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Purpose: Patients injected with thorotrast, a radiologic contrast medium used from the 1920s to early 1950s, received chronic internal exposure to thorium-232, an α-emitter. Epidemiologic studies have observed markedly elevated risks of death from hepatic and hematologic cancers and extensive chromosomal damage among these patients. Few investigations have correlated multiple measures of genetic damage to determine whether these have independent induction kinetics. The distribution of chromosomal aberrations (CA) and mutant frequencies (MF) at the hypoxanthine phosphoribosyltransferase (hprt) locus was evaluated in eight long-term thorotrast survivors (mean exposure time = 47.4 years) and five individuals who received a nonradioactive contrast medium during the same era. ::Materials and methods: Peripheral blood lymphocytes were harvested from whole blood, CA were scored in 500 complete metaphases and a clonal assay was used to determine hprtMF. Symmetrical aberrations were not evaluated. Differences in frequencies and correlations between endpoints were assessed using nonparametric methods. ::Results: Thorotrast-exposed individuals differed from the comparison group in total number of multicentrics and centric and acentric rings (per 500 cells [median, mean +/- sd]: 11, 18.3 +/- 23.1 vs 2, 2.4 +/- 1.1, p = 0.04). There was no difference between the groups on hprtMF (12.6, 15.9 +/- 13.5 vs 16.6, 14.0 +/- 8.8 [x10[sup -6] ]; p = 1.0). Among the exposed, hprtMF was moderately correlated with the frequency of asymmetrical chromosomal aberrations, although the association was not statistically significant. ::Conclusion: Noting the limitations of small samples, long-term thorotrast survivors were observed to be at an increased risk for genetic damage. [ABSTRACT FROM AUTHOR]

Background and Objectives: To assess gender disparities in neurology researcher careers in the United States., Methods: A 34-question survey was distributed to 4,644 US-based American Academy of Neurology members who self-identified as researchers in 2020 addressing the following domains: research and funding, scholarly activities, coronavirus disease 2019 (COVID-19) effect, and local institutional climate., Results: A total of 700 (15%) individuals completed the survey (women, n = 231; men, n = 426), with 71% White and >80% conducting research. Women respondents were significantly younger than men, more likely to be assistant professors (32% vs 21%), and less likely to be full professors (18% vs 39%). Compared with men, women received equivalent grants and research support and had comparable or additional formal research training and mentorship. Women had less middle author publications (mean 5.8 [SD 9.2] vs mean 8.2 [SD 11.8], p = 0.03) compared with men but similar first or last author publications (mean 4.3[5.4] vs 6.1 [9.8], p = 0.05). A lower proportion of women presented research at grand rounds or at a national/international conference compared with men (58% vs 69%, p = 0.01). Women spent more time in nonprofessional responsibilities, were less satisfied with their work-life balance, and were less likely to agree with statements addressing equity/diversity and institutional climate. Respondents shared their concerns regarding how the pandemic was affecting neurology research careers, with a higher proportion of women reporting that family responsibilities affected research activities and lead to delayed submission of non-COVID-19-related manuscripts., Discussion: Our survey of US-based neurology researchers demonstrated continued gender-based disparities in academic rank, manuscript authorship, and invited speaking engagements, although funding opportunities and access to additional training were equivalent. Women were less likely than men to agree that neurology departments support diversity and equity and that the institutional climate was inclusive and transparent. The pandemic had affected both genders in research, but areas were different for women related to family responsibilities. This article also highlights additional areas of research and areas for intervention to improve and reduce gender disparities among neurology researchers., (© 2022 American Academy of Neurology.)

