Randomized trials of estrogen-alone and breast cancer incidence: a meta-analysis.

PURPOSE: In the Women's Health initiative (WHI) randomized clinical trial, conjugated equine estrogen (CEE)-alone significantly reduced breast cancer incidence (P = 0.005). As cohort studies had opposite findings, other randomized clinical trials were identified to conduct a meta-analysis of estrogen-alone influence on breast cancer incidence. METHODS: We conducted literature searches on randomized trials and: estrogen, hormone therapy, and breast cancer, and searches from a prior meta-analysis and reviews. In the meta-analysis, for trials with published relative risks (RR) and 95% confidence intervals (CI), each log-RR was multiplied by weight = 1/V, where V = variance of the log-RR, and V was derived from the corresponding 95% CI. For smaller trials with only breast cancer numbers, the corresponding log-RR = (O - E)/weight, where O is the observed case number in the oestrogen-alone group and E the corresponding expected case number, E = nP. RESULTS: Findings from 10 randomized trials included 14,282 participants and 591 incident breast cancers. In 9 smaller trials, with 1.2% (24 of 2029) vs 2.2% (33 of 1514) randomized to estrogen-alone vs placebo (open label, one trial) (RR 0.65 95% CI 0.38-1.11, P = 0.12). For 5 trials evaluating estradiol formulations, RR = 0.63 95% CI 0.34-1.16, P = 0.15. Combining the 10 trials, 3.6% (262 of 7339) vs 4.7% (329 of 6943) randomized to estrogen-alone vs placebo (overall RR 0.77 95% CI 0.65-0.91, P = 0.002). CONCLUSION: The totality of randomized clinical trial evidence supports a conclusion that estrogen-alone use significantly reduces breast cancer incidence.

Biomarker-assessed total energy intake and its cohort study association with all-cause mortality in postmenopausal females.

BACKGROUND: The association of total energy intake (EI) with all-cause mortality is uncertain as are the dependencies of this association on age and weight change history. OBJECTIVES: To identify an EI biomarker suitable for use in epidemiologic association studies and to study EI associations with total mortality in a Women's Health Initiative (WHI) cohort of postmenopausal United States females (1993-present). METHODS: EI biomarkers were developed based on doubly labeled water (DLW) total energy expenditure (TEE) and weight variation during the 2-wk DLW protocol period using the energy balance method in an embedded feeding study (n = 153). This along with 2 earlier WHI nutrition biomarker studies having TEE assessments (n = 1131 total), with 14.6 y (median) follow-up, constituted a prospective cohort for the study of EI and all-cause mortality. RESULTS: An empirical biomarker for log(EI) was developed that had a correlation of 0.73 with log(feeding study-consumed EI). The overall association between EI and mortality was nonsignificant. The association, however, depended on age (P = 0.009), with lower EI associated with lower mortality at younger ages, and also on preceding weight change history (P = 0.03). Among participants with stable or increasing weight, mortality hazard ratios (95% confidence intervals [CIs]) for a 12% lower EI were 0.66 (95% CI: 0.51, 0.87) at age 60, 0.84 (95% CI: 0.72, 0.98) at age 70, and 1.06 (95% CI: 0.87, 1.29) at age 80. Corresponding values for participants having preceding weight loss were 0.83 (95% CI: 0.61, 1.12) at age 60, 1.05 (95% CI: 0.87, 1.26) at age 70, and 1.33 (95% CI: 1.08, 1.63) at age 80. A previously considered EI biomarker, using a theoretical model for variation in body fat and fat-free mass components over time, gave similar results following rescaling. CONCLUSIONS: Lower EI is associated with lower all-cause mortality among younger postmenopausal females with stable or increasing weight and with higher mortality among older females with weight loss. This study was registered with clinicaltrials.gov as NCT00000611.

Dietary Intervention Favorably Influences Physical Functioning: The Women's Health Initiative Randomized Dietary Modification Trial.

