Intramuscular depot medroxyprogesterone acetate accentuates bone loss associated with tenofovir disoproxil fumarate-containing antiretroviral therapy initiation in young women living with HIV (the BONE: CARE study): a prospective cohort study in Uganda.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) and intramuscular depot medroxyprogesterone acetate (DMPA-IM) are independently associated with reduced bone mineral density (BMD). We aimed to assess the combined effects of DMPA-IM use and TDF initiation on BMD in young adult women living with HIV over two years, compared with age-matched people without HIV. METHODS: Th BONE: CARE study was a prospective cohort study that recruited women aged 18-35 years from 11 HIV care and general health facilities in Kampala, Uganda. The participants were classified into four groups on the basis of their combination of HIV status, TDF use, and DMPA-IM use, as follows: women living with HIV initiating TDF-containing antiretroviral therapy (ART) with DMPA-IM (HIV positive, DMPA positive, and TDF positive); women living with HIV using DMPA-IM but not eligible for ART as per local guidelines at the time of enrolment into the study (HIV positive, DMPA positive, and TDF negative); women living with HIV initiating TDF-containing ART without DMPA-IM (HIV positive, DMPA negative, and TDF positive); and controls without HIV using non-hormonal contraceptives (HIV negative, DMPA negative, and TDF negative). BMD of the lumbar spine, total hip, and femoral neck were measured using semiannual dual-energy x-ray absorptiometry at enrolment and at intervals every 6 months thereafter. We assessed percentage change in mean BMD. FINDINGS: Between March 30, 2016, and Oct 19, 2017, we enrolled 265 women living with HIV initiating ART (159 DMPA-IM users and 106 non-hormonal contraceptive users), 187 women living with HIV using DMPA-IM but not ART, and 69 controls without HIV. Mean age was 26·1 years (SD 4·2). BMD declined significantly from baseline in women living with HIV on TDF with versus without DMPA-IM at the lumbar spine (-3·406% [95% CI -3·969 to -2·844] vs -1·111% [-1·929 to -0·293]; p<0·0001), total hip (-3·856% [-4·449 to -3·264] vs -1·714% [-2·479 to -0·949]; p=0·0002), and femoral neck (-4·422% [-5·078 to -3·766] vs -1·999% [-3·022 to -0·976]; p=0·0002), increased in controls at the lumbar spine (1·5% change), and remained unchanged at total hip and femoral neck (-0·1% change). Concurrent use of TDF and DMPA-IM resulted in significantly greater BMD decline (p<0·0001) than TDF alone (lumbar spine -2·677% [95% CI -3·743 to -1·611]; p<0·0001; total hip -2·518% [-3·575 to -1·461]; p<0·0001; and femoral neck -2·907 [-4·132 to -1·683]; p<0·0001) or than controls (lumbar spine -4·970% [-6·391 to -3·549]; p<0·0001; total hip -4·151% [-5·579 to -2·724]; p<0.0001; and femoral neck -4·773% [-6·424 to -3·122]; p<0·0001) INTERPRETATION: Concomitant DMPA-IM use resulted in a doubling of BMD loss in women living with HIV initiating TDF-containing ART. Identification of safer contraceptive and bone-sparing ART options should be prioritised for optimal care of women living with HIV. FUNDING: National Institute of Allergy and Infectious Diseases of the US National Institutes of Health.

Bone Mineral Density in Antiretroviral Therapy-Naïve HIV-1-Infected Young Adult -Women Using Depot Medroxyprogesterone Acetate or Nonhormonal Contraceptives in Uganda.

