Early-life cumulative exposure to excess bodyweight and midlife cognitive function: longitudinal analysis in three British birth cohorts.

BACKGROUND: Excess bodyweight (BMI >25 kg/m2) in midlife (age 40-65 years) has been linked to future cognitive decline and an increased risk of dementia. Whether chronic exposure to excess bodyweight in the early decades of life (<40 years) is associated with compromised cognitive function by midlife, however, remains unclear. This study therefore aimed to test potential bidirectional direct and indirect pathways linking cumulative exposure to excess bodyweight and cognitive function in the early decades of life. METHODS: In this longitudinal analysis, harmonised measures of BMI and cognitive function were available in 19 742 participants aged 47-53 years recruited to the 1946 National Survey of Health and Development (n=2131), the 1958 National Child Development Study (n=9385), and the 1970 British Cohort Study (n=8226). Individual BMI trajectories spanning three decades from age 10-40 years were created for each participant and excess bodyweight duration, BMI change between ages, and cumulative excess bodyweight exposure were calculated. Harmonised measures of verbal and non-verbal ability, mathematical ability, and reading ability were used to create a latent factor for childhood cognitive function, and immediate and delayed recall, animal naming, and letter-search speed tests were used for midlife cognitive function. Multivariable linear regression and structural equation models (SEM) were used to test for potential bidirectional relationships between cognition and excess bodyweight in both individual cohorts and pooled datasets while accounting for other potential early-life confounders. FINDINGS: Increases in BMI during adolescence and greater cumulative exposure to excess bodyweight across early life were associated with lower midlife cognitive function in all cohorts (eg, pooled difference in cognitive function per 10 years excess bodyweight duration -0·10; 95% CI -0·12 to -0·08; p<0·001). Further adjustment for childhood cognitive function attenuated many of these associations towards the null (eg, pooled difference in cognitive function per 10 years excess bodyweight duration -0·04; 95% CI -0·06 to -0·02; p=0·001), however, with any remaining associations then fully attenuating once further adjusted for other early-life factors (eg, pooled difference in cognitive function per 10 years excess bodyweight duration 0, -0·03 to 0·01; p=0·38). In the reverse direction, low childhood cognition was associated with greater cumulative exposure to excess bodyweight over the next four decades, although much of this relationship was found to probably be explained via other potentially modifiable upstream early-life factors such as childhood disadvantage. SEM in all cohorts suggested the presence of modest direct and indirect pathways connecting earlier cognitive function to later excess bodyweight, but scarce evidence for an effect of early-life excess bodyweight on cognitive function by midlife. INTERPRETATION: The association between cumulative exposure to excess bodyweight in early life and lower cognitive function in midlife is probably confounded by a persistently lower cognitive function from childhood. Initiatives to improve early-life factors such as childhood disadvantage and education, however, might exert dual but independent benefits on both of these factors before old age. FUNDING: Alzheimer's Research UK, Diabetes Research and Wellness Foundation, Diabetes UK, British Heart Foundation, and Medical Research Council.

Loneliness Trajectories, Associated Factors and Subsequent Health in Children and Young People During the COVID-19 Pandemic: A National Matched Cohort Study.

Purpose: Loneliness is common amongst children and young people (CYP) and is an independent risk factor for poor health. This study aimed to i) determine whether subgroups of CYP with different loneliness trajectories (during the second year of the pandemic) exist; ii) examine associations with socio-demographic characteristics and subsequent health; and iii) understand whether associations between loneliness and subsequent health were modified by SARS-CoV-2 infection. Methods: A total of 5851 CYP (N=3260 SARS-CoV-2 positive and 2591 SARS-CoV-2 negative) provided data on loneliness (via the validated 3-item version of the UCLA Loneliness Scale for Children) at least twice in a 12-month period post PCR index-testing (conducted October 2020-March 2021). Latent class growth analyses were used to identify distinct classes of loneliness trajectories. Multinomial logistic regression was used to identify socio-demographic characteristics associated with class membership. Logistic regression models assessed the odds of reporting impairing symptoms 12-months post index-test. Results: Four distinct loneliness trajectories were identified: three mostly stable (low, medium, high) and one low-increasing trajectory. Being older, female, living in more deprived areas and testing negative were associated with greater odds of being in the highest vs lowest loneliness trajectory; eg OR for female vs male: 5.6 (95% CI:4.1,7.8); OR for 15-17 vs 11-14 years: 4.5 (95% CI:3.4,6.0). Following higher loneliness trajectories was associated with higher odds of experiencing impairing symptoms 12-months post index-test: ORadjusted (compared to lowest loneliness trajectory) were 15.9 (95% CI:11.9,21.3) (high loneliness), 6.5 (5.3,7.9) (medium loneliness) and 2.3 (1.9,2.8) (low-increasing loneliness). There was no evidence that this association was modified by PCR index-test result. Conclusion: About 5.3% of CYP were classified into a group experiencing (chronically) high loneliness. Being female, older and from more deprived areas were risk factors of belonging to this group. Results suggest that even small increases from low loneliness levels may be associated with worse health outcomes.

