Phytoestrogen blood levels and adverse outcomes in women with suspected ischemic heart disease.

BACKGROUND/OBJECTIVES: Prior studies linked higher blood phytoestrogen (phytoE) levels of daidzein to beneficial lipoprotein profiles, and higher genistein levels related to worse coronary microvascular dysfunction in women with suspected ischemic heart disease (IHD). However, relationships to adverse outcomes remain unclear. We investigated the associations between eight serum phytoE and major adverse cardiac events (MACE) including myocardial infarction, stroke, hospitalization for heart failure and angina, cardiovascular and all-cause mortality, in women undergoing functional coronary angiography (FCA) for suspected ischemia. SUBJECTS/METHODS: We evaluated 143 women enrolled in the Women's Ischemia Syndrome Evaluation (1996-2001) for serum phytoE levels and 10-year outcomes. Median follow-up duration was 6.08 years (range 0.01-8.16) for time to MACE and 9.11 years (range 0.01-11.08 years) for time to death. Kaplan-Meier plots were analyzed and Cox regression models adjusted for age, body mass index, hypertension, diabetes, dyslipidemia and tobacco use. RESULTS: The median age was 54.7 (range 20.6-76.1) years and BMI was 29.3 (range 18.4-57.2). Of the cohort, 80.4% had nonobstructive coronary artery disease, 56% had hypertension, 22.4% had diabetes, 58.1% had dyslipidemia and 59.4% of the women used tobacco. Each unit decrease in log glycitin was associated with increased MACE hazard (HR 1.97, 95% [CI 1.23, 3.14], p = 0.005). Glycitin absence was associated with earlier angina hospitalization (log rank p = 0.05). After 6 years, MACE increased with each unit decrease in log genistein (HR 6.17, 95% [CI 1.81, 20.8], p = 0.0036). Other phytoE did not show statistically significant associations with outcomes. CONCLUSIONS: Among women with suspected IHD undergoing clinically indicated invasive FCA, low serum glycitin was associated with increased MACE and earlier angina hospitalization, while low genistein was associated with increased MACE after 6 years. Future studies are needed regarding phytoE, nutrition, outcomes and possibly supplementation.

Effect of Adding a Work-Focused Intervention to Integrated Care for Depression in the Veterans Health Administration: A Randomized Clinical Trial.

Importance: Thousands of working-age veterans with depression experience impaired occupational functioning. Objectives: To test whether the Veterans Health Administration (VHA) integrated care (IC) program combined with telephonic work-focused counseling, known as Be Well at Work (BWAW), is superior to IC alone for improving occupational functioning and depression, to determine whether these effects persist 4 months later, and to determine whether the return on investment is positive. Design, Setting, and Participants: In this randomized clinical trial conducted from October 21, 2014, to December 6, 2019, patients undergoing IC at VHA facilities were screened for eligibility and randomized to IC alone or IC plus BWAW. Blinded interviewers administered questionnaires before the intervention, immediately after completion of the intervention at month 4, and at month 8. Eligibility criteria were individuals 18 years or older who were working at least 15 hours per week in a job they had occupied for at least 6 months, were experiencing work limitations, and had current major depressive disorder or persistent depressive disorder. Exclusion criteria were individuals who could not read or speak English, had planned maternity leave, or had a history of bipolar disorder or psychosis. Data analyses were conducted from January 1, 2018, to December 6, 2019. Interventions: Integrated care is multidisciplinary depression care involving screening, clinical informatics, measurement-based care, brief behavioral interventions, and referral as needed to specialty mental health care. Be Well at Work counseling involves 8 biweekly telephone sessions and 1 telephone booster visit after 4 months. Doctoral-level psychologists helped patients to identify barriers to functioning and to adopt new work-focused cognitive-behavioral and work-modification strategies. Main Outcomes and Measures: The primary outcome was the adjusted mean group difference in changes from before to after intervention (hereafter, adjusted effect) in the percentage of at-work productivity loss, measured with the Work Limitations Questionnaire (range, 0%-25%). The secondary outcome was adjusted effect in the Patient Health Questionnaire 9-item symptom severity score (range, 0-27, with 0 indicating no symptoms and 27, severe symptoms). Results: Of 670 veterans referred for participation, 287 veterans (42.8%) consented and completed eligibility screening, and 253 veterans (37.8%) were randomized. Among these 253 patients (mean [SD] age, 45.7 [11.6] years; 218 [86.2%] men; 135 [53.4%] white), 114 (45.1%) were randomized to IC and 139 (54.9%) were randomized to IC plus BWAW. At the 4-month follow-up, patients who received IC plus BWAW had greater reductions in at-work productivity loss (adjusted effect, -1.7; 95% CI, -3.1 to -0.4; P = .01) and depression symptom severity (adjusted effect, -2.1; 95% CI, -3.5 to -0.7; P = .003). The improvements from IC plus BWAW persisted 4 months after intervention (at-work productivity loss mean difference, -0.5; 95% CI, -1.9 to 0.9; P = .46; depression symptom severity mean difference, 0.6; 95% CI -0.9 to 2.1; P = .44). The cost per patient participating in BWAW was $690.98, and the return on investment was 160%. Conclusions and Relevance: These findings suggest that adding this work-focused intervention to IC improves veterans' occupational and psychiatric outcomes, reducing obstacles to having a productive civilian life. Trial Registration: ClinicalTrials.gov Identifier: NCT02111811.

