from £10 867 (SD 5880) to £23 188 (17 223) between hospitals. 11 organisational factors were independently associated with mortality, 24 with number of days in hospital, and 25 with inpatient costs. Having all patients assessed by an orthogeriatrician within 72 h of admission was associated with a mean cost saving of £529 (95% CI 148-910) per patient and a lower 365-day mortality (odds ratio 0·85 [95% CI 0·76-0·94]). Consultant orthogeriatrician attendance at clinical governance meetings was associated with cost savings of £356 (95% CI 188-525) and 1·47 fewer days (95% CI 0·89-2·05) in the hospital in the 365 days after hip fracture per patient. The provision of physiotherapy to patients on weekends was associated with a cost saving of £676 (95% CI 67-1285) per patient and with 2·32 fewer days (0·35-4·29) in hospital in the 365 days after hip fracture. INTERPRETATION: Multiple, potentially modifiable hospital-level organisational factors associated with important clinical outcomes and inpatient costs were identified that should inform initiatives to improve the effectiveness and efficiency of hip fracture services. FUNDING: Versus Arthritis.

Menopausal symptoms by HIV status and association with health-related quality of life among women in Zimbabwe: a cross-sectional study.

BACKGROUND: The scale-up of antiretroviral therapy programmes has resulted in increased life expectancy of people with HIV in Africa. Little is known of the menopausal experiences of African women, including those living with HIV. We aimed to determine the prevalence and severity of self-reported menopause symptoms in women at different stages of menopause transition, by HIV status, and evaluate how symptoms are related to health-related quality of life (HRQoL). We further sought to understand factors associated with menopause symptoms. METHODS: A cross-sectional study recruited women resident in Harare, Zimbabwe, sampled by age group (40-44/45-49/50-54/55-60 years) and HIV status. Women recruited from public-sector HIV clinics identified two similarly aged female friends (irrespective of HIV status) with phone access. Socio-demographic and medical details were recorded and women staged as pre-, peri- or post-menopause. The Menopausal Rating Scale II (MRS), which classified symptom severity, was compared between those with and without HIV. Linear and logistic regression determined factors associated with menopause symptoms, and associations between symptoms and HRQoL. RESULTS: The 378 women recruited (193[51.1%] with HIV), had a mean (SD) age of 49.3 (5.7) years; 173 (45.8%), 51 (13.5%) and 154 (40.7%) were pre-, peri and post-menopausal respectively. Women with HIV reported more moderate (24.9% vs. 18.1%) and severe (9.7% vs. 2.6%) menopause symptoms than women without HIV. Peri-menopausal women with HIV reported higher MRS scores than those pre- and post-menopausal, whereas in HIV negative women menopausal stage was not associated with MRS score (interaction p-value = 0.014). With increasing severity of menopause symptoms, lower mean HRQoL scores were observed. HIV (OR 2.02[95% CI 1.28, 3.21]), mood disorders (8.80[2.77, 28.0]), ≥ 2 falls/year (4.29[1.18, 15.6]), early menarche (2.33[1.22, 4.48]), alcohol consumption (2.16[1.01, 4.62]), food insecurity (1.93[1.14, 3.26]) and unemployment (1.56[0.99, 2.46]), were all associated with moderate/severe menopause symptoms. No woman reported use of menopausal hormone therapy. CONCLUSIONS: Menopausal symptoms are common and negatively impact HRQoL. HIV infection is associated with more severe menopause symptoms, as are several modifiable factors, including unemployment, alcohol consumption, and food insecurity. Findings highlight an unmet health need in ageing women in Zimbabwean, especially among those living with HIV.

Frequency, duration, and type of physiotherapy in the week after hip fracture surgery - analysis of implications for discharge home, readmission, survival, and recovery of mobility.