Chronic inflammation does not mediate the effect of adiposity on grip strength: results from a multivariable Mendelian randomization study.

The relationship between adiposity and grip strength (GS) is complex. We investigated whether one pathway through which adiposity affects GS was via chronic inflammation. 367,583 UK Biobank participants had body mass index (BMI), waist-hip-ratio (WHR), C-reactive protein (CRP) and GS data. Univariable Mendelian randomization (MR) and multivariable Mendelian randomization (MVMR) analyses (using inverse variance weighted (IVW) weighted median estimates (WME) and MR-Egger models) estimated total, direct and indirect effects of adiposity traits on GS using genetic instruments for BMI and WHR (exposures) and CRP (mediator). Observational findings suggested higher BMI was associated with stronger grip, e.g., in males, per standard deviation (SD) higher BMI, GS was higher by 0.48 kg (95% confidence interval(CI):0.44,0.51), independent of CRP. For males MR estimates were directionally consistent; for females, estimates were consistent with the null. Observational findings for WHR suggested that higher WHR was associated with weaker grip. In multivariable MR-IVW analyses, effects in males were consistent with the null. In females, there were consistent effects such that higher WHR was associated with stronger grip, e.g., 1-SD higher WHR was associated with 1.25 kg (MVMR-Egger; 95% CI:0.72,1.78) stronger grip, independent of CRP. Across sexes and adiposity indicators, CRP's mediating role was minor. Greater adiposity may increase GS in early old age, but effects vary by sex and adiposity location. There was no evidence that inflammation mediated these effects.

Effect of Isoenergetic Substitution of Cheese with Other Dairy Products on Blood Lipid Markers in the Fasted and Postprandial State: An Updated and Extended Systematic Review and Meta-Analysis of Randomized Controlled Trials in Adults.

Consumption of fat as part of a cheese matrix may differentially affect blood lipid responses when compared with other dairy foods. This systematic review was conducted to compare the impact of consuming equal amounts of fat from cheese and other dairy products on blood lipid markers in the fasted and postprandial state. Searches of PubMed (Medline), Cochrane Central and Embase databases were conducted up to mid-June 2022. Eligible human randomized controlled trials (RCTs) investigated the effect of isoenergetic substitution of hard or semi-hard cheese with other dairy products on blood lipid markers. Risk of bias (RoB) was assessed using the Cochrane RoB 2.0 tool. Random-effects meta-analyses assessed the effect of ≥2 similar dietary replacements on the same blood lipid marker. Of 1491 identified citations, 10 articles were included (RoB: all some concerns). Pooled analyses of 7 RCTs showed a reduction in fasting total cholesterol, LDL-C and HDL-C concentrations after ≥14 d mean daily intake of 135 g cheese (weighted mean difference [WMD]: -0.24 mmol/L; 95% confidence interval (CI): -0.34, -0.15; I2 = 59.8%, WMD: -0.19 mmol/L; 95% CI: -0.27, -0.12; I2 = 42.8%, and WMD: -0.04 mmol/L; 95% CI: -0.08, -0.00; I2 = 58.6%, respectively) relative to ∼52 g/d butter. We found no evidence of a benefit from replacing cheese for ≥14 d with milk on fasting blood lipid markers (n = 2). Limited postprandial RCTs, described in narrative syntheses, suggested that cheese-rich meals may induce differential fed-state lipid responses compared with some other dairy matrix structures, but not butter (n ≤ 2). In conclusion, these findings indicate that dairy fat consumed in the form of cheese has a differential effect on blood lipid responses relative to some other dairy food structures. However, owing to considerable heterogeneity and limited studies, further confirmation from RCTs is warranted. TRIAL REGISTRATION NUMBER: This systematic review protocol was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42022299748.

Cluster-Randomized Comparative Effectiveness Trial of Physician-Directed Clinical Decision Support Versus Patient-Directed Education to Promote Appropriate Use of Opioids for Chronic Pain.