Most studies evaluating BMD in human immunodeficiency virus (HIV)-infected populations have focused on antiretroviral therapy (ART)-experienced patients. In this study, the association between HIV-1 and/or depot medroxyprogesterone acetate (DMPA) and BMD among untreated HIV-1-infected women in a resource-limited setting was assessed before long-term exposure to ART. The data were then compared with that of the 2005-2008 United States National Health and Nutrition Examination Survey data for non-Hispanic White and Black women. Women aged 18-35 years, recruited from health facilities in Kampala, Uganda, were classified based on their combination of HIV-1 status and DMPA use: (i) HIV-1-infected current DMPA users, (ii) HIV-1-infected previous DMPA users, (iii) HIV-1-infected nonhormonal-contraceptive users, and (iv) HIV-uninfected nonhormonal-contraceptive users. All HIV-1-infected women reported being ART-naïve at baseline. BMD was measured at the lumbar spine, total hip, and femoral neck using DXA. Multivariate linear regression was used to assess the association between HIV-1 and/or DMPA and BMD Z-scores. Baseline data were analyzed for 452 HIV-1-infected (220 nonhormonal users, and 177 current and 55 previous DMPA users) and 69 HIV-1-uninfected nonhormonal-contraceptive users. The mean age was 26.1 years (SD, 4.2) with a median duration of DMPA use among current users of 24.0 months [medians (interquartile range), 12-48]. A higher proportion of HIV-1-infected previous (12.7%) or current DMPA users (20.3%) and nonhormonal users (15.0%) had low BMD (Z-score ≤-2 at any of the three sites) compared with age-matched HIV-1-uninfected women (2.9%). HIV-1 infection and DMPA use were independently associated with significantly lower mean BMD Z-scores at all sites, with the greatest difference being among HIV-1-infected current DMPA users (5.6%-8.0%) versus uninfected nonhormonal users. Compared with non-Hispanic White and Black women, the Ugandan local reference population had generally lower mean BMD at all sites. Newer treatment interventions are needed to mitigate BMD loss in HIV-1-infected women in resource-limited settings. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Adenomyosis incidence, prevalence and treatment: United States population-based study 2006-2015.

BACKGROUND: Adenomyosis symptoms are disabling. Population-based data on incidence and prevalence of adenomyosis are lacking that could guide future evidence-based treatments and clinical management. OBJECTIVE: To evaluate the incidence, 10-year secular trends, and prevalence of adenomyosis diagnoses and to describe symptoms and treatment patterns in a large U.S. cohort. STUDY DESIGN: We performed a retrospective population-based cohort study of women aged 16-60 years in 2006-2015, enrolled in Kaiser Permanente Washington, a mixed-model health insurance and care delivery system. Adenomyosis diagnoses identified by ICD codes from the International Classification of Diseases 9th and 10th editions and potential covariates were extracted from computerized databases. Women with prior hysterectomy, and for incidence estimates women with prior adenomyosis diagnoses, were excluded. Linear trends in incidence rates over the 10-year study period were evaluated using Poisson regression. Rates and trend tests were examined for all women adjusting for age using direct standardization to the 2015 study population, by age groups, and by race/ethnicity. Chart reviews were performed to validate diagnostic accuracy of ICD codes in identifying adenomyosis incidence. Symptoms and treatment patterns at diagnosis and in the following 5 years were assessed. RESULTS: A total of 333,693 women contributed 1,185,855 woman-years (2006-2015) for incidence calculations. Associated symptom-related codes (menorrhagia or abnormal uterine bleeding, dysmenorrhea or pelvic pain, dyspareunia, and infertility) were observed in 90.8%; 18.0% had co-occurrent endometriosis codes and 47.6% had co-occurrent uterine fibroid codes. The overall adenomyosis incidence was 1.03% or 28.9 per 10,000 woman-years, with a high of 30.6 in 2007 and a low of 24.4 in 2014. Overall age-adjusted estimated incidence rates declined during the 10-year study interval (linear trend P < .05). Incidence was highest for women aged 41-45 years (69.1 per 10,000 woman-years in 2008) and was higher for black (highest 44.6 per 10,000 woman-years in 2011) vs white women (highest 27.9 per 10,000 woman-years in 2010). Overall prevalence in 2015 was 0.8% and was highest among women aged 41-45 years (1.5%). Among the 624 potential adenomyosis cases identified by diagnostic codes in 2012-2015 and with sufficient information in the medical record to determine true case status, 490 were confirmed as incident cases, yielding a 78.5% (95% confidence interval, 75.1%, 81.7%) positive predictive value of adenomyosis ICD-9/ICD-10 codes for identifying an incident adenomyosis case. Health care burden was substantial: 82.0% of women had hysterectomies, nearly 70% had imaging studies suggestive of adenomyosis, and 37.6% used chronic pain medications. CONCLUSION: Adenomyosis burden to the individual and the health care system is high. Incidence rates are disproportionately high among black women. These findings are of concern, as currently available long-term medical therapies remain limited beyond hysterectomy. Our data and methodologies are novel and could serve as a foundation to guide clinicians and health care systems to develop clinical management plans and track outcomes for women with adenomyosis.

Pandemic Uropathogenic Fluoroquinolone-resistant Escherichia coli Have Enhanced Ability to Persist in the Gut and Cause Bacteriuria in Healthy Women.

