The impact of HIV infection on skeletal maturity in peripubertal children in Zimbabwe: a cross-sectional study

Introduction HIV infection and its treatment compromises skeletal development (growth and maturation). Skeletal maturity is assessed as bone age (BA) on hand and wrist radiographs. BA younger than chronological age (CA) indicates delayed development. We conducted a cross-sectional study to determine differences between BA and CA (i.e., skeletal maturity deviation [SMD]), and risk factors associated with SMD in peripubertal children with and without HIV established on antiretroviral therapy (ART) including use of tenofovir disoproxil fumarate (TDF). Methods Children with HIV taking ART for at least two years and a comparison group of HIV-negative children, aged 8–16 years and frequency-matched by age and sex, were recruited from HIV clinics and local schools in the same catchment area, in Harare, Zimbabwe. BA was assessed from non-dominant hand-wrist radiographs using the Tanner Whitehouse 3 method. Negative SMD values correspond to delayed development, i.e., BA younger than CA. Multivariable linear regression models determined factors associated with SMD overall, and in children with HIV. Results In total, 534 participants (54% males) were included; by design CA was similar in males and females, whether living with or without HIV. Mean (SD) SMD was more negative in CWH than in HIV-negative children in both males [-1.4(1.4) vs. -0.4(1.1) years] and females [-1.1(1.3) vs. -0.0(1.2) years]. HIV infection and weight-for-age Z-score<-2 were associated with more negative SMD in both males and females after adjusting for socio-economic status, orphanhood, pubertal stage, and calcium intake. Age at ART initiation was associated with SMD in both males and females with those starting ART later more delayed: starting ART aged 4–8 years 1.14 (-1.84, -0.43), or over 8 years 1.47 (-2.30, -0.65) (p-value for trend < 0.001). Similar non-significant trends were seen in males. TDF exposure TDF exposure whether < 4years or ≥ 4 years was not associated with delayed development. Conclusion Perinatally-acquired HIV infection and being underweight were independently associated with delayed skeletal maturation in both males and females. Starting ART later was independently associated with skeletal maturation delay in CWH. Given the known effects of delayed development on later health, it is important to find interventions to ensure healthy weight gain through early years and in CWH to initiate ART as early as possible

Recent sarcopenia definitions—prevalence, agreement and mortality associations among men: findings from population‐based cohorts

Background The 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in individuals and prediction of important health-related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes. Methods White men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over courses of 2.4–6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength <27 kg and ALM index <7.0 kg/m2), SDOC (grip strength <35.5 kg and gait speed <0.8 m/s) and Modified SDOC (grip strength <35.5 kg and gait speed <1.0 m/s). Cohen's kappa statistic was used to assess agreement between original definitions (EWGSOP2 and SDOC). Presence versus absence of sarcopenia according to each definition in relation to mortality risk was examined using Cox regression with adjustment for age and weight; estimates were combined across cohorts using random-effects meta-analysis. Results Mean (SD) age of participants (n = 9170) was 74.3 (4.9) years; 5929 participants died during a mean (SD) follow-up of 12.1 (5.5) years. The proportion with sarcopenia according to each definition was EWGSOP2 (1.1%), SDOC (1.7%) and Modified SDOC (5.3%). Agreement was weak between EWGSOP2 and SDOC (κ = 0.17). Pooled hazard ratios (95% CI) for mortality for presence versus absence of each definition were EWGSOP2 [1.76 (1.42, 2.18), I2: 0.0%]; SDOC [2.75 (2.28, 3.31), I2: 0.0%]; and Modified SDOC [1.93 (1.54, 2.41), I2: 58.3%]. Conclusions There was low prevalence and poor agreement among recent sarcopenia definitions in community-dwelling cohorts of older white men. All indices of sarcopenia were associated with mortality. The strong relationship between sarcopenia and mortality, regardless of the definition, illustrates that identification of appropriate management and lifecourse intervention strategies for this condition is of paramount importance

Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts

Background Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited. Aim We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors. Methods Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4–6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell’s Concordance Index (C-index). Results Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed. Conclusions Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors

Identification of risk factors for hospital admission using multiple-failure survival models: a toolkit for researchers

Background: The UK population is ageing; improved understanding of risk factors for hospital admission is required. Linkage of the Hertfordshire Cohort Study (HCS) with Hospital Episode Statistics (HES) data has created a multiple-failure survival dataset detailing the characteristics of 2,997 individuals at baseline (1998-2004, average age 66 years) and their hospital admissions (regarded as ‘failure events’) over a 10 year follow-up. Analysis of risk factors using logistic regression or time to first event Cox modelling wastes information as an individual’s admissions after their first are disregarded. Sophisticated analysis techniques are established to examine risk factors for admission in such datasets but are not commonly implemented.Methods: We review analysis techniques for multiple-failure survival datasets (logistic regression; time to first event Cox modelling; and the Andersen and Gill [AG] and Prentice, Williams and Peterson Total Time [PWP-TT] multiple-failure models), outline their implementation in Stata, and compare their results in an analysis of housing tenure (a marker of socioeconomic position) as a risk factor for different types of hospital admission (any; emergency; elective; &gt;7 days). The AG and PWP-TT models include full admissions histories in the analysis of risk factors for admission and account for within-subject correlation of failure times. The PWP-TT model is also stratified on the number of previous failure events, allowing an individual’s baseline risk of admission to increase with their number of previous admissions. Results: All models yielded broadly similar results: not owner-occupying one’s home was associated with increased risk of hospital admission. Estimated effect sizes were smaller from the PWP-TT model in comparison with other models owing to it having accounted for an increase in risk of admission with number of previous admissions. For example, hazard ratios [HR] from time to first event Cox models were 1.67(95%CI: 1.36,2.04) and 1.63(95%CI:1.36,1.95) for not owner-occupying one’s home in relation to risk of emergency admission or death among women and men respectively; corresponding HRs from the PWP-TT model were 1.34(95%CI:1.15,1.56) for women and 1.23(95%CI:1.07,1.41) for men. Conclusion: The PWP-TT model may be implemented using routine statistical software and is recommended for the analysis of multiple-failure survival datasets which detail repeated hospital admissions among older people.<br/