BACKGROUND: In the Women's Health Initiative Dietary Modification randomized trial, the dietary intervention reduced breast cancer mortality by 21% (P = .02) and increased physical activity as well. OBJECTIVE: Therefore, the aim was to examine whether or not these lifestyle changes attenuated age-related physical functioning decline. DESIGN: In a randomized trial, the influence of 8 years of a low-fat dietary pattern intervention was examined through 20 years of cumulative follow-up. PARTICIPANTS AND SETTING: From 1993 to 1998, 48,835 postmenopausal women, ages 50 to 79 years with no prior breast cancer and negative baseline mammogram were randomized at 40 US clinical centers to dietary intervention or usual diet comparison groups (40 out of 60). The intervention significantly reduced fat intake and increased vegetable, fruit, and grain intake. MAIN OUTCOME MEASURES: In post hoc analyses, physical functioning, assessed using the RAND 36-Item Short Form Health Survey, evaluated quality or limitations of 10 hierarchical physical activities. Longitudinal physical functioning, reported against a disability threshold (when assistance in daily activities is required) was the primary study outcome. STATISTICAL ANALYSES PERFORMED: Semiparametric linear mixed effect models were used to contrast physical functioning trajectories by randomization groups. RESULTS: Physical functioning score, assessed 495,317 times with 11.0 (median) assessments per participant, was significantly higher in the intervention vs comparison groups through 12 years of cumulative follow-up (P = .001), representing a reduction in age-related functional decline. The intervention effect subsequently attenuated and did not delay time to the disability threshold. Among women in the dietary intervention vs comparison groups, aged 50 to 59 years, who were physically inactive at entry, a persistent, statistically significant, favorable influence on physical functioning with associated delay in crossing the disability threshold by approximately a year was seen (P value for interaction = .007). CONCLUSIONS: In the Women's Health Initiative Dietary Modification randomized trial, a dietary intervention that significantly reduced breast cancer mortality also significantly reduced age-related functional decline through 12 years, which was attenuated with longer follow-up.

Association of Lifestyle Intervention With Risk for Cardiovascular Events Differs by Level of Glycated Hemoglobin.

PURPOSE: We reevaluated the Action for Health in Diabetes (Look AHEAD) intensive lifestyle intervention (ILI) to assess whether the effect of ILI on cardiovascular disease (CVD) prevention differed by baseline glycated hemoglobin (HbA1c). METHODS: Look AHEAD randomized 5145 adults, aged 45 to 76 years with type 2 diabetes and overweight/obesity to ILI or a diabetes support and education (DSE) control group for a median of 9.6 years. ILI focused on achieving weight loss through decreased caloric intake and increased physical activity. We assessed the parent trial's primary composite CVD outcome. We evaluated additive and multiplicative heterogeneity of the intervention on CVD risk by baseline HbA1c. RESULTS: Mean baseline HbA1c was 7.3% (SD 1.2) and ranged from 4.4% (quintile 1) to 14.5% (quintile 5). We observed additive and multiplicative heterogeneity of the association between ILI and CVD (all P < .001) by baseline HbA1c. Randomization to ILI was associated with lower CVD risk for HbA1c quintiles 1 [hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.53, 0.88] and 2 (HR: 0.80, 95% CI: 0.66, 0.96) and associated with higher CVD risk for HbA1c quintile 5 (HR: 1.27, 95% CI: 1.02, 1.58), compared to DSE. CONCLUSION: Among adults with type 2 diabetes and overweight/obesity, randomization to a lifestyle intervention was differentially associated with CVD risk by baseline HbA1c such that it was associated with lower risk at lower HbA1c levels and higher risk at higher HbA1c levels. There is a critical need to develop and tailor lifestyle interventions to be successful for individuals with type 2 diabetes and high HbA1c.

Menopausal hormone therapy and change in physical activity in the Women's Health Initiative hormone therapy clinical trials.

OBJECTIVE: The menopausal transition results in a progressive decrease in circulating estrogen levels. Experimental evidence in rodents has indicated that estrogen depletion leads to a reduction of energy expenditure and physical activity. It is unclear whether treatment with estrogen therapy increases physical activity level in postmenopausal women. METHODS: A total of 27,327 postmenopausal women aged 50-79 years enrolled in the Women's Health Initiative randomized double-blind trials of menopausal hormone therapy. Self-reported leisure-time physical activity at baseline, and years 1, 3, and 6 was quantified as metabolic equivalents (MET)-h/wk. In each trial, comparison between intervention and placebo groups of changes in physical activity levels from baseline to follow-up assessment was examined using linear regression models. RESULTS: In the CEE-alone trial, the increase in MET-h/wk was greater in the placebo group compared with the intervention group at years 3 ( P = 0.002) and 6 ( P < 0.001). Similar results were observed when analyses were restricted to women who maintained an adherence rate ≥80% during the trial or who were physically active at baseline. In the CEE + MPA trial, the primary analyses did not show significant differences between groups, but the increase of MET-h/wk was greater in the placebo group compared with the intervention group at year 3 ( P = 0.004) among women with an adherence rate ≥80%. CONCLUSIONS: The results from this clinical trial do not support the hypothesis that estrogen treatment increases physical activity among postmenopausal women.

The long-term effect of intentional weight loss on changes in bone mineral density in persons with type 2 diabetes: results from the Look AHEAD randomized trial.

