Yuefang Chang

Optimism, Cynical Hostility, and Incident Coronary Heart Disease and Mortality in the Women’s Health Initiative

Background— Trait optimism (positive future expectations) and cynical, hostile attitudes toward others have not been studied together in relation to incident coronary heart disease (CHD) and mortality in postmenopausal women. Methods and Results— Participants were 97 253 women (89 259 white, 7994 black) from the Women’s Health Initiative who were free of cancer and cardiovascular disease at study entry. Optimism was assessed by the Life Orientation Test–Revised and cynical hostility by the cynicism subscale of the Cook Medley Questionnaire. Cox proportional hazard models produced adjusted hazard ratios (AHRs) for incident CHD (myocardial infarction, angina, percutaneous coronary angioplasty, or coronary artery bypass surgery) and total mortality (CHD, cardiovascular disease, or cancer related) over ≈8 years. Optimists (top versus bottom quartile [“pessimists”]) had lower age-adjusted rates (per 10 000) of CHD (43 versus 60) and total mortality (46 versus 63). The most cynical, hostile women (top versus bottom quartile) had higher rates of CHD (56 versus 44) and total mortality (63 versus 46). Optimists (versus pessimists) had a lower hazard of CHD (AHR 0.91, 95% CI 0.83 to 0.99), CHD-related mortality (AHR 0.70, 95% CI 0.55 to 0.90), cancer-related mortality (blacks only; AHR 0.56, 95% CI 0.35 to 0.88), and total mortality (AHR 0.86, 95% CI 0.79 to 0.93). Most (versus least) cynical, hostile women had a higher hazard of cancer-related mortality (AHR 1.23, 95% CI 1.09 to 1.40) and total mortality (AHR 1.16, 95% CI 1.07 to 1.27; this effect was pronounced in blacks). Effects of optimism and cynical hostility were independent. Conclusions— Optimism and cynical hostility are independently associated with important health outcomes in black and white women. Future research should examine whether interventions designed to change attitudes would lead to altered risk.

Changes in cardiovascular risk factors during the perimenopause and postmenopause and carotid artery atherosclerosis in healthy women.

Background and Purpose The objectives of this study were to describe the changes in cardiovascular risk factors during the perimenopausal and early postmenopausal years and correlate those changes in risk factors with carotid intimal-medial thickness (IMT) and plaque index measured 5 to 8 years after menopause. Methods Participants were women (n=372) from Allegheny County, Pennsylvania, enrolled in the Healthy Women Study who had been postmenopausal for at least 5 years. Risk factor changes were measured during the perimenopause, ie, between the premenopausal and first year postmenopausal examinations, and during the early postmenopause, ie, between the first and fifth year postmenopausal examinations. Carotid ultrasound scans measured IMT and plaque at examinations 5 to 8 years after menopause among 314 of the women. Results Increases in LDL cholesterol and triglycerides and declines in HDL cholesterol were greater during perimenopause than postmenopause, whereas increases in blood pressure and fasting glucose levels were greater during postmenopause. Premenopausal systolic and pulse pressure, LDL and HDL cholesterol, triglycerides, and body mass index predicted IMT and plaque. Only the change in pulse pressure between premenopausal and first year postmenopausal examinations was related to both IMT and plaque. Conclusions Absolute risk for cardiovascular disease increases substantially in midlife, with a particularly adverse effect on lipid metabolism at the menopause. Premenopausal levels of risk factors are adequate to identify which women should be targeted for intervention.

Major depression during and after the menopausal transition: Study of Women's Health Across the Nation (SWAN)

BACKGROUND It is unclear whether risk for major depression during the menopausal transition or immediately thereafter is increased relative to pre-menopause. We aimed to examine whether the odds of experiencing major depression were greater when women were peri- or post-menopausal compared to when they were pre-menopausal, independent of a history of major depression at study entry and annual measures of vasomotor symptoms (VMS), serum levels of, or changes in, estradiol (E2), follicular stimulating hormone (FSH) or testosterone (T) and relevant confounders. METHOD Participants included the 221 African American and Caucasian women, aged 42-52 years, who were pre-menopausal at entry into the Pittsburgh site of a community-based study of menopause, the Study of Womens Health Across the Nation (SWAN). We conducted the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) to assess diagnoses of lifetime, annual and current major depression at baseline and at annual follow-ups. Psychosocial and health factors, and blood samples for assay of reproductive hormones, were obtained annually. RESULTS Women were two to four times more likely to experience a major depressive episode (MDE) when they were peri-menopausal or early post-menopausal. Repeated-measures logistic regression analyses showed that the effect of menopausal status was independent of history of major depression and annually measured upsetting life events, psychotropic medication use, VMS and serum levels of or changes in reproductive hormones. History of major depression was a strong predictor of major depression throughout the study. CONCLUSIONS The risk of major depression is greater for women during and immediately after the menopausal transition than when they are pre-menopausal.