PURPOSE: To examine the association between physiotherapy access after hip fracture and discharge home, readmission, survival, and mobility recovery. METHODS: A 2017 Physiotherapy Hip Fracture Sprint Audit was linked to hospital records for 5383 patients. Logistic regression was used to estimate the association between physiotherapy access in the first postoperative week and discharge home, 30-day readmission post-discharge, 30-day survival and 120-days mobility recovery post-admission adjusted for age, sex, American Society of Anesthesiology grade, Hospital Frailty Risk Score and prefracture mobility/residence. RESULTS: Overall, 73% were female and 40% had high frailty risk. Patients who received ≥2 hours of physiotherapy (versus less) had 3% (95% Confidence Interval: 0-6%), 4% (2-6%), and 6% (1-11%) higher adjusted probabilities of discharge home, survival, and outdoor mobility recovery, and 3% (0-6%) lower adjusted probability of readmission. Recipients of exercise (versus mobilisation alone) had 6% (1-12%), 3% (0-7%), and 11% (3-18%) higher adjusted probabilities of discharge home, survival, and outdoor mobility recovery, and 6% (2-10%) lower adjusted probability of readmission. Recipients of 6-7 days physiotherapy (versus 0-2 days) had 8% (5-11%) higher adjusted probability of survival. For patients with dementia, improved probability of survival, discharge home, readmission and indoor mobility recovery were observed with greater physiotherapy access. CONCLUSION: Greater access to physiotherapy was associated with a higher probability of positive outcomes. For every 100 patients, greater access could equate to an additional eight patients surviving to 30-days and six avoiding 30-day readmission. The findings suggest a potential benefit in terms of home discharge and outdoor mobility recovery. CONTRIBUTION OF THE PAPER.

Disparities in the Prevalence of Osteoporosis and Osteopenia in Men and Women Living in Sub-Saharan Africa, the UK, and the USA.

PURPOSE: To review the rising prevalence of osteopenia and osteoporosis in sub-Saharan Africa and the challenges this poses to governments and healthcare services. Using existing studies, we compare the prevalence of osteopenia and osteoporosis in men and women from sub-Saharan Africa to US and UK cohorts. Context-specific disparities in healthcare are discussed particularly the challenges in diagnosis and treatment of osteoporosis. RECENT FINDINGS: There are few epidemiological data describing the burden of osteoporosis in sub-Saharan Africa. In the studies and cohorts presented here, osteoporosis prevalence varies by sex, country and area of residence, but is generally higher in African populations, than has previously been appreciated. Risk factors contributing to poorer bone health include HIV, malnutrition and "inflammaging." Reprioritization towards care of ageing populations is urgently required. Equitable access to implementable preventative strategies, diagnostic services, treatments and pathways of care for bone health (for example embedded within HIV services) need now to be recognized and addressed by policy makers.

Evaluation of two methods of bone age assessment in peripubertal children in Zimbabwe.

