Association Between Intensity and Timing of Specialty Palliative Care and Hospice Exposure With Quality of End-of-Life Care.

Background: Gaps remain in our understanding of the intensity and timing of specialty palliative care (SPC) exposure on end-of-life (EOL) outcomes. Objective: Examine the association between intensity and timing of SPC and hospice (HO) exposure on EOL care outcomes. Design, Settings, Participants: Data for this cohort study were drawn from 2021 adult decedents from Kaiser Permanente Southern California and Colorado (n = 26,251). Caregivers of a decedent subgroup completed a postdeath care experience survey from July to August 2022 (n = 424). Measurements: SPC intensity (inpatient, outpatient, and home-based) and HO exposure in the five years before death were categorized as: (1) No SPC or HO; (2) SPC-only; (3) HO-only; and (4) SPC-HO. Timing of SPC exposure (<90 or 90+ days) before death was stratified by HO enrollment. Death in the hospital and potentially burdensome treatments in the last 14 days of life were extracted from electronic medical records (EMRs) and claims. EOL care experience was obtained from the caregiver survey. Results: Among the EMR cohort, exposure to SPC and HO were: No SPC or HO (38%), SPC-only (14%; of whom, 55% received inpatient SPC only), HO-only (20%), and SPC-HO (28%). For decedents who did not enroll in HO, exposure to SPC 90+ days versus <90 days before death was associated with lower risk of receiving potentially burdensome treatments (adjusted relative risk, aRR: 0.69 [95% confidence interval, CI: 0.62-0.76], p < 0.001) and 23% lower risk of dying in the hospital (aRR: 0.77 [95% CI: 0.73-0.81], p < 0.001). Caregivers of patients in the HO-only (aRR: 1.27 [95% CI: 0.98-1.63], p = 0.07) and SPC-HO cohorts (aRR: 1.19 [95% CI: 0.93-1.52], p = 0.18) tended to report more positive care experience compared to the no SPC or HO cohort. Conclusion: Earlier exposure to SPC was important in reducing potentially burdensome treatments and death in the hospital for decedents who did not enroll in HO. Increasing availability and access to community-based SPC is needed.

Telemedicine-based inspiratory muscle training and walking promotion with lung cancer survivors following curative intent therapy: a parallel-group pilot randomized trial.

PURPOSE: Following curative-intent therapy of lung cancer, many survivors experience dyspnea and physical inactivity. We investigated the feasibility, acceptability, safety, and potential efficacy of inspiratory muscle training (IMT) and walking promotion to disrupt a postulated "dyspnea-inactivity" spiral. METHODS: Between January and December 2022, we recruited lung cancer survivors from Kaiser Permanente Colorado who completed curative-intent therapy within 1-6 months into a phase-IIb, parallel-group, pilot randomized trial (1:1 allocation). The 12-week intervention, delivered via telemedicine, consisted of exercise training (IMT + walking), education, and behavior change support. Control participants received educational materials on general exercise. We determined feasibility a priori: enrollment of ≥ 20% eligible patients, ≥ 75% retention, study measure completion, and adherence. We assessed acceptability using the Telemedicine-Satisfaction-and-Usefulness-Questionnaire and safety events that included emergency department visits or hospitalizations. Patient-centered outcome measures (PCOMs) included dyspnea (University-of-California-San-Diego-Shortness-of-Breath-Questionnaire), physical activity (activPAL™ steps/day), functional exercise capacity (mobile-based-six-minute-walk-test), and health-related quality of life (HRQL, St.-George's-Respiratory-Questionnaire). We used linear mixed-effects models to assess potential efficacy. RESULTS: We screened 751 patients, identified 124 eligible, and consented 31 (25%) participants. Among 28 participants randomized (14/group), 22 (11/group) completed the study (79% retention). Intervention participants returned > 90% of self-reported activity logs, completed > 90% of PCOMs, and attended > 90% of tele-visits; 75% of participants performed IMT at the recommended dose. Participants had high satisfaction with tele-visits and found the intervention useful. There was no statistically significant difference in safety events between groups. Compared to control participants from baseline to follow-up, intervention participants had statistically significant and clinically meaningful improved HRQL (SGRQ total, symptom, and impact scores) (standardized effect size: -1.03 to -1.30). CONCLUSIONS: Among lung cancer survivors following curative-intent therapy, telemedicine-based IMT + walking was feasible, acceptable, safe, and had potential to disrupt the "dyspnea-inactivity" spiral. Future efficacy/effectiveness trials are warranted and should incorporate IMT and walking promotion to improve HRQL. TRIAL REGISTRATION: ClinicalTrials.gov NCT05059132.