Intentional weight loss has been shown to increase bone loss short term but the long-term effects are not known. Data from the Look AHEAD clinical trial shows that a long term intentional weight loss intervention was associated with greater bone loss at the hip in men. PURPOSE: Intentional weight loss has been shown to increase bone loss short term and increase frailty fracture risk, but the long-term effects on bone mineral density (BMD) are not known. METHODS: Data from a subgroup from the Look AHEAD (LA) multicenter, randomized clinical trial was used to evaluate whether a long term intentional weight loss intervention would increase bone loss. In a preplanned substudy, BMD was assessed at 5 of the 16 LA clinical centers using dual-energy X-ray absorptiometry at baseline, year 8, and the observational visit 12.6-16.3 years after randomization (year 12-16). RESULTS: At year 8, bone density loss (%) was greater in the Intensive Lifestyle Intervention (ILI) group compared with the control group (DSE) for the femoral neck (p = 0.0122) but this finding was not observed at the year 12-16 visit. In analyses stratified by gender, bone density loss (%) was greater at the total hip for men in the ILI group than the DSE group at both the year 8 and year 12-16 visits (year 8 p = 0.0263 and year 12-16 p = 0.0062). This finding was not observed among women. CONCLUSION: Long term intentional weight loss was associated with greater bone loss at the hip in men. These results taken with the previously published Look AHEAD data from the entire clinical trial showing increased frailty fracture risk with weight loss in the ILI group suggest that when intentional weight loss is planned, consideration of bone density preservation and fracture prevention strategies is warranted. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00017953. June 21, 2001.

The Efficacy of Individualized, Community-Based Physical Activity to Aid Smoking Cessation: A Randomized Controlled Trial.

Objective: The efficacy of individualized, community-based physical activity as an adjunctive smoking cessation treatment to enhance long-term smoking cessation rates was evaluated for the Lifestyle Enhancement Program (LEAP). Methods: The study was a two-arm, parallel-group, randomized controlled trial. All participants (n = 392) received cessation counseling and a nicotine patch and were randomized to physical activity (n = 199; YMCA membership and personalized exercise programming from a health coach) or an equal contact frequency wellness curriculum (n = 193). Physical activity treatment was individualized and flexible (with each participant selecting types of activities and intensity levels and being encouraged to exercise at the YMCA and at home, as well as to use "lifestyle" activity). The primary outcome (biochemically verified prolonged abstinence at 7-weeks (end of treatment) and 6- and 12-months postcessation) and secondary outcomes (7-day point prevalent tobacco abstinence (PPA), total minutes per week of leisure time physical activity and strength training) were assessed at baseline, 7 weeks, 6 months, and 12 months. Results: Prolonged abstinence in the physical activity and wellness groups was 19.6% and 25.4%, respectively, at 7-weeks, 15.1% and 16.6% at 6-months, and 14.1% and 17.1% at 12 months (all between-group P values >0.18). Similarly, PPA rates did not differ significantly between groups at any follow-up. Change from baseline leisure-time activity plus strength training increased significantly in the physical activity group at 7 weeks (P = 0.04). Across treatment groups, an increase in the number of minutes per week in strength training from baseline to 7 weeks predicted prolonged abstinence at 12 months (P ≤ 0.001). Further analyses revealed that social support, fewer years smoked, and less temptation to smoke were associated with prolonged abstinence over 12 months in both groups. Conclusions: Community-based physical activity programming, delivered as adjunctive treatment with behavioral/pharmacological cessation treatment, did not improve long-term quit rates compared to adjunctive wellness counseling plus behavioral/pharmacological cessation treatment. This trial is registered with https://beta.clinicaltrials.gov/study/NCT00403312, registration no. NCT00403312.

Healthy Lifestyle Index and Risk of Cardiovascular Disease Among Postmenopausal Women With Normal Body Mass Index.

Background A lifestyle comprising a healthy diet, light alcohol consumption, no smoking, and moderate or intense physical activity has been associated with reduced risk of cardiovascular disease (CVD). We examined the association of a healthy lifestyle index (HLI), derived from scores for each of these components plus waist circumference, with the risk of incident CVD and CVD subtypes in postmenopausal women with normal body mass index (18.5-<25.0 kg/m2). Methods and Results We studied 40 118 participants in the Women's Health Initiative, aged 50 to 79 years at enrollment, with a normal body mass index and no history of CVD. The HLI score was categorized into quintiles. We estimated multivariable adjusted hazard ratios (HR) and 95% CIs for the association of HLI with risk of CVD and CVD subtypes using Cox regression models. A total of 3821 cases of incident CVD were ascertained during a median follow-up of 20.1 years. Compared with the lowest quintile (unhealthiest lifestyle), higher HLI quintiles showed inverse associations with the risk of CVD (HRquintile-2=0.74 [95% CI, 0.67-0.81]; HRquintile-3=0.66 [95% CI, 0.60-0.72]; HRquintile-4=0.57 [95% CI, 0.51-0.63]; and HRquintile-5=0.48 [95% CI, 0.43-0.54], P-trend=<0.001). HLI was also inversely associated with risks of stroke, coronary heart disease, myocardial infarction, angina, and coronary revascularization. Subgroup analyses, stratified by age (≤63 years vs >63 years), body mass index (

Race and Ethnicity and Fracture Prediction Among Younger Postmenopausal Women in the Women's Health Initiative Study.