OBJECTIVES: Bone age (BA) measurement in children is used to evaluate skeletal maturity and helps in the diagnosis of growth disorders in children. The two most used methods are Greulich and Pyle (GP), and Tanner and Whitehouse 3 (TW3), both based upon assessment of a hand-wrist radiograph. To our knowledge no study has compared and validated the two methods in sub-Saharan Africa (SSA), and only a few have determined BA despite it being a region where skeletal maturity is often impaired for example by HIV and malnutrition. This study aimed to compare BA as measured by two methods (GP and TW3) against chronological age (CA) and determine which method is most applicable in peripubertal children in Zimbabwe. METHODS: We conducted a cross-sectional study of boys and girls who tested negative for HIV. Children and adolescents were recruited by stratified random sampling from six schools in Harare, Zimbabwe. Non-dominant hand-wrist radiographs were taken, and BA assessed manually using both GP and TW3. Paired sample Student t-tests were used to calculate the mean differences between BA and chronological age (CA) in boys and girls. Bland-Altman plots compared CA to BA as determined by both methods, and agreement between GP and TW3 BA. All radiographs were graded by a second radiographer and 20 % of participants of each sex were randomly selected and re-graded by the first observer. Intraclass correlation coefficient assessed intra- and inter-rater reliability and coefficient of variation assessed precision. RESULTS: We recruited 252 children (111 [44 %] girls) aged 8.0-16.5 years. The boys and girls were of similar mean ± SD CA (12.2 ± 2.4 and 11.7 ± 1.9 years) and BA whether assessed by GP (11.5 ± 2.8 and 11.5 ± 2.1 years) or TW3 (11.8 ± 2.5 and 11.8 ± 2.1 years). In boys BA was lower than CA by 0.76 years (95 % CI: -0.95, -0.57) when using GP, and by 0.43 years (95 % CI: -0.61, -0.24) when using TW3. Among the girls there was no difference between BA and CA by either GP [-0.19 years (95 % CI: -0.40, 0.03)] or TW3 [0.07 years (95 % CI: -0.16, 0.29)]. In both boys and girls, there were no systematic differences between CA and TW3 BA across age groups whereas agreement improved between CA and GP BA as children got older. Inter-operator precision was 1.5 % for TW3 and 3.7 % for GP (n = 252) and intra-operator precision was 1.5 % for TW3 and 2.4 % for GP (n = 52). CONCLUSION: The TW3 BA method had better precision than GP and did not systematically differ from CA, meaning that TW3 is the preferred method of assessment of skeletal maturity in Zimbabwean children and adolescents. TW3 and GP methods do not agree for estimates of BA and therefore cannot be used interchangeably. The systematic differences in GP BA assessments over age means it is not appropriate for use in all age groups or stages of maturity in this population.

Risk Factors and 120-Day Functional Outcomes of Delirium After Hip Fracture Surgery: A Prospective Cohort Study Using the UK National Hip Fracture Database (NHFD).

OBJECTIVES: To identify risk factors of postoperative delirium among hip fracture patients with normal preoperative cognition, and examine associations with returning home or recovery of mobility. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: We used the National Hip Fracture Database (NHFD) to identify patients presenting with hip fracture in England (2018-2019), but excluded those with abnormal cognition [abbreviated mental test score (AMTS) < 8] on presentation. METHODS: We examined the results of routine delirium screening performed using the 4 A's Test (4AT), to assess alertness, attention, acute change, and orientation in a 4-item mental test. Associations between 4AT score and return home or to outdoor mobility at 120 days were estimated, and risk factors identified for abnormal 4AT scores: (1) 4AT ≥4 suggesting delirium and (2) 4AT = 1-3 being an intermediate score not excluding delirium. RESULTS: Overall, 63,502 patients (63%) had a preoperative AMTS ≥8, in whom a postoperative 4AT score ≥4 suggestive of delirium was seen in 4454 (7%). These patients were less likely to return home [odds ratio (OR), 0.46; 95% CI, 0.38-0.55] or regain outdoor mobility (OR, 0.63; 95% CI, 0.53-0.75) by 120 days. Multiple factors including any deficit in preoperative AMTS and malnutrition were associated with higher risk of 4AT ≥4, while use of preoperative nerve blocks was associated with lower risk (OR, 0.88; 95% CI, 0.81-0.95). Poorer outcomes were also seen in 12,042 (19%) patients with 4AT = 1-3; additional risk factors associated with this score included socioeconomic deprivation and surgical procedure types that were not compliant with National Institute of Health and Care Excellence guidance. CONCLUSION AND IMPLICATIONS: Delirium after hip fracture surgery significantly reduces the likelihood of returning home or to outdoor mobility. Our findings underline the importance of measures to prevent postoperative delirium, and aid the identification of high-risk patients for whom delirium prevention might potentially improve outcomes.

Rare and Common Variants in GALNT3 May Affect Bone Mass Independently of Phosphate Metabolism.