Increasing Patient Access to MRI Examinations in an Integrated Multispecialty Practice.

A multidisciplinary team evaluated and improved the MRI processes within the authors' integrated health care system, with the aim to increase patient access to MRI. The authors created a SMART (specific, measurable, achievable, relevant, and time-based) goal of decreasing the average number of days to wait for MRI examination by 50%, from 15 to 7.5 days, while also creating capacity to meet demand for same-day and next-day MRI appointment requests. The current performance metrics and processes were compared with available benchmarking and best practice data. Several work groups were created to empower and support frontline teams to identify and capture improvement opportunities. Across all MRI processes, teams focused on creating standard work, advancing practice to top of scope, removing waste, improving communication, reducing rework, and improving patient experience. Patient access to MRI was monitored, measured as the average number of days to wait from the time of scheduling to the MRI examination and time to the third-available appointment. The authors also monitored secondary outcomes (patient satisfaction, throughput metrics) and a balancing measure (technical repeat examination rates). The access improved after intervention: the average number of days to wait for MRI access decreased from 14.2 days to 5.8 days after the intervention (-8.4 days, -59.2%, P < .0001) and third-available appointment decreased from 18 days to 0 days. Ten to 20 same-day and next-day appointments became routinely available. The throughput metrics improved, and balancing measures were not changed. This project resulted in significant improvements in patient access to MRI examinations. The findings demonstrate the value of a multidisciplinary team applying comprehensive improvement strategies to increase patient access to complex services, such as MRI. ©RSNA, 2021.

No date for the PROM: the association between patient-reported health events and clinical coding in primary care.

OBJECTIVE: It is unclear whether data from patient-reported outcome measures (PROMs) are captured and used by clinicians despite policy initiatives. We examined the extent to which fall risk and urinary incontinence (UI) reported on PROMS and provided to clinicians prior to a patient visit are subsequently captured in the electronic medical record (EMR). Additionally, we aimed to determine whether the use of PROMs and EMR documentation is higher for visits where PROM data was provided to clinicians. DESIGN: We conducted a cross-sectional patient-reported risk assessment survey and semi-structured interviews with clinicians to identify themes related to the use of PROMs. SETTING: Fourteen primary care clinics in the US (eight intervention and six control clinics), between October 2013 and May 2015. PARTICIPANTS: Primary care clinicians and older adult (≥66 years) patients completing a 46-item health risk assessment, including PROMs for fall risk and UI. INTERVENTION: Risk assessment results provided to the clinician or nurse practitioners prior to the clinic visit in intervention clinics; data was not provided in control clinics. MAIN OUTCOME: 1) Agreement between ICD-9 codes of fall risk or UI in the EMR and patient-reports, and 2) clinician experience of PROMs use and impact on coding. RESULTS: A total of 505 older adult patients were included in the study, 176 at control clinics and 329 at intervention clinics. While patient reports of fall risk and UI were readily captured by PROMs, this information was only coded in the EMR between 3% - 14% of the time (poor Kappa agreement). Intervention clinics performed slightly better than control clinics. Clinician interviews (n = 16) revealed low use of PROMs data with multiple barriers cited including poor access to data, high quantity of data, interruption to workflow, and a lack of training on PROMs. CONCLUSIONS: Current strategies of providing PROMs data prior to clinic visits may not be an effective way of communicating important health information to busy clinicians; ultimately resulting in underuse. Better systems of presenting PROMs data, and clinician training on the importance of PROMs and their use, is needed.

Chronic Condition Measurement Requires Engagement, Not Measurement Alone.