We compared the effectiveness of physician-directed clinical decision support (CDS) administered via electronic health record versus patient-directed education to promote the appropriate use of opioids by conducting a cluster-randomized trial involving 82 primary care physicians and 951 of their patients with chronic pain. Primary outcomes were satisfaction with patient-physician communication consumer assessment of health care providers and system clinician and group survey (CG-CAHPS) and pain interference patient-reported outcomes measurement information system. Secondary outcomes included physical function (patient-reported outcomes measurement information system), depression (PHQ-9), high-risk opioid prescribing (>90 morphine milligram equivalents per day [≥90 mg morphine equivalent/day]), and co-prescription of opioids and benzodiazepines. We used multi-level regression to compare longitudinal difference-in-difference scores between arms. The odds of achieving the maximum CG-CAHPS score were 2.65 times higher in the patient education versus the CDS arm (P = .044; 95% confidence interval [CI] 1.03-6.80). However, baseline CG-CAHPS scores were dissimilar between arms, making these results challenging to interpret definitively. No difference in pain interference was found between groups (Coef = -0.64, 95% CI -2.66 to 1.38). The patient education arm experienced higher odds of Rx ≥ 90 milligrams morphine equivalent/day (odds ratio = 1.63; P = .010; 95% CI 1.13, 2.36). There were no differences between groups in physical function, depression, or co-prescription of opioids and benzodiazepines. These results suggest that patient-directed education may have the potential to improve satisfaction with patient-physician communication, whereas physician-directed CDS via electronic health records may have greater potential to reduce high-risk opioid dosing. More evidence is needed to ascertain the relative cost-effectiveness between strategies. PERSPECTIVE: This article presents the results of a comparative-effectiveness study of 2 broadly used communication strategies to catalyze dialog between patients and primary care physicians around chronic pain. The results add to the decision-making literature and offer insights about the relative benefits of physician-directed versus patient-directed interventions to promote the appropriate use of opioids.

The relationship between adiposity and cognitive function: a bidirectional Mendelian randomization study in UK Biobank.

BACKGROUND: There may be a bidirectional relationship between cognition and adiposity, whereby poor cognition leads to increased adiposity and vice versa. We aimed to determine whether these findings are causal, by undertaking a bidirectional Mendelian randomization (MR) study. METHODS: A total of 378 877 UK Biobank participants had three adiposity indicators [body fat percentage (BF%), body mass index (BMI) and waist-hip ratio] and two cognitive function measures (reaction time, visual memory). We examined observational associations between each adiposity indicator and cognitive function and vice versa. Using bidirectional inverse-variance weighted MR, we estimated the strength of the adiposity-cognitive function association using genetic instruments for adiposity indicators as our exposures, and we repeated this in the opposite direction using instruments for cognitive function. RESULTS: In the direction adiposity to cognitive function, MR analyses were generally directionally consistent with observational findings, but all confidence intervals contained the null. In the opposite direction, MR estimates for all adiposity measures on reaction time were imprecise and directionally inconsistent. MR estimates for the effects of visual memory on all adiposity measures indicated worse visual memory was associated with lower adiposity. For example, a 1-unit worse visual memory score was associated with a 1.32% [ß = -1.32; 95% confidence interval (CI): -0.77,-1.88] and 3.57% (ß = -3.64; 95% CI: -1.84,-5.15) lower absolute body fat percentage and relative body mass index, respectively. CONCLUSIONS: Observational associations of adiposity on cognitive function are likely not causal. In the reverse direction, our consistent findings that worse visual memory is associated with three adiposity indicators provide support for a causal link between worse visual memory and lower adiposity.

Does moderate to vigorous physical activity mediate the association between depression and physical function in midlife: Evidence from two British birth cohort studies.

