Study protocol: Novel Methods for Implementing Measurement-Based Care with youth in Low-Resource Environments (NIMBLE).

BACKGROUND: For youth receiving care in community mental health centers, comorbidities are the rule rather than the exception. Using measurement-based care (MBC), or the routine evaluation of symptoms to inform care decisions, as the foundation of treatment for youth with comorbid problems significantly improves the impact of psychotherapy by focusing care and building engagement and alliance. MBC increases the rate of symptom improvement, detects clients who would otherwise deteriorate, and alerts clinicians to non-responders. Despite its demonstrated utility, MBC is rarely implemented with fidelity; less than 15% of providers report using MBC per recommendations. Previous efforts to support MBC implementation have yielded suboptimal outcomes, in part, due to organizations' challenges with identifying and prioritizing barriers and selecting and developing strategies to overcome them. New methods are needed for identifying and prioritizing barriers, and matching strategies to barriers to optimize MBC implementation and treatment quality to improve youth mental health outcomes in community settings. METHODS: Pragmatic implementation methods will be piloted in four diverse community mental health centers. Methods include (a) rapid evidence synthesis; (b) rapid ethnography; (c) design kits (e.g., kits with disposable cameras, journals, maps); (d) barrier prioritization, and (e) causal pathway diagramming. These activities will generate actionable barriers; subsequently, we will use facilitated group processes to prioritize barriers and develop causal pathway diagrams to match strategies to barriers to create implementation plans that optimize MBC fidelity (Aim 1). We will track strategy deployment for 6 months, then compare MBC fidelity for another 6 months post-implementation with data from 2 years of historical controls (Aim 2). Finally, we will co-design a toolkit for design kit methods with youth and the practice and scientific communities (Aim 3). DISCUSSION: Optimizing MBC implementation in community mental health centers could transform youth mental health care by ensuring the most pressing symptoms are targeted early in treatment. The discussion section highlights expected challenges and limits to using the five methods, including recruitment and engagement given the high pressure on community mental health settings. TRIAL REGISTRATION: Clinicaltrials.gov. NCT05644756 . Registered on 18 November 2022. This trial was retrospectively registered.

Healthcare provider perspectives on delivering next generation rotavirus vaccines in five low-to-middle-income countries.

BACKGROUND: Live oral rotavirus vaccines (LORVs) have significantly reduced rotavirus hospitalizations and deaths worldwide. However, LORVs are less effective in low- and middle-income countries (LMICs). Next-generation rotavirus vaccines (NGRVs) may be more effective but require administration by injection or a neonatal oral dose, adding operational complexity. Healthcare providers (HPs) were interviewed to assess rotavirus vaccine preferences and identify delivery issues as part of an NGRV value proposition. OBJECTIVE: Determine HP vaccine preferences about delivering LORVs compared to injectable (iNGRV) and neonatal oral (oNGRV) NGRVs. METHODS: 64 HPs from Ghana, Kenya, Malawi, Peru, and Senegal were interviewed following a mixed-method guide centered on three vaccine comparisons: LORV vs. iNGRV; LORV vs. oNGRV; oNGRV vs. iNGRV. HPs reviewed attributes for each vaccine in the comparisons, then indicated and explained their preference. Additional questions elicited views about co-administering iNGRV+LORV for greater public health impact, a possible iNGRV-DTP-containing combination vaccine, and delivering neonatal doses. RESULTS: Almost all HPs preferred oral vaccine options over iNGRV, with many emphasizing an aversion to additional injections. Despite this strong preference, HPs described challenges delivering oral doses. Preferences for LORV vs. oNGRV were split, marked by disparate views on rotavirus disease epidemiology and the safety, need, and feasibility of delivering neonatal vaccines. Although overwhelmingly enthusiastic about an iNGRV-DTP-containing combination option, several HPs had concerns. HP views were divided on the feasibility of co-administering iNGRV+LORV, citing challenges around logistics and caregiver sensitization. CONCLUSION: Our findings provide valuable insights on delivering NGRVs in routine immunization. Despite opposition to injectables, openness to co-administering LORV+iNGRV to improve efficacy suggests future HP support of iNGRV if adequately informed of its advantages. Rationales for LORV vs. oNGRV underscore needs for training on rotavirus epidemiology and stronger service integration. Expressed challenges delivering existing LORVs merit further examination and indicate need for improved delivery.

