Comparative safety of conjugated estrogens/bazedoxifene versus estrogen/progestin combination hormone therapy among women in the United States: a multidatabase cohort study.

OBJECTIVE: To assess the risk of select safety outcomes including endometrial cancer, endometrial hyperplasia, and breast cancer among women using conjugated estrogens/bazedoxifene (CE/BZA) as compared with estrogen/progestin combination hormone therapy (EP). METHODS: We conducted a new-user cohort study in five US healthcare claims databases representing more than 92 million women. We included CE/BZA or EP new users from May 1, 2014, to August 30, 2019. EP users were propensity score (PS) matched to users of CE/BZA. Incidence of endometrial cancer, endometrial hyperplasia, breast cancer, and eight additional cancer and cardiovascular outcomes were ascertained using claims-based algorithms. Rate ratios (RR) and differences pooled across databases were estimated using random-effects models. RESULTS: The study population included 10,596 CE/BZA and 33,818 PS-matched EP new users. Rates of endometrial cancer and endometrial hyperplasia were slightly higher among CE/BZA users (1.6 and 0.4 additional cases per 10,000 person-years), although precision was limited because of small numbers of cases (endometrial cancer: RR, 1.50 [95% confidence interval {CI}, 0.79-2.88]; endometrial hyperplasia: RR, 1.69 [95% CI, 0.51-5.61]). Breast cancer incidence was lower in CE/BZA users (9.1 fewer cases per 10,000 person-years; RR, 0.79; 95% CI, 0.58-1.05). Rates of other outcomes were slightly higher among CE/BZA users, but with confidence intervals compatible with a wider range of possible associations. CONCLUSIONS: CE/BZA users might experience slightly higher rates of endometrial cancer and endometrial hyperplasia, and a lower rate of breast cancer, than EP users in the first years of use.

The epidemiology of gynaecologic health: contemporary opportunities and challenges.

The field of reproductive epidemiology has primarily focused on reproductive outcomes and gynaecologic cancers. The study of non-cancerous, gynaecologic conditions (eg, uterine fibroids, endometriosis) has not received serious treatment in existing epidemiology textbooks and reproductive epidemiology curricula. Further, these conditions do not neatly fit into the other common subdisciplines within epidemiology (eg, infectious disease, cardiovascular, injury and occupational epidemiology and so on). In this commentary, we identify and illustrate three critical challenges to advancing the epidemiologic research of non-cancerous, gynaecologic conditions. With greater investment and a patient-centred approach, epidemiology can advance knowledge about this critical area of human welfare.

Reasons for hormonal contraceptive use in a cohort of African-American women living in the Detroit area.

OBJECTIVES: To characterize reasons for hormonal contraceptive (HC) use in 1,455 African-American women, aged 23-35 years. STUDY DESIGN: The community-based cohort members were recruited from the Detroit, Michigan area in 2010-2012. HC history was collected via telephone interview. RESULTS: Seven percent reported HC use exclusively for non-contraceptive purposes, and 49% reported non-contraceptive reasons in addition to contraception. Non-contraceptive reasons were reported for all HC types, but were most common for combined oral contraceptives. Primary reasons were for irregular cycles, heavy bleeding, and pain. CONCLUSIONS: In this large cohort of Black women, HC use to treat menstrual problems was common. IMPLICATIONS: HCs were commonly used for both pregnancy prevention and management of menstrual symptoms, but some women used HCs exclusively for menstrual symptom relief. The importance for women of non-contraceptive reasons for HC use may not be adequately recognized, and published data on Black women's reasons for HC use remain limited.

A case-crossover analysis of the relationship of air pollution with out-of-hospital sudden unexpected death in Wake County, North Carolina (2013-2015).

Out-of-hospital sudden unexpected deaths are non-accidental deaths that occur without obvious underlying causes and may account for 10% of natural deaths before age 65. Short-term exposure to ambient air pollution is associated with all-cause (non-accidental) and cause-specific (e.g., cardiovascular) mortality, and with immediate exposures often yielding the highest magnitude risk estimates. Few studies have focused on short-term exposure to air pollution and sudden unexpected deaths. Using the University of North Carolina Sudden Unexpected Death in North Carolina population, we examine associations between short-term criteria air pollutant exposures with sudden unexpected deaths using a time-stratified case-crossover design, with data on criteria air pollutants from the Environmental Protection Agency's Air Quality System. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression with air pollutant exposures scaled to roughly inter-quartile ranges; models were adjusted for average temperature and relative humidity on event day and preceding 3 days. Potential for confounding by co-pollutants were examined in two pollutant models. ORs for PM2.5 at lag day 1 were elevated (adjusted OR for 5 µg/m3 increase: 1.17 (0.98, 1.40)), and were robust to co-pollutant adjustment. Elevated odds were observed for SO2 at lag day 0, and reduced odds for O3 at lag day 0; however, these associations were somewhat attenuated toward the null (SO2) or were not robust (O3) to co-pollutant adjustment. This analysis in a racially and socioeconomically diverse cohort, with a more inclusive definition of sudden unexpected death than is typically employed offers evidence that PM2.5 may be a clinically relevant trigger of sudden unexpected deaths in susceptible individuals.