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common physical and psychosocial consequences of cancer and cancer treatment to help healthcare professionals who work with survivors of adult-onset cancer in the posttreatment period. This portion of the guidelines describes recommendations regarding the management of anthracycline-induced cardiotoxicity and lymphedema. In addition, recommendations regarding immunizations and the prevention of infections in cancer survivors are included., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Objective: To study and provide an update on the state of clinical research in neurology in the United States., Methods: US American Academy of Neurology members and chairs of departments of neurology were surveyed regarding clinical research in 2016. NIH data on the neuroscience pipeline and extramural grant funding were also collected., Results: The response rate was 32% (n = 254) for nonchair researchers and 58% (n = 67) for department chairs. Researcher respondents were on average 50 years old, 66% were men, and 81% were actively conducting clinical research, with phase II/III clinical trials and outcome measure studies being the most common type of research conducted. Time to conduct research, recruitment, and administrative burden were the major barriers reported. According to department chairs, funding and training opportunities in patient-oriented research have increased over the last 10 years. Overall, applicants to neuroscience-specific NIH institutes for extramural funding have decreased over the same time period., Conclusions: The state of clinical research in neurology has remained relatively stable over the last 10 years, but neurologists still have barriers in conducting clinical research. There has been an interval decrease in neuroscience applicants for NIH funding, which raises concerns about the pipeline and future of clinical research in neurology. These results will serve as a reference for the development of solutions to these issues., (© 2018 American Academy of Neurology.)

Introduction: It is accepted that newborns lose weight in the first few days of life. Baby-Friendly practices that support breastfeeding may affect newborn weight loss. The objective of this study were: 1) To determine whether Baby-Friendly practices are associated with term newborn weight loss day 0-2 in three feeding categories (exclusively breastfed, mixed formula fed and breastfed, and formula fed). 2) To determine whether Baby-Friendly practices increase exclusive breast feeding rates in different ethnic populations., Materials and Methods: This was a retrospective case-control study. Term newborn birth weight, neonatal weights days 0-2, feeding type, type of birth, and demographic information were collected for 1,000 births for the year before Baby-Friendly designation (2010) and 1,000 in 2013 (after designation). Ultimately 683 in the first group and 518 in the second met the inclusion criteria., Results: Mean weight loss decreased day 0-2 for infants in all feeding types after the initiation of Baby-Friendly practices. There was a statistically significant effect of Baby-Friendly designation on weight loss for day 0-2 in exclusively breastfed infants (p < 0.01) after controlling for birth weight. Exclusive breast feeding increased in all ethnic groups after Baby-Friendly practices were put in place., Conclusion: There was a decrease in mean weight loss day 0-2 regardless of feeding type after Baby-Friendly designation. Exclusive breast feeding increased in the presence of Baby-Friendly practices.

Background: Atopic, eosinophilic, and TH2-high asthma phenotypes may overlap, but the extent is unknown. Understanding the overlap across these phenotypes may be useful in guiding asthma patient care., Objective: To examine the frequency and overlap of atopic, eosinophilic, and TH2-high asthma phenotypes., Methods: We analyzed 2005 to 2006 data from the National Health and Nutrition Examination Survey. Patients with asthma were identified based on the participant self-report. Eosinophilic asthma was defined as a blood eosinophil cutoff point of ≥150, 300, or 400/μL. Atopic asthma was defined as having an allergen-specific IgE level of ≥0.35 IU/mL for any of the 9 perennial allergens tested. TH2-high asthma was defined as a total serum IgE of ≥100 IU/mL and a blood eosinophil count of ≥140/μL., Results: The study included 269 children and 310 adults. Depending on the eosinophil cutoff used, 31% to 78% of children and 21% to 69% of adults with asthma were classified as having eosinophilic asthma. In addition, 63% of children and 61% of adults were classified as having atopic disease and 48% of children and 37% of adults as having TH2-high asthma. At a higher eosinophil cutoff point, a greater proportion of eosinophilic asthma can be classified as atopic or TH2 high, but a lower proportion of atopic or TH2-high asthma can be classified as eosinophilic. Approximately 70% or more of children and adults with asthma were 1 of these 3 phenotypes., Conclusion: A considerable overlap among eosinophilic, atopic, and TH2-high asthma phenotypes exists in a general asthma population., (Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The nation is faced with a shortage of subspecialty physicians, including burn surgeons. Exposure to a specialty in medical school has been shown to influence students' career choices. The authors postulate that exposure to burn surgery increases their interest in the field. Students from a medical school with an American Burn Association-verified burn center and from a school without a burn center were anonymously surveyed and asked to report their interest and knowledge regarding burn surgery using a 5-point Likert scale. They were asked about their current year in school, gender, overall interest in surgery, and any prior exposure to burn surgery (eg, preceptorship or rotation). Students were asked whether exposure to burn surgery or to a strong mentor might increase their interest in the field. Finally, they were asked to pick the most important factor in a list of deterrents to pursuing a career in burn surgery. Predictors of interest in burn surgery were determined with regression analyses. A total of 380 of 662 students responded to the survey (57.4%). Significant predictors of interest in burn surgery were an interest in surgery (P < .001, odds ratio [OR] = 56.3), prior exposure to burn surgery (P = .02, OR = 5.7), and year in school (P = .006, OR = 1.7). First- and second-year students were more likely to report interest in burn surgery (P < .001). Gender and medical school attended were not significant predictors. Prior exposure to burn surgery became a stronger predictor in subgroup analysis of the fourth-year students (P < .001, OR = 24.5). The majority of students reported that exposure to burn surgery (76%) and a strong mentor (87%) would make them more likely to consider burn surgery as a career. "Not interested in surgery" was the most important deterrent to pursuing a career in burn surgery, which was selected by 33% of students. However, 25% of students chose "I don't know anything about burn surgery" as the most important deterrent. Factors specific to burn surgery were less frequently selected (eg, wound care and hot operating room). The majority of students reported ignorance of the field of burns: 64% disagreed that they understood what a burn surgeon does on a daily basis, and 74% agreed they did not know enough about the field to consider it as a career. Exposure to burn surgery in the form of a clinical rotation fosters medical student interest. However, the majority of medical students lack knowledge about the field of burn surgery. Many consider this a deterrent to selecting it as a career. More exposure during medical school and strong mentorship may influence more students to become burn surgeons. Mentorship and recruiting efforts should be focused on students with a general interest in surgery.