Patient-reported outcome measures (PROMs) have great promise, but evidence of success is mixed. This study uses data from Dartmouth-Hitchcock Medical Center and Kaiser-Permanente Colorado to evaluate providing PROMs directly to the primary care physician. We compared changes over time in urinary incontinence, falls, and mental and physical health between clinics providing augmented PROMs (N = 202 patients) and control clinics (N = 102 patients). Both the control and treatment groups exhibited improvements, but there was no significant difference in outcomes over time. These results suggest that measuring and printing out PROMs for primary care physicians will not result in better patient outcomes without physician clinical engagement.

Apoyo con Cariño (support with caring): RCT protocol to improve palliative care outcomes for Latinos with advanced medical illness.

Latinos are more likely to experience uncontrolled pain, and institutional death, and are less likely to engage in advance care planning. Efforts to increase access to palliative care must maximize primary palliative care and community based models to meet the ever-growing need in a culturally sensitive and congruent manner. Patient navigator interventions are community-based, culturally tailored models of care that have been successfully implemented to improve disease prevention, early diagnosis, and treatment. We have developed a patient navigation intervention to improve palliative care outcomes for seriously ill Latinos. We describe the protocol for a National Institute of Nursing Research-funded randomized controlled trial designed to determine the effectiveness of the manualized patient navigator intervention. We aim to enroll 240 Latino adults with non-cancer, advanced medical illness from both urban and rural clinical sites. Participants will be randomized to the intervention group (five palliative care patient navigator visits plus bilingual educational materials) or control group (usual care plus bilingual educational materials). Outcomes include quality of life (Functional Assessment of Chronic Illness Therapy), advance care planning (Advance Care Planning Engagement survey), pain (Brief Pain Inventory), symptom management (Edmonton Symptom Assessment Scale-revised), hospice utilization, and cost and utilization of healthcare resources. This culturally tailored, evidence-based, theory-driven, innovative patient navigation intervention has significant potential to improve palliative care for Latinos, and facilitate health equity in palliative and end-of-life care.

Bisphosphonate Drug Holiday and Fracture Risk: A Population-Based Cohort Study.

Holidays from bisphosphonates (BPs) may help to prevent rare adverse events such as atypical femoral fractures, but may be appropriate only if risk of osteoporosis-related fractures does not increase. Our objective was to compare the incidence of osteoporosis-related fractures among women who had a BP holiday to those who continued to use BPs. This retrospective cohort study, conducted within four Kaiser Permanente integrated health system regions, included 39,502 women aged ≥45 years with ≥3 years exposure to BP. Participants with a BP holiday (≥12 months with no use) were compared to persistent (use with ≥50% adherence) and nonpersistent (use with <50% adherence) users for incident osteoporosis-related fractures. The BP holiday (n = 11,497), nonpersistent user (n = 10,882), and persistent user groups (n = 17,123) were observed for 156,657 person-years. A total of 5199 osteoporosis-related fractures (including 1515 hip fractures and 2147 vertebral fractures) were observed. Compared to the persistent use group, there was a slight difference in overall osteoporosis-related fracture risk (HR 0.92; 95% CI, 0.84 to 0.99)and no difference in hip fracture risk (HR 0.95; 95% CI, 0.83 to 1.10) for the BP holiday group. A slight reduction in risk of vertebral fracture was observed (HR 0.83; 95% CI, 0.74 to 0.95). Compared to the nonpersistent user group, the BP holiday group was at decreased risk for osteoporosis-related fractures (HR 0.71; 95% CI, 0.65 to 0.79), vertebral fractures (HR 0.68; 95% CI, 0.59 to 0.78), and hip fractures (HR 0.59; 95% CI, 0.50 to 0.70). Women who undertake a BP holiday from BP of ≥12 months duration for any reason after ≥3 years of BP use do not appear to be at greater risk of osteoporosis-related fragility fracture, hip, or vertebral fractures compared to ongoing BP users. In our cohort, BP holiday remains a viable strategy for balancing the benefits and potential harms associated with long-term BP use. © 2018 American Society for Bone and Mineral Research.

Food Insecurity in Older Adults in an Integrated Health Care System.