Beyond frequency: who is most bothered by vasomotor symptoms?

Objective: Most menopausal women report vasomotor symptoms (hot flashes, night sweats). However, not all women with vasomotor symptoms, including frequent symptoms, are bothered by them. The primary aim was to identify correlates of vasomotor symptom bother beyond symptom frequency. Design: The Study of Womens Health Across the Nation participants reporting vasomotor symptoms at annual visit 7 comprised the sample (N = 1,042). Assessments included hot flash and night sweats frequency (number per week) and bother (1, not at all- 4, very much). Negative affect (index of depressive symptoms, anxiety, perceived stress, negative mood), symptom sensitivity, sleep problems, and vasomotor symptom duration (number of years) were examined cross-sectionally in relation to bother in ordinal logistic regression models with symptom frequency and covariates. Hot flashes and night sweats were considered separately. Results: In multivariable models controlling for hot flash frequency, negative affect (odds ratio [OR] = 1.27, 95% CI: 1.08-1.51), symptom sensitivity (OR = 1.18, 95% CI: 1.03-1.37), sleep problems (OR = 1.38, 95% CI: 1.04-1.85), poorer health (OR = 1.24, 95% CI: 1.03-1.48), duration of hot flashes (OR = 1.14, 95% CI: 1.06-1.23), younger age (OR = 0.94, 95% CI: 0.89-0.99), and African American race (vs white, OR = 1.59, 95% CI: 1.12-2.26) were associated with hot flash bother. After controlling for night sweats frequency and covariates, sleep problems (OR = 1.84, 95% CI:1.33-2.55) and night sweats duration (OR = 1.10, 95% CI: 1.02-1.20) were associated with night sweats bother. Conclusions: Beyond frequency, factors associated with bothersome hot flashes include mood, symptom sensitivity, symptom duration, sleep problems, age, and race. Correlates of bothersome night sweats include sleep problems and symptom duration. In addition to reducing frequency, interventions for vasomotor symptoms might consider addressing modifiable factors related to symptom bother.

MRI Is Unnecessary to Clear the Cervical Spine in Obtunded/Comatose Trauma Patients: The Four-Year Experience of a Level I Trauma Center

BACKGROUND Cervical (C)-spine clearance protocols exist both to identify traumatic injury and to expedite rigid collar removal. Computed tomography (CT) of the C-spine in trauma patients facilitates the removal of immobilization collars in patients who are neurologically intact, and magnetic resonance imaging (MRI) has become an indispensable adjunct for evaluating trauma patients with neurologic deficits. Yet, the management of patients with impaired mental status who lack neurologic deficits attributable to the spinal cord remains controversial. C-spine MRI has been suggested and employed as an imaging modality to exclude occult C-spine instability in this population of patients. However, currently available data are inconclusive as to the necessity of MRI in the C-spine clearance of obtunded or comatose trauma patients with a normal CT. METHODS The records of patients undergoing contemporaneous CT and MRI of the C-spine in a level I trauma center from January 2003 to December 2006 were retrospectively analyzed. From this group, patients admitted with a Glasgow Coma Scale score </=13 and a normal C-spine CT with sagittal and coronal reconstructions were identified. Patients were excluded if a neurologic deficit potentially referable to the spinal cord was identified. The results of C-spine MRI in this group were tabulated and analyzed. RESULTS A total of 690 patients were identified who had undergone contemporaneous C-spine CT and MRI. Of this group, 180 patients (26.2%) were identified as having a normal CT with sagittal and coronal reconstructions, no neurologic deficit, and Glasgow Coma Scale score </=13. Within this group, the average time interval between CT and MRI was 4.6 days (median, 4 days). Among these 180 patients, C-spine MRI identified 38 patients (21.1%) with acute traumatic findings in the cervical spine. However, none of these patients had a missed unstable injury and no patient required surgery or developed evidence of delayed instability. CONCLUSION Our data suggests that, outside of its appropriate application to patients with a neurologic deficit, MRI is unlikely to uncover unstable C-spine injuries in patients who are obtunded or comatose when C-spine CT using modern imaging protocols is normal.