Importance: The best approach to identify younger postmenopausal women for osteoporosis screening is uncertain. The Fracture Risk Assessment Tool (FRAX), which includes self-identified racial and ethnic information, and the Osteoporosis Self-assessment Tool (OST), which does not, are risk assessment tools recommended by US Preventive Services Task Force guidelines to identify candidates for bone mineral density (BMD) testing in this age group. Objective: To compare the ability of FRAX vs OST to discriminate between younger postmenopausal women who do and do not experience incident fracture during a 10-year follow-up in the 4 racial and ethnic groups specified by FRAX. Design, Setting, and Participants: This cohort study of Women's Health Initiative participants included 67 169 women (baseline age range, 50-64 years) with 10 years of follow-up for major osteoporotic fracture (MOF; including hip, clinical spine, forearm, and shoulder fracture) at 40 US clinical centers. Data were collected from October 1993 to December 2008 and analyzed between May 11, 2022, and February 23, 2023. Main Outcomes and Measures: Incident MOF and BMD (in a subset of 4607 women) were assessed. The area under the receiver operating characteristic curve (AUC) for FRAX (without BMD information) and OST was calculated within each racial and ethnic category. Results: Among the 67 169 participants, mean (SD) age at baseline was 57.8 (4.1) years. A total of 1486 (2.2%) self-identified as Asian, 5927 (8.8%) as Black, 2545 (3.8%) as Hispanic, and 57 211 (85.2%) as White. During follow-up, 5594 women experienced MOF. For discrimination of MOF, AUC values for FRAX were 0.65 (95% CI, 0.58-0.71) for Asian, 0.55 (95% CI, 0.52-0.59) for Black, 0.61 (95% CI, 0.56-0.65) for Hispanic, and 0.59 (95% CI, 0.58-0.59) for White women. The AUC values for OST were 0.62 (95% CI, 0.56-0.69) for Asian, 0.53 (95% CI, 0.50-0.57) for Black, 0.58 (95% CI, 0.54-0.62) for Hispanic, and 0.55 (95% CI, 0.54-0.56) for White women. For discrimination of femoral neck osteoporosis, AUC values were excellent for OST (range, 0.79 [95% CI, 0.65-0.93] to 0.85 [95% CI, 0.74-0.96]), higher for OST than FRAX (range, 0.72 [95% CI, 0.68-0.75] to 0.74 [95% CI, 0.60-0.88]), and similar in each of the 4 racial and ethnic groups. Conclusions and Relevance: These findings suggest that within each racial and ethnic category, the US FRAX and OST have suboptimal performance in discrimination of MOF in younger postmenopausal women. In contrast, for identifying osteoporosis, OST was excellent. The US version of FRAX should not be routinely used to make screening decisions in younger postmenopausal women. Future investigations should improve existing tools or create new approaches to osteoporosis risk assessment for this age group.

Total energy expenditure as assessed by doubly labeled water and all-cause mortality in a cohort of postmenopausal women.

BACKGROUND: The association of TEE with all-cause mortality is uncertain, as is the dependence of this association on age. OBJECTIVES: To examine the association between TEE and all-cause mortality, and its age interaction, in a Women's Health Initiative (WHI) cohort of postmenopausal United States women (1992-present). METHODS: A cohort of 1131 WHI participants having DLW TEE assessment of ∼10.0 y (median) following WHI enrollment with ∼13.7 y (median) of subsequent follow-up, was used to study the EE associations with all-cause mortality. To enhance the comparability of TEE and total EI, key analyses excluded participants having >5% weight change between WHI enrollment and DLW assessment. The influence of participant age on mortality associations was examined, as was the ability of concurrent and earlier weight and height measurements to explain the results. RESULTS: There were 308 deaths following the TEE assessment through 2021. TEE was unrelated to overall mortality (P = 0.83) in this cohort of generally healthy, older (mean 71 y at TEE assessment) United States women. However, this potential association varied with age (P = 0.003). Higher TEE was associated with a higher mortality rate at the age of 60 y and a lower mortality rate at the age of 80 y. Within the weight-stable subset (532 participants, 129 deaths), TEE was weakly positively related to overall mortality (P = 0.08). This association also varied with age (P = 0.03), with mortality HRs (95% CIs) for a 20% increment in TEE of 2.33 (1.24, 4.36) at the age of 60 y, 1.49 (1.10, 2.02) at 70 y of age, and 0.96 (0.66, 1.38) at 80 y of age. This pattern remained, although was somewhat attenuated, following control for baseline weight and weight changes between WHI enrollment and TEE assessment. CONCLUSIONS: Higher EE is associated with higher all-cause mortality among younger postmenopausal women, only partially explained by weight and weight change. This study is registered with clinicaltrials.gov identifier: NCT00000611.