OBJECTIVES: To estimate food insecurity prevalence and develop a statistical prediction model for food insecurity. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Colorado. PARTICIPANTS: Adult members who completed a pre-Medicare Annual Wellness Visit survey. MEASUREMENTS: Food insecurity was assessed using a single screening question. Sociodemographic and clinical characteristics from electronic health records and self-reported characteristics from the survey were used to develop the prediction model. RESULTS: Of 130,208 older adult members between January 2012 and December 2015, 50,097 (38.5%) completed food insecurity screening, 2,859 of whom (5.7% of respondents) reported food insecurity. The prevalence of food insecurity was 10.0% or greater among individuals who were black or Hispanic, had less than high school education, had Medicaid insurance, were extremely obese, had poor health status or quality of life, had depression or anxiety, had impairments in specific activities of daily living, had other nutritional risk factors, or were socially isolated (all p<.001). A multivariable model based on these and other characteristics showed moderate discrimination (c-statistic = 0.74) between individuals with food insecurity and those without and 14.3% of individuals in the highest quintile of risk reported food insecurity. CONCLUSION: Food insecurity is prevalent even in older adults with private-sector healthcare coverage. Specific individual characteristics, and a model based on those characteristics, can identify older adults at higher risk of food insecurity. System-level interventions will be necessary to connect older adults with community-based food resources.

Lessons learned from community-based participatory research: establishing a partnership to support lesbian, gay, bisexual and transgender ageing in place.

Background: Due to a history of oppression and lack of culturally competent services, lesbian, gay, bisexual and transgender (LGBT) seniors experience barriers to accessing social services. Tailoring an evidence-based ageing in place intervention to address the unique needs of LGBT seniors may decrease the isolation often faced by this population. Objective: To describe practices used in the formation of a community-based participatory research (CBPR), partnership involving social workers, health services providers, researchers and community members who engaged to establish a LGBT ageing in place model called Seniors Using Supports To Age In Neighborhoods (SUSTAIN). Methods: A case study approach was employed to describe the partnership development process by reflecting on past meeting minutes, progress reports and interviews with SUSTAIN's partners. Results: Key partnering practices utilized by SUSTAIN included (i) development of a shared commitment and vision; (ii) identifying partners with intersecting spheres of influence in multiple communities of identity (ageing services, LGBT, health research); (iii) attending to power dynamics (e.g. equitable sharing of funds); and (iv) building community capacity through reciprocal learning. Although the partnership dissolved after 4 years, it served as a successful catalyst to establish community programming to support ageing in place for LGBT seniors. Conclusion: Multi-sector stakeholder involvement with capacity to connect communities and use frameworks that formalize equity was key to establishing a high-trust CBPR partnership. However, lack of focus on external forces impacting each partner (e.g. individual organizational strategic planning, community funding agency perspectives) ultimately led to dissolution of the SUSTAIN partnership even though implementation of community programming was realized.

Perspectives of LGBTQ Older Adults on Aging in Place: A Qualitative Investigation.

This qualitative study conducted by a community-research partnership used multiple types of data collection to examine variables relevant for LGBTQ older adults who wished to age in place in their urban Denver neighborhood. Focus groups, interviews, and a town hall meeting were used to identify barriers and supports to aging in place. Participants (N = 73) identified primarily as lesbian or gay, aged 50-69, and lived with a partner. Ageism, heterosexism, and cisgenderism emerged as cross-cutting themes that negatively impact access to health care, housing, social support, home assistance, and legal services. Resilience from weathering a lifetime of discrimination was identified as a strength to handle aging challenges. Recommendations for establishing an aging in place model included establishing welcoming communities and resource centers and increasing cultural competence of service providers. This study provides a unique contribution to understanding the psychosocial, medical, and legal barriers for successfully aging in place.

A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity.

OBJECTIVE: To evaluate the safety and tolerability of alternate-day fasting (ADF) and to compare changes in weight, body composition, lipids, and insulin sensitivity index (Si) with those produced by a standard weight loss diet, moderate daily caloric restriction (CR). METHODS: Adults with obesity (BMI ≥30 kg/m(2) , age 18-55) were randomized to either zero-calorie ADF (n = 14) or CR (-400 kcal/day, n = 12) for 8 weeks. Outcomes were measured at the end of the 8-week intervention and after 24 weeks of unsupervised follow-up. RESULTS: No adverse effects were attributed to ADF, and 93% completed the 8-week ADF protocol. At 8 weeks, ADF achieved a 376 kcal/day greater energy deficit; however, there were no significant between-group differences in change in weight (mean ± SE; ADF -8.2 ± 0.9 kg, CR -7.1 ± 1.0 kg), body composition, lipids, or Si. After 24 weeks of unsupervised follow-up, there were no significant differences in weight regain; however, changes from baseline in % fat mass and lean mass were more favorable in ADF. CONCLUSIONS: ADF is a safe and tolerable approach to weight loss. ADF produced similar changes in weight, body composition, lipids, and Si at 8 weeks and did not appear to increase risk for weight regain 24 weeks after completing the intervention.