Understanding poor health behaviours as predictors of different types of hospital admission in older people: findings from the Hertfordshire Cohort Study

BACKGROUND:Rates of hospital admission are increasing, particularly among older people. Poor health behaviours cluster but their combined impact on risk of hospital admission among older people in the UK is unknown.METHODS: 2997 community-dwelling men and women (aged 59-73) participated in the Hertfordshire Cohort Study (HCS). We scored (from 0 to 4) number of poor health behaviours engaged in at baseline (1998-2004) out of: current smoking, high weekly alcohol, low customary physical activity and poor diet. We linked HCS with Hospital Episode Statistics and mortality data to 31/03/2010 and analysed associations between the score and risk of different types of hospital admission: any; elective; emergency; long stay (&gt;7?days); 30-day readmission (any, or emergency).RESULTS: 32%, 40%, 20% and 7% of men engaged in 0, 1, 2 and 3/4 poor health behaviours; corresponding percentages for women 51%, 38%, 9%, 2%. 75% of men (69% women) experienced at least one hospital admission. Among men and women, increased number of poor health behaviours was strongly associated (p&lt;0.01) with greater risk of long stay and emergency admissions, and 30-day emergency readmissions. Hazard ratios (HRs) for emergency admission for 3/4 poor health behaviours in comparison with none were: men, 1.37 (95% CI 1.11 to 1.69); women, 1.84 (95% CI 1.22 to 2.77). Associations were unaltered by adjustment for age, body mass index and comorbidity.CONCLUSIONS: Clustered poor health behaviours are associated with increased risk of hospital admission among older people in the UK. Lifecourse interventions to reduce number of poor health behaviours could have substantial beneficial impact on health and use of healthcare in later life

Grip strength among community-dwelling older people predicts hospital admission during the following decade

Background: lower grip strength on admission to hospital is known to be associated with longer stay, but the link between customary grip and risk of future admission is less clear.Objective: to compare grip strength with subsequent risk of hospital admission among community-dwelling older people in a UK setting.Design: cohort study with linked administrative data.Setting: Hertfordshire, UK.Subjects: a total of 2,997 community-dwelling men and women aged 59–73 years at baseline.Methods: the Hertfordshire Cohort Study (HCS) participants completed a baseline assessment between 1998 and 2004, during which grip strength was measured. Hospital Episode Statistics and mortality data to March 2010 were linked with the HCS database. Statistical models were used to investigate the association of grip strength with subsequent elective, emergency and long-stay hospitalisation and readmission.Results: there was a statistically significant negative association between grip strength and all classes of admission in women [unadjusted hazard ratio per standard deviation (SD) decrease in grip strength for: any admission/death 1.10 (95% CI: 1.06, 1.14), elective admission/death 1.09 (95% CI: 1.05, 1.13), emergency admission/death 1.21 (95% CI: 1.13, 1.31), long-stay admission/death 1.22 (95% CI: 1.13, 1.32) and unadjusted relative risk per SD decrease in grip strength for 30-day readmission/death 1.30 (95% CI: 1.19, 1.43)]. These associations remained significant after adjustment for potential confounding factors (age, height, weight for height, smoking, alcohol, social class). In men, unadjusted rates for emergency admission/death, long-stay admission/death and readmission/death were significantly associated with grip strength; associations that similarly withstood adjustment.Conclusion: this study provides the first evidence that grip strength among community-dwelling men and women in the UK is associated with risk of hospital admission over the following decad

A healthy conversation skills intervention to support changes to physical activity and dietary behaviours in community-dwelling older adults during the COVID-19 pandemic

Aims: physical activity (PA) and nutrition are important determinants of health in late adulthood. However, low levels of PA and poor nutrition are common in older adults and have become more prevalent during the COVID-19 pandemic. We hypothesised that Healthy Conversation Skills could be used to support health behaviour changes beneficial for health in older adults and thus conducted a study nested within the UK Hertfordshire Cohort Study.Methods: between November 2019 and March 2020, 176 participants were visited at home. A trained researcher administered a questionnaire and undertook anthropometric and physical performance tests. A total of 89 participants were randomised to the control group and received a healthy living leaflet; 87 participants in the intervention group were interviewed using Healthy Conversation Skills at the initial visit with follow-up telephone calls at 1, 3, 6 and 9 months. Follow-up at 1 year by postal questionnaire assessed change in PA and diet. In total, 155 participants (79 control and 76 intervention) completed the baseline and 1-year follow-up.Results: at baseline, median (lower quartile, upper quartile) age (years) was 83.1 (81.5, 85.5) and median PA time (min/day) from walking, cycling and sports was 30.0 (15.0, 60.0). In total, 95% of participants completed the intervention; the total response rate for postal questionnaires was 94%. There were no statistically significant differences in outcomes between the trial arms. In women, there was a tendency for greater increases in diet quality in the intervention group compared to the control group (p = 0.075), while among men, there was a tendency for reduced decline in self-reported physical function in the intervention group compared to the control group (p = 0.081).Conclusions: we have shown that it is viable to utilise Healthy Conversation Skills via telephone to promote healthier lifestyles in older adults. Larger appropriately powered studies to determine the efficacy of such an intervention are now warranted.</p

Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities

10.1038/s41467-019-13694-1Nature Communications10