Effect of intratrial mean 25(OH)D concentration on diabetes risk, by race and weight: an ancillary analysis in the D2d study.

BACKGROUND: Higher serum 25-hydroxyvitamin D [25(OH)D] is associated with lower type 2 diabetes risk. 25(OH)D varies due to skin pigmentation and weight. OBJECTIVES: This analysis aims to determine whether the effect of vitamin D differs among people of color and those with overweight/obesity (who have higher diabetes risk) compared with individuals who are White or have normal weight. METHODS: The D2d study is a randomized clinical trial in people with prediabetes that tested the effects of daily vitamin D3 4000 IU vs. placebo on diabetes risk (median followup 2.5 y). We compared baseline and intratrial mean 25(OH)D concentrations, defined as the mean of all available annual 25(OH)D values, among groups defined by self-reported race and body mass index (BMI). We used Cox proportional hazards models to assess the associations between intratrial mean 25(OH)D and diabetes risk by race- and BMI-based groups. RESULTS: Asian (n=130), Black (n=616), and White (n=1616) participants were included. Both baseline and intratrial mean 25(OH)D concentrations differed significantly by race groups (both P < 0.001) and were lower in Asian and Black vs. White participants, and in those with higher vs. lower BMI adjusted for race (both P < 0.001). Compared with those with lower concentrations, Black and White participants with intratrial mean 25(OH)D ≥ 40 ng/mL had significantly reduced diabetes risk [HR (95% CI): Black: 0.51 (0.29, 0.92); White: 0.42 (0.30, 0.60)] and with a similar reduction in diabetes risk among Asian participants: 0.39 (0.14, 1.11). Compared with those with lower concentrations, participants with baseline BMI < 40 kg/m2 who achieved intratrial mean 25(OH)D concentrations ≥ 40 ng/mL had a significantly reduced diabetes risk. There was no statistically significant interaction between intratrial 25(OH)D and race or between intratrial 25(OH)D and BMI on diabetes risk. CONCLUSIONS: Among people with prediabetes, particularly for Black and White race groups and those with BMI < 40 kg/m2, the optimal 25(OH)D concentration may be ≥ 40 ng/mL to optimize diabetes-prevention efforts. This trial was registered at clinicaltrials.gov as NCT01942694.

The Association of Total Knee Arthroplasty With Weight Loss in the Look AHEAD (Action for Health in Diabetes) Clinical Trial.

BACKGROUND: Patients who have obesity seldom lose weight after total knee arthroplasty (TKA). The Look AHEAD (Action for Health in Diabetes) trial randomized patients with type 2 diabetes who were overweight or had obesity to a 10-year intensive lifestyle intervention (ILI) or diabetes support and education (DSE). METHODS: Of the total 5,145 participants enrolled who had a median 14-year follow-up, a subset of 4,624 met inclusion criteria. The ILI aimed at achieving and maintaining a 7% weight loss and included weekly counseling the first 6 months, with decreasing frequency thereafter. This secondary analysis was undertaken to determine what effects a TKA had on patients participating in a known successful weight loss program and specifically if there was a negative impact on weight loss or their Physical Component Score. RESULTS: The analysis suggests that the ILI remained effective for maintaining or losing weight after TKA. Participants in ILI had significantly greater percent weight loss than those in DSE both before and after TKA (ILI-DSE before TKA: -3.6% (-5.0, -2.3); after TKA: -3.7% (-4.1, -3.3); both P < .0001). When comparing percent weight loss before to after TKA, there was no significant difference within either the DSE or ILI group (least square means ± standard error ILI: -0.36% ± 0.3, P = .21; DSE: -0.41% ± 0.29, P = .16). Physical Component Scores improved after TKA (P < .001), but no difference was found between TKA ILI and DSE groups before or after surgery. CONCLUSION: Participants who had a TKA did not have an altered ability to adhere to intervention goals to maintain weight loss or obtain further weight loss. The data suggest patients who have obesity can lose weight after TKA on a weight loss program.

Home Literacy Experiences and Shared Reading Practices: Preschoolers With Hearing Loss.