We report that fluoroquinolone-resistant Escherichia coli are found in feces of 8.8% of healthy women, with most bacteria belonging to pandemic multidrug-resistant ST131-H30R or ST1193 clonal groups. Moreover, these highly uropathogenic clonal groups demonstrate an especially prolonged gut persistence and high rate of bacteriuria without documented urinary tract infection.

Identification and validation of uterine perforation, intrauterine device expulsion, and breastfeeding in four health care systems with electronic health records.

OBJECTIVE: To validate algorithms identifying uterine perforations and intrauterine device (IUD) expulsions and to ascertain availability of breastfeeding status at the time of IUD insertion. STUDY DESIGN AND SETTING: Four health care systems with electronic health records (EHRs) participated: Kaiser Permanente Northern California (KPNC), Kaiser Permanente Southern California (KPSC), Kaiser Permanente Washington (KPWA), and Regenstrief Institute (RI). The study included women ≤50 years of age with an IUD insertion. Site-specific algorithms using structured and unstructured data were developed and a sample validated by EHR review. Positive predictive values (PPVs) of the algorithms were calculated. Breastfeeding status was assessed in a random sample of 125 women at each research site with IUD placement within 52 weeks postpartum. RESULTS: The study population included 282,028 women with 325,582 IUD insertions. The PPVs for uterine perforation were KPNC 77%, KPSC 81%, KPWA 82%, and RI 47%; PPVs for IUD expulsion were KPNC 77%, KPSC 87%, KPWA 68%, and RI 37%. Across all research sites, breastfeeding status at the time of IUD insertion was determined for 94% of those sampled. CONCLUSIONS: Algorithms with a high PPV for uterine perforation and IUD expulsion were developed at 3 of the 4 research sites. Breastfeeding status at the time of IUD insertion could be determined at all research sites. Our findings suggest that a study to evaluate the associations of breastfeeding and postpartum IUD insertions with risk of uterine perforation and IUD expulsion can be successfully conducted retrospectively; however, automated application of algorithms must be supplemented with chart review for some outcomes at one research site due to low PPV.

Identification of Incident Uterine Fibroids Using Electronic Medical Record Data.

INTRODUCTION: Uterine fibroids are the most common benign tumors of the uterus and are associated with considerable morbidity. Diagnosis codes have been used to identify fibroid cases, but their accuracy, especially for incident cases, is uncertain. METHODS: We performed medical record review on a random sample of 617 women who received a fibroid diagnosis during 2012-2014 to assess diagnostic accuracy for incident fibroids. We developed 2 algorithms aimed at improving incident case-finding using classification and regression tree analysis that incorporated additional electronic health care data on demographics, symptoms, treatment, imaging, health care utilization, comorbidities and medication. Algorithm performance was assessed using medical record as gold standard. RESULTS: Medical record review confirmed 482 fibroid cases as incident, resulting a 78 percent positive predictive value (PPV) for incident cases based on diagnosis codes alone. Incorporating additional electronic data, the first algorithm classified 395 women with a pelvic ultrasound on diagnosis date but none before as incident cases. Of these, 344 were correctly classified, yielding an 87 percent PPV, 71 percent sensitivity, and 62 percent specificity. A second algorithm built on the first algorithm and further classified women based on a fibroid diagnosis code of 218.9 in 2 years after incident diagnosis and lower body mass index; yielded 93 percent PPV, 53 percent sensitivity, and 85 percent specificity. CONCLUSIONS: Compared to diagnosis codes alone, our algorithms using fibroid diagnosis codes and additional electronic data improved identification of incident cases with higher PPV, and high sensitivity or specificity to meet different aims of future studies seeking to identify incident fibroids from electronic data.

Adolescent use of combined hormonal contraception and peak bone mineral density accrual: A meta-analysis of international prospective controlled studies.

