Variability in sleep disturbance, physical activity and quality of life by level of depressive symptoms in women with Type 2 diabetes.

AIMS: To examine (1) the prevalence of depressive symptoms in women with Type 2 diabetes, (2) the associations between depressive symptoms and the following dependent variables: sleep disturbance; physical activity; physical health-related; and global quality of life, and (3) the potential moderating effects of antidepressants and optimism on the relationship between depressive symptoms and dependent variables. METHODS: Participants in the Women's Health Initiative who had Type 2 diabetes and data on depressive symptoms (N=8895) were included in the analyses. In multivariable linear regression models controlling for sociodemographic, medical and psychosocial covariates, we examined the main effect of depressive symptoms, as well as the interactions between depressive symptoms and antidepressant use, and between depressive symptoms and optimism, on sleep disturbance, physical activity, physical health-related quality of life; and global quality of life. RESULTS: In all, 16% of women with Type 2 diabetes reported elevated depressive symptoms. In multivariable analyses, women with depressive symptoms had greater sleep disturbance (P<0.0001) and lower global quality of life (P<.0001). We found evidence of significant statistical interaction in the models for quality-of-life outcomes: the increased risk of poor physical health-related quality of life associated with antidepressant use was stronger in women without vs with depressive symptoms, and the association between greater optimism and higher global quality of life was stronger in women with vs without depressive symptoms. CONCLUSIONS: To improve health behaviours and quality of life in women with Type 2 diabetes, sociodemographic and medical characteristics may identify at-risk populations, while psychosocial factors including depression and optimism may be important targets for non-pharmacological intervention.

Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models.

Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer's disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women's Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers. Female EFAD transgenic mice (5xFAD+/-/human APOE ɛ3 or ɛ4+/+) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral ß-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aß deposits, both exacerbated by APOE ɛ4. Moreover, nPM exposure increased Aß oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in ɛ4 carriers. The underlying mechanisms may involve increased cerebral Aß production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits.

Cognitive function and retinal and ischemic brain changes: the Women's Health Initiative.

OBJECTIVE: To examine the association between retinopathy and cognitive decline or brain lesions and volumes in older women. METHODS: This study included 511 women aged 65 and older who were simultaneously enrolled in the Women's Health Initiative Memory Study and the Sight Examination Study. In this analysis, we examined the link between retinopathy, assessed using fundus photography (2000-2002), cognitive performance over time assessed by the modified Mini-Mental State Examination (3MSE) (1996-2007), and white matter hyperintensities and lacunar infarcts in the basal ganglia. RESULTS: Presence of retinopathy was associated with poorer 3MSE scores (mean difference = 1.01, SE: 0.43) (p = 0.019) over a 10-year follow-up period and greater ischemic volumes in the total brain (47% larger, p = 0.04) and the parietal lobe (68% larger, p = 0.01) but not with measures of regional brain atrophy. CONCLUSIONS: The correspondence we found between retinopathy and cognitive impairment, along with larger ischemic lesion volumes, strengthens existing evidence that retinopathy as a marker of small vessel disease is a risk factor for cerebrovascular disease that may influence cognitive performance and related brain changes. Retinopathy may be useful as a clinical tool if it can be shown to be an early marker related to neurologic outcomes.

Postmenopausal hormone therapy and subclinical cerebrovascular disease: the WHIMS-MRI Study.

OBJECTIVE: The Women's Health Initiative Memory Study (WHIMS) hormone therapy (HT) trials reported that conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA) increases risk for all-cause dementia and global cognitive decline. WHIMS MRI measured subclinical cerebrovascular disease as a possible mechanism to explain cognitive decline reported in WHIMS. METHODS: We contacted 2,345 women at 14 WHIMS sites; scans were completed on 1,424 (61%) and 1,403 were accepted for analysis. The primary outcome measure was total ischemic lesion volume on brain MRI. Mean duration of on-trial HT or placebo was 4 (CEE+MPA) or 5.6 years (CEE-Alone) and scans were conducted an average of 3 (CEE+MPA) or 1.4 years (CEE-Alone) post-trial termination. Cross-sectional analysis of MRI lesions was conducted; general linear models were fitted to assess treatment group differences using analysis of covariance. A (two-tailed) critical value of alpha = 0.05 was used. RESULTS: In women evenly matched within trials at baseline, increased lesion volumes were significantly related to age, smoking, history of cardiovascular disease, hypertension, lower post-trial global cognition scores, and increased incident cases of on- or post-trial mild cognitive impairment or probable dementia. Mean ischemic lesion volumes were slightly larger for the CEE+MPA group vs placebo, except for the basal ganglia, but the differences were not significant. Women assigned to CEE-Alone had similar mean ischemic lesion volumes compared to placebo. CONCLUSIONS: Conjugated equine estrogen-based hormone therapy was not associated with a significant increase in ischemic brain lesion volume relative to placebo. This finding was consistent within each trial and in pooled analyses across trials.