Home literacy experiences and observed parent and child behaviors during shared book reading were investigated in preschool-age children with hearing loss and with typical hearing to examine the relationships between those factors and children's language skills. The methods involved parent-reported home literacy experiences and videotaped parent-child dyads during shared book reading. Children's language skills were tested using the Preschool Language Scale-4. The results indicated significant differences between groups for home literacy experiences and observed parent and child behaviors. Parents of children with hearing loss were found to read more frequently to their children than parents of children with typical hearing, yet scored lower for literacy strategies and teaching techniques compared to parents of children with typical hearing. Children with hearing loss scored lower in interactive reading behaviors compared to children with typical hearing. For children with hearing loss, frequency of book reading and child interactive reading behaviors were strong predictive factors for children's language skills. These results suggest that families of children with hearing loss would benefit from professional support as they read storybooks to their children. Similarly, children with hearing loss should be encouraged to be more interactive during shared book reading.

Association of Type 2 Diabetes Subgroups With Cognitive Status Without Modification From Lifestyle Intervention.

CONTEXT: Type 2 diabetes is a risk factor for incident dementia but whether risk and treatment/prevention strategies differ by diabetes subgroup is unknown. OBJECTIVE: We assessed (1) whether specific type 2 diabetes (T2D) subgroups are associated with mild cognitive impairment (MCI) or probable dementia (PD), and (2) whether T2D subgroups modified the association of the Action for Health in Diabetes (Look AHEAD) multidomain intensive lifestyle intervention (ILI) with MCI/PD. METHODS: We included 3760 Look AHEAD participants with T2D and overweight or obesity randomly assigned to 10 years of ILI or diabetes support and education. We used k-means clustering techniques with data on age of diabetes diagnosis, body mass index, waist circumference, and glycated hemoglobin (HbA1c) to characterize diabetes subgroups at randomization. Prevalent MCI/PD were centrally adjudicated based on standardized cognitive tests and other health information 10 to 13 years after randomization. We estimated marginal probabilities for prevalent MCI/PD among T2D subgroups with adjustment for potential confounders and attrition and examined whether ILI modified any associations. RESULTS: Four distinct T2D subgroups were identified, characterized by older age at diabetes onset (43% of sample), high HbA1c (13%), severe obesity (23%), and younger age at onset (22%). Unadjusted prevalence of MCI/PD (314 cases, 8.4%) differed across T2D subgroup (older onset = 10.5%, severe obesity = 9.0%, high HbA1c = 7.9%, and younger onset = 4.0%). Adjusted probability for MCI/PD within T2D subgroup was highest for the severe obesity subgroup and lowest for the younger onset subgroup but did not differ by ILI arm (interaction P value = 0.84). CONCLUSIONS: Among individuals with T2D and overweight or obesity, probability of MCI/PD differed by T2D subgroup. Probability of MCI/PD was highest for a subgroup characterized by severe obesity. CLINICALTRIALS.GOV IDENTIFIER: NCT00017953.

Psychological resilience in older adults with type 2 diabetes from the Look AHEAD Trial.

BACKGROUND: There is growing interest in identifying factors associated with healthy aging. This cross-sectional study evaluated associations of psychological resilience with factors associated with aging in older adults with type 2 diabetes mellitus (T2DM). METHODS: Participants were 3199 adults (72.2 ± 6.2 years of age, 61% female, 61% White, body mass index [BMI] = 34.2 ± 8.2 kg/m2 ) with T2DM enrolled in Look AHEAD (a multi-site randomized clinical trial comparing an intensive lifestyle intervention for weight loss to diabetes education and support). Participants were followed observationally after the 10-year intervention was discontinued. The following items were assessed approximately 14.4 years post-randomization in a cross-sectional analysis: Brief Resilience Scale; overnight hospitalizations in past year; physical functioning measured objectively (gait speed, grip strength) and via self-report (Pepper Assessment Tool for Disability; physical quality of life [QOL; SF-36]); a measure of phenotypic frailty based on having ≥3 of unintentional weight loss, low energy, slow gait, reduced grip strength, and physical inactivity. Depressive symptoms (PHQ-9) and mental QOL (SF-36) were also measured. Logistic/linear/multinomial regression was used to evaluate the association of variables with resilience adjusted for age, race/ethnicity, and gender. RESULTS: Greater psychological resilience was associated with lower BMI, fewer hospitalizations, better physical functioning (i.e., lower self-reported disability, better physical QOL, faster gait speed, greater grip strength, lower likelihood of frailty), fewer depressive symptoms, and greater mental QOL (all p < 0.05). Psychological resilience moderated the relationship of number of hospitalizations in the past year with self-reported disability and grip strength. CONCLUSIONS: Psychological resilience is associated with better physical function and QOL among older adults. Results should be interpreted cautiously given cross-sectional nature of analyses. Exploring the clinical benefits of resilience is consistent with efforts to shift the narrative on aging beyond "loss and decline" to highlight opportunities to facilitate healthy aging.