National stakeholder preferences for next-generation rotavirus vaccines: Results from a six-country study.

BACKGROUND: Currently available live, oral rotavirus vaccines (LORVs) have significantly reduced severe rotavirus hospitalizations and deaths worldwide. However, LORVs are not as effective in low- and middle-income countries (LMIC) where rotavirus disease burden is highest. Next-generation rotavirus vaccine (NGRV) candidates in development may have a greater public health impact where they are needed most. The feasibility and acceptability of possible new rotavirus vaccines were explored as part of a larger public health value proposition for injectable NGRVs in LMICs. OBJECTIVE: To assess national stakeholder preferences for currently available LORVs and hypothetical NGRVs and understand rationales and drivers for stated preferences. METHODS: Interviews were conducted with 71 national stakeholders who influence vaccine policy and national programming. Stakeholders from Ghana, Kenya, Malawi, Peru, Senegal, and Sri Lanka were interviewed using a mixed-method guide. Vaccine preferences were elicited on seven vaccine comparisons involving LORVs and hypothetical NGRVs based on information presented comparing the vaccines' attributes. Reasons for vaccine preference were elicited in open-ended questions, and the qualitative data were analyzed on key preference drivers. RESULTS: Nearly half of the national stakeholders interviewed preferred a highly effective standalone, injectable NGRV over current LORVs. When presented as having similar efficacy to the LORV, however, very few stakeholders preferred the injectable NGRV, even at substantially lower cost. Similarly, a highly effective standalone injectable NGRV was generally not favored over an equally effective oral NGRV following a neonatal-infant schedule, despite higher cost of the neonatal option. An NGRV-DTP-containing combination vaccine was strongly preferred over all other options, whether delivered alone with efficacy similar to current LORVs or co-administered alongside an LORV (LORV + NGRV-DTP) to increase efficacy. CONCLUSION: Results from these national stakeholder interviews provide valuable insights to inform ongoing and future NGRV research and development.

Evaluation of diagnostic ultrasound use in a breast cancer detection strategy in Northern Peru.

To evaluate the diagnostic impact of point-of-care breast ultrasound by trained primary care physicians (PCPs) as part of a breast cancer detection program using clinical breast exam in an underserved region of Peru. Medical records and breast ultrasound images of symptomatic women presenting to the Breast Cancer Detection Model (BCDM) in Trujillo, Peru were collected from 2017-2018. Performance was measured against final outcomes derived from regional cancer center medical records, fine needle aspiration results, patient follow-up (sensitivity, specificity, positive, and negative predictive values), and by percent agreement with the retrospective, blinded interpretation of images by a fellowship-trained breast radiologist, and a Peruvian breast surgeon. The diagnostic impact of ultrasound, compared to clinical breast exam (CBE), was calculated for actual practice and for potential impact of two alternative reporting systems. Of the 171 women presenting for breast ultrasound, 23 had breast cancer (13.5%). Breast ultrasound used as a triage test (current practice) detected all cancer cases (including four cancers missed on confirmatory CBE). PCPs showed strong agreement with radiologist and surgeon readings regarding the final management of masses (85.4% and 80.4%, respectively). While the triage system yielded a similar number of biopsies as CBE alone, using the condensed and full BI-RADS systems would have reduced biopsies by 60% while identifying 87% of cancers immediately and deferring 13% to six-month follow-up. Point-of-care ultrasound performed by trained PCPs improves diagnostic accuracy for managing symptomatic women over CBE alone and enhances access. Greater use of BI-RADS to guide management would reduce the diagnostic burden substantially.

Clinical and Immunologic Outcomes After Immediate or Deferred Antiretroviral Therapy Initiation During Primary Human Immunodeficiency Virus Infection: The Sabes Randomized Clinical Study.