Predictors of adherence in the Women's Health Initiative Calcium and Vitamin D Trial.

The authors analyzed data from the Women's Health Initiative (WHI) Calcium and Vitamin D Supplementation Trial (CaD) to learn more about factors affecting adherence to clinical trial study pills (both active and placebo). Most participants (36,282 postmenopausal women aged 50-79 years) enrolled in CaD 1 year after joining either a hormone trial or the dietary modification trial of WHI. The WHI researchers measured adherence to study pills by weighing the amount of remaining pills at an annual study visit; adherence was primarily defined as taking > or = 80% of the pills. The authors in this study examined a number of behavioral, demographic, procedural, and treatment variables for association with study pill adherence. They found that relatively simple procedures (ie, phone contact early in the study [4 weeks post randomization] and direct social contact) later in the trial may improve adherence. Also, at baseline, past pill-use experiences, personal supplement use, and relevant symptoms may be predictive of adherence in a supplement trial.

No effect of HRT on health-related quality of life in postmenopausal women with heart disease.

AIM: Previous clinical studies suggest hormone replacement therapy (HRT) alleviates menopausal symptoms and may improve health-related quality of life (HRQL). Most studies on HRT and HRQL were limited in duration (12 months or less) and scope (few and non-standard HRQL measures). The aim of this paper is to assess HRQL in the Estrogen Replacement and Atherosclerosis (ERA) trial. METHODS: A subset of women within a randomized, blinded, placebo-controlled secondary prevention trial has been studied in outpatient and community settings at 5 US sites. A total of 246 postmenopausal women with angiographically documented heart disease (mean age 66 years, 83% Caucasian) were enrolled in the ERA trial. Participants received either 0.625 mg/day conjugated equine estrogen only, estrogen plus 2.5 mg/day medroxyprogesterone acetate, or placebo. HRQL was assessed using validated questionnaire instruments at baseline and follow-up (mean 3.2 years of trial). Physical and mental functioning, life satisfaction, depressive symptoms, urinary incontinence, sleep disturbance, and frequency and intensity of physical symptoms were evaluated. RESULTS: In this group of women with established coronary disease, active therapy was not significantly associated with more favorable outcomes for any HRQL. The estrogen-only group reported more urinary incontinence than the placebo group (p<0.05). Analyses restricted to adherent women (those who took > or = 80% of pills) showed a similar pattern of results, showing that the estrogen only group reported significantly higher urinary incontinence compared to placebo (p<0.01). CONCLUSION: The hormone replacement regimens in the ERA trial did not improve HRQL of postmenopausal women with heart disease.

The health-related quality of life and survival of small-cell lung cancer patients: results of a companion study to CALGB 9033.

The purposes of this study were 2-fold: to evaluate the impact of the schedule dependency of etoposide (3-day IV short course vs. a 21-day oral prolonged course) with cisplatin on the quality of life of small-cell lung cancer (SCLC) patients; and to examine the effect of baseline quality of life variables on long-term survival, after adjustment for known demographic and clinical prognostic factors. Participants were 70 patients enrolled in the cancer and leukemia group B (CALGB) protocol 9033. Quality of life was assessed at baseline, 6 and 12 weeks by: the EORTC QLQ-30, the Centers for epidemiology studies--Depression short form, the medical outcomes study (MOS) social support questionnaire, and a scale of sleep quality. Contrary to expectations, study results suggested no significant differences in the patients' life quality and treatment response based on whether they received etoposide in a 3-day IV vs. a 21-day oral regimen. The use of the baseline variables in predicting overall survival indicated that patients who were non-white and with liver involvement had decreased survival. Brain involvement, being male, and higher depressive symptoms were also found to be borderline significant in predicting decreased survival in this patient population.