The Memphis Pandemic Health Informatics System (MEMPHI-SYS)-Creating a Metropolitan COVID-19 Data Registry Linked Directly to Community Testing to Enhance Population Health Surveillance.

The current coronavirus disease (COVID-19) pandemic has placed unprecedented strain on underfunded public health resources in the Southeastern United States. The Memphis, TN, metropolitan region has lacked infrastructure for health data exchange.This manuscript describes a multidisciplinary initiative to create a community-focused COVID-19 data registry, the Memphis Pandemic Health Informatics System (MEMPHI-SYS). MEMPHI-SYS leverages test result data updated directly from community-based testing sites, as well as a full complement of public health data sets and knowledge-based informatics. It has been guided by relationships with community stakeholders and is managed alongside the largest publicly funded community-based COVID-19 testing response in the Mid-South. MEMPHI-SYS has supported interactive Web-based analytic resources and informs federally funded COVID-19 outreach directed toward neighborhoods most in need of pandemic support.MEMPHI-SYS provides an instructive case study of how to collaboratively establish the technical scaffolding and human relationships necessary for data-driven, health equity-focused pandemic surveillance, and policy interventions.

Changes in Dietary Intake of Methionine, Folate/Folic Acid and Vitamin B12 and Survival in Postmenopausal Women with Breast Cancer: A Prospective Cohort Study.

BACKGROUND: Previous experimental studies showed that limiting methionine in the diet of animals or in cell culture media suppresses mammary cancer cell proliferation or metastasis. However, no previous study has investigated the associations of changes in methionine intake with survival among breast cancer survivors. We aimed to examine the association between changes in dietary intake of methionine, folate/folic acid, and vitamin B12 from before to after diagnosis of breast cancer, and mortality among breast cancer survivors. METHODS: We included 1553 postmenopausal women from the Women's Health Initiative who were diagnosed with invasive breast cancer and completed a food frequency questionnaire both before and after breast cancer diagnosis. Multivariable Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence (CIs) of all-cause and breast cancer mortality associated with changes in methionine intake and changes in folate/folic acid and vitamin B12 intake. RESULTS: Relative to pre-diagnosis, 28% of women decreased methionine intake by ≥20%, 30% of women increased methionine intake by ≥20%, and 42% of women had a relatively stable methionine intake (±19.9%) following breast cancer diagnosis. During a mean 16.1 years of follow up, there were 772 deaths in total, including 195 deaths from breast cancer. Compared to women with relatively stable methionine intake, women with decreased methionine intake had lower risks of all-cause (HR 0.78, 95% CI 0.62-0.97) and breast cancer mortality (HR 0.58, 95% CI 0.37-0.91) in fully adjusted models. In contrast, increased methionine intake or changes in folate/folic acid or vitamin B12 intake were not associated with all-cause or breast cancer mortality. CONCLUSIONS: Among breast cancer survivors, decreased methionine intake after breast cancer diagnosis was associated with lower risk of all-cause and breast cancer mortality.

Longer-Term All-Cause and Cardiovascular Mortality With Intensive Blood Pressure Control: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive blood pressure control reduced cardiovascular morbidity and mortality. However, the legacy effect of intensive treatment is unknown. Objective: To evaluate the long-term effects of randomization to intensive treatment with the incidence of cardiovascular and all-cause mortality approximately 4.5 years after the trial ended. Design, Setting, and Participants: In this secondary analysis of a multicenter randomized clinical trial, randomization began on November 8, 2010, the trial intervention ended on August 20, 2015, and trial close-out visits occurred through July 2016. Patients 50 years and older with hypertension and increased cardiovascular risk but without diabetes or history of stroke were included from 102 clinic sites in the US and Puerto Rico. Analyses were conducted between October 2021 and February 2022. Interventions: Randomization to systolic blood pressure (SBP) goal of less than 120 mm Hg (intensive treatment group; n = 4678) vs less than 140 mm Hg (standard treatment group; n = 4683). Main Outcomes and Measures: Extended observational follow-up for mortality via the US National Death Index from 2016 through 2020. In a subset of 2944 trial participants, outpatient SBP from electronic health records during and after the trial were examined. Results: Among 9361 randomized participants, the mean (SD) age was 67.9 (9.4) years, and 3332 (35.6%) were women. Over a median (IQR) intervention period of 3.3 (2.9-3.9) years, intensive treatment was beneficial for both cardiovascular mortality (hazard ratio [HR], 0.66; 95% CI, 0.49-0.89) and all-cause mortality (HR, 0.83; 95% CI, 0.68-1.01). However, at the median (IQR) total follow-up of 8.8 (8.3-9.3) years, there was no longer evidence of benefit for cardiovascular mortality (HR, 1.02; 95% CI, 0.84-1.24) or all-cause mortality (HR, 1.08; 95% CI, 0.94-1.23). In a subgroup of participants, the estimated mean outpatient SBP among participants randomized to intensive treatment increased from 132.8 mm Hg (95% CI, 132.0-133.7) at 5 years to 140.4 mm Hg (95% CI, 137.8-143.0) at 10 years following randomization. Conclusions and Relevance: The beneficial effect of intensive treatment on cardiovascular and all-cause mortality did not persist after the trial. Given increasing outpatient SBP levels in participants randomized to intensive treatment following the trial, these results highlight the importance of consistent long-term management of hypertension. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Weight Loss Interventions and Skeletal Health in Persons with Diabetes.