Background: The residual risk of hepatitis B is higher than for other markers such as human immunodeficiency virus and hepatitis C virus in nonendemic countries. Evaluating the potential for further risk reduction requires a better understanding of the relationship between donor selection criteria, immigration from endemic countries, and public health vaccination strategies., Study Design and Methods: Age and sex trends of hepatitis B surface antigen (HBsAg)-positive donors from 1997 to 2006 were analyzed using a Poisson model. All HBsAg-positive donors in 2005/2006 plus four matched control donors for every HBsAg-positive donor who participated were invited to participate in a risk factor interview and predictors of HBsAg positivity identified by logistic regression. A survey of 40,000 donors who did not react for all markers asked about vaccination history and country of birth., Results: Most HBsAg-positive donations were from first-time donors (86%), have been decreasing in donors under the age of 30 (p < 0.01), and were correlated with geographic regions with more donors from higher-prevalence countries (p < 0001). Birth in a higher-prevalence country predicted HBsAg positivity (p < 0.01). Fifty-six percent of donors reported being vaccinated for hepatitis including approximately 80 percent of donors under age 30 who reported being vaccinated as part of regular school programs., Conclusion: HBsAg-positive donations are decreasing in donors under age 30, those most frequently vaccinated through provincial vaccination programs. HBsAg-positive donations largely reflect immigration from high-prevalence countries without other deferrable risk factors, mainly chronic cases that will be detected by current testing. Furthermore, risk of incident infections should decrease with increasing vaccination rates in donors, especially the younger cohort now receiving universal vaccination.

HLA-B*5701 testing to provide risk stratification for abacavir hypersensitivity has the potential to reduce incidence of hypersensitivity reactions in susceptible individuals. Early experience with clinical HLA-B*5701 testing of the first 100 specimens, from a large clinical reference laboratory in the United States, is presented. Patient samples were tested using a two-step approach. The first step allowed rapid identification of most HLA-B*5701-negative samples in a high throughput mode. The second step involved resolution of putative positives by DNA sequencing to identify B*5701 specifically as well as other B57 subtypes. Test reporting included a phone call from a genetic counselor to obtain the ethnic background and indication for testing and to provide a patient-specific interpretation. The patients population was comprised of Caucasians, 84%; Hispanics, 13%; and African Americans, 3%. Among the 100 samples tested, 92% were HLA-B*5701-negative and 8% were positive for the HLA-B*5701 allele. All HLA-B*5701 allele positives were identified in Caucasian patients. Where the indication for testing was obtainable (57 patients), pre-abacavir therapy screening was the indication 67% of the time. Clarification of previous suspected history of hypersensitivity was the indication 33% of the time. Among samples tested to help clarify a previous history of hypersensitivity, 16/19 or 84% did not carry the HLA-B*5701 allele whereas 3/19 (16%) were carriers of the HLA-B*5701 allele. Early utilization of HLA-B*5701 testing in community practice was not always consistent with the clinical indications for testing. Post-test communication assisted in providing physician education and interpretation of patient-specific results.