Optimizing research in symptomatic uterine fibroids with development of a computable phenotype for use with electronic health records.

BACKGROUND: Women with symptomatic uterine fibroids can report a myriad of symptoms, including pain, bleeding, infertility, and psychosocial sequelae. Optimizing fibroid research requires the ability to enroll populations of women with image-confirmed symptomatic uterine fibroids. OBJECTIVE: Our objective was to develop an electronic health record-based algorithm to identify women with symptomatic uterine fibroids for a comparative effectiveness study of medical or surgical treatments on quality-of-life measures. Using an iterative process and text-mining techniques, an effective computable phenotype algorithm, composed of demographics, and clinical and laboratory characteristics, was developed with reasonable performance. Such algorithms provide a feasible, efficient way to identify populations of women with symptomatic uterine fibroids for the conduct of large traditional or pragmatic trials and observational comparative effectiveness studies. Symptomatic uterine fibroids, due to menorrhagia, pelvic pain, bulk symptoms, or infertility, are a source of substantial morbidity for reproductive-age women. Comparing Treatment Options for Uterine Fibroids is a multisite registry study to compare the effectiveness of hormonal or surgical fibroid treatments on women's perceptions of their quality of life. Electronic health record-based algorithms are able to identify large numbers of women with fibroids, but additional work is needed to develop electronic health record algorithms that can identify women with symptomatic fibroids to optimize fibroid research. We sought to develop an efficient electronic health record-based algorithm that can identify women with symptomatic uterine fibroids in a large health care system for recruitment into large-scale observational and interventional research in fibroid management. STUDY DESIGN: We developed and assessed the accuracy of 3 algorithms to identify patients with symptomatic fibroids using an iterative approach. The data source was the Carolina Data Warehouse for Health, a repository for the health system's electronic health record data. In addition to International Classification of Diseases, Ninth Revision diagnosis and procedure codes and clinical characteristics, text data-mining software was used to derive information from imaging reports to confirm the presence of uterine fibroids. Results of each algorithm were compared with expert manual review to calculate the positive predictive values for each algorithm. RESULTS: Algorithm 1 was composed of the following criteria: (1) age 18-54 years; (2) either ≥1 International Classification of Diseases, Ninth Revision diagnosis codes for uterine fibroids or mention of fibroids using text-mined key words in imaging records or documents; and (3) no International Classification of Diseases, Ninth Revision or Current Procedural Terminology codes for hysterectomy and no reported history of hysterectomy. The positive predictive value was 47% (95% confidence interval 39-56%). Algorithm 2 required ≥2 International Classification of Diseases, Ninth Revision diagnosis codes for fibroids and positive text-mined key words and had a positive predictive value of 65% (95% confidence interval 50-79%). In algorithm 3, further refinements included ≥2 International Classification of Diseases, Ninth Revision diagnosis codes for fibroids on separate outpatient visit dates, the exclusion of women who had a positive pregnancy test within 3 months of their fibroid-related visit, and exclusion of incidentally detected fibroids during prenatal or emergency department visits. Algorithm 3 achieved a positive predictive value of 76% (95% confidence interval 71-81%). CONCLUSION: An electronic health record-based algorithm is capable of identifying cases of symptomatic uterine fibroids with moderate positive predictive value and may be an efficient approach for large-scale study recruitment.

Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): A systematic review.

A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra-epithelial neoplasia (CIN). A total of 45 studies presented data on post-treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon-alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow-up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow-up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post-treatment HPV persistence estimates varied widely and were influenced by patient age, HPV-type, detection method, treatment method, and minimum HPV post-treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post-treatment HPV DNA testing practices and persistence estimates.

Differences between health and ethical vegetarians. Strength of conviction, nutrition knowledge, dietary restriction, and duration of adherence.

Little research has been published concerning the differences between health oriented and ethically oriented vegetarians. The present study compared differences in conviction, nutrition knowledge, dietary restriction, and duration of adherence to vegetarianism between the two groups. Subjects completed an online survey and were grouped by original reason for becoming vegetarian (n=292, 58 health, 234 ethical), and current reason for remaining vegetarian (n=281, 49 health, 232 ethical). Whether grouped by current or original motivation, ethical vegetarians scored higher on the conviction instrument than health vegetarians and exhibited somewhat greater dietary restriction (significant when grouped by current motivation) and had been vegetarian for longer (significant when grouped by original motivation). Nutrition knowledge did not differ between the two groups. The results suggest that ethical vegetarians could experience stronger feelings of conviction and consume fewer animal products than health vegetarians, and may remain vegetarian longer. More research is necessary to understand how vegetarians' eating behaviors are influenced by their motivational profiles.