OBJECTIVE: Many women use combined hormonal contraceptives (CHC) during adolescence during which they are accruing peak areal bone mineral density (BMD) that relates to lifetime fracture risk. To build BMD requires formation with which CHC-related exogenous oestrogen may interfere. We compared peak BMD accrual in adolescents using and not using CHC. DESIGN/PARTICIPANTS: We performed literature searches for prospective published peer-reviewed articles providing 12- to 24-month BMD change in adolescent (12- to 19-year-old) women using CHC vs CHC-unexposed control women. METHODS: Meta-analyses used random-effects models to assess BMD change rate at lumbar spine (LS) and other sites in adolescent CHC users vs CHC nonusers. RESULTS: Literature searches yielded 84 publications of which nine were eligible. Adolescent-only data were sought from cohorts with wider age inclusions. The 12-month LS meta-analysis with eight paired comparisons in 1535 adolescents showed a weighted mean BMD difference of -0.02 (95% confidence interval [CI]: -0.05 to 0.00) g/cm2 in CHC-exposed adolescents (P = 0.04). The 24-month LS meta-analysis with five paired comparisons in 885 adolescents showed a highly significant weighted mean BMD difference of -0.02 (95% CI: -0.03 to -0.01) g/cm2 in CHC-exposed adolescents (P = 0.0006). Heterogeneities by I2 were 96% and 85%, respectively. Insufficient data for other bone sites precluded quantitative analysis. CONCLUSION: Given that adolescent exposure to CHC appears to be increasing, this evidence for potential impairment of peak spinal BMD accrual is of concern and suggests a potential public health problem. Randomized controlled trial data are needed to determine CHC effects on adolescent bone health.

The Uropathogenic Escherichia coli Subclone Sequence Type 131-H30 Is Responsible for Most Antibiotic Prescription Errors at an Urgent Care Clinic.

BACKGROUND: The pandemic spread of antibiotic resistance increases the likelihood of ineffective empirical therapy. The recently emerged fluoroquinolone-resistant Escherichia coli sequence type (ST) 131-H30R subclone (H30) is a leading cause of multidrug-resistant urinary tract infection (UTI) and bloodstream infection worldwide. METHODS: We studied the relative impact of H30 on the likelihood that bacteria isolated from urine of urgent care patients would be resistant to the empirically prescribed antibiotic regimen for UTI. RESULTS: Of 750 urinalysis-positive urine samples from urgent care patients with suspected UTI, 306 (41%) yielded E. coli, from 35 different clonal groups (clonotypes). H30 predominated (14% prevalence overall), especially among older patients (age ≥70 years: 26%) and those with diabetes (43%) or urinary catheterization (60%). Resistance to the empirically selected antibiotic regimen occurred in 16% (40/246) of patients overall, 28% (20/71) of older patients, 30% (8/27) of patients with diabetes, 60% (3/5) of catheterized patients, and 71% (22/30) of those with H30. H30's contribution to such mismatched antibiotic selection was 55% overall, 70% among older patients, and 100% among patients with diabetes or a urinary catheter. Among patients with ≥2 of these factors (older age, diabetes, or urinary catheter), 24% of all urinalysis-positive urine samples yielded H30, with a 92% likelihood of resistance to the selected empirical therapy. CONCLUSIONS: The multidrug-resistant H30 subclone of E. coli ST131 is responsible for the great majority of mismatched empirical antibiotic prescriptions for suspected UTI at an urgent care clinic among patients ≥70 years old or with diabetes or urinary catheterization.

Rapid and Extensive Expansion in the United States of a New Multidrug-resistant Escherichia coli Clonal Group, Sequence Type 1193.

We describe the rapid and ongoing emergence across multiple US cities of a new multidrug-resistant Escherichia coli clone-sequence type (ST) 1193-resistant to fluoroquinolones (100%), trimethoprim-sulfamethoxazole (55%), and tetracycline (53%). ST1193 is associated with younger adults (age <40 years) and currently comprises a quarter of fluoroquinolone-resistant clinical E. coli urine isolates.

A US population-based study of uterine fibroid diagnosis incidence, trends, and prevalence: 2005 through 2014.