Anabolic treatment options for osteoporosis remain limited. One approach to discovering novel anabolic drug targets is to identify genetic causes of extreme high bone mass (HBM). We investigated a pedigree with unexplained HBM within the UK HBM study, a national cohort of probands with HBM and their relatives. Whole exome sequencing (WES) in a family with HBM identified a rare heterozygous missense variant (NM_004482.4:c.1657C > T, p.Arg553Trp) in GALNT3, segregating appropriately. Interrogation of data from the UK HBM study and the Anglo-Australasian Osteoporosis Genetics Consortium (AOGC) revealed an unrelated individual with HBM with another rare heterozygous variant (NM_004482.4:c.831 T > A, p.Asp277Glu) within the same gene. In silico protein modeling predicted that p.Arg553Trp would disrupt salt-bridge interactions, causing instability of GALNT3, and that p.Asp277Glu would disrupt manganese binding and consequently GALNT3 catalytic function. Bi-allelic loss-of-function GALNT3 mutations alter FGF23 metabolism, resulting in hyperphosphatemia and causing familial tumoral calcinosis (FTC). However, bone mineral density (BMD) in FTC cases, when reported, has been either normal or low. Common variants in the GALNT3 locus show genome-wide significant associations with lumbar, femoral neck, and total body BMD. However, no significant associations with BMD are observed at loci coding for FGF23, its receptor FGFR1, or coreceptor klotho. Mendelian randomization analysis, using expression quantitative trait loci (eQTL) data from primary human osteoblasts and genome-wide association studies data from UK Biobank, suggested increased expression of GALNT3 reduces total body, lumbar spine, and femoral neck BMD but has no effect on phosphate concentrations. In conclusion, rare heterozygous loss-of-function variants in GALNT3 may cause HBM without altering phosphate concentration. These findings suggest that GALNT3 may affect BMD through pathways other than FGF23 regulation, the identification of which may yield novel anabolic drug targets for osteoporosis. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The Impact of Human Immunodeficiency Virus and Menopause on Bone Mineral Density: A Longitudinal Study of Urban-Dwelling South African Women.

An estimated 25% of South African women live with human immunodeficiency virus (HIV). Antiretroviral therapy roll-out has improved life expectancy, so many more women now reach menopause. We aimed to quantify changes in bone mineral density (BMD) during the menopausal transition in urban-dwelling South African women with and without HIV and determine whether HIV infection modified the effect of menopause on BMD changes. A 5-year population-based longitudinal study recruited women aged 40-60 years residing in Soweto and collected demographic and clinical data, including HIV status, anthropometry, and BMD, at baseline and at 5-year follow-up. All women were staged as pre-, peri-, or postmenopausal at both time points. Multivariable linear regression assessed relationships and interactions between HIV infection, menopause, and change in BMD. At baseline, 450 women had mean age 49.5 (SD 5.7) years, 65 (14.4%) had HIV, and 140 (31.1%), 119 (26.4%), and 191 (42.4%) were pre-, peri-, and postmenopausal, respectively; 34/205 (13.6%) women ≥50 years had a total hip (TH) or lumbar spine (LS) T-score ≤ -2.5. At follow-up 38 (8.4%), 84 (18.7%), and 328 (72.9%) were pre-, peri-, and postmenopausal. Those with HIV at baseline lost more total body (TB) BMD (mean difference -0.013 [95% confidence interval -0.026, -0.001] g/cm2 , p = 0.040) and gained more weight 1.96 [0.32, 3.60] kg; p = 0.019 than HIV-uninfected women. After adjusting for age, baseline weight, weight change, and follow-up time, the transition from pre- to postmenopause was associated with greater TB BMD losses in women with HIV (-0.092 [-0.042, -0.142] g/cm2 ; p = 0.001) than without HIV (-0.038 [-0.016, -0.060] g/cm2 , p = 0.001; interaction p = 0.034). Similarly, in women who were postmenopausal at both time points, those with HIV lost more TB BMD (-0.070 [-0.031, -0.108], p = 0.001) than women without HIV (-0.036 [-0.015, -0.057], p = 0.001, interaction p = 0.049). Findings were consistent but weaker at the LS and TH. Menopause-related bone loss is greater in women with HIV, suggesting women with HIV may be at greater risk of osteoporotic fractures. HIV services should consider routine bone health assessment in midlife women as part of long-term HIV care delivery. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Development and Validation of Multivariable Prediction Models for In-Hospital Death, 30-Day Death, and Change in Residence After Hip Fracture Surgery and the "Stratify-Hip" Algorithm.

