Risk Factors for Incident Polycystic Ovary Syndrome Diagnosis.

Objective: While highly prevalent, risk factors for incident polycystic ovary syndrome (PCOS) are poorly delineated. Using a population-based cohort, we sought to identify predictors of incident PCOS diagnosis. Materials and Methods: A matched case-control analysis was completed utilizing patients enrolled in Kaiser Permanente Washington from 2006 to 2019. Inclusion criteria included female sex, age 16-40 years, and ≥3 years of prior enrollment with ≥1 health care encounter. PCOS cases were identified using International Classification of Diseases codes. For each incident case (n = 2,491), 5 patients without PCOS (n = 12,455) were matched based on birth year and enrollment status. Potential risk factors preceding diagnosis included family history of PCOS, premature menarche, parity, race, weight gain, obesity, valproate use, metabolic syndrome, epilepsy, prediabetes, and types 1 and 2 diabetes. Potential risk factors for incident PCOS diagnosis were assessed with univariate and multivariable conditional logistic regressions. Results: Mean age of PCOS cases was 26.9 years (SD 6.8). PCOS cases, compared with non-PCOS, were more frequently nulliparous (70.9% versus 62.4%) and in the 3 years prior to index date were more likely to have obesity (53.8% versus 20.7%), metabolic syndrome (14.5% versus 4.3%), prediabetes (7.4% versus 1.6%), and type 2 diabetes (4.1% versus 1.7%) (p < 0.001 for all comparisons). In multivariable models, factors associated with higher risk for incident PCOS included the following: obesity (compared with nonobese) Class I-II (body-mass index [BMI], 30-40 kg/m2; odds ratio [OR], 3.8; 95% confidence interval [CI], 3.4-4.2), Class III (BMI > 40 kg/m2; OR, 7.5, 95% CI, 6.5-8.7), weight gain (compared with weight loss or maintenance) of 1-10% (OR, 1.7, 95% CI, 1.3-2.1), 10-20% (OR, 1.9; 95% CI, 1.5-2.4), and >20% (OR, 2.6; 95% CI, 1.9-3.6), prediabetes (OR, 2.7; 95% CI, 2.1-3.4), and metabolic syndrome (OR, 1.8: 95% CI, 1.5-2.1). Conclusion: Excess weight gain, obesity, and metabolic dysfunction may play a key role in the ensuing phenotypic expression of PCOS. Treatment and prevention strategies targeted at preventing weight gain in early reproductive years may help reduce the risk of this syndrome.

Mortality risk after COVID-19 vaccination: A self-controlled case series study.

BACKGROUND: Although previous studies found no-increased mortality risk after COVID-19 vaccination, residual confounding bias might have impacted the findings. Using a modified self-controlled case series (SCCS) design, we assessed the risk of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes after primary series COVID-19 vaccination. METHODS: We analyzed all deaths between December 14, 2020, and August 11, 2021, among individuals from eight Vaccine Safety Datalink sites. Demographic characteristics of deaths in recipients of COVID-19 vaccines and unvaccinated individuals were reported. We conducted SCCS analyses by vaccine type and death outcomes and reported relative incidences (RI). The observation period for death spanned from the dates of emergency use authorization to the end of the study period (August 11, 2021) without censoring the observation period upon death. We pre-specified a primary risk interval of 28-day and a secondary risk interval of 14-day after each vaccination dose. Adjusting for seasonality in mortality analyses is crucial because death rates vary over time. Deaths among unvaccinated individuals were included in SCCS analyses to account for seasonality by incorporating calendar month in the models. RESULTS: For Pfizer-BioNTech (BNT162b2), RIs of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes were below 1 and 95 % confidence intervals (CIs) excluded 1 across both doses and both risk intervals. For Moderna (mRNA-1273), RI point estimates of all outcomes were below 1, although the 95 % CIs of two RI estimates included 1: cardiac-related (RI = 0.78, 95 % CI, 0.58-1.04) and non-COVID-19 cardiac-related mortality (RI = 0.80, 95 % CI, 0.60-1.08) 14 days after the second dose in individuals without pre-existing cancer and heart disease. For Janssen (Ad26.COV2.S), RIs of four cardiac-related death outcomes ranged from 0.94 to 0.98 for the 14-day risk interval, and 0.68 to 0.72 for the 28-day risk interval and 95 % CIs included 1. CONCLUSION: Using a modified SCCS design and adjusting for temporal trends, no-increased risk was found for non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes among recipients of the three COVID-19 vaccines used in the US.