BACKGROUND: In addition to demonstrated public health benefits on reducing transmission, it remains unclear how early antiretroviral therapy (ART) must be started after acquisition of human immunodeficiency virus (HIV) to maximize individual benefits. METHODS: We conducted an open-label randomized clinical study in Lima, Peru among adult men who have sex with men and transgender women with acute (HIV-antibody negative/HIV-1 RNA positive) or recent (confirmed negative HIV-antibody or RNA test within 3 months) HIV infection, who were randomized to start ART immediately versus defer by 24 weeks. We evaluated outcomes by treatment arm and immunologic markers by days since estimated date of detectible infection (EDDI). RESULTS: Of 216 participants, 105 were assigned to immediate arm and 111 to deferred arm (median age 26.8 years, 37% with acute HIV). The incidence of non-ART-related adverse events was lower in immediate versus deferred arm (83 vs 123/100 person-years, IRR 0.67 (95% confidence interval [CI] .47, .95; P = .02), the difference dominated by fewer infections in those treated immediately. After 24 weeks of ART, between-group differences in CD4/CD8 cell ratio lessened (P = .09 overall), but differences between those initiating ART ≤ 30 days from EDDI (median 1.03, interquartile range [IQR] 0.84, 1.37), and those initiating > 90 days (0.88, IQR 0.61, 1.11) remained, P = .02. Principal components analysis of 20 immune biomarkers demonstrated distinct patterns between those starting ART > 90 days from EDDI versus those starting within 30 or 90 days (both P < .001). CONCLUSIONS: To our knowledge, this is the only evaluation of randomized ART initiation during primary HIV and provides evidence to explicitly consider acute HIV in World Health Organization recommendations for universal ART. CLINICAL TRIALS REGISTRATION: NCT01815580.

Risk factors and prevalence of symptoms of sexually transmitted infections in Rural Mayan Villages in Guatemala.

In this study, we identify and describe the risk factors and symptoms that are suggestive of sexually transmitted infections (STIs) in rural Mayan villages of Guatemala. We used the World Health Organization's syndromic guidelines for diagnosis and management of STIs to design questionnaires and to identify STI symptoms among indigenous Mayans who presented to mobile clinics in villages served by Guatemala Village Health (GVH). Symptoms that include abdominal pain or pain on urination, genital discharge, itching and sores were highest among younger participants. Lack of male participation in sexual health matters constitutes an important determinant of risk of exposure.

Recall Efforts Successfully Increase Follow-Up for Cervical Cancer Screening Among Women With Human Papillomavirus in Honduras.

Scaling up coverage of routine cervical screening in low-resource settings must be accompanied by efforts to retain women throughout the screening cascade and continuum of care, including adequate follow-up of abnormal results. The Scale-Up Project implemented human papillomavirus (HPV) testing for cervical cancer screening within public-sector health facilities in Honduras between 2015 and 2019. Women who were HPV-positive but did not have visually confirmed cervical lesions upon visual inspection with acetic acid (VIA-negative) were instructed to return to the health center after 1 year for repeat HPV testing. The current evaluation assessed the effectiveness of recall strategies to prompt women to return for retesting. Clinic staff placed reminder phone calls and followed up with short message service (SMS) or home visits, if needed. We summarized number of contacts, type of contacts, and time elapsed until return to the clinic, and used log-binomial regression to identify factors associated with return to the clinic. We identified 558 women who were initially HPV-positive VIA-negative from 8 clinics as needing repeat HPV testing 1 year later. Mean age was 43.2 years. Nearly all women (98.6%) were successfully contacted and 75.1% completed repeat HPV testing. The majority of contacts (65.4%) were phone calls, and nearly half of women who returned to the clinic (42.9%) did so after 1 contact. Mean days between contact and presentation at the clinic was 10.7 (standard deviation: 14.7). Women who required 3 or more contacts were 21% less likely to return for repeat HPV testing (prevalence ratio: 0.79; 95% confidence interval=0.69,0.90; P<.001) as compared to women who received only 1 contact. Reminder phone calls were highly successful at recalling women for HPV retesting in Honduras. This low-touch intervention should be included as part of standard follow-up to retain women throughout the continuum of cervical cancer screening and treatment.