Tracking low back problems in a major self-insured workforce: toward improvement in the patient's journey.

OBJECTIVE: To assess the cost outcomes of treatment approaches to care for back problems in a major self-insured workforce, using published guidelines to focus on low back pain. METHODS: Longitudinally tracked episodes of three types of International Classification of Diseases, Ninth Revision diagnosis code-identified back problems (n=14,787) during 2001 to 2009. Identified five patterns of care on the basis of the first 6 weeks of claims and compared their total costs per episode with tests that included splits by episode type and duration, use of guidelines, and propensity-derived adjustments. RESULTS: Care congruent with 10 of 11 guidelines was linked to lower total costs. Of the five patterns, complex medical management and chiropractic reported the highest and lowest rates, respectively, of guideline-incongruent use of imaging, surgeries, and medications, and the highest and lowest total costs. CONCLUSIONS: Approaches marked by higher resource utilization and lower guideline congruence are linked to greater low back pain total costs. Total cost is a needed input for guideline development.

Acute hypotension associated with intraoperative cell salvage using a leukocyte depletion filter during management of obstetric hemorrhage due to amniotic fluid embolism.

Amniotic fluid embolism (AFE) is a rare but catastrophic obstetric complication that can lead to profound coagulopathy and hemorrhage. The role of cell salvage and recombinant human Factor VIIa (rFVIIa) administration in such cases remains unclear. We present a case of AFE and describe our experience with the use of cell salvage and rFVIIa administration during the resuscitation. Cell salvage and transfusion through a leukocyte depletion filter was attempted after the diagnosis of AFE was made, but the attempted transfusion was immediately followed by hypotension and a worsening of hemodynamics. rFVIIa, on the contrary, was used with clinical improvement in coagulopathy and without apparent adverse thrombotic effect.

Organizational and market influences on physician performance on patient experience measures.

OBJECTIVE: To examine the extent to which medical group and market factors are related to individual primary care physician (PCP) performance on patient experience measures. DATA SOURCES: This study employs Clinician and Group CAHPS survey data (n=105,663) from 2,099 adult PCPs belonging to 34 diverse medical groups across California. Medical group directors were interviewed to assess the magnitude and nature of financial incentives directed at individual physicians and the adoption of patient experience improvement strategies. Primary care services area (PCSA) data were used to characterize the market environment of physician practices. STUDY DESIGN: We used multilevel models to estimate the relationship between medical group and market factors and physician performance on each Clinician and Group CAHPS measure. Models statistically controlled for respondent characteristics and accounted for the clustering of respondents within physicians, physicians within medical groups, and medical groups within PCSAs using random effects. PRINCIPAL FINDINGS: Compared with physicians belonging to independent practice associations, physicians belonging to integrated medical groups had better performance on the communication ( p=.007) and care coordination ( p=.03) measures. Physicians belonging to medical groups with greater numbers of PCPs had better performance on all measures. The use of patient experience improvement strategies was not associated with performance. Greater emphasis on productivity and efficiency criteria in individual physician financial incentive formulae was associated with worse access to care ( p=.04). Physicians located in PCSAs with higher area-level deprivation had worse performance on the access to care ( p=.04) and care coordination ( p<.001) measures. CONCLUSIONS: Physicians from integrated medical groups and groups with greater numbers of PCPs performed better on several patient experience measures, suggesting that organized care processes adopted by these groups may enhance patients' experiences. Physicians practicing in markets with high concentrations of vulnerable populations may be disadvantaged by constraints that affect performance. Future studies should clarify the extent to which performance deficits associated with area-level deprivation are modifiable.