Background: Obstructive sleep apnea (OSA) is a common medical condition with significant adverse consequences, but OSA remains undiagnosed in many individuals. The Berlin questionnaire is a validated instrument that is used to identify individuals who are at risk for OSA., Design: We conducted an analysis of data from the Sleep in America 2005 Poll of The National Sleep Foundation (NSF). The NSF poll is an annual telephone interview of a representative sample of US adults., Participants: The 2005 NSF poll included 1,506 adults. The mean age of participants was 49 years (775 were women)., Measurements: The Berlin questionnaire was embedded in the NSF poll. This instrument includes questions about snoring, witnessed apneas, self-reported hypertension, and daytime sleepiness. Height and weight were included for the calculation of body mass index (BMI). The NSF poll included detailed demographic information and extensive questions related to all aspects of sleep., Results: Of the 1,506 respondents, 26% (31% of men and 21% of women) met the Berlin questionnaire criteria indicating a high risk of OSA. The risk of OSA increased up to age 65 years. A significant number of obese individuals (57%) were at high risk for OSA. Those whose Berlin questionnaire scores indicated a high risk for OSA were more likely to report subjective sleep problems, a negative impact of sleep on quality of life, and a chronic medical condition than those who were at lower risk., Conclusions: As many as one in four American adults could benefit from evaluation for OSA. Considering the serious adverse health and quality-of-life consequences of OSA, efforts to expedite diagnosis and treatment are indicated.

Background: No nationally accepted set of quality indicators exists in obstetrics. A set of 10 outcome measures and three quality improvement tools was developed as part of a study evaluating the effects of teamwork on obstetric care in 15 institutions and > 28,000 patients. Each outcome was assigned a severity weighting score., Measures: Three new obstetrical quality improvement outcome tools were developed. The Adverse Outcome Index (AOI) is the percent of deliveries with one or more adverse events. The average AOI during the pre-implementation data collection period of the teamwork study was 9.2% (range, 5.9%-16.6%). The Weighted Adverse Outcome Score (WAOS) describes the adverse event score per delivery. It is the sum of the points assigned to cases with adverse outcomes divided by the number of deliveries. The average WAOS for the preimplementation period was 3 points (range, 1.0-6.0). The Severity Index (SI) describes the severity of the outcomes. It is the sum of the adverse outcome scores divided by the number of deliveries with an identified adverse outcome. The average SI for the pre-implementation period was 31 points (range, 16-49)., Discussion: The outcome measures and the AOI, WAOS, and SI can be used to benchmark ongoing care within and among organizations. These tools may be useful nationally for determining quality obstetric care.

Definitive approaches to most infectious diseases following renal transplantation have not been established, leading to different approaches at different transplant centers. To study the extent of these differences, we conducted a survey of the practices surrounding specific infectious diseases at US renal transplant centers. A survey containing 103 questions covering viral, bacterial, mycobacterial and protozoal infections was developed. Surveys were sent to program directors at all U.S. renal transplant centers. Responses were received from 147 of 245 (60%) transplant centers and were proportionately represented all centers with respect to program size and geographical location. Pre-transplant donor and recipient screening for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and cytomegalovirus (CMV) is uniform, but great discrepancy exists in the testing for other agents. HCV seropositive donors are used in 49% of centers. HIV seropositivity remains a contraindication to transplantation, although 13% of centers indicated they have experience with such patients. Post-transplant, there is wide variety in approach to CMV and Pneumocystis carinii (PCP) prophylaxis. Similarly divergent practices affect post-transplant vaccinations, with 54% of centers routinely vaccinating all patients according to customary guidelines in non-transplant populations. In contrast, 22% of centers indicated they do not recommend vaccination in any patients. We believe an appreciation of the differences in approaches to post-transplant infectious complications may encourage individual centers to analyse the results of their own practices. Such analysis may assist in the design of studies to answer widespread and important questions regarding the care of patients following renal transplantation.