Perceptions Prediagnosis and Social Experiences Postdiagnosis Among a Sample of High-Risk Peruvian Men Who Have Sex With Men.

This pilot study examines associations of perceived stigma pre-diagnosis with experienced stigma and social support post-diagnosis with qualitative data; and quantifies the interplay between pre- and post-diagnosis social factors on depressive symptoms among a sample of newly diagnosed Peruvian men who have sex with men (n = 67 total). Qualitative findings highlight the differences between perceptions of stigma pre-disclosure and actual social experiences post-disclosure for most participants. Perceived stigma pre-diagnosis was significantly related to post-diagnosis social support, B = -0.35, p = 0.03, and marginally associated with experienced stigma, B = 0.29, p = 0.07. Pre-diagnosis perceived stigma was associated with greater depressive symptoms, but only among individuals who reported higher amounts of social support, B = 0.55, p = 0.01. Findings suggest the importance of addressing social perceptions in order to optimize the beneficial effects of social support resources among newly diagnosed individuals.

Impact of pre-diagnosis awareness of HIV-related stigma and dispositional coping on linkage to HIV care among newly diagnosed HIV+ Peruvian patients.

A substantial body of literature has characterized how psychosocial factors, including HIV-related stigma and coping, are associated with HIV testing and HIV care utilization post-diagnosis. Less is known about if certain psychosocial characteristics pre-diagnosis may also predict linkage to care among individuals who receive an HIV-positive diagnosis. We examined if pre-diagnosis awareness/perception about HIV-related stigma and dispositional coping styles predicted linkage to HIV care within three months post-diagnosis with a secondary analysis of 604 patients from a randomized controlled trial (Sabes Study). Awareness/perception about HIV-related stigma, dispositional maladaptive and adaptive coping were measured before patients underwent an HIV test. Linkage to care was measured as receipt of care within three months of receiving the diagnosis. After adjusting for covariates, individuals who reported greater dispositional maladaptive coping pre-diagnosis had lower odds of linking to care, OR = 0.82, 95%CI [0.67, 1.00], p = .05. There was also a non-significant inverse association between dispositional adaptive coping pre-diagnosis and linkage to care. These preliminary data suggest the need for further longitudinal research and highlight the potential utility of pre-diagnosis psychosocial assessment and tailored counseling when providing positive HIV diagnosis results.

Model for Early Detection of Breast Cancer in Low-Resource Areas: The Experience in Peru.

PURPOSE: Late-stage breast cancer detection should be something of the past; however, it is still all too common in low-resource areas, including Peru, where 57% of women diagnosed with cancer are diagnosed at stage III or IV disease. Early detection of breast cancer is feasible in low-resource semirural and rural areas where mammography is rarely accessible. METHODS: PATH collaborated with Peruvian health institutions at local, regional, and national levels to design and implement a model of care for the early detection of breast cancer in Peru. The model includes training health promoters for community outreach, professional midwives in clinical breast exam, doctors to perform fine-needle aspiration biopsy sampling with ultrasound to triage, and patient navigators to ensure patients follow through with treatment. RESULTS: In a northern region of Peru, 400 individuals, including health promoters, midwives, doctors, and volunteers, received early-detection training in two phases. In Peru, local health professionals continue to refine and improve methods and materials using locally available resources, and the Peruvian health information system now includes specific breast cancer detection categories. Despite challenges and limited resources, the model is effective, and partnership with government health administrations improves health systems and benefits the population. CONCLUSION: Given the absence of screening mammography, the public health challenge is to bring breast cancer early detection and diagnostic services closer to women's homes and to ensure appropriate follow-up and care. The model is eminently transferable with appropriate adaptation and should now be tested in other settings within and outside of Peru.

Design Strategy of the Sabes Study: Diagnosis and Treatment of Early HIV Infection Among Men Who Have Sex With Men and Transgender Women in Lima, Peru, 2013-2017.