PURPOSE OF REVIEW: Weight loss is recommended for improving glycemic control and reducing cardiovascular risk factors in persons with diabetes. However, both diabetes and weight loss have been associated with detrimental skeletal health. This review aims to summarize recent study findings on the effects of lifestyle interventions for weight loss on skeletal health among persons with type 2 diabetes (T2D). RECENT FINDINGS: A few large-scale observational studies have demonstrated an increased fragility fracture risk associated with weight loss among persons with T2D. Randomized control trials in persons with T2D also have shown that intentional lifestyle interventions for weight loss are associated with a greater decrease in bone mineral density (BMD) and an increase in the risk of fracture. The biological mechanisms underlying the compromised bone health during lifestyle interventions for weight loss are complex and not yet conclusive. However, there is evidence to suggest that bone loss and increased fracture risk during intentional weight loss may be mitigated by some intervention approaches, such as high protein intake, calcium supplementation, and resistance and balance training. There is still a lack of studies investigating the effects of different interventions for weight loss on skeletal health among persons with T2D. However, certain types of diet and physical activity intervention combined with bone monitoring and fracture risk prediction may help achieve weight loss goals and maintain skeletal health among persons with T2D during intentional weight loss.

Intensive Versus Standard Blood Pressure Lowering and Days Free of Cardiovascular Events and Serious Adverse Events: a Post Hoc Analysis of Systolic Blood Pressure Intervention Trial.

BACKGROUND: Communication of the benefits and harms of blood pressure lowering strategy is crucial for shared decision-making. OBJECTIVES: To quantify the effect of intensive versus standard systolic blood pressure lowering in terms of the number of event-free days DESIGN: Post hoc analysis of the Systolic Blood Pressure Intervention Trial PARTICIPANTS: A total of 9361 adults 50 years or older without diabetes or stroke who had a systolic blood pressure of 130-180 mmHg and elevated cardiovascular risk INTERVENTIONS: Intensive (systolic blood pressure goal <120 mmHg) versus standard blood pressure lowering (<140 mmHg) MAIN MEASURES: Days free of major adverse cardiovascular events (MACE), serious adverse events (SAE), and monitored adverse events (hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, or acute kidney injury) over a median follow-up of 3.33 years KEY RESULTS: The intensive treatment group gained 14.7 more MACE-free days over 4 years (difference, 14.7 [95% confidence interval: 5.1, 24.4] days) than the standard treatment group. The benefit of the intensive treatment varied by cognitive function (normal: difference, 40.7 [13.0, 68.4] days; moderate-to-severe impairment: difference, -15.0 [-56.5, 26.4] days; p-for-interaction=0.009) and self-rated health (excellent: difference, -22.7 [-51.5, 6.1] days; poor: difference, 156.1 [31.1, 281.2] days; p-for-interaction=0.001). The mean overall SAE-free days were not significantly different between the treatments (difference, -14.8 [-35.3, 5.7] days). However, the intensive treatment group had 28.5 fewer monitored adverse event-free days than the standard treatment group (difference, -28.5 [-40.3, -16.7] days), with significant variations by frailty status (non-frail: difference, 38.8 [8.4, 69.2] days; frail: difference, -15.5 [-46.6, 15.7] days) and self-rated health (excellent: difference, -12.9 [-45.5, 19.7] days; poor: difference, 180.6 [72.9, 288.4] days; p-for-interaction <0.001). CONCLUSIONS: Over 4 years, intensive systolic blood pressure lowering provides, on average, 14.7 more MACE-free days than standard treatment, without any difference in SAE-free days. Whether this time-based effect summary improves shared decision-making remains to be elucidated. TRIAL REGISTRATION: ClinicalTrials.gov Registration: NCT01206062.