Assessing capacity for providing culturally competent services to LGBT older adults.

This qualitative, interview-based study assessed the cultural competence of health and social service providers to meet the needs of LGBT older adults in an urban neighborhood in Denver, Colorado, known to have a large LGBT community. Only 4 of the agencies were categorized as "high competency"; 12 were felt to be "seeking improvement" and 8 were considered "not aware." These results indicate significant gaps in cultural competency for the majority of service providers. Social workers are well-suited to lead efforts directed at improving service provision and care competencies for the older LGBT community.

Association of serum dehydroepiandrosterone sulfate and cognition in older adults: sex steroid, inflammatory, and metabolic mechanisms.

OBJECTIVE: Dehydroepiandrosterone sulfate (DHEAS) levels and cognitive function decline with age, and a role for DHEAS in supporting cognition has been proposed. Higher DHEAS levels may be associated with better cognitive performance, although potential mechanisms for this relationship are not well established. METHOD: We performed a cross-sectional study of the relationship between serum DHEAS and three aspects of cognition--executive function, working memory, and processing speed--in 49 men and 54 women, aged 60-88 years, with low serum DHEAS levels. We examined three potential mechanisms of DHEAS action--sex hormone sufficiency, inflammatory status, and glucose regulation. RESULTS: After adjustment for multiple covariates, higher serum DHEAS levels were associated with better working memory (standardized beta coefficient 0.50, p < .05), with a trend toward better executive function (standardized beta coefficient 0.37, p < .10) in men only. There was a nonsignificant trend toward a negative association between levels of tumor necrosis factor α (TNFα) and working memory in the combined population (standardized beta coefficient -0.22, p < .10). None of the glucoregulatory measures was associated with cognitive function. CONCLUSIONS: The relationship between DHEAS and cognition is complex and differs by sex and cognitive domain. This study supports the need for further investigations of the sex-specific effects of DHEAS on cognition and its underlying mechanisms of action.

A novel index of whole body antilipolytic insulin action.

OBJECTIVE: Assessment of antilipolytic insulin action is important in obesity research, but extensive isotopic tracer studies are not always feasible. We evaluated whether an index of antilipolytic insulin action could be derived from readily available insulin and glycerol concentrations obtained during clamps or oral glucose tolerance tests (OGTT). DESIGN AND METHODS: We evaluated data collected from 29 subjects who had undergone a 3-stage hyperinsulinemic-euglycemic clamp (4, 8, and 40 mU/m(2)/min) with infusion of [(2) H5 ]glycerol to calculate the glycerol rate of appearance (GLYRA). Exponential decay curves for GLYRA across insulin concentrations were generated for each individual and suppression of lipolysis was calculated as the insulin concentration needed to half-maximally suppress GLYRA (GLYRA EC50). Areas under the curve for glycerol (GLYAUC) and insulin (INSAUC) were calculated and their products (INSAUC × GLYAUC) were calculated as an index of insulin suppression of lipolysis. RESULTS: The clamp index was highly correlated with GLYRA EC50 (r = 0.862, P < 0.001), as was an OGTT-derived index (r = 0.720, P < 0.01). CONCLUSIONS: These findings suggest that the products of the insulin and glycerol AUC from either a clamp or an OGTT are good biomarkers of the antilipolytic action of insulin and are comparable with direct measurement by isotopic tracer methods.

N-acetyl-4-aminophenol and musculoskeletal adaptations to resistance exercise training.