BACKGROUND: Despite considerable public health burden, uterine fibroid population-based incidence estimates are few. Secular trends over time are even more limited. OBJECTIVE: We sought to evaluate the incidence, 10-year secular trends, and prevalence of uterine fibroid diagnoses and describe the proportion of symptomatic women. STUDY DESIGN: We performed a retrospective population-based cohort study of women, aged 18-65 years, enrolled 2005 through 2014 in Kaiser Permanente Washington. Uterine fibroid diagnoses identified by International Classification of Diseases, Ninth Revision codes and potential covariates were extracted from computerized databases. Women with prior hysterectomy and, for incidence estimates, women with prior fibroid diagnoses were excluded. Linear trends in incidence rates over the 10-year study period were evaluated using Poisson regression models. Rates and trend tests were examined for all women, by age groups, and by race/ethnicity. RESULTS: Associated International Classification of Diseases, Ninth Revision symptom-related codes were observed in 90% of incident cases. Incidence rates for fibroid diagnoses were highest for the age group 45-49 years, 240.3 per 10,000 woman-years in 2014, and for black women across all years. Overall age-adjusted estimated incidence rates declined during the 10-year study interval, from 139.4 per 10,000 woman-years in 2005 to 101.4 in 2014 (P value trend .0008). Overall prevalence in 2014 was 9.6%, and was highest among women aged 50-54 years (15.9%). Black women had higher prevalence (18.5%) than other racial/ethnic groups. CONCLUSION: We found a decreasing trend of new uterine fibroid diagnoses among predominantly symptomatic women ages 18-65 years in a recent 10-year interval. This finding was due, perhaps in part, to secular trends of decreasing hysterectomies. Nonetheless, uterine fibroids remain a common health burden, with a prevalence of nearly 10%. Rates are disproportionately high and occur at younger ages for black women, and possibly for other non-white racial/ethnic groups. These findings are of concern, as current available long-term medical therapies remain limited.

Serum cholesterol trajectories in the 10 years prior to lymphoma diagnosis.

PURPOSE: Many studies suggest a role for cholesterol in cancer development. Serum cholesterol levels have been observed to be low in newly diagnosed lymphoma cases. The objective of these analyses was to examine the time-varying relationship of cholesterol with lymphomagenesis in the 10 years prior to diagnosis by lymphoma subtype. METHODS: Participants were selected from the combined membership of six National Cancer Institute-funded Cancer Research Network health plans from 1998 to 2008, excluding members with human immunodeficiency virus, cancer (except lymphoma), or organ transplants. Incident lymphoma cases within this population were ascertained and matched with up to five controls. Total serum cholesterol, high-density lipoprotein, and low-density lipoprotein were collected from plan databases. Multilevel, multivariable longitudinal models were fit after choosing the best polynomial order by deviance statistics for selected lymphoma histotypes to examine pre-diagnosis cholesterol trajectories: Hodgkin lymphoma (n = 519) and all non-Hodgkin lymphomas combined (n = 12,635) as well as six subtypes of the latter. RESULTS: For all categories, lymphoma cases had statistically significantly lower estimated total serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels than controls in the years prior to diagnosis/index date. Between-group differences were most pronounced 3-4 years prior to diagnosis, when cases' cholesterol levels declined steeply. CONCLUSIONS: This analysis is the first to examine changes in serum cholesterol for a decade prior to lymphoma diagnosis. A drop in cholesterol levels was evident several years before diagnosis. Our results suggest that cholesterol-related pathways have an important relationship with lymphomagenesis and low cholesterol could be a preclinical lymphoma marker.

Statin use and risk of multiple myeloma: An analysis from the cancer research network.

Animal and human data suggest statins may be protective against developing multiple myeloma; however, findings may be biased by the interrelationship with lipid levels. We investigated the association between statin use and risk of multiple myeloma in a large US population, with an emphasis on accounting for this potential bias. We conducted a case-control study nested within 6 US integrated healthcare systems participating in the National Cancer Institute-funded Cancer Research Network. Adults aged ≥40 years who were diagnosed with multiple myeloma from 1998-2008 were identified through cancer registries (N = 2,532). For each case, five controls were matched on age, sex, health plan, and membership duration prior to diagnosis/index date. Statin prescriptions were ascertained from electronic pharmacy records. To address potential biases related to lipid levels and medication prescribing practices, multivariable marginal structural models were used to model statin use (≥6 cumulative months) and risk of multiple myeloma, with examination of multiple latency periods. Statin use 48-72 months prior to diagnosis/index date was associated with a suggestive 20-28% reduced risk of developing multiple myeloma, compared to non-users. Recent initiation of statins was not associated with myeloma risk (risk ratio range 0.90-0.99 with 0-36 months latency). Older patients had more consistent protective associations across all latency periods (risk ratio range 0.67-0.87). Our results suggest that the association between statin use and multiple myeloma risk may vary by exposure window and age. Future research is warranted to investigate the timing of statin use in relation to myeloma diagnosis.

A Survey of Women's Awareness of and Reasons for Lack of Postfracture Osteoporotic Care.