Nurse Care Management for Opioid Use Disorder Treatment: The PROUD Cluster Randomized Clinical Trial.

Importance: Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments. Objective: To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization. Design, Setting, and Participants: The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention or usual care (UC) stratified by system (5 systems were notified on February 28, 2018, and 1 system with delayed data use agreement on August 31, 2018). Data were obtained from electronic health records and insurance claims. An implementation monitoring team collected qualitative data. Primary care patients were included if they were 16 to 90 years old and visited a participating clinic from up to 3 years before a system's randomization date through 2 years after. Intervention: The PROUD intervention included 3 components: (1) salary for a full-time OUD nurse care manager; (2) training and technical assistance for nurse care managers; and (3) 3 or more PC clinicians agreeing to prescribe buprenorphine. Main Outcomes and Measures: The primary outcome was a clinic-level measure of patient-years of OUD treatment (buprenorphine or extended-release injectable naltrexone) per 10 000 PC patients during the 2 years postrandomization (follow-up). The secondary outcome, among patients with OUD prerandomization, was a patient-level measure of the number of days of acute care utilization during follow-up. Results: During the baseline period, a total of 130 623 patients were seen in intervention clinics (mean [SD] age, 48.6 [17.7] years; 59.7% female), and 159 459 patients were seen in UC clinics (mean [SD] age, 47.2 [17.5] years; 63.0% female). Intervention clinics provided 8.2 (95% CI, 5.4-∞) more patient-years of OUD treatment per 10 000 PC patients compared with UC clinics (P = .002). Most of the benefit accrued in 2 health systems and in patients new to clinics (5.8 [95% CI, 1.3-∞] more patient-years) or newly treated for OUD postrandomization (8.3 [95% CI, 4.3-∞] more patient-years). Qualitative data indicated that keys to successful implementation included broad commitment to treat OUD in PC from system leaders and PC teams, full financial coverage for OUD treatment, and straightforward pathways for patients to access nurse care managers. Acute care utilization did not differ between intervention and UC clinics (relative rate, 1.16; 95% CI, 0.47-2.92; P = .70). Conclusions and Relevance: The PROUD cluster randomized clinical trial intervention meaningfully increased PC OUD treatment, albeit unevenly across health systems; however, it did not decrease acute care utilization among patients with OUD. Trial Registration: ClinicalTrials.gov Identifier: NCT03407638.

Incidence, prevalence, and trends in polycystic ovary syndrome diagnosis: a United States population-based study from 2006 to 2019.

