Menopausal hormone replacement therapy and risk of ovarian cancer

Context  The association between menopausal hormone replacement therapy and ovariancancer is unclear. Objective  To determine whether hormone replacement therapy using estrogen only,estrogen-progestin only, or both estrogen only and estrogen-progestin increasesovarian cancer risk. Design  A 1979-1998 cohort study of former participants in the Breast CancerDetection Demonstration Project, a nationwide breast cancer screening program. Setting  Twenty-nine US clinical centers. Participants  A total of 44 241 postmenopausal women (mean age at start of follow-up,56.6 years). Main Outcome Measure  Incident ovarian cancer. Results  We identified 329 women who developed ovarian cancer during follow-up.In time-dependent analyses adjusted for age, menopause type, and oral contraceptiveuse, ever use of estrogen only was significantly associated with ovarian cancer(rate ratio [RR], 1.6; 95% confidence interval [CI], 1.2-2.0). Increasingduration of estrogen-only use was significantly associated with ovarian cancer:RRs for 10 to 19 years and 20 or more years were 1.8 (95% CI, 1.1-3.0) and3.2 (95% CI, 1.7-5.7), respectively (P value fortrend <.001), and we observed a 7% (95% CI, 2%-13%) increase in RR peryear of use. We observed significantly elevated RRs with increasing durationof estrogen-only use across all strata of other ovarian cancer risk factors,including women with hysterectomy. The RR for estrogen-progestin use afterprior estrogen-only use was 1.5 (95% CI, 0.91-2.4), but the RR for estrogen-progestin–onlyuse was 1.1 (95% CI, 0.64-1.7). The RRs for less than 2 years and 2 or moreyears of estrogen-progestin–only use were 1.6 (95% CI, 0.78-3.3) and0.80 (95% CI, 0.35-1.8), respectively, and there was no evidence of a durationresponse (P value for trend = .30). Conclusion  Women who used estrogen-only replacement therapy, particularly for 10or more years, were at significantly increased risk of ovarian cancer in thisstudy. Women who used short-term estrogen-progestin–only replacementtherapy were not at increased risk, but risk associated with short-term andlonger-term estrogen-progestin replacement therapy warrants further investigation.      

HPV DNA testing of self-collected vaginal samples compared with cytologic screening to detect cervical cancer

Context  More than half of the women diagnosed as having cervical cancer in the United States have not been screened within the last 3 years, despite many having had contact with the health care system. In many other regions of the world, there is only limited access to cervical cancer screening. Objective  To determine whether testing of self-collected vaginal swabs for human papillomavirus (HPV) DNA can be used to screen for cervical disease in women aged 35 years and older. Design  Cross-sectional observational study comparing Papanicolaou smears with HPV DNA testing of self-collected vaginal swabs. Setting  Outpatient clinics in a periurban settlement outside of Cape Town, South Africa, between January 1998 and April 1999. Participants  Screening was performed on 1415 previously unscreened black South African women aged 35 to 65 years. Intervention  Women self-collected a vaginal swab for HPV testing in the clinic and were then screened using 4 different tests: Papanicolaou smear, direct visual inspection of the cervix after the application of 5% acetic acid, cervicography, and HPV DNA testing of a clinician-obtained cervical sample. Women with abnormal results on any of the screening tests were referred for colposcopy. Main Outcome Measure  Biopsy-confirmed high-grade cervical squamous intraepithelial lesions or invasive cancer. Results  High-grade squamous intraepithelial lesions were identified in 47 (3.4%) of 1365 women adequately assessed, and there were 9 cases of invasive cancer. Of women with high-grade disease, 66.1% (95% confidence interval [CI], 52.1%-77.8%) had high-risk HPV detected in self-collected vaginal samples, and 67.9% (95% CI, 53.9%-79.4%) had an abnormal Papanicolaou smear (P = .78). The false-positive rates for HPV DNA testing of self-collected vaginal samples and Papanicolaou smears were 17.1% (95% CI, 15.1%-19.3%) and 12.3% (95% CI, 10.5%-14.2%), respectively (P<.001). A high-risk type of HPV DNA was detected in 83.9% (95% CI, 71.2%-91.9%) of women with high-grade disease and 15.5% (95% CI, 13.6%-17.7%) of women with no evidence of cervical disease using a clinician-obtained cervical sample. Conclusions  These results indicate that HPV testing of self-collected vaginal swabs is less specific than but as sensitive as Papanicolaou smears for detecting high-grade cervical disease in women aged 35 years and older, and HPV testing offers an important new way to increase screening in settings where cytology is not readily performed.      