Phytoestrogens and coronary microvascular function in women with suspected myocardial ischemia: a report from the Women's Ischemia Syndrome Evaluation (WISE) Study.

AIMS: Soy phytoestrogens are popular, but information on their coronary effects in patients with suspected ischemic heart disease is limited. Accordingly, we investigated the relationship between blood phytoestrogen levels and coronary reactivity in women with suspected myocardial ischemia referred for coronary angiography. METHODS: Coronary flow velocity reserve (CFVR) and volumetric flow reserve (VFR) to adenosine (ADO) and nitroglycerin (NTG) (nonendothelial-dependent responses) and acetylcholine (ACH) (endothelial-dependent response) were assessed in 106 women from the Women's Ischemia Syndrome Evaluation (WISE). Blood phytoestrogen (daidzein and genistein) and estrogen (estradiol) levels were correlated with coronary reactivity measures. RESULTS: Participants were mostly postmenopausal (79%), mean age 56 years, and 24% had obstructive coronary artery disease (CAD) at angiography. Genistein blood levels were negatively correlated with nonendothelial-dependent coronary flow responses. The highest genistein tertile (>6.1 ng/mL) had a CFVR of 2.1 +/- 0.5 (mean +/- SD) and VFRADO of 1.0 +/- 0.6, and both were significantly (p= 0.0001) lower compared with the other genistein tertiles combined. Similar associations were noted for CFVR(NTG) and VFR(NTG) (p = 0.03 and p = 0.01, respectively). The highest genistein tertile was associated with lower CFVR(ACH) compared with the other tertiles (p = 0.03). In multivariable modeling, blood genistein levels were significant independent predictors of coronary flow responses to ADO. There were no significant correlations between coronary reactivity variables and daidzein or endogenous estrogen. CONCLUSIONS: In women with suspected myocardial ischemia, higher genistein blood levels are associated with impaired nonendothelial-dependent and endothelial-dependent coronary microvascular function.

Use of risk-adjusted change in health status to assess the performance of integrated service networks in the Veterans Health Administration.

OBJECTIVE: Health outcome assessments have become an expectation of regulatory and accreditation agencies. We examined whether a clinically credible risk adjustment methodology for the outcome of change in health status can be developed for performance assessment of integrated service networks. STUDY DESIGN: Longitudinal study. SETTING: Outpatient. STUDY PARTICIPANTS: Thirty-one thousand eight hundred and twenty-three patients from 22 Veterans Health Administration (VHA) integrated service networks were followed for 18 months. MAIN MEASURE: The physical (PCS) and mental (MCS) component scales from the Veterans Rand 36-items Health Survey (VR-36) and mortality. The outcomes were decline in PCS (decline in PCS scores greater than -6.5 points or death) and MCS (decline in MCS scores greater than -7.9 points). RESULTS: Four thousand three hundred and twenty-eight (13.6%) patients showed a decline in PCS scores greater than -6.5 points, 4322 (13.5%) had a decline in MCS scores by more than -7.9 points, and 1737 died (5.5%). Multivariate logistic regression models were used to adjust for case-mix. The models performed reasonably well in cross-validated tests of discrimination (c-statistics = 0.72 and 0.68 for decline in PCS and MCS, respectively) and calibration. The resulting risk-adjusted rates of decline in PCS and MCS and ranks of the networks differed considerably from unadjusted ratings. CONCLUSION: It is feasible to develop clinically credible risk adjustment models for the outcomes of decline in PCS and MCS. Without adequate controls for case-mix, we could not determine whether poor patient outcomes reflect poor performance, sicker patients, or other factors. This methodology can help to measure and report the performance of health care systems.