The Sabes Study evaluated a treatment-as-prevention intervention among cisgender men who have sex with men and transgender women in Lima, Peru-populations disproportionately affected by the human immunodeficiency virus (HIV) epidemic. The intervention was designed to prevent onward transmission of HIV by identifying HIV-negative high-risk individuals, testing them monthly for the presence of HIV, and then rapidly treating those who became HIV-positive. The main outcome of interest was the development of a model predicting the population-level impact of early detection of HIV infection and immediate initiation of antiretroviral therapy in this population. From July 2013 to September 2015, a total of 3,337 subjects were screened for HIV; 2,685 (80.5%) were negative, and 2,109 began monthly testing. We identified 256 individuals shortly after HIV acquisition, 216 of whom were enrolled in the treatment phase of the study. All participants were followed for 48 weeks (follow-up ended in 2017) and were then referred to the Peruvian Ministry of Health to continue receiving free HIV care and treatment. Initial findings from this intervention demonstrate that it is possible to recruit high-risk individuals, screen them for HIV, continue to test those who are initially HIV-negative in order to identify incident cases shortly after acquisition, and then rapidly link them to health care.

Knowledge and preferences concerning acute HIV testing programs among both Peruvian men who have sex with men and transgender women.

Immediate antiretroviral therapy (ART) for acute HIV infection (AHI) may decrease HIV transmission in high-risk populations. This study evaluated knowledge of AHI and AHI testing program preferences in Lima, Peru through four semi-structured focus groups with high-risk men who have sex with men (MSM) ( n = 20) and transgender women (TW) ( n = 16). Using content analysis, emergent themes included knowledge of AHI symptoms, AHI transmission potential, and the HIV testing window period, and preferences concerning point of care results. Participants demonstrated low familiarity with the term AHI, but many correctly identified AHI symptoms. However, these symptoms may not motivate testing because they overlap with common viral illnesses and AIDS. Some were aware that infectiousness is highest during AHI, and believe this knowledge would facilitate HIV testing. The shortened window period with AHI testing would encourage testing following high-risk sex. Delayed result notification would not decrease AHI testing demand among MSM, although it might for some TW.

A study of caloric restriction versus standard diet in overweight men with newly diagnosed prostate cancer: a randomized controlled trial.

INTRODUCTION: Obese men have an increased risk of prostate cancer (PCa)-specific mortality. Potential mechanisms include insulin and related proteins. We investigate whether a short-term caloric restriction diet in overweight/obese men with newly diagnosed PCa can lead to measurable changes in patient anthropometrics and insulin-related proteins. METHODS: Overweight and obese PCa patients choosing active surveillance or radical prostatectomy were randomized to a 6-week, caloric-restricted diet or to continue their current diet. Changes from baseline to end of study in anthropometrics, dietary constituents and serum proteins (insulin, c-peptide, IGF-1, adiponectin, IGF-BP3) were compared between the intervention and control groups using a Generalized Estimating Equation model. RESULTS: Nineteen patients were randomized to the intervention (N = 10) or control (N = 9) group. Men in the intervention group had a 1.7% (3.7 lbs) mean decline in weight versus 1.0% (2.0 lbs) in controls (P < 0.05), and a reduced intake of calories, total and saturated fat, protein and starch (all P < 0.1 compared to controls). There was a significant difference (P = 0.002) in mean serum IGFBP-3 between the intervention (+2.8%) and control group (-6.9%). Other biomarkers changed with the diet intervention to a degree similar to previous weight loss studies but were not statistically significant compared with controls. CONCLUSION: In this small pilot study, a 6-week caloric restricted diet in men with newly diagnosed PCa produced changes in weight, diet and serum proteins possibly related to prognosis. These results support larger-scale trials testing longer-term weight loss effects on potential PCa progression biomarkers.

Self-monitoring and eating-related behaviors are associated with 12-month weight loss in postmenopausal overweight-to-obese women.