Mental health, social functioning, and disability in postwar Afghanistan

Context  More than 2 decades of conflict have led to widespread human suffering and population displacement in Afghanistan. In 2002, the Centers for Disease Control and Prevention and other collaborating partners performed a national population-based mental health survey in Afghanistan. Objective  To provide national estimates of mental health status of the disabled (any restriction or lack of ability to perform an activity in the manner considered normal for a human being) and nondisabled Afghan population aged at least 15 years. Design, Setting, and Participants  A national multistage, cluster, population-based mental health survey of 799 adult household members (699 nondisabled and 100 disabled respondents) aged 15 years or older conducted from July to September 2002. Fifty district-level clusters were selected based on probability proportional to size sampling. One village was randomly selected in each cluster and 15 households were randomly selected in each village, yielding 750 households. Main Outcome Measures  Demographics, social functioning as measured by selected questions from the Medical Outcomes Study 36-Item Short-Form Health Survey, depressive symptoms measured by the Hopkins Symptoms Checklist-25, trauma events and symptoms of posttraumatic stress disorder (PTSD) measured by the Harvard Trauma Questionnaire, and culture-specific symptoms of mental illness and coping mechanisms. Results  A total of 407 respondents (62.0%) reported experiencing at least 4 trauma events during the previous 10 years. The most common trauma events experienced by the respondents were lack of food and water (56.1%) for nondisabled persons and lack of shelter (69.7%) for disabled persons. The prevalence of respondents with symptoms of depression was 67.7% (95% confidence interval [CI], 54.6%-80.7%) and 71.7% (95% CI, 65.0%-78.4%), and symptoms of anxiety 72.2% (95% CI, 63.8%-80.7%) and 84.6% (95% CI, 74.1%-95.0%) for nondisabled and disabled respondents, respectively. The prevalence of symptoms of PTSD was similar for both groups (nondisabled, 42.1%; 95% CI, 34.2%-50.1%; and disabled, 42.2%; 95% CI, 29.2%-55.2%). Women had significantly poorer mental health status than men did. Respondents who were disabled had significantly lower social functioning and poorer mental health status than those who were nondisabled. Feelings of hatred were high (84% of nondisabled and 81% of disabled respondents). Coping mechanisms included religious and spiritual practices; focusing on basic needs, such as higher income, better housing, and more food; and seeking medical assistance. Conclusions  In this nationally representative survey of Afghans, prevalence rates of symptoms of depression, anxiety, and PTSD were high. These data underscore the need for donors and health care planners to address the current lack of mental health care resources, facilities, and trained mental health care professionals in Afghanistan.      

Mental health and health-related quality of life among adult Latino primary care patients living in the United States with previous exposure to political violence

Context  Although political violence continues in parts of Central America, South America, and Mexico, little is known about its relationship to the health of Latino immigrants living in the United States. Objective  To determine (1) rates of exposure to political violence among Latino adult primary care patients who have immigrated to the United States from Central America, South America, and Mexico and its impact on mental health and health-related quality of life and (2) frequency of disclosure of political violence to primary care clinicians. Design, Setting, and Participants  Two-stage cluster design survey of a systematic sample of Latino immigrant adults in 3 community-based primary care clinics in Los Angeles, conducted from July 2001 to February 2002. Main Outcome Measures  Reports of exposure to political violence in home country before immigrating to the United States and communication with clinicians about political violence; self-reported measures of health-related quality of life using the Medical Outcomes Study Short Form 36 (MOS SF-36); symptoms of depression, anxiety, and alcohol disorders using the Primary Care Evaluation of Mental Disorders (PRIME-MD); and symptoms of posttraumatic stress disorder (PTSD) using the PTSD Checklist–Civilian Version (PCL-C). Results  A total of 638 (69%) of 919 eligible patients participated. The nonresponse rates did not differ by age, sex, recruitment sites, or clinic sessions. In weighted analyses, 54% of participants reported political violence experiences in their home countries, including 8% who reported torture. Of those exposed to political violence, 36% had symptoms of depression and 18% had symptoms of PTSD vs 20% and 8%, respectively, among those not exposed to political violence. Controlling for age, sex, country, years lived in the United States, acculturation, income, health insurance status, and recruitment site in a subsample of 512 participants (56%), those who reported political violence exposure were more likely to meet symptom criteria for PTSD (adjusted odds ratio [AOR], 3.4; 95% confidence interval [CI], 1.4-8.4) and to have symptoms of depression (AOR, 2.8; 95% CI, 1.4-5.4) and symptoms of panic disorder (AOR, 4.8; 95% CI, 1.6-14.4) than participants not reporting political violence. Those exposed to political violence reported more chronic pain and role limitations due to physical problems, as well as worse physical functioning and lower perceptions of general health than those who were not exposed to political violence. Only 3% of the 267 patients who had experienced political violence reported ever telling a clinician about it after immigrating; none reported their current physician asking about political violence. Conclusion  Latino immigrants in primary care in Los Angeles have a high prevalence of exposure to political violence before immigrating to the United States and associated impairments in mental health and health-related quality of life.      

Detection of bladder cancer using a point-of-care proteomic assay

Context  A combination of methods is used for diagnosis of bladder cancer because no single procedure detects all malignancies. Urine tests are frequently part of an evaluation, but have either been nonspecific for cancer or required specialized analysis at a laboratory. Objective  To investigate whether a point-of-care proteomic test that measures the nuclear matrix protein NMP22 in voided urine could enhance detection of malignancy in patients with risk factors or symptoms of bladder cancer. Design, Setting, and Patients  Twenty-three academic, private practice, and veterans’ facilities in 10 states prospectively enrolled consecutive patients from September 2001 to May 2002. Participants included 1331 patients at elevated risk for bladder cancer due to factors such as history of smoking or symptoms including hematuria and dysuria. Patients at risk for malignancy of the urinary tract provided a voided urine sample for analysis of NMP22 protein and cytology prior to cystoscopy. Main Outcome Measures  The diagnosis of bladder cancer, based on cystoscopy with biopsy, was accepted as the reference standard. The performance of the NMP22 test was compared with voided urine cytology as an aid to cancer detection. Testing for the NMP22 tumor marker was conducted in a blinded manner. Results  Bladder cancer was diagnosed in 79 patients. The NMP22 assay was positive in 44 of 79 patients with cancer (sensitivity, 55.7%; 95% confidence interval [CI], 44.1%-66.7%), whereas cytology test results were positive in 12 of 76 patients (sensitivity, 15.8%; 95% CI, 7.6%-24.0%). The specificity of the NMP22 assay was 85.7% (95% CI, 83.8%-87.6%) compared with 99.2% (95% CI, 98.7%-99.7%) for cytology. The proteomic marker detected 4 cancers that were not visualized during initial endoscopy, including 3 that were muscle invasive and 1 carcinoma in situ. Conclusion  The noninvasive point-of-care assay for elevated urinary NMP22 protein can increase the accuracy of cystoscopy, with test results available during the patient visit.      