BACKGROUND: Mental health and physical health are intrinsically linked, yet the mechanisms are not well understood. We investigated whether moderate-vigorous physical activity (MVPA) mediated the association between depression and physical function (PF) in midlife. METHODS: Individuals from two UK birth cohorts born within one week in 1958 (n = 7278) and 1970 (n = 6097) with data on depression (ages 33/34; Malaise Inventory), MVPA (age 42; self-reported) and PF (ages 50/56; Short Form-36 subscale). Covariates included sex, childhood and adulthood social class, maternal mental health, childhood mood, alcohol consumption, smoking habits, sleep, marital status, BMI and long-standing illness/disability. Linear or multinomial logistic regression models examined associations between depression, MVPA and PF. We used a parametric g-computation mediation analysis approach to estimate percent differences in PF. RESULTS: Depression was associated with less frequent MVPA and poorer PF. Lower MVPA was associated with worse PF. The direct effect - randomised analogue not operating via MVPA - of depression on PF was -18.8 % (95%CI:--25.8,-11.8) and -15.8 % (20.6,-11.0) in the 1958 and 1970 cohorts, respectively. The indirect effect - operating via MVPA - was -0.5 % (-1.0,-0.03) and -0.2 % (-0.6, 0.3), resulting in a total proportion mediated of 3.1 % (0.1, 6.0) and 0.9 % (-1.6, 3.4). LIMITATIONS: MVPA was self-reported. Intermediate confounders and mediators were measured at the same age, however associations did not change in sensitivity analysis considering age 46 MVPA (1958 cohort). CONCLUSIONS: Although higher MVPA was protective against poor PF, there was only minor evidence that it mediated the association between depression and PF. Further investigation into other potential mediators of pathways from mental to physical health is needed.

The associations of maternal and paternal obesity with latent patterns of offspring BMI development between 7 and 17 years of age: pooled analyses of cohorts born in 1958 and 2001 in the United Kingdom.

OBJECTIVE: We aimed to 1) describe how the UK obesity epidemic reflects a change over time in the proportion of the population demonstrating adverse latent patterns of BMI development and 2) investigate the potential roles of maternal and paternal BMI in this secular process. METHODS: We used serial BMI data between 7 and 17 years of age from 13220 boys and 12711 girls. Half the sample was born in 1958 and half in 2001. Sex-specific growth mixture models were developed. The relationships of maternal and paternal BMI and weight status with class membership were estimated using the 3-step BCH approach, with covariate adjustment. RESULTS: The selected models had five classes. For each sex, in addition to the two largest normal weight classes, there were "normal weight increasing to overweight" (17% of boys and 20% of girls), "overweight increasing to obesity" (8% and 6%), and "overweight decreasing to normal weight" (3% and 6%) classes. More than 1-in-10 children from the 2001 birth cohort were in the "overweight increasing to obesity" class, compared to less than 1-in-30 from the 1958 birth cohort. Approximately 75% of the mothers and fathers of this class had overweight or obesity. When considered together, both maternal and paternal BMI were associated with latent class membership, with evidence of negative departure from additivity (i.e., the combined effect of maternal and paternal BMI was smaller than the sum of the individual effects). The odds of a girl belonging to the "overweight increasing to obesity" class (compared to the largest normal weight class) was 13.11 (8.74, 19.66) times higher if both parents had overweight or obesity (compared to both parents having normal weight); the equivalent estimate for boys was 9.01 (6.37, 12.75). CONCLUSIONS: The increase in obesity rates in the UK over more than 40 years has been partly driven by the growth of a sub-population demonstrating excess BMI gain during adolescence. Our results implicate both maternal and paternal BMI as correlates of this secular process.

Magnitude, trends and drivers of the coexistence of maternal overweight/obesity and childhood undernutrition in Ethiopia: Evidence from Demographic and Health Surveys (2005-2016).

Ethiopia faces a rising problem of overweight and obesity alongside a high prevalence of undernutrition; a double burden of malnutrition (DBM). This study aimed to quantify the magnitude and trends of household-level DBM-defined as the coexistence of maternal overweight/obesity and child undernutrition (i.e., stunting or anaemia)-in Ethiopia between 2005, 2011 and 2016 and understand the potential drivers influencing DBM and the change in DBM over time. Data come from the Ethiopian Demographic and Health Surveys. National and regional prevalence estimates of the DBM were calculated (n = 13,107). Equiplots were produced to display inequalities in the distribution of DBM. Factors associated with DBM were explored using pooled multivariable logistic regression analyses for 2005, 2011 and 2016 (n = 9358). These were also included in a logistic regression decomposition analysis to understand their contribution to the change in DBM between 2005 and 2016 (n = 5285). The prevalence of household-level DBM at the national level was low, with a modest increase from 2.4% in 2005% to 3.5% in 2016. This masks important within-country variability, with substantially higher prevalence in Addis Ababa (22.8%). Factors positively associated with DBM were maternal age (odds ratio [OR] = 1.04 [1.02, 1.06]), urban residence (OR = 3.12 [2.24, 4.36]), wealth (OR = 1.14 [1.06, 1.24]) and the number of children <5 in the household (OR = 1.30 [1.12, 1.49]). Overall, 70.5% of the increase in DBM between 2005 and 2016 was attributed to increased wealth, urban residence and region. Double-duty actions that address multiple forms of malnutrition are urgently needed in urban settings.