OBJECTIVES: To identify women's beliefs and other factors associated with lack of osteoporosis (OP) pharmacotherapy (OP-RX) during the 6 months after a fragility fracture, including the woman's perspective on fracture risk, OP, and treatment. DESIGN: Cross-sectional. SETTING: Group Health Cooperative, a mixed-model delivery system. PARTICIPANTS: Female Group Health Cooperative enrollees aged 55 and older with an OP-related fracture according to diagnostic and procedure codes from January 1, 2013, to March 30, 2014 (N = 985). MEASUREMENTS: OP-RX and participant characteristics were ascertained from electronic health records including medications dispensed. A mailed survey was used to obtain data on health behaviors; OP-related history; concern about, knowledge of, and perceived risk of future fracture; beliefs about OP-RX; sources of information on OP; postfracture discussions with providers; and provider recommendations. RESULTS: The response rate was 73%. Of 634 eligible respondents, 84% did not undergo OP-RX during the 6 months after fracture. Fewer than 20% of women thought that OP caused their fracture, 52% did not think they were at risk of future fracture, and 75% did not think or know whether OP-RX reduces risk of fracture. Knowledge about OP and the benefits of treatment was higher in the 16% of women who underwent OP-RX after their fracture. Women reported low levels of engagement with their healthcare providers regarding OP and fracture risk management. CONCLUSION: These findings suggest low awareness about OP and its contribution to fracture risk, lack of understanding about the benefits of pharmacotherapy, and limited discussion about OP with primary care physicians. Information about individual's beliefs and knowledge gaps can help design targeted patient and provider education to improve treatment rates.

Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection.

Despite the known clonal distribution of antibiotic resistance in many bacteria, empiric (pre-culture) antibiotic selection still relies heavily on species-level cumulative antibiograms, resulting in overuse of broad-spectrum agents and excessive antibiotic/pathogen mismatch. Urinary tract infections (UTIs), which account for a large share of antibiotic use, are caused predominantly by Escherichia coli, a highly clonal pathogen. In an observational clinical cohort study of urgent care patients with suspected UTI, we assessed the potential for E. coli clonal-level antibiograms to improve empiric antibiotic selection. A novel PCR-based clonotyping assay was applied to fresh urine samples to rapidly detect E. coli and the urine strain's clonotype. Based on a database of clonotype-specific antibiograms, the acceptability of various antibiotics for empiric therapy was inferred using a 20%, 10%, and 30% allowed resistance threshold. The test's performance characteristics and possible effects on prescribing were assessed. The rapid test identified E. coli clonotypes directly in patients' urine within 25-35 minutes, with high specificity and sensitivity compared to culture. Antibiotic selection based on a clonotype-specific antibiogram could reduce the relative likelihood of antibiotic/pathogen mismatch by ≥ 60%. Compared to observed prescribing patterns, clonal diagnostics-guided antibiotic selection could safely double the use of trimethoprim/sulfamethoxazole and minimize fluoroquinolone use. In summary, a rapid clonotyping test showed promise for improving empiric antibiotic prescribing for E. coli UTI, including reversing preferential use of fluoroquinolones over trimethoprim/sulfamethoxazole. The clonal diagnostics approach merges epidemiologic surveillance, antimicrobial stewardship, and molecular diagnostics to bring evidence-based medicine directly to the point of care.

Use of Electronic Health Data to Estimate Heart Failure Events in a Population-Based Cohort with CKD.

BACKGROUND AND OBJECTIVES: Studies that use electronic health data typically identify heart failure (HF) events from hospitalizations with a principal diagnosis of HF. This approach may underestimate the total burden of HF among persons with CKD. We assessed the accuracy of algorithms for identifying validated HF events from hospitalizations and outpatient encounters, and we used this validation information to estimate the rate of HF events in a large CKD population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We identified a cohort of 15,141 adults age 18-89 years with an eGFR<60 ml/min per 1.73 m2 from 2008 to 2011. Potential HF events during follow-up were randomly sampled for validation with medical record review. Positive predictive values from the validation study were used to estimate the rate of validated HF events in the full cohort. RESULTS: A total of 1864 participants had at least one health care encounter that qualified as a potential HF event during 2.7 years of mean follow-up. Among 313 potential events that were randomly sampled for validation, positive predictive values were 92% for hospitalizations with a principal diagnosis of HF, 32% for hospitalizations with a secondary diagnosis of HF, and 70% for qualifying outpatient HF encounters. Through use of this validation information in the full cohort, the rate of validated HF events estimated from the most comprehensive algorithm that included principal and secondary diagnosis hospitalizations and outpatient encounters was 35.2 events/1000 person-years (95% confidence interval, 33.1 to 37.4), compared with 9.5 events/1000 person-years (95% confidence interval, 8.7 to 10.5) from the algorithm that included only principal diagnosis hospitalizations. Outpatient encounters accounted for 20% of the total number of validated HF events. CONCLUSIONS: In studies that rely on electronic health data, algorithms that include hospitalizations with a secondary diagnosis of HF and outpatient HF encounters more fully capture the burden of HF, although validation of HF events may be necessary with this approach.