Adult weight change and risk of postmenopausal breast cancer

Context  Endogenous hormones are a primary cause of breast cancer. Adiposity affects circulating hormones, particularly in postmenopausal women, and may be a modifiable risk factor for breast cancer. Objective  To assess the associations of adult weight change since age 18 years and since menopause with the risk of breast cancer among postmenopausal women. Design, Setting, and Participants  Prospective cohort study within the Nurses' Health Study. A total of 87 143 postmenopausal women, aged 30 to 55 years and free of cancer, were followed up for up to 26 years (1976-2002) to assess weight change since age 18 years. Weight change since menopause was assessed among 49 514 women who were followed up for up to 24 years. Main Outcome Measure  Incidence of invasive breast cancer. Results  Overall, 4393 cases of invasive breast cancer were documented. Compared with those who maintained weight, women who gained 25.0 kg or more since age 18 years were at an increased risk of breast cancer (relative risk [RR], 1.45; 95% confidence interval [CI], 1.27-1.66; P<.001 for trend), with a stronger association among women who have never taken postmenopausal hormones (RR,1.98; 95% CI, 1.55-2.53). Compared with weight maintenance, women who gained 10.0 kg or more since menopause were at an increased risk of breast cancer (RR, 1.18; 95% CI, 1.03-1.35; P  = .002 for trend). Women who had never used postmenopausal hormones, lost 10.0 kg or more since menopause, and kept the weight off were at a lower risk than those who maintained weight (RR, 0.43; 95% CI, 0.21-0.86; P = .01 for weight loss trend). Overall, 15.0% (95% CI, 12.8%-17.4%) of breast cancer cases in this population may be attributable to weight gain of 2.0 kg or more since age 18 years and 4.4% (95% CI, 3.6%-5.5%) attributable to weight gain of 2.0 kg or more since menopause. Among those who did not use postmenopausal hormones, the population attributable risks are 24.2% (95% CI, 19.8%-29.1%) for a weight gain since age 18 years and 7.6% (95% CI, 5.9%-9.7%) for weight gain since menopause. Conclusions  These data suggest that weight gain during adult life, specifically since menopause, increases the risk of breast cancer among postmenopausal women, whereas weight loss after menopause is associated with a decreased risk of breast cancer. Thus, in addition to other known benefits of healthy weight, our results provide another reason for women approaching menopause to maintain or lose weight, as appropriate.      

Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial

Context  The effects of continuous combined hormone therapy on gynecologic cancers have not been investigated previously in a randomized trial setting. Objective  To determine the possible associations of estrogen plus progestin on gynecologic cancers and related diagnostic procedures. Design, Setting, and Participants  Randomized, double-blind, placebo-controlled trial of 16 608 postmenopausal women, who had not had a hysterectomy at baseline and who had been recruited from 40 US clinical centers between September 1993 and October 1998 (average follow-up, 5.6 years). Intervention  One tablet per day containing 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate (n = 8506) or placebo (n = 8102). Main Outcome Measure  Incident invasive cancer of the ovary and endometrium. Results  In 5.6 years of follow-up, there were 32 cases of invasive ovarian cancer, 58 cases of endometrial cancer, 1 case of nonendometrial uterine cancer, 13 cases of cervical cancer, and 7 cases of other gynecologic cancers. The hazard ratio (HR) for invasive ovarian cancer in women assigned to estrogen plus progestin compared with placebo was 1.58 (95% confidence interval [CI], 0.77-3.24). The HR for endometrial cancer was 0.81 (95% CI, 0.48-1.36). No appreciable differences were found in the distributions of tumor histology, stage, or grade for either cancer site. The incidence of other gynecologic cancers was low and did not differ by randomization assignment. More women taking estrogen plus progestin required endometrial biopsies (33% vs 6%; P<.001). Conclusions  This randomized trial suggests that continuous combined estrogen plus progestin therapy may increase the risk of ovarian cancer while producing endometrial cancer rates similar to placebo. The increased burden of endometrial biopsies required to assess vaginal bleeding further limits the acceptability of this regimen. These data provide additional support for caution in the use of continuous combined hormones.      