There are few studies on the long-term sequelae of radionuclides ingested or injected into the human body. Patients exposed to radioactive Thorotrast in the 1930s through the early 1950s provide a singular opportunity, since the administration of this radiographic contrast agent resulted in continuous exposure to alpha particles throughout life at a low dose rate. We evaluated cause-specific mortality among an international cohort of 3,143 patients injected during cerebral angiography with either Thorotrast (n = 1,736) or a similar but nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized mortality ratios (SMRs) for Thorotrast and comparison patients were calculated, and relative risks (RR), adjusted for population, age and sex, were obtained by multivariate statistical modeling. Most patients were followed until death, with only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the study. All-cause mortality (n = 1,599 deaths) was significantly elevated among Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly increased relative risks were found for several categories, including cancer (RR 2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and benign liver disorders (RR 6.5). Nonsignificant increases were seen for respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The relative risk due to all causes increased steadily after angiography to reach a threefold RR at 40 or more years (P < 0.001). Excess cancer deaths were observed for each decade after Thorotrast injection, even after 50 years (SMR 8.6; P < 0.05). Increasing cumulative dose of radiation was directly associated with death due to all causes combined, cancer, respiratory disease, benign liver disease, and other types of digestive disease. Our study confirms the relationship between Thorotrast and increased mortality due to cancer, benign liver disease, and benign hematological disease, and suggests a possible relationship with respiratory disorders and other types of digestive disease. The cumulative excess risk of cancer death remained high up to 50 years after injection with >20 ml Thorotrast and approached 50%.

To investigate whether factors influencing ovarian function affect risk of uterine leiomyomata, we examined prospectively the association of new diagnoses confirmed by ultrasound or hysterectomy with body mass index, weight change, height, and cigarette smoking among 94,095 premenopausal women with intact uteri, who were ages 25-42 years at the start of follow-up in 1989. We assessed body mass index and cigarette smoking from responses on the study questionnaire completed just before diagnosis. During 322,775 person-years, 2,967 new cases of uterine leiomyomata confirmed by ultrasound or hysterectomy were reported. Risk among all cases confirmed by ultrasound or hysterectomy increased with increasing adult body mass index. The multivariate relative risks (RR) and 95% confidence intervals (CI) according to body mass index categories of <20.0, 20.0-21.9, 22.0-23.9, 24.0-25.9, 26.0-27.9, 28.0-29.9, and > or =30.0 were 0.90 (95% CI = 0.79-1.03), 1.00 (referent), 1.08 (95% CI = 0.97-1.21), 1.16 (95% CI = 1.03-1.31), 1.21 (95% CI = 1.05-1.40), 1.36 (95% CI = 1.16-1.59), and 1.23 (95% CI = 1.09-1.39), respectively. The RRs for hysterectomy-confirmed cases generally were higher. Similarly, risk was positively associated with weight gain since age 18 years. Body mass index at age 18 years, height, and cigarette smoking were unrelated to risk of uterine leiomyomata. Elevated adult body mass index is associated with a modest increased risk of uterine leiomyomata among premenopausal women.