Promoting adherence and retention to clinical trials in special populations: a women's health initiative workshop.

This paper describes a Women's Health Initiative workshop on promoting adherence and retention in randomized clinical trials among ethnic minority women, participants of lower socioeconomic status, and older women. Workshop objectives were: (1) to increase knowledge of demographic and cultural characteristics of diverse groups, (2) to increase awareness of how diversity can affect interactions in clinical research, (3) to explore how research staff behavior can influence adherence and retention, and (4) to increase knowledge of strategies to enhance adherence and retention in special populations. The workshop emphasized the importance of understanding beliefs, values, and experiences that are common in diverse groups of individuals, while at the same time recognizing and respecting individual differences that result from varying life circumstances and experiences. We discuss strategies to increase cultural competence, reduce stereotypes and discrimination, and create a culturally relevant and sensitive research environment.

Adherence to pharmacological interventions. Current trends and future directions. The Pharmacological Intervention Working Group.

The complexity of adherence to pharmacological interventions is frequently underestimated. Consequently, little research has been done to understand, improve, or evaluate the effects of adherence to drug protocols. While efforts to better measure and increase adherence require dedicated resources, improved adherence in existing clinical research can potentially cut costs in trial size and length. This paper outlines strategies to facilitate research on adherence to pharmacological interventions including: reporting of adherence data, changing how we conceptualize adherence to pharmaceuticals, understanding issues unique to older adults' pill-taking behavior, and creating standardized methodologies to measure adherence. Further, we describe some promising research areas that may lead to effective interventions: adherence "typologies" and modality matching. Control Clin Trials 2000;21:218S-225S

Enhancing adherence in randomized controlled clinical trials.

This paper identifies individual and systematic primary, secondary, and tertiary prevention approaches that can be used to enhance adherence in randomized controlled trials. Specifically, strategies such as these are discussed: careful screening during enrollment, use of a run-in period, fully informing participants of the study burden, explaining randomization, determining the participant's prior history with treatment interventions, establishing and using a tracking system, clearly specifying adherence measures, and staff training in communication and negotiation. These strategies have been gathered over time from our experiences working in multiple randomized controlled trials. Research on factors that promote or detract from adherence should be a standard part of randomized controlled trials. Control Clin Trials 2000;21:226S-232S

Factors related to sleep disturbance in older adults experiencing knee pain or knee pain with radiographic evidence of knee osteoarthritis.

OBJECTIVES: To describe the types and frequencies of sleep complaints and the biopsychosocial factors associated with sleep disturbance in a large community sample of older adults experiencing knee pain or knee pain with radiographic evidence of knee osteoarthritis (OA). DESIGN: Baseline analyses of an observational prospective study. SETTING AND PARTICIPANTS: Participants were 429 men and women aged 65 years and older experiencing knee pain or knee pain with radiographic evidence of OA enrolled in the Observational Arthritis Study in Seniors (OASIS). MEASUREMENTS: Demographic variables (age, gender, ethnicity, education), health (X-rays of knee rated for OA severity, medical conditions, medication use, smoking status, body mass index, self-rated health), physical functioning (self-rated physical functioning, physical performance), knee pain, and psychosocial functioning (social support, depression) were measured. RESULTS: Problems with sleep onset, sleep maintenance, and early morning awakenings occurred at least weekly among 31%, 81%, and 51% of participants, respectively. Bivariate correlates of greater sleep disturbance in those with OA were less education, cardiovascular disease, more arthritic joints, poorer self-rated health, poorer physical functioning, poorer physical performance, knee pain, depression, and less social support. In regression analyses, each set of variables representing the domains of health, physical functioning, pain, and psychosocial functioning contributed to the prediction of sleep disturbance beyond the demographic set. Finally, in a simultaneous model, white race (trend, P = .06), poorer self-rated health, poorer physical functioning, and depressive symptoms were predictive of sleep disturbance. CONCLUSIONS: Sleep disturbance is common in older adults experiencing knee pain or knee pain with radiographic evidence of OA and is best understood through the consideration of demographic, physical health, physical functioning, pain, and psychosocial variables. Interventions that take into account the multidetermined nature of sleep disturbance in knee pain or knee OA are most likely to be successful.