Magnesium intake in relation to risk of colorectal cancer in women

Context  Animal studies have suggested that dietary magnesium may play a role in the prevention of colorectal cancer, but data in humans are lacking. Objective  To evaluate the hypothesis that a high magnesium intake reduces the risk of colorectal cancer in women. Design, Setting, and Participants  The Swedish Mammography Cohort, a population-based prospective cohort of 61 433 women aged 40 to 75 years without previous diagnosis of cancer at baseline from 1987 to 1990. Main Outcome Measure  Incident invasive colorectal cancer. Results  During a mean of 14.8 years (911 042 person-years) of follow-up, 805 incident colorectal cancer cases were diagnosed. After adjustment for potential confounders, we observed an inverse association of magnesium intake with the risk of colorectal cancer (P for trend = .006). Compared with women in the lowest quintile of magnesium intake, the multivariate rate ratio (RR) was 0.59 (95% confidence interval [CI], 0.40-0.87) for those in the highest quintile. The inverse association was observed for both colon (RR, 0.66; 95% CI, 0.41-1.07) and rectal cancer (RR, 0.45; 95% CI, 0.22-0.89). Conclusion  This population-based prospective study suggests that a high magnesium intake may reduce the occurrence of colorectal cancer in women.      

Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial

Context  Few depressed older adults receive effective treatment in primary care settings. Objective  To determine the effectiveness of the Improving Mood–Promoting Access to Collaborative Treatment (IMPACT) collaborative care management program for late-life depression. Design  Randomized controlled trial with recruitment from July 1999 to August 2001. Setting  Eighteen primary care clinics from 8 health care organizations in 5 states. Participants  A total of 1801 patients aged 60 years or older with major depression (17%), dysthymic disorder (30%), or both (53%). Intervention  Patients were randomly assigned to the IMPACT intervention (n = 906) or to usual care (n = 895). Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care expert and who offered education, care management, and support of antidepressant management by the patient's primary care physician or a brief psychotherapy for depresssion, Problem Solving Treatment in Primary Care. Main Outcome Measures  Assessments at baseline and at 3, 6, and 12 months for depression, depression treatments, satisfaction with care, functional impairment, and quality of life. Results  At 12 months, 45% of intervention patients had a 50% or greater reduction in depressive symptoms from baseline compared with 19% of usual care participants (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.71-4.38; P<.001). Intervention patients also experienced greater rates of depression treatment (OR, 2.98; 95% CI, 2.34-3.79; P<.001), more satisfaction with depression care (OR, 3.38; 95% CI, 2.66-4.30; P<.001), lower depression severity (range, 0-4; between-group difference, -0.4; 95% CI, -0.46 to -0.33; P<.001), less functional impairment (range, 0-10; between-group difference, -0.91; 95% CI, -1.19 to -0.64; P<.001), and greater quality of life (range, 0-10; between-group difference, 0.56; 95% CI, 0.32-0.79; P<.001) than participants assigned to the usual care group. Conclusion  The IMPACT collaborative care model appears to be feasible and significantly more effective than usual care for depression in a wide range of primary care practices.      

Symptomatic hyponatremia during treatment of dehydrating diarrheal disease with reduced osmolarity oral rehydration solution

Context  In May 2002, the World Health Organization and the United Nations Children's Fund recommended that the formulation of oral rehydration solution (ORS) for treatment of patients with diarrhea be changed to one with a reduced osmolarity and that safety of the new formulation, particularly development of symptomatic hyponatremia, be monitored. Objective  To measure the rates of symptomatic hyponatremia during treatment of patients with diarrhea with reduced osmolarity ORS. Design, Settings, and Patients  A phase 4 trial conducted at the Dhaka hospital (December 1, 2002-November 30, 2003) and Matlab hospital (February 2, 2003-January 31, 2004) of the International Centre for Diarrhoeal Disease Research Bangladesh: Centre for Health and Population Research, Dhaka, Bangladesh. All patients admitted with uncomplicated watery diarrhea were treated with the newly recommended ORS and monitored. Patients developing neurological symptoms (seizure or altered consciousness) were transferred to the special care ward for treatment and investigated to identify the cause of the symptoms. Patient records of the Dhaka hospital were reviewed during the previous year when the old ORS formulation was used. Intervention  Reduced osmolarity ORS. Main Outcome Measure  Incidence rate of symptomatic hyponatremia in a 1-year period. Results  A total of 53 280 patients, including 22 536 children younger than 60 months, were monitored at the Dhaka and Matlab hospitals. Twenty-four patients, none older than 36 months, developed seizures or altered consciousness associated with hyponatremia, with an overall incidence rate of 0.05% (95% confidence interval [CI], 0.03%-0.07%) at the Dhaka hospital and 0.03% (95% CI, 0.01%-0.09%) at the Matlab hospital. During the previous year, 47 patients at the Dhaka hospital had symptoms associated with hyponatremia, for an estimated incidence rate of 0.10% (95% CI, 0.07%-0.13%). The reduction in the rates was statistically significant (odds ratio, 0.50; 95% CI, 0.29-0.85; P = .009). Conclusion  The risk of symptoms associated with hyponatremia in patients treated with the reduced osmolarity ORS is minimal and did not increase with the change in formulation.      