Objective: To quantify the incidence of uterine leiomyoma confirmed by hysterectomy, ultrasound, or pelvic examination according to age and race among premenopausal women., Methods: From September 1989 through May 1993, 95,061 premenopausal nurses age 25-44 with intact uteri and no history of uterine leiomyoma were followed to determine incidence rates of uterine leiomyoma. The self-reported diagnosis was confirmed in 93% of the medical records obtained for a sample of cases. Using pooled logistic regression, we estimated relative risks (RRs) of uterine leiomyoma according to race and examined whether adjustment for other potential risk factors could explain the variation in the race-specific rates., Results: During 327,065 woman-years, 4181 new cases of uterine leiomyoma were reported. The incidence rates increased with age, and the age-standardized rates of ultrasound- or hysterectomy-confirmed diagnoses per 1000 woman-years were 8.9 among white women and 30.6 among black women. After further adjustment for marital status, body mass index, age at first birth, years since last birth, history of infertility, age at first oral contraceptive use, and current alcohol consumption, the rates among black women were significantly greater for diagnoses confirmed by ultrasound or hysterectomy (RR 3.25; 95% confidence interval [CI] 2.71, 3.88) and by hysterectomy (RR 1.82; 95% CI 1.17, 2.82) compared with rates among white women. We observed similar RRs when the cohort was restricted to participants who reported undergoing a screening physical examination within the 2 years before baseline., Conclusion: A higher prevalence of known risk factors did not explain the excess rate of uterine leiomyoma among premenopausal black women.

African-Americans and probably Latinos are at increased risk of stroke compared with white, non-Latino Americans. This study seeks to determine if the known risk factors for stroke can account for this increased risk. In this case-control study controls (neighborhood volunteers) were group-matched to acute stroke cases by ethnicity in a ratio of approximately 2:1 for African-Americans and Latinos and 1:1 for whites. Extensive historical, clinical and laboratory data were collected on each subject. For each ethnic group cases were somewhat older and less well-educated than the volunteer controls. Patients in each ethnic group were similar with regard to time from stroke onset to hospital admission, stroke severity, length of stay, discharge disposition and mortality rate. With minor exceptions the distributions of stroke subtypes within each ethnic group appeared similar to those previously reported. Subject recruitment for this case-control study was completed in the manner and time frame planned. Analysis of risk factor information from this sample should provide valuable information regarding the relative risk associated with the major modifiable risk factors for stroke in the minority groups studied.

Background: Telangiectatic matting and hyperpigmentation are some of the most commonly observed side effects of sclerotherapy. Cutaneous necrosis is relatively rare and often of limited sequelae but most commonly related to extravasation of sclerosant. Physicians treating varicosities and telangiectasia by sclerotherapy must be familiar with causes and means for minimization of all three side effects., Objective: This review article discusses the proposed etiology, risk factors, approach for minimizing, and suggested treatment for the three side effects of cutaneous necrosis, telangiectatic matting, and hyperpigmentation., Results: Cutaneous necrosis may occur with the injection of any sclerosing agent even under ideal circumstances and does not necessarily represent physician error. When sclerosant extravasation occurs, dilution must occur immediately. Telangiectatic matting is a recognized complication occurring in approximately 15-20% of patients treated by sclerotherapy. Although the exact mechanism of the phenomena remains unknown, reactive inflammatory and/or angiogenic mechanisms are felt to play a role. Patients are advised that telangiectatic matting is usually not permanent and usually resolves spontaneously in 3-12 months. Postsclerosis pigmentation is defined as the appearance of persistent, increased pigmentation running the course of an ectatic blood vessel treated by sclerotherapy. The general incidence of hyperpigmentation ranges from 10 to 30%. Although hyperpigmentation may persist for months, its presence rarely deters patients from continuing treatment. Spontaneous resolution occurs in 70% at 6 months with 99% resolution occurring within 1 year., Conclusions: With understanding the etiology, risk factors, and ways to minimize these side effects our goal is to reduce their incidence. Attempting prevention may ultimately be the most effective means of treatment. Dermatol Surg 1995;21:19-29., Learning Objectives: After studying the following article, participant should be able to: 1. Understand the definition and potential causes of cutaneous necrosis, telangiectatic matting, and hyperpigmentation following sclerotherapy. 2. Advise patients prior to treatment on the common risks involved in sclerotherapy and to advise them on the relative incidence. 3. Understand the concept of minimal sclerosant concentration and how it can help the physician to choose sclerosing solution concentrations to minimize risks.

Sudden infant death syndrome is the leading cause of death for infants between one month and one year of age. Studies outside the US have shown that a change in infant sleep position is connected to a significant decrease in the SIDS rate. This information has lead to an educational campaign in this country to promote back and side sleeping for healthy infants.