BACKGROUND: Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age, yet US incidence estimates do not exist, and prevalence estimates vary widely. OBJECTIVE: A population-based US study estimated the incidence, prevalence, and trends of polycystic ovary syndrome by age, race and ethnicity, and diagnosing provider type. STUDY DESIGN: A retrospective cohort study of patients enrolled in Kaiser Permanente Washington from 2006 to 2019 was conducted. All members identified as female, aged 16 to 40 years with at least 3 years of enrollment and at least 1 healthcare encounter during that time, were eligible for inclusion. Individuals were excluded if they had a history of oophorectomy or hysterectomy. Polycystic ovary syndrome cases were identified using the International Classification of Diseases diagnosis codes (International Classification of Diseases, Ninth Revision, 256.4 or International Classification of Diseases, Tenth Revision, E28.2). Individuals with a polycystic ovary syndrome diagnosis before study entry were excluded from incidence rate estimations. The incidence rates were adjusted by age using direct standardization to the 2010 US census data. Temporal trends in incidence were assessed using weighted linear regression (overall) and Poisson regression (by age, race and ethnicity, and provider type). Prevalent cases were defined as patients with a polycystic ovary syndrome diagnosis at any time before the end of 2019. Medical record review of 700 incident cases diagnosed in 2011-2019 was performed to validate incident cases identified by International Classification of Diseases codes using the Rotterdam criteria. RESULTS: Among 177,527 eligible patients who contributed 586,470 person-years, 2491 incident polycystic ovary syndrome cases were identified. The mean age at diagnosis was 26.9 years, and the mean body mass index was 31.6 kg/m2. Overall incidence was 42.5 per 10,000 person-years; the rates were similar over time but increased in individuals aged 16 to 20 years from 31.0 to 51.9 per 10,000 person-years (P=.01) and decreased among those aged 26 to 30 years from 82.8 to 45.0 per 10,000 person-years (P=.02). A small decreasing temporal trend in incidence rates was only observed among non-Hispanic White individuals (P=.01). The incidence rates by diagnosing provider type varied little over time. Among the 58,241 patients who contributed person-time in 2019, 3036 (5.2%) had a polycystic ovary syndrome International Classification of Diseases diagnosis code; the prevalence was the highest among the Hawaiian and Pacific Islander group (7.6%) followed by Native American and Hispanic groups. Medical record review classified 60% as definite or probable incident, 14% as possible incident, and 17% as prevalent polycystic ovary syndrome. The overall positive predictive value of polycystic ovary syndrome International Classification of Diseases diagnosis code for identifying definite, probable, or possible incident polycystic ovary syndrome was 76% (95% confidence interval, 72%-79%). CONCLUSION: Among a cohort of nonselected females in the United States, we observed stable rates of incident polycystic ovary syndrome diagnoses over time. The incidence of polycystic ovary syndrome was 4- to 5-fold greater than reported for the United Kingdom. The prevalence of polycystic ovary syndrome (5.2%) was almost double before the published US estimates (2.9%) based on the International Classification of Diseases codes. Race and ethnicity and provider type did not seem to have a major impact on temporal rates. Incident diagnoses increased over time in younger and decreased in older age groups, perhaps related to shifting practice patterns with greater awareness among practitioners of the impact of polycystic ovary syndrome on long-term health outcomes and improved prevention efforts. Moreover, increasing obesity rates may be a factor driving the earlier ages at diagnosis.

Active Postlicensure Safety Surveillance for Recombinant Zoster Vaccine Using Electronic Health Record Data.

Recombinant zoster vaccine (RZV) (Shingrix; GlaxoSmithKline, Brentford, United Kingdom) is an adjuvanted glycoprotein vaccine that was licensed in 2017 to prevent herpes zoster (shingles) and its complications in older adults. In this prospective, postlicensure Vaccine Safety Datalink study using electronic health records, we sequentially monitored a real-world population of adults aged ≥50 years who received care in multiple US Vaccine Safety Datalink health systems to identify potentially increased risks of 10 prespecified health outcomes, including stroke, anaphylaxis, and Guillain-Barré syndrome (GBS). Among 647,833 RZV doses administered from January 2018 through December 2019, we did not detect a sustained increased risk of any monitored outcome for RZV recipients relative to either historical (2013-2017) recipients of zoster vaccine live, a live attenuated virus vaccine (Zostavax; Merck & Co., Inc., Kenilworth, New Jersey), or contemporary non-RZV vaccine recipients who had an annual well-person visit during the 2018-2019 study period. We confirmed prelicensure trial findings of increased risks of systemic and local reactions following RZV. Our study provides additional reassurance about the overall safety of RZV. Despite a large sample, uncertainty remains regarding potential associations with GBS due to the limited number of confirmed GBS cases that were observed.

Baseline representativeness of patients in clinics enrolled in the PRimary care Opioid Use Disorders treatment (PROUD) trial: comparison of trial and non-trial clinics in the same health systems.