BACKGROUND: To develop and validate the stratify-hip algorithm (multivariable prediction models to predict those at low, medium, and high risk across in-hospital death, 30-day death, and residence change after hip fracture). METHODS: Multivariable Fine-Gray and logistic regression of audit data linked to hospital records for older adults surgically treated for hip fracture in England/Wales 2011-14 (development n = 170 411) and 2015-16 (external validation, n = 90 102). Outcomes included time to in-hospital death, death at 30 days, and time to residence change. Predictors included age, sex, pre-fracture mobility, dementia, and pre-fracture residence (not for residence change). Model assumptions, performance, and sensitivity to missingness were assessed. Models were incorporated into the stratify-hip algorithm assigning patients to overall low (low risk across outcomes), medium (low death risk, medium/high risk of residence change), or high (high risk of in-hospital death, high/medium risk of 30-day death) risk. RESULTS: For complete-case analysis, 6 780 of 141 158 patients (4.8%) died in-hospital, 8 693 of 149 258 patients (5.8%) died by 30 days, and 4 461 of 119 420 patients (3.7%) had residence change. Models demonstrated acceptable calibration (observed:expected ratio 0.90, 0.99, and 0.94), and discrimination (area under curve 73.1, 71.1, and 71.5; Brier score 5.7, 5.3, and 5.6) for in-hospital death, 30-day death, and residence change, respectively. Overall, 31%, 28%, and 41% of patients were assigned to overall low, medium, and high risk. External validation and missing data analyses elicited similar findings. The algorithm is available at https://stratifyhip.co.uk. CONCLUSIONS: The current study developed and validated the stratify-hip algorithm as a new tool to risk stratify patients after hip fracture.

Fracture prevalence and its association with bone density among children living with HIV in Zimbabwe.

OBJECTIVES: HIV infection impairs bone density in children living with HIV (CLWH). We aimed to determine the prevalence of self-reported fracture (past or current), associated risk factors and disability, by HIV status in Zimbabwean children. DESIGN: Cross-sectional study. METHODS: We recruited CLWH aged 8-16 years taking antiretroviral therapy (ART) for ≥2 years from HIV clinics, and HIV-uninfected children from schools in Harare. Interviewer-administered questionnaires collected data on fracture site and management, sociodemographics, dietary calcium and vitamin D, physical activity and HIV history. Dual-energy X-ray absorptiometry (DXA) measured size-adjusted bone density. RESULTS: We recruited 303 CLWH [mean (SD) age 12.5 (2.5) years; 50% female] and 306 children without HIV [12.5 (2.5) years; 51% female]. Median age at HIV diagnosis in CLWH was 3.0 years [interquartile range (IQR) 1.2, 5.9], and median ART duration 8.1 years [IQR 6.2, 9.5]. 53.8% CLWH had self-reported disability and/or functional impairment, vs. 29.4% children without HIV. Fracture prevalence was 5.9% with no difference by HIV status [21/306 (6.9%) vs. 14/303 (4.6%), P  = 0.24]. Male sex was associated with fractures. Low size-adjusted bone density ( Z -score < -2) was associated with prevalent fractures in CLWH {risk ratio [RR] 1.14 (95% confidence interval (CI) -0.02, 2.29]}, but not in children without HIV [RR -0.04 (-2.00, 1.91)], P -interaction = 0.27. All sought medical attention for their fracture(s), but CLWH were less often admitted to hospital [2/14 (14.3%) vs. 7/21 (33.3%)]. CONCLUSION: Prevalent fractures may be associated with low lumbar spine bone density in CLWH. Fracture surveillance and strategies to reduce future fracture risk are warranted as CLWH enter adulthood.