N-acetyl-4-aminophenol (ACET) may impair musculoskeletal adaptations to progressive resistance exercise training (PRT) by inhibiting exercise-induced muscle protein synthesis and bone formation. To test the hypothesis that ACET would diminish training-induced increases in fat-free mass (FFM) and osteogenesis, untrained men (n = 26) aged ≥50 years participated in 16 weeks of high-intensity PRT and bone-loading exercises and were randomly assigned to take ACET (1,000 mg/day) or placebo (PLAC) 2 h before each exercise session. Total body FFM was measured by DXA at baseline and week 16. Serum bone-specific alkaline phosphatase (BAP) and C-terminal crosslinks of type-I collagen (CTX) were measured at baseline and week 16. Vastus lateralis muscle biopsies were performed at baseline and weeks 3 and 16 for prostanoid, anabolic, and catabolic gene expression by RT-PCR. In exercise-compliant men (ACET, n = 10; PLAC, n = 7), the increase in FFM was not different between groups (p = 0.91). The changes in serum BAP and CTX were not different between groups (p > 0.7). There were no significant changes in any of the target genes at week 3. After 16 weeks of PRT, the mRNA expressions of the anabolic marker p70S6K (p = 0.003) and catabolic marker muscle-atrophy F-box (MAFbx) (p = 0.03) were significantly reduced as compared to baseline in ACET. The mRNA expression of the prostanoids were unchanged (all p ≥ 0.40) in both groups. The administration of ACET (1,000 mg) prior to each exercise session did not impair PRT-induced increases in FFM or significantly alter bone formation markers in middle aged and older men.

Increasing dietary fat elicits similar changes in fat oxidation and markers of muscle oxidative capacity in lean and obese humans.

In lean humans, increasing dietary fat intake causes an increase in whole-body fat oxidation and changes in genes that regulate fat oxidation in skeletal muscle, but whether this occurs in obese humans is not known. We compared changes in whole-body fat oxidation and markers of muscle oxidative capacity differ in lean (LN) and obese (OB) adults exposed to a 2-day high-fat (HF) diet. Ten LN (BMI = 22.5±2.5 kg/m², age = 30±8 yrs) and nine OB (BMI = 35.9±4.93 kg/m², 38±5 yrs, Mean±SD) were studied in a room calorimeter for 24hr while consuming isocaloric low-fat (LF, 20% of energy) and HF (50% of energy) diets. A muscle biopsy was obtained the next morning following an overnight fast. 24h respiratory quotient (RQ) did not significantly differ between groups (LN: 0.91±0.01; OB: 0.92±0.01) during LF, and similarly decreased during HF in LN (0.86±0.01) and OB (0.85±0.01). The expression of pyruvate dehydrogenase kinase 4 (PDK4) and the fatty acid transporter CD36 increased in both LN and OB during HF. No other changes in mRNA or protein were observed. However, in both LN and OB, the amounts of acetylated peroxisome proliferator-activated receptor γ coactivator-1-α (PGC1-α) significantly decreased and phosphorylated 5-AMP-activated protein kinase (AMPK) significantly increased. In response to an isoenergetic increase in dietary fat, whole-body fat oxidation similarly increases in LN and OB, in association with a shift towards oxidative metabolism in skeletal muscle, suggesting that the ability to adapt to an acute increase in dietary fat is not impaired in obesity.

CCR5 expression is elevated on endocervical CD4+ T cells in healthy postmenopausal women.

BACKGROUND: New HIV-1 infections are increasing in older American women largely through heterosexual transmission. Activated CD4+ T cells and CCR5 expression are linked to HIV-1 susceptibility, but whether these parameters are altered in the cervix of older women is unknown. METHODS: Whole blood and in some instances endocervical brush samples were collected from healthy premenopausal (n = 22) and postmenopausal women (n = 24). Percentages of HLA-DR(DR)+CD38(38)+CD4+ T cells and HIV-1 chemokine coreceptor expression were determined by flow cytometry. RESULTS: Percentages of DR+38+CD4+ T cells were 6 times greater in cervix (median: 6.4%) than blood (median: 1.1%; P < 0.001) but did not differ within each compartment between premenopausal and postmenopausal women (P = 0.2). Postmenopausal women had greater percentages of CCR5+CD4+ and CCR5+DR+38+CD4+ T cells compared with premenopausal women in cervix (median: 70% vs. 42%, P = 0.005; and 80% vs. 57%; P = 0.05, respectively) and blood (medians: 22% vs. 13%, and 76% vs. 62%, respectively; P < 0.001). Postmenopausal women had more CCR5 molecules on cervical DR+38+CD4+ T cells (median: 3176) than premenopausal women (median: 1776; P = 0.02). Age and percent CCR5+CD4+ and CCR5+DR+38+CD4+ cells were linearly related in cervix (r(2) = 0.47, P < 0.001 and r(2) = 0.25, P = 0.01, respectively) and blood (r(2) = 0.20, P = 0.001 and r(2) = 0.31, P < 0.001; respectively), but confounding of age with menopause could not be excluded. Cervical CXCR4 expression did not differ substantially between premenopausal and postmenopausal women. CONCLUSIONS: Elevated cervical CCR5 expression in postmenopausal women may increase their risk for HIV-1 acquisition. Studies are needed to confirm whether elevated CCR5 expression confers increased HIV-1 susceptibility in postmenopausal women, and if it is related to hormonal or nonhormonal effects of aging.