Effects of estrogen replacement on the progression of coronary-artery atherosclerosis.

BACKGROUND: Heart disease is a major cause of illness and death in women. To understand better the role of estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects. METHODS: We randomly assigned a total of 309 women with angiographically verified coronary disease to receive 0.625 mg of conjugated estrogen per day, 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or placebo. The women were followed for a mean (+/-SD) of 3.2+/-0.6 years. Base-line and follow-up coronary angiograms were analyzed by quantitative coronary angiography. RESULTS: Estrogen and estrogen plus medroxyprogesterone acetate produced significant reductions in low-density lipoprotein cholesterol levels (9.4 percent and 16.5 percent, respectively) and significant increases in high-density lipoprotein cholesterol levels (18.8 percent and 14.2 percent, respectively); however, neither treatment altered the progression of coronary atherosclerosis. After adjustment for measurements at base line, the mean (+/-SE) minimal coronary-artery diameters at follow-up were 1.87+/-0.02 mm, 1.84+/-0.02 mm, and 1.87+/-0.02 mm in women assigned to estrogen, estrogen plus medroxyprogesterone acetate, and placebo, respectively. The differences between the values for the two active-treatment groups and the value for the placebo group were not significant. Analyses of several secondary angiographic outcomes and subgroups of women produced similar results. The rates of clinical cardiovascular events were also similar among the treatment groups. CONCLUSIONS: Neither estrogen alone nor estrogen plus medroxyprogesterone acetate affected the progression of coronary atherosclerosis in women with established disease. These results suggest that such women should not use estrogen replacement with an expectation of cardiovascular benefit.

The estrogen replacement and atherosclerosis (ERA) study: study design and baseline characteristics of the cohort.

The Estrogen Replacement and Atherosclerosis (ERA) trial is a three-arm, randomized, placebo-controlled, double-blind trial to evaluate the effects of estrogen replacement therapy (0.625 mg/day oral conjugated estrogen) with or without continuous low-dose progestin (2.5 mg oral medroxyprogesterone acetate/day) versus placebo on progression of atherosclerosis. A total of 309 postmenopausal women at five sites underwent baseline coronary angiography and were randomized. Participants will have repeat coronary angiography after an average of 3.25 years of treatment. The primary outcome of interest will be change in minimum diameter of the major epicardial segments, as assessed by quantitative coronary angiography. The primary aim is to test the hypothesis that either form of hormone therapy will slow the progression or induce regression of coronary atherosclerosis compared to placebo. The secondary aims are to assess the effects of the two treatments versus placebo on endothelial function (measured using flow-mediated vasodilator responses), on several presumed mediators of estrogen's effect on atherosclerosis (i.e., plasma lipids and lipoproteins, blood pressure, glucose metabolism, hemostatic factors, and antioxidant activity), on other factors that influence the development of coronary heart disease (i.e., diet, smoking status, exercise, weight, and health-related quality of life issues), and on clinical cardiovascular events. The ERA trial is the first angiographic endpoint clinical trial to examine the effects of postmenopausal hormone replacement on coronary atherosclerosis in women. It will provide an unparalleled opportunity to determine if either regimen of hormone therapy is effective in slowing the progress of angiographically defined coronary atherosclerosis. This study will complement other estrogen replacement trials, such as the PEPI, HERS, and Women's Health Initiative studies, to provide a more comprehensive examination of the effects of estrogen replacement on cardiovascular risk factors, anatomic and functional manifestations of atherosclerosis, and risk for coronary heart disease in postmenopausal women. Control Clin Trials 2000;21:257-285

Profile of men randomized to the prostate cancer prevention trial: baseline health-related quality of life, urinary and sexual functioning, and health behaviors.