BACKGROUND: Pragmatic primary care trials aim to test interventions in "real world" health care settings, but clinics willing and able to participate in trials may not be representative of typical clinics. This analysis compared patients in participating and non-participating clinics from the same health systems at baseline in the PRimary care Opioid Use Disorders treatment (PROUD) trial. METHODS: This observational analysis relied on secondary electronic health record and administrative claims data in 5 of 6 health systems in the PROUD trial. The sample included patients 16-90 years at an eligible primary care visit in the 3 years before randomization. Each system contributed 2 randomized PROUD trial clinics and 4 similarly sized non-trial clinics. We summarized patient characteristics in trial and non-trial clinics in the 2 years before randomization ("baseline"). Using mixed-effect regression models, we compared trial and non-trial clinics on a baseline measure of the primary trial outcome (clinic-level patient-years of opioid use disorder (OUD) treatment, scaled per 10,000 primary care patients seen) and a baseline measure of the secondary trial outcome (patient-level days of acute care utilization among patients with OUD). RESULTS: Patients were generally similar between the 10 trial clinics (n = 248,436) and 20 non-trial clinics (n = 341,130), although trial clinics' patients were slightly younger, more likely to be Hispanic/Latinx, less likely to be white, more likely to have Medicaid/subsidized insurance, and lived in less wealthy neighborhoods. Baseline outcomes did not differ between trial and non-trial clinics: trial clinics had 1.0 more patient-year of OUD treatment per 10,000 patients (95% CI: - 2.9, 5.0) and a 4% higher rate of days of acute care utilization than non-trial clinics (rate ratio: 1.04; 95% CI: 0.76, 1.42). CONCLUSIONS: trial clinics and non-trial clinics were similar regarding most measured patient characteristics, and no differences were observed in baseline measures of trial primary and secondary outcomes. These findings suggest trial clinics were representative of comparably sized clinics within the same health systems. Although results do not reflect generalizability more broadly, this study illustrates an approach to assess representativeness of clinics in future pragmatic primary care trials.

Validation of international classification of diseases, tenth revision, clinical modification diagnosis codes for heart failure subtypes.

PURPOSE: To estimate the positive predictive value (PPV) of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes for identifying HF subtypes. METHODS: We validated ICD-10-CM HF diagnosis codes among Kaiser Permanente Washington enrollees who were ≥18 years of age and had an ICD-10-CM HF diagnosis code during 2017-2018 and a procedure code for an echocardiogram in the 12 months before through 6 months after the HF code. Left ventricular ejection fraction (LVEF) ascertained from medical chart review was used as the gold standard for classifying patients as having reduced ejection fraction (rEF), mid-range ejection fraction (mEF), or preserved ejection fraction (pEF). RESULTS: Among 6194 eligible patients, we randomly sampled 1000 for medical chart review. A total of 974 patients had LVEF information in their chart. The ICD-10-CM HF code group with the highest PPV for rEF was I50.20-I50.23, "Systolic (congestive) heart failure," PPV = 41.4% (95% CI, 34.5-48.7%); and the highest PPV for mEF or rEF was also I50.20-I50.23, PPV = 70.2% (95% CI, 63.1-76.4%). The highest PPV for pEF was the I50.30-I50.33 group, "Diastolic (congestive) heart failure," PPV = 92.0% (95% CI, 88.1-94.7%); and the highest PPV for mEF or pEF was also I50.30-I50.33, PPV = 97.7% (95% CI, 95.1-99.0%). CONCLUSIONS: If the accuracy measure of greatest interest is PPV, our results suggest that ICD-10-CM HF codes alone may not be adequate for identifying patients with rEF but may be adequate for identifying patients with pEF. HF coding practices may vary across settings, which may impact generalizability of our findings.

Patient and tumour characteristics of screening-age adults diagnosed with screen-detected versus symptomatic colon cancer.