The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women: Results From the MORE Randomized Trial

Context  Raloxifene hydrochloride is a selective estrogen receptor modulator that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting. Objective  To determine whether women taking raloxifene have a lower risk of invasive breast cancer. Design and Setting  The Multiple Outcomes of Raloxifene Evaluation (MORE), a multicenter, randomized, double-blind trial, in which women taking raloxifene or placebo were followed up for a median of 40 months (SD, 3 years), from 1994 through 1998, at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the United States and Europe. Participants  A total of 7705 postmenopausal women, younger than 81 (mean age, 66.5) years, with osteoporosis, defined by the presence of vertebral fractures or a femoral neck or spine T-score of at least 2.5 SDs below the mean for young healthy women. Almost all participants (96%) were white. Women who had a history of breast cancer or who were taking estrogen were excluded. Intervention  Raloxifene, 60 mg, 2 tablets daily; or raloxifene, 60 mg, 1 tablet daily and 1 placebo tablet; or 2 placebo tablets. Main Outcome Measures  New cases of breast cancer, confirmed by histopathology. Transvaginal ultrasonography was used to assess the endometrial effects of raloxifene in 1781 women. Deep vein thrombosis or pulmonary embolism were determined by chart review. Results  Thirteen cases of breast cancer were confirmed among the 5129 women assigned to raloxifene vs 27 among the 2576 women assigned to placebo (relative risk [RR], 0.24; 95% confidence interval [CI], 0.13-0.44; P<.001). To prevent 1 case of breast cancer, 126 women would need to be treated. Raloxifene decreased the risk of estrogen receptor–positive breast cancer by 90% (RR, 0.10; 95% CI, 0.04-0.24), but not estrogen receptor–negative invasive breast cancer (RR, 0.88; 95% CI, 0.26-3.0). Raloxifene increased the risk of venous thromboembolic disease (RR, 3.1; 95% CI, 1.5-6.2), but did not increase the risk of endometrial cancer (RR, 0.8; 95% CI, 0.2-2.7). Conclusion  Among postmenopausal women with osteoporosis, the risk of invasive breast cancer was decreased by 76% during 3 years of treatment with raloxifene.      

Does this patient have a family history of cancer? An evidence-based analysis of the accuracy of family cancer history

Harvey J. Murff, MD, MPH; David R. Spigel, MD; Sapna Syngal, MD, MPH

JAMA. 2004;292:1480-1489.

Context  A family history of certain cancers is associated with an increased risk of developing cancer. Both cancer screening and genetic services referral decisions are often based on self-reported pedigree information.

Objective  To determine the accuracy of self-reported family cancer history information.

Data Sources  English-language articles were retrieved by searching MEDLINE (1966-June 2004) using Medical Subject Headings family, genetic predisposition to disease, medical history taking, neoplasm, and reproducibility of results. Additional articles were identified through bibliography searches.

Study Selection  Original studies in which investigators validated self-reported family history by reviewing the identified relatives' medical records, death certificate, or cancer registry information were included, as well as studies that evaluated breast, colon, ovarian, endometrial, and prostate cancers.

Data Extraction  Two of the 3 investigators independently reviewed and abstracted data for estimating the likelihood ratios (LRs) of self-reported family cancer history information. Only data from studies that evaluated both positive and negative family cancer histories were included within the analyses. A total of 14 studies met the search criteria and were included in the review.

Data Synthesis  For patients without a personal history of cancer, the positive and negative LRs of a family history of the following cancers in a first-degree relative were 23.0 (95% confidence interval [CI], 6.4-81.0) and 0.25 (95% CI, 0.10-0.63) for colon cancer; 8.9 (95% CI, 5.4-15.0) and 0.20 (95% CI, 0.08-0.49) for breast cancer; 14.0 (95% CI, 2.2-83.4) and 0.68 (95% CI, 0.31-1.52) for endometrial cancer; 34.0 (95% CI, 5.7-202.0) and 0.51 (95% CI, 0.13-2.10) for ovarian cancer; and 12.3 (95% CI, 6.5-24.0) and 0.32 (95% CI, 0.18-0.55) for prostate cancer, respectively. Positive predictive values tended to be better in articles concerning first-degree relatives compared with second-degree relatives.

Conclusions  Patient-reported family cancer histories for first-degree relatives are accurate and valuable for breast and colon cancer risk assessments. Negative family history reports for ovarian and endometrial cancers are less useful, although the prevalence of these malignancies within families is low.

     

Depressive symptoms and health-related quality of life: the Heart and Soul Study

Context  Little is known regarding the extent to which patient-reported health status, including symptom burden, physical limitation, and quality of life, is determined by psychosocial vs physiological factors among patients with chronic disease. Objective  To compare the contributions of depressive symptoms and measures of cardiac function to the health status of patients with coronary artery disease. Design, Setting, and Participants  Cross-sectional study of 1024 adults with stable coronary artery disease recruited from outpatient clinics in the San Francisco Bay Area between September 2000 and December 2002. Main Measures  Measurement of depressive symptoms using the Patient Health Questionnaire (PHQ); assessment of cardiac function by measuring left ventricular ejection fraction on echocardiography, exercise capacity on treadmill testing, and ischemia on stress echocardiography; and measurement of a range of health status outcomes, including symptom burden, physical limitation, and quality of life, using the Seattle Angina Questionnaire. Participants were also asked to rate their overall health as excellent, very good, good, fair, or poor. Results  Of the 1024 participants, 201 (20%) had depressive symptoms (PHQ score =" BORDER="0">10). Participants with depressive symptoms were more likely than those without depressive symptoms to report at least mild symptom burden (60% vs 33%; P<.001), mild physical limitation (73% vs 40%; P<.001), mildly diminished quality of life (67% vs 31%; P<.001), and fair or poor overall health (66% vs 30%; P<.001). In multivariate analyses adjusting for measures of cardiac function and other patient characteristics, depressive symptoms were strongly associated with greater symptom burden (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3-2.7; P = .002), greater physical limitation (OR, 3.1; 95% CI, 2.1-4.6; P<.001), worse quality of life (OR, 3.1; 95% CI, 2.2-4.6; P<.001), and worse overall health (OR, 2.0; 95% CI, 1.3-2.9; P<.001). Although decreased exercise capacity was associated with worse health status, left ventricular ejection fraction and ischemia were not. Conclusions  Among patients with coronary disease, depressive symptoms are strongly associated with patient-reported health status, including symptom burden, physical limitation, quality of life, and overall health. Conversely, 2 traditional measures of cardiac function—ejection fraction and ischemia—are not. Efforts to improve health status should include assessment and treatment of depressive symptoms.      

Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial

Context  Basic research provides plausible mechanisms and observational studies suggest that apparently healthy persons, who self-select for high intakes of vitamin E through diet or supplements, have decreased risks of cardiovascular disease and cancer. Randomized trials do not generally support benefits of vitamin E, but there are few trials of long duration among initially healthy persons. Objective  To test whether vitamin E supplementation decreases risks of cardiovascular disease and cancer among healthy women. Design, Setting, and Participants  In the Women’s Health Study conducted between 1992 and 2004, 39 876 apparently healthy US women aged at least 45 years were randomly assigned to receive vitamin E or placebo and aspirin or placebo, using a 2 x 2 factorial design, and were followed up for an average of 10.1 years. Intervention  Administration of 600 IU of natural-source vitamin E on alternate days. Main Outcome Measures  Primary outcomes were a composite end point of first major cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and total invasive cancer. Results  During follow-up, there were 482 major cardiovascular events in the vitamin E group and 517 in the placebo group, a nonsignificant 7% risk reduction (relative risk [RR], 0.93; 95% confidence interval [CI], 0.82-1.05; P = .26). There were no significant effects on the incidences of myocardial infarction (RR,  1.01; 95% CI, 0.82-1.23; P = .96) or stroke (RR, 0.98; 95% CI, 0.82-1.17; P = .82), as well as ischemic or hemorrhagic stroke. For cardiovascular death, there was a significant 24% reduction (RR, 0.76; 95% CI, 0.59-0.98; P = .03). There was no significant effect on the incidences of total cancer (1437 cases in the vitamin E group and 1428 in the placebo group; RR, 1.01; 95% CI, 0.94-1.08; P = .87) or breast (RR, 1.00; 95% CI, 0.90-1.12; P = .95), lung (RR, 1.09; 95% CI, 0.83-1.44; P = .52), or colon cancers (RR, 1.00; 95% CI, 0.77-1.31; P = .99). Cancer deaths also did not differ significantly between groups. There was no significant effect of vitamin E on total mortality (636 in the vitamin E group and 615 in the placebo group; RR, 1.04; 95% CI, 0.93-1.16; P = .53). Conclusions  The data from this large trial indicated that 600 IU of natural-source vitamin E taken every other day provided no overall benefit for major cardiovascular events or cancer, did not affect total mortality, and decreased cardiovascular mortality in healthy women. These data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women.      

Serum Estradiol Level and Risk of Breast Cancer During Treatment With Raloxifene

Context  As endogenous estradiol increases, risk of breast cancer increases. Raloxifene competes with endogenous estrogen for binding to estrogen receptors in breast tissue. A woman's estradiol level may alter the effects of raloxifene on breast cancer and other outcomes. Objective  To test the hypothesis that raloxifene reduces breast cancer risk more in women with relatively high estradiol levels than in women with very low estradiol levels. Design  Analysis of the Multiple Outcomes of Raloxifene Evaluation, a randomized, double-blind, placebo-controlled trial conducted from 1994 to 1999. Setting  One hundred eighty community settings and medical practices in 25 countries including the United States. Participants  A total of 7290 postmenopausal women aged 80 years or younger with osteoporosis who had baseline serum estradiol concentrations measured by a central laboratory using a sensitive assay. Women with a history of breast cancer or estrogen use were excluded. Intervention  Participants were randomly assigned to receive 60 mg/d or 120 mg/d of raloxifene (n = 4843) or matching placebo (n = 2447) for 4 years. Main Outcome Measure  New cases of histopathologically confirmed breast cancer in the treatment and placebo groups, stratified by estradiol levels. Results  In the placebo group, women with estradiol levels greater than 10 pmol/L (2.7 pg/mL) had a 6.8-fold higher rate of breast cancer (3.0% per 4 years; 95% confidence interval [CI], 1.8%-4.1%) than that of women with undetectable estradiol levels (0.6% per 4 years; 95% CI, 0%-1.1%; P = .005 for trend). Women with estradiol levels greater than 10 pmol/L in the raloxifene group had a rate of breast cancer that was 76% (95% CI, 53%-88%) lower than that of women with estradiol levels greater than 10 pmol/L in the placebo group (absolute rate reduction, 2.2% [95% CI, 1.0%-3.5%; number needed to treat = 45]). In contrast, women with undetectable estradiol levels had similar breast cancer risk whether or not they were treated with raloxifene (risk difference, -0.1%; 95% CI, -0.8% to 0.6%; P = .02 for the interaction). In this cohort, treating women with estradiol levels greater than 10 pmol/L with raloxifene for 4 years would have avoided 47% of breast cancer cases. Conclusions  Measurement of estradiol level by sensitive assay in postmenopausal women identifies those at high risk of breast cancer who may benefit most from raloxifene. If confirmed, this suggests that measuring estradiol and treating women with high estradiol levels could substantially reduce the rate of breast cancer among postmenopausal women.      