PURPOSE: To describe men who agreed to be randomized to the Prostate Cancer Prevention Trial (PCPT), a 7-year, double-blind placebo-controlled study of the efficacy of finasteride in preventing prostate cancer. METHODS: Comprehensive health-related quality-of-life data are presented for 18,882 randomized PCPT participants. RESULTS: PCPT participants are highly educated, middle to upper income, and primarily white (92%). Participants reported healthy lifestyles. The mean American Urological Association Symptom Index score was well below the maximum entry score of less than 19; existing urinary symptoms were generally not bothersome. The scores for two sexual functioning scales could range from 0 to 100, with higher scores reflecting worse sexual functioning. The mean score for the Sexual Problem Scale was 19.2 out of 100, and the mean Sexual Activities Scale was 44.1 out of 100. Scores for seven of the eight Medical Outcomes Study 36-item Short-Form Health Survey scales (higher scores are better) were 10 to 20 points higher than those reported by a general population sample and differed minimally by race but not by age. Previously reported associations between sexual dysfunction and hypertension, diabetes, and depression were also observed. Men who never smoked reported less sexual dysfunction than did those who either had quit or still smoked. CONCLUSION: Individuals who are likely to enroll in primary prevention trials have a high socioeconomic status, healthy lifestyle behaviors, and better health than the general population. These data help oncologists design chemoprevention trials with respect to the selection of health-related quality-of-life assessments and recruitment strategies.

Therapeutic approaches to dermatotoxicity by sulfur mustard. I. Modulaton of sulfur mustard-induced cutaneous injury in the mouse ear vesicant model.

The mouse ear edema model is recognized for its usefulness in studying skin responses and damage following exposure to chemical irritants, and for evaluating pharmacological agents against chemically induced skin injury. We recently modified the mouse ear edema model for use with sulfur mustard (HD) and used this model to study the protective effect of 33 topically applied compounds comprising five pharmaceutical strategies (anti-inflammatories, protease inhibitors, scavengers/chelators, poly(ADP-ribose) polymerase (PARP) inhibitors, calcium modulators/chelators) against HD-induced dermatotoxicity. Pharmacological modulation of HD injury in mouse ears was established by a reduction in edema or histopathology (epidermal necrosis and epidermal-dermal separation) at 24 h following topical liquid HD exposure. Ten of the 33 compounds administered as single topical pretreatments up to 2 h prior to HD challenge produced significant reductions in edema. Five of these ten also produced significant reductions in histological endpoints. Three candidates (olvanil, indomethacin, hydrocortisone) showing protection at 24 h were evaluated further for 'extended protection' at 48 and 72 h after HD challenge and showed significant modulation of edema at 48 h but not at 72 h. Olvanil also showed significant reductions in histology at 48 and 72 h. Olvanil and indomethacin were shown to reduce significantly the edema at 24 h post-exposure when administered topically 10 min after HD challenge, with olvanil additionally protecting against epidermal necrosis. These results demonstrate prophylactic and treatment effects of pharmacological agents against HD-induced skin injury in an in vivo model and support the continued use of the mouse ear vesicant model (MEVM) for evaluating medical countermeasures against HD.

A cutaneous full-thickness liquid sulfur mustard burn model in weanling swine: clinical pathology and urinary excretion of thiodiglycol.

Sulfur mustard (bis(2-chloroethyl)sulfide, HD) is a well-known blistering chemical warfare agent. We have developed a cutaneous full-thickness HD burn model in weanling pigs for efficacy testing of candidate treatment regimens. This report addresses clinical pathology findings and the urinary excretion profile of a major HD metabolite (thiodiglycol, TDG) in this model. Six female Yorkshire pigs were exposed to HD liquid on the ventral surface for 2 h, generating six 3-cm diameter full-thickness dermal lesions per pig. Blood samples were collected throughout a 7-day observation period for hematology and serum chemistry examinations. Urine was collected in metabolism cages. Routine urinalysis was performed and the urine analyzed for TDG using gas chromatography/mass spectrometry. Examination of clinical pathology parameters revealed subtle HD-related changes that are suggestive of a mild hemolytic episode. No other signs of clinically significant systemic toxicities were noted, including bone marrow suppression. Thiodiglycol was detected at the earliest time point tested (6-8 h post-exposure) at levels ranging from 0.66 to 4.98 microg ml(-1) with a mean of 2.14 microg ml(-1). Thiodiglycol concentrations were the highest for half of the animals at this earliest time point and at 24-48 h for the others. By the evening of day 3, the mean level had reached 50 ng ml(-1). Mean levels remained 10-40 ng ml(-1) for the remainder of the 7-day observation period, with the highest individual concentration noted during this period of 132 ng ml(-1). Our results are in general agreement with the TDG excretion profiles previously described for rodent models and humans. Urinary excretion of absorbed HD in our weanling pig wound healing model appears to follow the same pattern as is seen in other laboratory animals models. In general, urinary excretion of TDG appears to peak within the first 1-4 days following exposure, with detectable levels after 1 week. Relatively high urinary TDG levels may thus indicate agent exposure within the previous 96 h. Low levels significantly above natural background levels may indicate either exposure to low levels of agent or exposure that occurred more than 4 days prior to collection of the sample.