Utilization of medical services by Veterans Health Study (VHS) respondents.

The first objective of this study was to profile Veterans Health Study (VHS) respondents' use of medical services-the types of services used, use of a regular source of care, and the propensity to use services for selected symptoms. We focused on differential use of VA and non-VA services and highlighted differences in use by age group. The second objective was to use multivariate analysis to identify factors associated with respondents' use of any medical services and with VA services specifically. We incorporated 2 self-reported variables not used in previous studies of VA utilization-health status and disease burden. Patients receiving ambulatory care services in 4 VA ambulatory outpatient clinics in the greater Boston area were eligible for inclusion in the VHS. A sample of 2425 community-dwelling male veterans was randomly selected from among veterans receiving ambulatory services at Boston-area VA facilities. This analysis focuses on 1909 respondents for whom we had complete data. Interviews and questionnaires were used to collect cross-sectional, observational data on sociodemographic, economic, and clinical characteristics; health status; disease burden; and service-connected disability (SCD) rating. To measure health status, we used 2 summary measures, the Physical Component Summary (PCS) and the Mental Component Summary (MCS), derived from the 8 scales of the Medical Outcomes Study Short Form 36-item Health Survey (MOS SF-36). To measure disease burden, we used the Physical Comorbidity Index (PHYCI) and Mental Comorbidity Index (MENCI), composed of 30 physical and 6 mental health conditions and symptoms, respectively. Information on the availability of non-VA insurance was obtained from administrative VA files. Information on utilization prior to the interview was self-reported. Recall periods of 3 and 12 months were used for ambulatory and inpatient services, respectively. We used descriptive statistics to profile respondents and their utilization patterns. We used multivariate probit models to identify respondent characteristics associated with use of any medical services, medical visits, mental health visits, and hospital stays. Independent variables used in the models were socioeconomic and demographic characteristics, and measures of disease burden, health status, and VA eligibility. The respondents relied heavily on the VA for medical care: 74% of the respondents said the VA was their regular source of care; 72% of all the respondents and 87% of those who had used any medical service in the recall period had used a VA service; 68% of those who were hospitalized used a VA hospital; and 76% of the medical care the respondents received and 60% of their hospital stays were in VA facilities. Younger veterans (aged 22-44) used substantially more mental health services than older respondents, but they were less likely than older veterans to have seen a doctor recently for most of the medical symptoms studied. PHYCI and PCS were significantly related to use of any medical services and to use of inpatient services; MENCI and MCS were significantly related to use of mental health services (P<.05 for each, respectively). Lower income and lack of alternatives to VA care were directly related to use of any VA services and VA inpatient services. Information on the reasons for differential use of VA and non-VA services can be useful to the VA as it serves an aging veteran population, seeks to provide comprehensive care to a wider spectrum of veterans, and moves into a more competitive healthcare marketplace.

Patient-reported measures of health: The Veterans Health Study.

The goal of the Veterans Health Study (VHS) was to extend the work of the Medical Outcomes Study (MOS) into the VA, by developing methodology for monitoring patient-based outcomes of care for use in ambulatory outpatient care. The principal objective of the VHS was developing valid and reliable measures to assess general health-related quality of life (HRQoL) and identifying the presence of selected health conditions, their severity, and their impact on HRQoL. In this article, we provide an overview of the historical context, framework, objectives, and applications of the VHS for the purpose of assessing the health outcomes of veteran patients. The VHS is a prospective observational study that has followed 2425 VA patients for up to 2 years. The patients were sampled from users of the Veterans Affairs (VA) ambulatory care system in the Boston area. The health conditions selected were hypertension, diabetes, chronic lung disease, osteoarthritis of the knee, chronic low-back pain, and alcohol-related problems. These conditions were chosen because they are both prevalent in the VA and have measurable impacts on HRQoL. One of the cornerstones of the VHS was the development of the Veterans SF-36, modified from the MOS SF-36 for use in veteran ambulatory populations. Other key accomplishments included the development of patient-based disease-specific measures of health and the establishment of methods and logistics for comprehensive health outcomes research in large health care systems such as the VA, using these patient-based measures. Selected measures developed in the VHS, eg, the Veterans SF-36, have been integrated into the VA outcomes measurement system. The scope of the VHS is unique; it resulted in the development of a broad range of patient-focused process and outcome measures, as well as methodologies for assessing large numbers of patients, that have been widely used in the VA outpatient health care system for monitoring health outcomes across the nation.