Mental health symptoms following war and repression in eastern Afghanistan

Context  Decades of armed conflict, suppression, and displacement resulted in a high prevalence of mental health symptoms throughout Afghanistan. Its Eastern province of Nangarhar is part of the region that originated the Taliban movement. This may have had a distinct impact on the living circumstances and mental health condition of the province's population. Objectives  To determine the rate of exposure to traumatic events; estimate prevalence rates of symptoms of posttraumatic stress disorder (PTSD), depression, and anxiety; identify resources used for emotional support and risk factors for mental health symptoms; and assess the present coverage of basic needs in Nangarhar province, Afghanistan. Design, Setting, and Participants  A cross-sectional multicluster sample survey of 1011 respondents aged 15 years or older, conducted in Nangarhar province during January and March 2003; 362 households were represented with a mean of 2.8 respondents per household (72% participation rate). Main Outcome Measures  Posttraumatic stress disorder symptoms and traumatic events using the Harvard Trauma Questionnaire; depression and general anxiety symptoms using the Hopkins Symptom Checklist; and resources for emotional support through a locally informed questionnaire. Results  During the past 10 years, 432 respondents (43.7%) experienced between 8 and 10 traumatic events; 141 respondents (14.1%) experienced 11 or more. High rates of symptoms of depression were reported by 391 respondents (38.5%); anxiety, 524 (51.8%); and PTSD, 207 (20.4%). Symptoms were more prevalent in women than in men (depression: odds ratio [OR], 7.3 [95% confidence interval {CI}, 5.4-9.8]; anxiety: OR, 12.8 [95% CI, 9.0-18.1]; PTSD: OR, 5.8 [95% CI, 3.8-8.9]). Higher rates of symptoms were associated with higher numbers of traumas experienced. The main resources for emotional support were religion and family. Medical care was reported to be insufficient by 228 respondents (22.6%). Conclusions  In this survey of inhabitants of Nangarhar province, Afghanistan, prevalence rates of having experienced multiple traumatic events and having symptoms of anxiety, depression, and PTSD were high. These findings suggest that mental health symptoms in this region should be addressed at the population and primary health care level.      

Anxiety, depression, and posttraumatic stress in Iranian survivors of chemical warfare

Context  In the 1980-1988 Iran-Iraq War, extensive use of chemical weapons resulted in high rates of morbidity and mortality. While much is known about the physical consequences of chemical warfare, there is a paucity of information about the long-term effects of chemical attacks on mental health. Objective  To assess the long-term psychological impact of chemical warfare on a civilian population. Design, Setting, and Participants  Cross-sectional randomized survey conducted in July 2004 of 153 civilians in 3 towns exposed to warfare in northwestern Iran: Oshnaviyeh (low-intensity conventional warfare), Rabat (high-intensity conventional warfare), and Sardasht (both high-intensity conventional warfare and chemical weapons). Main Outcome Measures  Full or partial posttraumatic stress disorder (PTSD) diagnosis, anxiety symptoms, and depressive symptoms were assessed using Farsi versions of the Clinician-Administered PTSD Scale, Hamilton Scale for Anxiety, and Beck Depression Inventory, respectively. Results  Overall participation rate was 93%. Respondents had a mean age of 45 years and were all of Kurdish ethnicity. Among individuals exposed to both high-intensity warfare and chemical weapons, prevalence rates for lifetime PTSD, current PTSD, major anxiety symptoms, and severe depressive symptoms were 59%, 33%, 65%, and 41%, respectively. Among the low-intensity warfare group, the corresponding rates were 8%, 2%, 18%, and 6%, respectively, while intermediate rates were found among those exposed to high-intensity warfare but not to chemical weapons (31%, 8%, 26%, and 12%, respectively). Compared with individuals exposed to low-intensity warfare, those exposed to both high-intensity warfare and chemical weapons were at higher risk for lifetime PTSD (odds ratio [OR], 18.6; 95% confidence interval [CI], 5.8-59.4), current PTSD (OR, 27.4; 95% CI, 3.4-218.2), increased anxiety symptoms (OR, 14.6; 95% CI, 6.0-35.6), and increased depressive symptoms (OR, 7.2; 95% CI, 3.3-15.9). Exposure to high-intensity warfare but not to chemical weapons was also significantly associated with lifetime PTSD (OR, 5.4; 95% CI, 1.7-17.6), compared with those in the low-intensity warfare group. Further, compared with individuals exposed to high-intensity warfare alone, those exposed to both high-intensity warfare and chemical weapons were at higher risk for lifetime PTSD (OR, 3.4; 95% CI, 1.5-7.4), current PTSD (OR, 6.2; 95% CI, 2.0-20.1), increased anxiety symptoms (OR, 5.6; 95% CI, 2.5-12.6), and increased depressive symptoms (OR, 3.7; 95% CI, 1.8-7.2). Conclusion  Exposure to chemical warfare is an extreme traumatic event that has long-lasting adverse consequences on mental health.      