Symptom relief and side effects of postmenopausal hormones: results from the Postmenopausal Estrogen/Progestin Interventions Trial.

OBJECTIVE: To assess pair-wise differences between placebo, estrogen, and each of three estrogen-progestin regimens on selected symptoms. METHODS: This was a 3-year, multicenter, double-blind, placebo-controlled trial in 875 postmenopausal women aged 45-64 years at baseline. Participants were assigned randomly to one of five groups: 1) placebo, 2) daily conjugated equine estrogens, 3) conjugated equine estrogens plus cyclical medroxyprogesterone acetate, 4) conjugated equine estrogens plus daily medroxyprogesterone acetate, and 5) conjugated equine estrogens plus cyclical micronized progesterone. Symptoms were self-reported using a checklist at 1 and 3 years. Factor analysis reduced 52 symptoms to a set of six symptom groups. RESULTS: In intention-to-treat analyses at 1 year, each active treatment demonstrated a marked, statistically significant, protective effect against vasomotor symptoms compared with placebo (odds ratios [ORs] 0.17-0.28); there was no additional benefit of estrogen-progestin over estrogen alone. Only progestin-containing regimens were significantly associated with higher levels of breast discomfort (OR 1.92-2.27). Compared with placebo, women randomized to conjugated equine estrogens reported no increase in perceived weight. Those randomized to medroxyprogesterone acetate reported less perceived weight gain (OR 0.61-0.69) than placebo. Anxiety, cognitive, and affective symptoms did not differ by treatment assignment. Analyses restricted to adherent women were not materially different than those using intention-to-treat, except that women adherent to medroxyprogesterone acetate and micronized progesterone regimens reported fewer musculoskeletal symptoms (OR 0.62-0.68). CONCLUSION: These results confirm the usefulness of post-menopausal hormone therapy for hot flashes, show convincingly that estrogen plus progestin causes breast discomfort, and demonstrate little influence of postmenopausal hormones on anxiety, cognition, or affect.

Adaptation and evaluation of the Liverpool Seizure Severity Scale and Liverpool Quality of Life battery for American epilepsy patients.

The Liverpool Seizure Severity Scale (LSSS) and the Liverpool Quality of Life (LQOL) battery were developed in Great Britain to assess the severity of seizure symptoms and the impact of epilepsy on patients' quality of life. The scales have been validated on British patients, but have not been validated for use with American patients. The objectives of this study were to adapt the scales to the American population and to evaluate their reliability and validity. After modifications recommended by focus groups with patients and epilepsy specialists, the scales were administered to a sample of 90 epilepsy patients who had experienced seizures within the previous 4 weeks. Comparisons of patients with generalized tonic-clonic seizures (n = 58) and partial seizures (n = 32) revealed significant differences on 9 of the 20 items on the LSSS as well as the total score. None of the six LQOL subscales (negative drug effects, positive drug effects, affect balance, sense of mastery, life fulfilment and impact of epilepsy) distinguished patients with different seizure types but five of the six subscales were significantly correlated with seizure severity. The internal consistency and test-retest reliability were adequate for both the LSSS and LQOL. Finally, five of the six LQOL scales were significantly correlated with independent measures of mental health, physical health and role functioning.