Several studies have examined the association between body mass index and infertility. We compared body mass index in 597 women diagnosed with ovulatory infertility at seven infertility clinics in the United States and Canada with 1,695 primiparous controls who recently gave birth. The obese women (body mass index > or = 27) had a relative risk of ovulatory infertility of 3.1 [95% confidence interval (CI) = 2.2-4.4], compared with women of lower body weight (body mass index 20-24.9). We found a small effect in women with a body mass index of 25-26.9 or less than 17 [relative risk (RR) = 1.2, 95% CI = 0.8-1.9; and RR = 1.6, 95% CI = 0.7-3.9, respectively). We conclude that the risk of ovulatory infertility is highest in obese women but is also slightly increased in moderately overweight and underweight women.

Background: Children diagnosed with retinoblastoma, a rare cancer of the eye, tend to develop and die of second primary cancers in childhood and adolescence, but few investigations have followed patients into adulthood. Retinoblastoma is frequently caused by inherited mutations of the RB1 tumor suppressor gene. Most patients with germline (hereditary) mutations have bilateral disease., Purpose: We sought to quantify the mortality from second malignancies among long-term survivors of retinoblastoma and to identify factors that predispose to these deaths., Methods: A retrospective cohort study examined mortality among 1603 patients enrolled at 1 year after diagnosis of retinoblastoma during the period 1914-1984. Data on demography, family history, and retinoblastoma treatment were collected by medical chart review and questionnaire interview. Number of deaths, by cause, was compared with the corresponding expected figure based on U.S. mortality data for the general population for 1925-1990., Results: Follow-up was complete for 1458 patients (91%) for a median of 17 years after retinoblastoma diagnosis. A total of 305 deaths occurred, 167 of them from retinoblastoma. There were 96 deaths from second primary tumors (relative risk [RR] = 30), 21 from other known causes (RR = 1.0), and 21 from ill-defined or unknown causes. Statistically significant excess mortality was found for second primary cancers of bone, connective tissue, and malignant melanoma and benign and malignant neoplasms of brain and meninges. Among 919 children with bilateral retinoblastoma, 90 deaths from second primary tumors occurred (RR = 60). Deaths from second tumors were more frequent among females (RR = 39) than males (RR = 22) (P = .007). The cumulative probability of death from second primary neoplasms was 26% at 40 years after bilateral retinoblastoma diagnosis, and additional cancer deaths occurred thereafter. Radiotherapy for retinoblastoma further increased the risk of mortality from second neoplasms. An excess of mortality from a second cancer, not seen in prior studies, was found among the 684 children with unilateral disease (RR = 3.1; 95% confidence interval = 1.0-7.3)., Conclusions: These findings implicate germinal mutations in the retinoblastoma gene in second cancer mortality. Radiotherapy treatment for retinoblastoma appears to further enhance the inborn susceptibility to development of a second cancer., Implications: Patients with retinoblastoma, particularly bilateral retinoblastoma, should have careful follow-up, and interventions should be developed to reduce mortality from a second cancer.

Over 1.5 billion prescriptions were filled by pharmacies in 1990, but little information exists on the effect that pharmaceutical agents have on female reproductive capacity. As part of a case-control study of risk factors for primary ovulatory infertility, we examined self-reported use of several prescription and nonprescription medications in 597 women with ovulatory infertility and 3,833 controls admitted for delivery at seven hospitals. Only women reporting use of a drug for at least 6 months, beginning before the onset of infertility in cases and before conception in controls, were considered exposed. An elevated risk of ovulatory infertility was found for women who ever used thyroid preparations [relative risk (RR) = 2.3, 95% confidence interval (CI) = 1.5-3.5] or antidepressants (RR = 2.9, 95% CI = 0.9-8.3), although the latter estimate was based on only five cases who reported having taken antidepressants. Current users of tranquilizers and ever-users for more than 2 years were also at greater risk of infertility than never-users (RR = 3.2, 95% CI = 1.1-8.5 and RR = 2.9, 95% CI = 0.8-11, respectively). Women who used asthma medication before age 21 had more than a twofold increase in risk of ovulatory infertility (RR = 2.5, 95% CI = 1.0-5.9).