Gains in Body Fat and Vasomotor Symptom Reporting Over the Menopausal Transition The Study of Women's Health Across the Nation

Although most women report vasomotor symptoms (hot flashes, night sweats) during midlife, their etiology and risk factors are incompletely understood. Body fat is positively associated with vasomotor symptoms cross-sectionally, but the longitudinal relation between changes in body fat and vasomotor symptoms is uncharacterized. The study aim was to examine whether gains in body fat were related to vasomotor symptom reporting over time. Measures of bioelectrical impedance for body fat, reproductive hormones, and reported vasomotor symptoms were assessed annually over 4 years from 2002 to 2006 among 1,659 women aged 47-59 years participating in the Study of Womens Health Across the Nation. Body fat change was examined in relation to vasomotor symptoms by using generalized estimating equations. Body fat gains were associated with greater odds of reporting hot flashes in models adjusted for age, site, race/ethnicity, education, smoking, parity, anxiety, and menopausal status (relative to stable body fat, gain: odds ratio = 1.23, 95% confidence interval: 1.02, 1.48; P = 0.03; loss: odds ratio = 1.07, 95% confidence interval: 0.89, 1.29; P = 0.45). Findings persisted controlling for estradiol, the free estradiol index, or follicle-stimulating hormone concentrations. The relations between body fat changes and night sweats were not statistically significant. Body fat gains are associated with greater hot flash reporting during the menopausal transition.

Lipid modulation in insulin-dependent diabetes mellitus: Effect on microvascular outcomes

Although hyperlipidemia is associated with the development of diabetes complications, the effect of lipid reduction on microvascular complications is unknown. We initiated a 2-year, randomized, double-blinded placebo-controlled pilot trial of simvastatin/diet vs. diet alone in Type 1 diabetic patients without overt nephropathy. Thirty-nine patients with LDL cholesterol 100-160 mg/dl, >10 year duration of diabetes and an albumin excretion rate (AER) <200 microg/min were recruited for study. The primary end-point was change in AER. Secondary end-points were change in ankle-brachial index, progression of retinopathy status, change in vibratory threshold, and development of new clinical neuropathy. Nineteen patients were treated with simvastatin and twenty with placebo. However, because of the lowering of drug initiation levels by the American Diabetes Association, the trial was terminated early with 2 subjects reaching 2 years, 17 reaching 18 months, 36 reaching 1 year, and all 6 months. Simvastatin significantly reduced total cholesterol (mean on treatment 173.4 vs. 191.4, P=.020) and LDL cholesterol (mean on treatment 105.0 vs. 127.7, P<.001). Simvastatin therapy was associated with a slower rise in AER compared to placebo, though the result was not statistically significant (median rate of change/month 0.004 vs. 0.029). There was a trend towards slower progression of neuropathy as measured by vibratory threshold (median change at 1 year 0.03 simvastatin vs. 0.94, P=.07). There was no difference in change in ankle-brachial index, clinical neuropathy status, or retinopathy status. In conclusion, treatment with simvastatin may have a beneficial effect on early nephropathy and diabetic neuropathy, justifying a fully powered trial. However, this would be difficult under current treatment guidelines.

The Long-Term Effects of Conventional and Atypical Antipsychotics in Patients With Probable Alzheimer’s Disease

OBJECTIVE The authors sought to determine the effects of conventional and atypical antipsychotic use on time to nursing home admission and time to death in a group of outpatients with mild to moderate probable Alzheimers disease. METHOD The authors examined time to nursing home admission and time to death in 957 patients with the diagnosis of probable Alzheimers disease who had at least one follow-up evaluation (mean follow-up time, 4.3 years [SD=2.7]; range, 0.78-18.0 years) using Cox proportional hazard models adjusted for age, gender, education level, dementia severity, hypertension, diabetes mellitus, heart disease, extrapyramidal signs, depression, psychosis, aggression, agitation, and dementia medication use. RESULTS A total of 241 patients (25%) were exposed to antipsychotics at some time during follow-up (conventional, N=138; atypical, N=95; both, N=8). Nursing home admission (63% compared with 23%) and death (69% compared with 34%) were more frequent in individuals taking conventional than atypical antipsychotics. In a model that included demographic and cognitive variables, hypertension, diabetes mellitus, heart disease, incident strokes, and extrapyramidal signs, only conventional antipsychotic use was associated with time to nursing home admission. However, the association was no longer significant after adjustment for psychiatric symptoms. Psychosis was strongly associated with nursing home admission and time to death, but neither conventional nor atypical antipsychotics were associated with time to death. CONCLUSIONS The use of antipsychotic medications, both conventional and atypical, was not associated with either time to nursing home admission or time to death after adjustment for relevant covariates. Rather, it was the presence of psychiatric symptoms, including psychosis and agitation, that was linked to increased risk of institutionalization and death after adjustment for exposure to antipsychotics.