Effects of simulated herbivory and resources on Chinese tallow tree (Sapium sebiferum, Euphorbiaceae) invasion of native coastal prairie.

Trade-offs associated with maintaining herbivory resistance and herbivory tolerance are frequently inferred in plant life histories. Invasive success for many non-native plants is often attributed to novel resistance that repels native herbivores. Chinese tallow tree (Sapium sebiferum, Euphorbiaceae) is a non-native invader that threatens ecosystems throughout the southeastern United States, including imperiled coastal prairie regions. Low herbivore loads due to costly resistance are generally assumed to give Sapium a competitive advantage over native plants. We predicted that if Sapium experienced higher damage levels it would show significant decreases in growth and reduced ability to compete with native prairie vegetation. We conducted full-factorial, paired greenhouse and field experiments designed to assess the effects of simulated leaf herbivory on Sapium growth in the presence of prairie vegetation at different levels of light and nitrogen. Contrary to our expectations, neither low-intensity, chronic defoliation nor high-intensity, acute defoliation negatively affected Sapium seedlings in any resource combination in either experiment. These studies reveal that Sapium possesses considerable phenotypic plasticity, and herbivory tolerance is a newly appreciated trait that likely contributes to its invasive potential.

Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial.

CONTEXT: Hormone replacement therapy (HRT) and antioxidant vitamins are widely used for secondary prevention in postmenopausal women with coronary disease, but no clinical trials have demonstrated benefit to support their use. OBJECTIVE: To determine whether HRT or antioxidant vitamin supplements, alone or in combination, influence the progression of coronary artery disease in postmenopausal women, as measured by serial quantitative coronary angiography. DESIGN, SETTING, AND PATIENTS: The Women's Angiographic Vitamin and Estrogen (WAVE) Trial, a randomized, double-blind trial of 423 postmenopausal women with at least one 15% to 75% coronary stenosis at baseline coronary angiography. The trial was conducted from July 1997 to January 2002 in 7 clinical centers in the United States and Canada. INTERVENTIONS: Patients were randomly assigned in a 2 x 2 factorial design to receive either 0.625 mg/d of conjugated equine estrogen (plus 2.5 mg/d of medroxyprogesterone acetate for women who had not had a hysterectomy), or matching placebo, and 400 IU of vitamin E twice daily plus 500 mg of vitamin C twice daily, or placebo. MAIN OUTCOME MEASURE: Annualized mean (SD) change in minimum lumen diameter (MLD) from baseline to concluding angiogram of all qualifying coronary lesions averaged for each patient. Patients with intercurrent death or myocardial infarction (MI) were imputed the worst rank of angiographic outcome. RESULTS: The mean (SD) interval between angiograms was 2.8 (0.9) years. Coronary progression, measured in mean (SD) change, worsened with HRT by 0.047 (0.15) mm/y and by 0.024 (0.15) mm/y with HRT placebo (P =.17); and for antioxidant vitamins by 0.044 (0.15) mm/y and with vitamin placebo by 0.028 (0.15) mm/y (P =.32). When patients with intercurrent death or MI were included, the primary outcome showed an increased risk for women in the active HRT group (P =.045), and suggested an increased risk in the active vitamin group (P =.09). Fourteen patients died in the HRT group and 8 in the HRT placebo group (hazard ratio [HR], 1.8; 95% confidence interval [CI], 0.75-4.3), and 16 in the vitamin group and 6 in the vitamin placebo group (HR, 2.8; 95% CI, 1.1-7.2). Death, nonfatal MI, or stroke occurred in 26 HRT patients vs 15 HRT controls (HR, 1.9; 95% CI, 0.97-3.6) and in 26 vitamin patients and 18 vitamin controls (HR, 1.5; 95% CI, 0.80-2.9). There was no interaction between the 2 treatment interventions. CONCLUSION: In postmenopausal women with coronary disease, neither HRT nor antioxidant vitamin supplements provide cardiovascular benefit. Instead, a potential for harm was suggested with each treatment.