Effect of breast augmentation on the accuracy of mammography and cancer characteristics

Context  Breast augmentation is not associated with an increased risk of breast cancer; however, implants may interfere with the detection of breast cancer thereby delaying cancer diagnosis in women with augmentation. Objective  To determine whether mammography accuracy and tumor characteristics are different for women with and without augmentation. Design, Setting, and Participants  A prospective cohort of 137 women with augmentation and 685 women without augmentation diagnosed with breast cancer between January 1, 1995, and October 15, 2002, matched (1:5) by age, race/ethnicity, previous mammography screening, and mammography registry, and 10 533 women with augmentation and 974 915 women without augmentation and without breast cancer among 7 mammography registries in Denver, Colo; Lebanon, NH; Albuquerque, NM; Chapel Hill, NC; San Francisco, Calif; Seattle, Wash; and Burlington, Vt. Main Outcome Measures  Comparison between women with and without augmentation of mammography performance measures and cancer characteristics, including invasive carcinoma or ductal carcinoma in situ, tumor stage, nodal status, size, grade, and estrogen-receptor status. Results  Among asymptomatic women, the sensitivity of screening mammography based on the final assessment was lower in women with breast augmentation vs women without (45.0% [95% confidence interval {CI}, 29.3%-61.5%] vs 66.8% [95% CI, 60.4%-72.8%]; P = .008), and specificity was slightly higher in women with augmentation (97.7% [95% CI, 97.4%-98.0%] vs 96.7% [95% CI, 96.6%-96.7%]; P<.001). Among symptomatic women, both sensitivity and specificity were lower for women with augmentation compared with women without but these differences were not significant. Tumors were of similar stage, size, estrogen-receptor status, and nodal status but tended to be lower grade (P = .052) for women with breast augmentation vs without. Conclusions  Breast augmentation decreases the sensitivity of screening mammography among asymptomatic women but does not increase the false-positive rate. Despite the lower accuracy of mammography in women with augmentation, the prognostic characteristics of tumors are not influenced by augmentation.      

Caloric restriction and incidence of breast cancer

Context  Restricting caloric intake is one of the most effective ways to extend lifespan and to reduce spontaneous tumor occurrence in experimental animals, but whether similar associations hold in humans has not been appropriately studied. Objective  To determine whether caloric restriction in early life reduces the risk of invasive breast cancer. Design, Setting, and Participants  Retrospective cohort study using data from the Swedish Inpatient Registry, the Swedish Cancer Registry, the Swedish Death Registry, and the Swedish Fertility Registry. Participants were 7303 Swedish women hospitalized for anorexia nervosa prior to age 40 years between 1965 and 1998. Women were excluded (n = 31) if they were diagnosed with cancer prior to their first discharge from hospitalization for anorexia nervosa. Main Outcome Measure  Incidence of invasive breast cancer. Results  Compared with the Swedish general population, women hospitalized for anorexia nervosa prior to age 40 years had a 53% (95% confidence interval [CI], 3%-81%) lower incidence of breast cancer; nulliparous women with anorexia nervosa had a 23% (95% CI, 79% higher to 75% lower) lower incidence, and parous women with anorexia nervosa had a 76% (95% CI, 13%-97%) lower incidence. Conlusions  Severe caloric restriction in humans may confer protection from invasive breast cancer. Low caloric intake prior to first birth followed by a subsequent pregnancy appears to be associated with an even more pronounced reduction in risk.      

Screen-and-treat approaches for cervical cancer prevention in low-resource settings: a randomized controlled trial

Context  Non–cytology-based screen-and-treat approaches for cervical cancer prevention have been developed for low-resource settings, but few have directly addressed efficacy. Objective  To determine the safety and efficacy of 2 screen-and-treat approaches for cervical cancer prevention that were designed to be more resource-appropriate than conventional cytology-based screening programs. Design, Setting, and Patients  Randomized clinical trial of 6555 nonpregnant women, aged 35 to 65 years, recruited through community outreach and conducted between June 2000 and December 2002 at ambulatory women’s health clinics in Khayelitsha, South Africa. Interventions  All patients were screened using human papillomavirus (HPV) DNA testing and visual inspection with acetic acid (VIA). Women were subsequently randomized to 1 of 3 groups: cryotherapy if she had a positive HPV DNA test result; cryotherapy if she had a positive VIA test result; or to delayed evaluation. Main Outcome Measures  Biopsy-confirmed high-grade cervical cancer precursor lesions and cancer at 6 and 12 months in the HPV DNA and VIA groups compared with the delayed evaluation (control) group; complications after cryotherapy. Results  The prevalence of high-grade cervical intraepithelial neoplasia and cancer (CIN 2+) was significantly lower in the 2 screen-and-treat groups at 6 months after randomization than in the delayed evaluation group. At 6 months, CIN 2+ was diagnosed in 0.80% (95% confidence interval [CI], 0.40%-1.20%) of the women in the HPV DNA group and 2.23% (95% CI, 1.57%-2.89%) in the VIA group compared with 3.55% (95% CI, 2.71%-4.39%) in the delayed evaluation group (P<.001 and P = .02 for the HPV DNA and VIA groups, respectively). A subset of women underwent a second colposcopy 12 months after enrollment. At 12 months the cumulative detection of CIN 2+ among women in the HPV DNA group was 1.42% (95% CI, 0.88%-1.97%), 2.91% (95% CI, 2.12%-3.69%) in the VIA group, and 5.41% (95% CI, 4.32%-6.50%) in the delayed evaluation group. Although minor complaints, such as discharge and bleeding, were common after cryotherapy, major complications were rare. Conclusion  Both screen-and-treat approaches are safe and result in a lower prevalence of high-grade cervical cancer precursor lesions compared with delayed evaluation at both 6 and 12 months. Trial Registration  http://clinicaltrials.gov Identifier: NCT00233727.