Lifestyle-based interventions, which typically promote various behavior modification strategies, can serve as a setting for evaluating specific behaviors and strategies thought to promote or hinder weight loss. The aim of our study was to test the associations of self-monitoring (ie, self-weighing and food journal completion) and eating-related (ie, dietary intake, diet-related weight-control strategies, and meal patterns) behaviors with weight loss in a sample of postmenopausal overweight-to-obese women enrolled in a 12-month dietary weight loss intervention. Changes in body weight and adoption of self-monitoring and eating-related behaviors were assessed in 123 participants. Generalized linear models tested associations of these behaviors with 12-month weight change after adjusting for potential confounders. Mean percent weight loss was 10.7%. In the final model, completing more food journals was associated with a greater percent weight loss (interquartile range 3.7% greater weight loss; P<0.0001), whereas skipping meals (4.3% lower weight loss; P<0.05) and eating out for lunch (at least once a week, 2.5% lower weight loss; P<0.01) were associated with a lower amount of weight loss. These findings suggest that a greater focus on dietary self-monitoring, home-prepared meals, and consuming meals at regular intervals may improve 12-month weight loss among postmenopausal women enrolled in a dietary weight loss intervention.

Adoption of diet-related self-monitoring behaviors varies by race/ethnicity, education, and baseline binge eating score among overweight-to-obese postmenopausal women in a 12-month dietary weight loss intervention.

Recent research has identified self-monitoring behaviors as important strategies for both initial weight loss and weight loss maintenance, but relatively little is known about adopters and nonadopters of these behaviors. To test our hypothesis that key characteristics distinguish adopters from nonadopters, we examined the demographic characteristics and eating behaviors (eg, restrained, uncontrolled, emotional, and binge eating) associated with more frequent compared with less frequent use of these behaviors. Baseline demographic characteristics and eating behaviors as well as 12-month self-monitoring behaviors (ie, self-weighing, food journaling, monitoring energy intake) were assessed in 123 postmenopausal women enrolled in a dietary weight loss intervention. Logistic regression models were used to test associations of self-monitoring use with demographic characteristics and eating behaviors. Nonwhites, compared with non-Hispanic whites, were less likely to monitor energy intake regularly (adjusted odds ratio [OR], 0.36; 95% confidence interval [CI], 0.13-0.97; P < .05), controlling for intervention arm and baseline body mass index. Participants with a college degree or higher education were less likely to self-weigh daily (adjusted OR, 0.30; 95% CI, 0.13-0.67; P < .01) compared with individuals who attended some college or less. Those with higher baseline binge eating scores were less likely to monitor energy intake (adjusted OR, 0.84; 95% CI, 0.73-0.97; P < .01) compared with participants with lower binge eating scores. In summary, use of diet-related self-monitoring behaviors varied by race/ethnicity, education, and binge eating score in postmenopausal women who completed a year-long dietary weight loss intervention. Improved recognition of groups less likely to self-monitor may be helpful in promoting these behaviors in future interventions.

Effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in overweight/obese postmenopausal women: a randomized controlled trial.

Obese and sedentary persons have increased risk for cancer; inflammation is a hypothesized mechanism. We examined the effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in 439 women. Overweight and obese postmenopausal women were randomized to 1-year: caloric restriction diet (goal of 10% weight loss, N = 118), aerobic exercise (225 min/wk of moderate-to-vigorous activity, N = 117), combined diet + exercise (N = 117), or control (N = 87). Baseline and 1-year high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), interleukin-6 (IL-6), leukocyte, and neutrophil levels were measured by investigators blind to group. Inflammatory biomarker changes were compared using generalized estimating equations. Models were adjusted for baseline body mass index (BMI), race/ethnicity, and age. Four hundred and thirty-eight (N = 1 in diet + exercise group was excluded) were analyzed. Relative to controls, hs-CRP decreased by geometric mean (95% confidence interval, P value): 0.92 mg/L (0.53-1.31, P < 0.001) in the diet and 0.87 mg/L (0.51-1.23, P < 0.0001) in the diet + exercise groups. IL-6 decreased by 0.34 pg/mL (0.13-0.55, P = 0.001) in the diet and 0.32 pg/mL (0.15-0.49, P < 0.001) in the diet + exercise groups. Neutrophil counts decreased by 0.31 × 10(9)/L (0.09-0.54, P = 0.006) in the diet and 0.30 × 10(9)/L (0.09-0.50, P = 0.005) in the diet + exercise groups. Diet and diet + exercise participants with 5% or more weight loss reduced inflammatory biomarkers (hs-CRP, SAA, and IL-6) compared with controls. The diet and diet + exercise groups reduced hs-CRP in all subgroups of baseline BMI, waist circumference, CRP level, and fasting glucose. Our findings indicate that a caloric restriction weight loss diet with or without exercise reduces biomarkers of inflammation in postmenopausal women, with potential clinical significance for cancer risk reduction.