Elevated Cardiac Troponin I and Relationship to Persistence of Electrocardiographic and Echocardiographic Abnormalities After Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— Cardiac injury persistence after aneurysmal subarachnoid hemorrhage (aSAH) is not well described. We hypothesized that post-aSAH cardiac injury, detected by elevated cardiac troponin I (cTnI), is related to aSAH severity and associated with electrocardiographic and structural echocardiographic abnormalities that are persistent. Methods— Prospective longitudinal study was conducted of patients with aSAH with Fisher grade ≥2 and/or Hunt/Hess grade ≥3. Serum cTnI was collected on Days 1 to 5; cohort dichotomized into peak cTnI ≥0.3 ng/mL (elevated) or cTnI <0.3 ng/mL. Relationships among cTnI and aSAH severity, 12-lead electrocardiography early (≤4 days) and late (≥7 days), Holter monitoring on Days 1 to 5, and transthoracic echocardiogram (left ventricular ejection fraction and regional wall motion abnormalities) early (Days 0 to 5) and late (Days 5 to 12) were evaluated. Results— Of 204 subjects, 31% had cTnI ≥0.3 ng/mL. cTnI ≥0.3 ng/mL was incrementally related to aSAH severity by admission symptoms (Hunt/Hess P=0.001) and blood load (Fisher P=0.028). More patients with cTnI ≥0.3 ng/mL had prolonged QTc on early (63% versus 30%, P<0.0001) and late electrocardiography (24% versus 7%, P=0.024). On Holter monitoring, more patients with cTnI ≥0.3 ng/mL had ventricular tachycardia/fibrillation (22% versus 9%, P=0.018) but not atrial fibrillation/flutter (P=0.241). Cardiac troponin I ≥0.3 ng/mL was associated with both early ejection fraction <50% (44% versus 5%, P<0.0001) and regional wall motion abnormalities (44% versus 4%, P<0.0001). Regional wall motion abnormalities predominated in basal and midventricular segments and persisted to some degree in 73% of patients affected, whereas ejection fraction <50% persisted in 59% of patients affected. Conclusions— Cardiac injury is incrementally worse with increasing aSAH severity and associated with persistent QTc prolongation and ventricular arrhythmias. Regional wall motion abnormalities and depressed ejection fraction persist to some degree in the majority of those affected.

Efficacy and cost-effectiveness analysis of external beam and stereotactic body radiation therapy in the treatment of spine metastases: a matched-pair analysis

OBJECT The objective of this study was to compare the palliative efficacy and cost effectiveness of external beam radiation therapy (EBRT) to stereotactic body radiation therapy (SBRT) as primary treatment for bone metastatic disease of the spinal column. METHODS Forty-four patients were matched based on age, primary tumor site, year of treatment, and location of metastasis. Outcomes of interest were pain relief, cost-effectiveness, toxicities, and need for further intervention. Pain relief was rated as excellent, good, fair, or poor, using a radiosurgical pain scale to combine visual analog scale and verbal descriptor ordinal scale scores. Medicare fee schedules were used to compute the charges for both the technical and professional components of care. Patients in the EBRT group were treated using a linear accelerator while patients in the SBRT group were treated with the CyberKnife robotic radiosurgery system. Patients received regular follow-up evaluations by a radiation oncologist and neurosurgeon. RESULTS Forty-four patients (22 pairs) were analyzed. At a follow-up of 1 month, there was no statistically significant difference in pain between the 2 groups (p = 0.11). Patients who underwent SBRT had the highest total gross charge; depending on technique, EBRT treatments ranged from 29% to 71% of the SBRT charge. Patients treated using EBRT had more acute toxicities, and more of these patients underwent further intervention at the treated spinal level. There were no late complications attributed to either treatment modality. CONCLUSIONS External beam radiation therapy remains an efficacious and cost-effective method of palliation of spine metastases. In this study, patients treated with EBRT had more acute toxicities and were more likely to require additional interventions at the treated sites. Stereotactic body radiation therapy, although more costly, resulted in comparable rates of pain relief and late treatment-related toxicity, and continues to show promise as an emerging modality for selected patients with spine metastases.