AIM: International studies have shown that most colon cancers are diagnosed among people with symptoms, but research is limited in the United States. Here, we conducted a retrospective study of adults aged 50-85 years diagnosed with stage I-IIIA colon cancer between 1995 and 2014 in two US healthcare systems. METHODS: Mode of detection (screening or symptomatic) was ascertained from medical records. We estimated unadjusted odds ratios (OR) and 95% confidence intervals (CI) comparing detection mode by patient factors at diagnosis (year, age, sex, race, smoking status, body mass index [BMI], Charlson score), prediagnostic primary care utilization, and tumour characteristics (stage, location). RESULTS: Of 1,675 people with colon cancer, 38.4% were screen-detected, while 61.6% were diagnosed following symptomatic presentation. Screen-detected cancer was more common among those diagnosed between 2010 and 2014 versus 1995-1999 (OR 1.65, 95% CI: 1.19-2.28), and those with a BMI of 25-<30 kg/m2 (OR 1.54, 95% CI: 1.21-1.98) or ≥30 kg/m2 (OR 1.52, 95% CI: 1.18-1.96) versus <25 kg/m2 . Screen-detected cancer was less common among people aged 76-85 (OR 0.50, 95% CI: 0.39-0.65) versus 50-64, those with comorbidity scores >0 (OR 0.71, 95% CI: 0.56-0.91 for score = 1, OR 0.34, 95% CI: 0.26-0.45 for score = 2+), and those with 2+ prediagnostic primary care visits (OR 0.53, 95% CI: 0.37-0.76) versus 0 visits. The odds of screen detection were lower among patients diagnosed with stage IIA (OR 0.33, 95% CI = 0.27-0.41) or IIB (OR 0.12, 95% CI: 0.06-0.24) cancers versus stage I. CONCLUSIONS: Most colon cancers among screen-eligible adults were diagnosed following symptomatic presentation. Even with increasing screening rates over time, research is needed to better understand why specific groups are more likely to be diagnosed when symptomatic and identify opportunities for interventions.

Incidence, prevalence, and trends in endometriosis diagnosis: a United States population-based study from 2006 to 2015.

BACKGROUND: Accurate estimates of incidence and prevalence of endometriosis among nonselected cohorts are lacking in the United States, and earlier reports have produced varying results. OBJECTIVE: This study aimed to define endometriosis incidence and prevalence in a US population and evaluate factors influencing these estimates over time. STUDY DESIGN: A 10-year retrospective cohort study using Kaiser Permanente Washington electronic health records database was completed. The primary analysis included women enrollees aged 16 to 60 years, from January 2006 to December 2015, who had a uterus, were continuously enrolled for at least 2 years before cohort entry and had at least 1 healthcare utilization. Secondary analysis included all women enrollees aged 16 to 60 years during this time. Incident endometriosis was identified using the International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes. Annual incidence rates were age-adjusted by direct standardization to the 2015 study population. Secular trends in incidence overall and by 5-year age group, race and ethnicity, diagnosis modality, and practitioner type were assessed using Poisson regression analyses. Prevalent cases were defined as women enrolled in 2015 and had an endometriosis diagnosis before the end of 2015. The prevalence rates of chronic pelvic pain and dysmenorrhea defined by the International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes in 2006-2015 were estimated. RESULTS: Among 332,056 eligible women who contributed 1,176,329 person-years during the 10-year study period, 2863 incident endometriosis cases were identified for an average incidence of 24.3 cases per 10,000 person-years. In our primary analysis, incidence rates declined over the study interval from a high of 30.2 per 10,000 person-years in 2006 to 17.4 per 10,000 person-years in 2015 and were highest among women aged 36 to 45 years in most years. Incidence rates were similar across race and ethnicity groups. The distribution of the 2863 incident cases by the diagnosis modality was as follows: 45.5% surgical, 5.7% imaging, and 48.8% clinical. Endometriosis incidence rates per 10,000 person-years were similar in women who were surgically and clinically diagnosed and decreased significantly from 2006 to 2015 (surgically diagnosed endometriosis dropped from 13.4 to 7.4 and clinically diagnosed endometriosis dropped from 16.1 to 8.9; P value of <.001 for linear trend over time for each). Incident case distribution by diagnosing provider was as follows: 73.6% obstetrician and gynecologist, 15.7% primary care provider, and 10.7% "other." Incidence of endometriosis diagnosed by an obstetrician and gynecologist and primary care provider decreased over the study interval (P<.001 for linear trend over time for each). Method of diagnosis and provider type did not differ by race and ethnicity. Among 135,162 women who contributed person-time in 2015, 2521 women were diagnosed with endometriosis, a prevalence rate of 1.9%. In our secondary analysis, the frequency of chronic pelvic pain diagnosis increased over the study interval from 3.0% in 2006 to 5.6% in 2015. CONCLUSION: The incidence rates of endometriosis declined over the 10-year study interval and did so uniformly across age groups, races and ethnicities, and the main diagnosing modalities and providers. Declining rates may reflect a shift in practice patterns in the United States away from the diagnosis of endometriosis both clinically and surgically, rather than favoring more general diagnoses of chronic pelvic pain. The prevalence of endometriosis in 2015 in the United States is in keeping with data from recent studies outside the United States using health record data.