Reduced-calorie dietary weight loss, exercise, and sex hormones in postmenopausal women: randomized controlled trial.

PURPOSE: Estrogens and androgens are elevated in obesity and associated with increased postmenopausal breast cancer risk, but the effect of weight loss on these biomarkers is unknown. We evaluated the individual and combined effects of a reduced-calorie weight loss diet and exercise on serum sex hormones in overweight and obese postmenopausal women. PATIENTS AND METHODS: We conducted a single-blind, 12-month, randomized controlled trial from 2005 to 2009. Participants (age 50 to 75 years; body mass index > 25.0 kg/m(2), exercising < 100 minutes/wk) were randomly assigned using a computer-generated sequence to (1) reduced-calorie weight loss diet ("diet"; n = 118), (2) moderate- to vigorous-intensity aerobic exercise ("exercise"; n = 117), (3) combined reduced-calorie weight loss diet and moderate- to vigorous-intensity aerobic exercise ("diet + exercise"; n = 117), or (4) control (n = 87). Outcomes were estrone concentration (primary) and estradiol, free estradiol, total testosterone, free testosterone, androstenedione, and sex hormone-binding globulin (SHBG) concentrations (secondary). RESULTS: Mean age and body mass index were 58 years and 30.9 kg/m(2), respectively. Compared with controls, estrone decreased 9.6% (P = .001) with diet, 5.5% (P = .01) with exercise, and 11.1% (P < .001) with diet + exercise. Estradiol decreased 16.2% (P < .001) with diet, 4.9% (P = .10) with exercise, and 20.3% (P < .001) with diet + exercise. SHBG increased 22.4% (P < .001) with diet and 25.8% (P < .001) with diet + exercise. Free estradiol decreased 21.4% (P < .001) with diet and 26.0% (P < .001) with diet + exercise. Free testosterone decreased 10.0% (P < .001) with diet and 15.6% (P < .001) with diet + exercise. Greater weight loss produced stronger effects on estrogens and SHBG. CONCLUSION: Weight loss significantly lowered serum estrogens and free testosterone, supporting weight loss for risk reduction through lowering exposure to breast cancer biomarkers.

Effect of diet and exercise, alone or combined, on weight and body composition in overweight-to-obese postmenopausal women.

Lifestyle interventions for weight loss are the cornerstone of obesity therapy, yet their optimal design is debated. This is particularly true for postmenopausal women; a population with a high prevalence of obesity yet toward whom fewer studies are targeted. We conducted a year-long, 4-arm randomized trial among 439 overweight-to-obese postmenopausal sedentary women to determine the effects of a calorie-reduced, low-fat diet (D), a moderate-intensity, facility-based aerobic exercise program (E), or the combination of both interventions (D+E), vs. a no-lifestyle-change control (C) on change in body weight and composition. The group-based dietary intervention had a weight-reduction goal of ≥10%, and the exercise intervention consisted of a gradual escalation to 45-min aerobic exercise 5 day/week. Participants were predominantly non-Hispanic whites (85%) with a mean age of 58.0 ± 5.0 years, a mean BMI of 30.9 ± 4.0 kg/m(2) and an average of 47.8 ± 4.4% body fat. Baseline and 12-month weight and adiposity measures were obtained by staff blinded to participants' intervention assignment. Three hundred and ninety nine women completed the trial (91% retention). Using an intention-to-treat analysis, average weight loss at 12 months was -8.5% for the D group (P < 0.0001 vs. C), -2.4% for the E group (P = 0.03 vs. C), and -10.8% for the D+E group (P < 0.0001 vs. C), whereas the C group experienced a nonsignificant -0.8% decrease. BMI, waist circumference, and % body fat were also similarly reduced. Among postmenopausal women, lifestyle-change involving diet, exercise, or both combined over 1 year improves body weight and adiposity, with the greatest change arising from the combined intervention.