Predictors of prediabetes/diabetes and hypertension in Ethiopia: Reanalysis of the 2015 NCD STEPS survey using causal path diagrams.

The objective of our study was to reanalyse the Ethiopia STEPwise approach to Surveillance Noncommunicable Disease Risk Factors survey (NCD STEPS), using causal path diagrams constructed using expert subject matter knowledge in conjunction with graphical model theory to map the underlying causal network of modifiable factors associated with prediabetes/diabetes and hypertension. We used data from the 2015 Ethiopia NCD STEPS representative cross-sectional survey (males; n = 3977 and females; n = 5823 aged 15-69 years) and performed directed acyclic graph-informed logistic regression analyses. In both sexes, a 1-unit higher in body mass index (BMI) and waist circumference (WC) were positively associated with prediabetes/diabetes (BMI: males: adjusted odds ratio [aOR]: 1.07 [95% confidence interval: 1.0, 1.1], females aOR: 1.03 [1.0, 1.1]; WC: males: aOR: 1.1 [0.9, 1.2], females: aOR: 1.2 [1.1, 1.3]) and hypertension (BMI: males: aOR: 1.2 [1.1, 1.2], females aOR: 1.1 [1.0, 1.1]; WC: males: aOR: 1.6 [1.4, 1.8], females: aOR: 1.3 [1.2, 1.5]). Although residing in urban settings was associated with higher odds of hypertension in both males (aOR: 1.79 [1.49, 2.16]) and females (aOR: 1.70 [1.49, 1.95]), it was only associated with prediabetes/diabetes in males (aOR: 1.56 [1.25, 1.96]). Males and females in pastoralist areas had lower odds of prediabetes/diabetes compared with their agrarian counterparts (males: aOR: 0.27 [0.14, 0.52], females: aOR: 0.31 [0.16, 0.58]). Physical activity was associated with lower odds of prediabetes/diabetes among females (aOR: 0.75 [0.58, 0.97]). Other diet-related modifiable factors such as consumption of fruit and vegetable, alcohol or salt were not associated with either prediabetes/diabetes or hypertension. Our findings highlight the need to implement interventions that prevent overweight/obesity and nutrition-related NCDs, particularly in urban areas.

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19.

OBJECTIVE: To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications. RESEARCH DESIGN AND METHODS: In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors. RESULTS: Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication. CONCLUSIONS: Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes.

Measuring maternal body composition by biomedical impedance can predict risk for gestational diabetes mellitus: a retrospective study among 22,223 women.

OBJECTIVES: This study aimed to identify which element of body composition measurements taken before 17th week gestation was the strongest risk factor for gestational diabetes mellitus (GDM) in Chinese pregnant women. DESIGN AND SETTING: A retrospective study was performed using data retrieved from the Electronic Medical Record database of Chongqing Health Center for Women and Children (China) from January 2014 to December 2015. PARTICIPANTS: A total of 22,223 women were included with singleton pregnancies and no preexisting diabetes who underwent bioelectrical impedance analysis (BIA) before 17 gestational weeks and 75-g OGTT at 24-28 gestational weeks. RESULTS: The prevalence of GDM from 2014 to 2015 was 27.13% (IADPSG). All indicators of BIA (total body water, fat mass, fat-free mass, percent body fat, muscle mass, visceral fat levels, proteins, bone minerals, basal metabolic rate, lean trunk mass), age, weight and body mass index (BMI) were risk factors that significantly increased the occurrence of GDM (p < .001 for all). Women older than 30 years or with a BMI more than 23, had a significantly higher GDM prevalence (34.89% and 34.77%). After adjusted covariates, visceral fat levels at the third quartile, the ORs of GDM were 1.142 (95% CI 1.032-1.263) in model I and 1.419 (95% CI 1.274-1.581) in model II used the first quartile as reference (p < .05 for both); bone minerals at the third quartile, the ORs of GDM were 1.124 (95% CI 1.020-1.238) in model I and 1.311 (95% CI 1.192-1.442) in model II (p < .05 for both). After adjusted for age, visceral fat levels and bone minerals, OR of GDM for percent body fat more than 28.77% at the third quartile was 1.334 (95% CI 1.201-1.482) in model II (p < .05 for both). CONCLUSIONS: Visceral fat levels, bone minerals and percent body fat were significantly associated with an increased risk of GDM, providing the reference ranges of visceral fat levels, bone minerals and percent body fat as predictive factors for Chinese women to estimate the risk of GDM by BIA during pregnancy.