A Novel 7-Single Nucleotide Polymorphism-Based Clonotyping Test Allows Rapid Prediction of Antimicrobial Susceptibility of Extraintestinal Escherichia coli Directly From Urine Specimens.

Background. Escherichia coli is a highly clonal pathogen. Extraintestinal isolates belong to a limited number of genetically related groups, which often exhibit characteristic antimicrobial resistance profiles. Methods. We developed a rapid clonotyping method for extraintestinal E coli based on detection of the presence or absence of 7 single nucleotide polymorphisms (SNPs) within 2 genes (fumC and fimH). A reference set of 2559 E coli isolates, primarily of urinary origin, was used to predict the resolving power of the 7-SNP-based typing method, and 582 representative strains from this set were used to evaluate test robustness. Results. Fifty-four unique SNP combinations ("septatypes") were identified in the reference strains. These septatypes yielded a clonal group resolution power on par with that of traditional multilocus sequence typing. In 72% of isolates, septatype identity predicted sequence type identity with at least 90% (mean, 97%) accuracy. Most septatypes exhibited highly distinctive antimicrobial susceptibility profiles. The 7-SNP-based test could be performed with high specificity and sensitivity using single or multiplex conventional polymerase chain reaction (PCR) and quantitative PCR. In the latter format, E coli presence and septatype identity were determined directly in urine specimens within 45 minutes with bacterial loads as low as 10(2) colony-forming units/mL and, at clinically significant bacterial loads, with 100% sensitivity and specificity. Conclusions. 7-SNP-based typing of E coli can be used for both epidemiological studies and clinical diagnostics, which could greatly improve the empirical selection of antimicrobial therapy.

The Pandemic H30 Subclone of Escherichia coli Sequence Type 131 Is Associated With Persistent Infections and Adverse Outcomes Independent From Its Multidrug Resistance and Associations With Compromised Hosts.

BACKGROUND: The H30 subclone within Escherichia coli sequence type 131 (ST131-H30) has emerged rapidly to become the leading antibiotic-resistant E. coli strain. Hypervirulence, multidrug resistance, and opportunism have been proposed as explanations for its epidemic success. METHODS: We assessed 1133 consecutive unique E. coli clinical isolates from 5 medical centers (2010-2011) for H30 genotype, which we compared with epidemiological and clinical data extracted from medical records by blinded reviewers. Using univariable and multivariable logistic regression analysis, we explored associations of H30 with underlying host characteristics, clinical presentations, management, and outcomes, adjusting for host characteristics. RESULTS: The H30 (n = 107) isolates were associated with hosts who were older, male, locally and systemically compromised, and healthcare and antibiotic exposed. With multivariable adjustment for host factors, H30 lost its numerous significant univariable associations with initial clinical presentation, but remained strongly associated with clinical persistence (odds ratio [OR], 3.47; 95% confidence interval [CI], 1.89-6.37), microbiological persistence (OR, 4.46; 95% CI, 2.38-8.38), subsequent hospital admission (OR, 2.68; 95% CI, 1.35-5.33), and subsequent new infection (OR, 1.73; 95% CI, 1.01-3.00). These host-adjusted associations remained strong even with added adjustment for resistance to the initially prescribed antibiotics, and the adverse outcome associations (subsequent hospital admission, new infection) were independent of clinical and microbiological persistence. CONCLUSIONS: In addition to targeting compromised hosts and resisting multiple antibiotics, H30 isolates may have an intrinsic ability to cause highly persistent infections and later adverse outcomes. The basis for these host- and resistance-independent associations is unclear, but they should be considered when managing patients with H30 infections.

Oral contraceptive use and fracture risk around the menopausal transition.