Associations between snacking and weight loss and nutrient intake among postmenopausal overweight to obese women in a dietary weight-loss intervention.

Snacking may play a role in weight control. The associations of timing and frequency of snacking with observed weight change and nutrient intake were assessed in an ancillary study to a 12-month randomized controlled trial in Seattle, WA. Overweight-to-obese postmenopausal women (n=123) enrolled in the two dietary weight-loss arms from 2007 to 2008 with complete data at 12 months were included in these analyses. Generalized linear models were used to test the associations between snacking and weight loss (percent) and nutrient intake at the 12-month time point. Participants were, on average, 58 years old and mainly non-Hispanic white (84%). Ninety-seven percent reported one or more snacks per day. Weight loss (percent) was significantly lower among mid-morning (10:30 am to 11:29 am) snackers (7.0%, 95% confidence interval: 4.3 to 9.7) compared to non-mid-morning snackers (11.4%, 95% confidence interval: 10.2 to 12.6; P=0.005). A higher proportion of mid-morning snackers reported more than one snack per day (95.7%), compared to afternoon (82.8%) and evening (80.6%) snackers, although differences were not statistically significant (P>0.005). Women who reported two or more snacks per day vs one or no snacks per day had higher fiber intake (P=0.027). Afternoon snackers had higher fruit and vegetable intake compared to non-afternoon-snackers (P=0.035). These results suggest that snack meals can be a source for additional fruits, vegetables, and fiber-rich foods; however, snacking patterns might also reflect unhealthy eating habits and impede weight-loss progress. Future dietary weight-loss interventions should evaluate the effects of timing, frequency, and quality of snacks on weight loss.

Dietary weight loss and exercise interventions effects on quality of life in overweight/obese postmenopausal women: a randomized controlled trial.

BACKGROUND: Although lifestyle interventions targeting multiple lifestyle behaviors are more effective in preventing unhealthy weight gain and chronic diseases than intervening on a single behavior, few studies have compared individual and combined effects of diet and/or exercise interventions on health-related quality of life (HRQOL). In addition, the mechanisms of how these lifestyle interventions affect HRQOL are unknown. The primary aim of this study was to examine the individual and combined effects of dietary weight loss and/or exercise interventions on HRQOL and psychosocial factors (depression, anxiety, stress, social support). The secondary aim was to investigate predictors of changes in HRQOL. METHODS: This study was a randomized controlled trial. Overweight/obese postmenopausal women were randomly assigned to 12 months of dietary weight loss (n = 118), moderate-to-vigorous aerobic exercise (225 minutes/week, n = 117), combined diet and exercise (n = 117), or control (n = 87). Demographic, health and anthropometric information, aerobic fitness, HRQOL (SF-36), stress (Perceived Stress Scale), depression [Brief Symptom Inventory (BSI)-18], anxiety (BSI-18) and social support (Medical Outcome Study Social Support Survey) were assessed at baseline and 12 months. The 12-month changes in HRQOL and psychosocial factors were compared using analysis of covariance, adjusting for baseline scores. Multiple regression was used to assess predictors of changes in HRQOL. RESULTS: Twelve-month changes in HRQOL and psychosocial factors differed by intervention group. The combined diet + exercise group improved 4 aspects of HRQOL (physical functioning, role-physical, vitality, and mental health), and stress (p ≤ 0.01 vs. controls). The diet group increased vitality score (p < 0.01 vs. control), while HRQOL did not change differently in the exercise group compared with controls. However, regardless of intervention group, weight loss predicted increased physical functioning, role-physical, vitality, and mental health, while increased aerobic fitness predicted improved physical functioning. Positive changes in depression, stress, and social support were independently associated with increased HRQOL, after adjusting for changes in weight and aerobic fitness. CONCLUSIONS: A combined diet and exercise intervention has positive effects on HRQOL and psychological health, which may be greater than that from exercise or diet alone. Improvements in weight, aerobic fitness and psychosocial factors may mediate intervention effects on HRQOL.