Impact of cardiometabolic multimorbidity and ethnicity on cardiovascular/renal complications in patients with COVID-19.

OBJECTIVE: Using a large national database of people hospitalised with COVID-19, we investigated the contribution of cardio-metabolic conditions, multi-morbidity and ethnicity on the risk of in-hospital cardiovascular complications and death. METHODS: A multicentre, prospective cohort study in 302 UK healthcare facilities of adults hospitalised with COVID-19 between 6 February 2020 and 16 March 2021. Logistic models were used to explore associations between baseline patient ethnicity, cardiometabolic conditions and multimorbidity (0, 1, 2, >2 conditions), and in-hospital cardiovascular complications (heart failure, arrhythmia, cardiac ischaemia, cardiac arrest, coagulation complications, stroke), renal injury and death. RESULTS: Of 65 624 patients hospitalised with COVID-19, 44 598 (68.0%) reported at least one cardiometabolic condition on admission. Cardiovascular/renal complications or death occurred in 24 609 (38.0%) patients. Baseline cardiometabolic conditions were independently associated with increased odds of in-hospital complications and this risk increased in the presence of cardiometabolic multimorbidity. For example, compared with having no cardiometabolic conditions, 1, 2 or ≥3 conditions was associated with 1.46 (95% CI 1.39 to 1.54), 2.04 (95% CI 1.93 to 2.15) and 3.10 (95% CI 2.92 to 3.29) times higher odds of any cardiovascular/renal complication, respectively. A similar pattern was observed for all-cause death. Compared with the white group, the South Asian (OR 1.19, 95% CI 1.10 to 1.29) and black (OR 1.53 to 95% CI 1.37 to 1.72) ethnic groups had higher risk of any cardiovascular/renal complication. CONCLUSIONS: In hospitalised patients with COVID-19, cardiovascular complications or death impacts just under half of all patients, with the highest risk in those of South Asian or Black ethnicity and in patients with cardiometabolic multimorbidity.

Progress in Water, Sanitation and Hygiene (WASH) coverage and potential contribution to the decline in diarrhea and stunting in Ethiopia.

Inadequate safe water supply and poor sanitation and hygiene continue to be important risk factors for diarrhoea and stunting globally. We used data from the four rounds of the Ethiopian Demographic and Health Survey and applied the new World Health Organization (WHO)/UNICEF Joint Monitoring Program (JMP) service standards to assess progress in water, sanitation and hygiene (WASH) coverage between 2000 and 2016. We also performed an age-disaggregated pooled linear probability regression analysis followed by a decomposition analysis to determine whether changes in WASH practices have contributed to the changing prevalence of diarrhoea and stunting in children under 5 years of age. We observed a significant increase in the coverage of safe drinking water and adequate sanitation facilities over the period. At the national level, the use of a basic water source increased from 18% in 2000 to 50% in 2016. Open defecation declined from 82% to 32% over the same period. However, in 2016, only 6% of households had access to a basic sanitation facility, and 40% of households had no handwashing facilities. The reduction in surface water use between 2000 and 2016 explained 6% of the decline in diarrhoea observed among children aged 0-5 months. In children aged 6-59 months, between 7% and 9% of the reduction in stunting were attributable to the reduction in open defecation over this period. Despite progress, improvements are still needed to increase basic WASH coverage in Ethiopia. Our findings showed that improvements in water and sanitation only modestly explained reductions in diarrhoea and stunting.

Contribution of 20-year body mass index and waist circumference history to poor cardiometabolic health in overweight/obese and normal weight adults: A cohort study.