A losing battle: weight regain does not restore weight loss-induced bone loss in postmenopausal women.

Previously, we reported significant bone mineral density (BMD) loss in postmenopausal women after modest weight loss. It remains unclear whether the magnitude of BMD change in response to weight loss is appropriate (i.e., proportional to weight loss) and whether BMD is recovered with weight regain. We now report changes in BMD after a 1-year follow-up. Subjects (n = 23) in this secondary analysis were postmenopausal women randomized to placebo as part of a larger trial. They completed a 6-month exercise-based weight loss program and returned for follow-up at 18 months. Dual-energy X-ray absorptiometry (DXA) was performed at baseline, 6, and 18 months. At baseline, subjects were aged 56.8 ± 5.4 years (mean ± s.d.), 10.0 ± 9.2 years postmenopausal, and BMI was 29.6 ± 4.0 kg/m(2). They lost 3.9 ± 3.5 kg during the weight loss intervention. During follow-up, they regained 2.9 ± 3.9 kg. Six months of weight loss resulted in a significant decrease in lumbar spine (LS) (-1.7 ± 3.5%; P = 0.002) and hip (-0.04 ± 3.5%; P = 0.03) BMD that was accompanied by an increase in a biomarker of bone resorption (serum C-terminal telopeptide of type I collagen, CTX: 34 ± 54%; P = 0.08). However, weight regain was not associated with LS (0.05 ± 3.8%; P = 0.15) or hip (-0.6 ± 3.0%; P = 0.81) bone regain or decreased bone resorption (CTX: -3 ± 37%; P = 0.73). The findings suggest that BMD lost during weight reduction may not be fully recovered with weight regain in hormone-deficient, postmenopausal women. Future studies are needed to identify effective strategies to prevent bone loss during periods of weight loss.

Acute sex hormone suppression reduces skeletal muscle sympathetic nerve activity.

OBJECTIVES: Comparisons of sympathetic nervous system activity (SNA) between young and older women have produced equivocal results, in part due to inadequate control for potential differences in sex hormone concentrations, age, and body composition. The aim of the present study was to determine the effect of a short-term reduction in sex hormones on tonic skeletal muscle sympathetic nerve activity (MSNA), an indirect measure of whole body SNA, using an experimental model of sex hormone deficiency in young women. We also assessed the independent effects of estradiol and progesterone add-back therapy on MSNA. METHODS: MSNA was measured in 9 women (30±2 years; mean±SE) on three separate occasions: during the mid-luteal menstrual cycle phase, on the fifth day of gonadotropin-releasing hormone antagonist (GnRHant) administration, and after 5 days add-back of either estradiol (n=4) or progesterone (n=3) during continued GnRHant administration. RESULTS: In response to GnRHant, there were significant reductions in serum estradiol and progesterone (both p<0.01) and MSNA (25.0±1.9 vs. 19.2±2.4 bursts/min, p=0.04). Continued GnRHant plus add-back estradiol or progesterone resulted in a nonsignificant decrease (19.2±1.7 vs. 12.1±1.9 bursts/min, p=0.07) or increase (16.2±1.7 vs. 21.0±6.0 bursts/min, p=0.39), respectively, in MSNA when compared with GnRHant alone. INTERPRETATION: The findings of this preliminary study suggest that short-term ovarian hormone suppression attenuates MSNA and that this may be related to the suppression of progesterone rather than estradiol.