OBJECTIVE: The effect of oral contraceptive (OC) use on risk of fracture remains unclear, and use during later reproductive life may be increasing. To determine the association between OC use during later reproductive life and risk of fracture across the menopausal transition, we conducted a population-based case-control study in a Pacific Northwest HMO, Group Health Cooperative. METHODS: For the January 2008 to March 2013 interval, 1,204 case women aged 45 to 59 years with incident fractures, and 2,275 control women were enrolled. Potential cases with fracture codes in automated data were adjudicated by electronic health record review. Potential control women without fracture codes were selected concurrently, sampling based on age. Participants received a structured study interview. Using logistic regression, associations between OC use and fracture risk were calculated as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Participation was 69% for cases and 64% for controls. The study sample was 82% white; mean age was 54 years. The most common fracture site for cases was the wrist/forearm (32%). Adjusted fracture risk did not differ between cases versus controls for OC use in the 10 years before menopause (OR 0.90, 95% CI 0.74, 1.11); for OC use after age 38 (OR 0.94, 95% CI 0.78, 1.14); for duration of use, or for other OC exposures. CONCLUSIONS: The current study does not show an association between fractures near the menopausal transition and OC use in the decade before menopause or after age 38. For women considering OC use at these times, fracture risk does not seem to be either reduced or-reassuringly-increased.

Assessing Trends in Chlamydia Positivity and Gonorrhea Incidence and Their Associations With the Incidence of Pelvic Inflammatory Disease and Ectopic Pregnancy in Washington State, 1988-2010.

BACKGROUND: Chlamydia and gonorrhea screening for women is beneficial if it prevents serious reproductive sequelae, such as pelvic inflammatory disease (PID) and ectopic pregnancy (EP). We assessed trends in PID and EP among women in Washington and their association with gonorrhea incidence and chlamydia positivity in a screened population of women over a 23 year period. METHODS: Using data on chlamydia positivity from the Infertility Prevention Project, gonorrhea incidence from state surveillance, and PID and EP hospitalizations from hospital discharge records, we assessed trends in each condition over time. In addition, we estimated total incidence of PID and EP by incorporating information on outpatient-treated cases in alternative populations using a Bayesian approach that accounted for uncertainty in the estimates. We assessed associations between each infection and PID/EP using a linear regression model that accounts for year-to-year correlation in data points. RESULTS: We observed substantial declines in both infections and in each outcome over time. For every 2% decrease in chlamydia positivity, there was a 35.7/100,000 decrease in estimated total PID incidence (P = 0.058) and 184.4/100,000 decrease in estimated total EP (P = 0.149). For every 32/100,000 decline in gonorrhea incidence, there was a 16.5/100,000 decrease in total PID (P = 0.292) and 159.8/100,000 decrease in total EP (P = 0.020). The associations with inpatient PID and EP were highly significant for both chlamydia and gonorrhea. CONCLUSIONS: These ecological data note concurrent and substantial declines in chlamydia positivity and gonorrhea incidence, and in PID and EP incidence in Washington from 1988 to 2010 during a time when widespread chlamydia screening was ongoing.

Early-life factors and endometriosis risk.

OBJECTIVE: To study early-life factors in relation to endometriosis risk in adulthood. DESIGN: Population-based case-control study. SETTING: Integrated healthcare system. PATIENT(S): Cases (n = 310) were women diagnosed for the first time with endometriosis between the years 1996 and 2001, and controls (n = 727) were women without a diagnosis of endometriosis randomly selected from the healthcare system population. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the associations between intrauterine diethylstilbestrol (DES) exposure, maternal smoking, mother's age at delivery, firstborn status, birth weight, fetal number, prematurity, and regular soy formula feeding during infancy and endometriosis were estimated using unconditional logistic regression, adjusting for frequency matching and confounding variables. Information on early-life factors was ascertained retrospectively by in-person interview, with information on maternal DES use and regular soy formula feeding directly gathered from the participant's mother or other family member. RESULT(S): We observed that women who were regularly fed soy formula as infants had more than twice the risk of endometriosis compared with unexposed women (aOR 2.4, 95% CI 1.2-4.9). Our data also suggested increased endometriosis risk with prematurity (aOR 1.7, 95% CI 0.9-3.1) and maternal use of DES (OR 2.0, 95% CI 0.8-4.9, adjusting only for frequency matching variables), although these confidence intervals included the null. CONCLUSION(S): Our results support the hypothesis that disruption of development during fetal and infant periods may increase the risk of endometriosis in adulthood.