BACKGROUND AND AIMS: We investigated the associations of 20-year body mass index (BMI) and waist circumference (WC) histories with risk of being 1) metabolically unhealthy overweight/obese (MUOO) vs metabolically healthy overweight/obese (MHOO) and 2) metabolically unhealthy normal weight (MUNW) vs metabolically healthy normal weight (MHNW). METHODS AND RESULTS: Participants comprised 3018 adults (2280 males; 738 females) with BMI and WC measured, every ~5 years, in 1991-1994, 1997-1999, 2002-2004, 2007-2009, and 2012-2013. Mean age in 2012-2013 was 69.3 years, with a range of 59.7-82.2 years. Duration was defined as the number of times a person was overweight/obese (or centrally obese) across the 5 visits, severity as each person's mean BMI (or WC), and variability as the within-person standard deviation of BMI (or WC). At the 2013-2013 visit, participants were categorised based on their weight (overweight/obese or normal weight; body mass index (BMI) ≥25 kg/m2) and health status (healthy or unhealthy; two or more of hypertension, low high-density lipoprotein cholesterol, high triglycerides, high glucose, and high homeostatic model assessment of insulin resistance). Logistic regression was used to estimate associations with the risk of being MUNW (reference MHNW) and MUOO (reference MHOO) at the last visit. BMI and WC severity were each related to increased risk of being unhealthy, with estimates being stronger among normal weight than overweight/obese adults. The estimates for variability exposures became null upon adjustment for severity. Individuals who were overweight/obese at all 5 time points had a 1.60 (0.96-2.67) times higher risk of being MUOO than MHOO compared to those who were only overweight/obese at one (i.e., the last) time point. The corresponding estimate for central obesity was 4.20 (2.88-6.12). Greater duration was also related to higher risk of MUNW than MHNW. CONCLUSION: Being overweight/obese yet healthy seems to be partially attributable to lower exposure to adiposity across 20 years of adulthood. The results highlight the importance of maintaining optimum and stable BMI and WC, both in adults who become and do not become overweight/obese.

The relationship of childhood adversity with diurnal cortisol patterns and C-reactive protein at 60-64 years of age in the 1946 National Survey of Health and Development.

BACKGROUND: Early life adversity is increasingly prevalent and associated with greater morbidity and mortality. It is hypothesised that the link between psychosocial early life adversity and poor health in adulthood is due to abnormal hypothalamic-pituitary-adrenal (HPA) axis functioning (often measured as cortisol patterning) and inflammation (often measured via c-reactive protein (CRP)). This study aimed to investigate the relationship between early life psychosocial adversity and cortisol patterning and CRP at 60-64 years of age. METHODS: The MRC National Survey of Health and Development (NSHD) was used. The analytic "cortisol sample" included 843 individuals and the "CRP sample" included 1150 individuals. Data on adversity experienced between ages 0-15 years were utilised to compose a cumulative childhood psychosocial early life adversity (ELA) score (0, 1, 2, 3+). CRP and salivary cortisol (waking, 30 min after waking, and evening) were collected at 60-64 years. Associations between the psychosocial ELA score and cortisol outcomes (cortisol awakening response (CAR), diurnal slope (DS), and evening and morning cortisol) were assessed using general linear regression. Tobit regression was used to assess the association between psychosocial ELA score and CRP. Adjustments were made for age at follow-up, sex, childhood maternal education, childhood paternal social class, childhood housing tenure, and birth weight. After testing for sex by ELA score interactions, analyses were repeated stratified by sex for the CRP sample. RESULTS: In fully adjusted models, individuals who experienced the highest level of childhood psychosocial adversity (3+) had a 24.63 (-41.49, -7.76) % lower waking cortisol and a 7.30 (1.49, 13.12) % lower decline in cortisol across the day compared to those with a psychosocial ELA score of zero. In females, the highest level of childhood psychosocial adversity, compared to the lowest, was associated with 32.61 (2.98, 62.25) % higher CRP at 60-64 years, which attenuated to 20.38% (-9.38, 50.14) upon adjustment for measures of early life socioeconomic position. Conversely, the association between childhood psychosocial adversity and CRP in males was null. CONCLUSIONS: Our results suggest that high-levels of psychosocial adversity in childhood might result in a lower morning cortisol and flatter DS in mid-to-late-adulthood. The finding that adversity was related to higher CRP in females but not males requires replication and further investigation.

Association Between Accelerometer-Assessed Physical Activity and Severity of COVID-19 in UK Biobank.

OBJECTIVE: To quantify the association between accelerometer-assessed physical activity and coronavirus disease 2019 (COVID-19) outcomes. METHODS: Data from 82,253 UK Biobank participants with accelerometer data (measured 2013-2015), complete covariate data, and linked COVID-19 data from March 16, 2020, to March 16, 2021, were included. Two outcomes were investigated: severe COVID-19 (positive test result from in-hospital setting or COVID-19 as primary cause of death) and nonsevere COVID-19 (positive test result from community setting). Logistic regressions were used to assess associations with moderate to vigorous physical activity (MVPA), total activity, and intensity gradient. A higher intensity gradient indicates a higher proportion of vigorous activity. RESULTS: Average MVPA was 48.1 (32.7) min/d. Physical activity was associated with lower odds of severe COVID-19 (adjusted odds ratio per standard deviation increase: MVPA, 0.75 [95% CI, 0.67 to 0.85]; total, 0.83 [0.74 to 0.92]; intensity, 0.77 [0.70 to 0.86]), with stronger associations in women (MVPA, 0.63 [0.52 to 0.77]; total, 0.76 [0.64 to 0.90]; intensity, 0.63 [0.53 to 0.74]) than in men (MVPA, 0.84 [0.73 to 0.97]; total, 0.88 [0.77 to 1.01]; intensity, 0.88 [0.77 to 1.00]). In contrast, when mutually adjusted, total activity was associated with higher odds of a nonsevere infection (1.10 [1.04 to 1.16]), whereas the intensity gradient was associated with lower odds (0.91 [0.86 to 0.97]). CONCLUSION: Odds of severe COVID-19 were approximately 25% lower per standard deviation (∼30 min/d) MVPA. A greater proportion of vigorous activity was associated with lower odds of severe and nonsevere infections. The association between total activity and higher odds of a nonsevere infection may be through greater community engagement and thus more exposure to the virus. Results support calls for public health messaging highlighting the potential of MVPA for reducing the odds of severe COVID-19.

Home-based virtual reality for chronic pain: protocol for an NIH-supported randomised-controlled trial.

INTRODUCTION: Chronic pain is highly prevalent and associated with a large burden of illness; there is a pressing need for safe, home-based, non-pharmacological, interventions. Virtual reality (VR) is a digital therapeutic known to be effective for acute pain, but its role in chronic pain is not yet fully elucidated. Here we present a protocol for the National Institute of Health (NIH) Back Pain Consortium (BACPAC) VR trial that evaluates the effectiveness of three forms of VR for patients with chronic lower back pain (cLBP), a highly prevalent form of chronic pain. METHODS AND ANALYSIS: The NIH BACPAC VR trial will randomise 360 patients with cLBP into one of three arms, each administered through a head-mounted display: 1) skills-based VR, a program incorporating principles of cognitive behavioural therapy, mindful meditation and physiological biofeedback therapy using embedded biometric sensors; 2) distraction-based VR, a program using 360-degree immersive videos designed to distract users from pain; and 3) sham VR, a non-immersive program using two-dimensional videos within a VR headset. Research participants will be monitored for 12 weeks using a combination of patient-reported outcomes administered via REDCap (Research Electronic Data Capture), wearable sensor data collected via Fitbit Charge 4 and electronic health record data. The primary outcome will be the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference scale. Secondary outcomes will include PROMIS Anxiety, PROMIS Sleep Disturbance, opioid prescription data and Pain Catastrophizing Scale Short Form. A subgroup analysis will explore patient level predictors for VR efficacy. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Institutional Review Board of Cedars-Sinai Health System in April 2020. The results will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04409353.

Early childhood weight gain: Latent patterns and body composition outcomes.

BACKGROUND: Despite early childhood weight gain being a key indicator of obesity risk, we do not have a good understanding of the different patterns that exist. OBJECTIVES: To identify and characterise distinct groups of children displaying similar early-life weight trajectories. METHODS: A growth mixture model captured heterogeneity in weight trajectories between 0 and 60 months in 1390 children in the Avon Longitudinal Study of Parents and Children. Differences between the classes in characteristics and body size/composition at 9 years were investigated. RESULTS: The best model had five classes. The "Normal" (45%) and "Normal after initial catch-down" (24%) classes were close to the 50th centile of a growth standard between 24 and 60 months. The "High-decreasing" (21%) and "Stable-high" (7%) classes peaked at the ~91st centile at 12-18 months, but while the former declined to the ~75th centile and comprised constitutionally big children, the latter did not. The "Rapidly increasing" (3%) class gained weight from below the 50th centile at 4 months to above the 91st centile at 60 months. By 9 years, their mean body mass index (BMI) placed them at the 98th centile. This class was characterised by the highest maternal BMI; highest parity; highest levels of gestational hypertension and diabetes; and the lowest socio-economic position. At 9 years, the "Rapidly increasing" class was estimated to have 68.2% (95% confidence interval [CI] 48.3, 88.1) more fat mass than the "Normal" class, but only 14.0% (95% CI 9.1, 18.9) more lean mass. CONCLUSIONS: Criteria used in growth monitoring practice are unlikely to consistently distinguish between the different patterns of weight gain reported here.

Distinct Body Mass Index Trajectories to Young-Adulthood Obesity and Their Different Cardiometabolic Consequences.

[Figure: see text].