Incident Dementia, Glycated Hemoglobin (HbA1c) Levels, and Potentially Preventable Hospitalizations in People Aged 65 and Older With Diabetes.

BACKGROUND: This study was aimed to determine whether incident dementia and HbA1c levels are associated with increased rates of potentially preventable hospitalizations (PPHs) in persons with diabetes. METHOD: A total of 565 adults aged 65+ ever treated for diabetes were enrolled from Adult Changes in Thought study. PPHs were from principal discharge diagnoses and included diabetes PPH (dPPH), respiratory PPH (rPPH), urinovolemic PPH (uPPH), cardiovascular PPH, and other PPH. Poisson generalized estimating equations estimated rate ratios (RRs) and 95% confidence intervals (CIs) for the associations between dementia or HbA1c measures and rate of PPHs. RESULTS: A total of 562 individuals contributed 3 602 dementia-free years, and 132 individuals contributed 511 dementia follow-up years. One hundred twenty-eight (23%) dementia-free individuals had 210 PPH admissions and a crude rate of 58 per 1 000 person-years, while 55 (42%) individuals with dementia had 93 PPH admissions and a crude rate of 182 per 1 000 person-years. The adjusted RR (95% CI) comparing rates between dementia and dementia-free groups were 2.27 (1.60, 3.21) for overall PPH; 5.90 (2.70, 12.88) for dPPH; 5.17 (2.49, 10.73) for uPPH; and 2.01 (1.06, 3.83) for rPPH. Compared with HbA1c of 7%-8% and adjusted for dementia, the RR (95% CI) for overall PPH was 1.43 (1.00, 2.06) for >8% HbA1c and 1.18 (0.85, 1.65) for <7% HbA1c. The uPPH RR was also increased, comparing >8% and <7% HbA1c levels. CONCLUSION: Incident dementia is associated with higher rates of PPHs among people with diabetes, especially PPHs due to diabetes, urinary tract infection (UTI), and dehydration. Potential evidence suggested that HbA1c levels of >8% versus lower levels are associated with higher rates of overall PPHs and UTI- and dehydration-related PPHs.

Changes in Clinician Attitudes Toward Sharing Visit Notes: Surveys Pre-and Post-Implementation.

BACKGROUND: Clinician perceptions before and after inviting patients to read office notes (open notes) are unknown. OBJECTIVE: To describe changes in clinicians' attitudes about sharing notes with patients. DESIGN, PARTICIPANTS, AND MAIN MEASURE: Survey of outpatient primary and specialty care clinicians who were from a large group practice and had one or more patients who accessed notes. The main outcome was percent change (before vs. after implementation) in clinician perception that online visit notes are beneficial overall. KEY RESULTS: Of the 563 invited clinicians, 400 (71%) took the baseline survey; 295 were eligible for a follow-up survey with 192 (65%) responding (119 primary care, 47 medical specialties, 26 surgical specialties). Before implementation, 29% agreed or somewhat agreed that visit notes online are beneficial overall, increasing to 71% following implementation (p<0.001); 44% switched beliefs from bad to good idea; and 2% reported the opposite change (p<0.001). This post-implementation change was observed in all clinician categories. Compared to pre-implementation, fewer clinicians had concerns about office visits taking longer (47% pre vs. 15% post) or requiring more time for questions (71% vs. 16%), or producing notes (57% vs. 28%). Before and after implementation, most clinicians reported being less candid in documentation (65% vs. 52%) and that patients would have more control of their care (72% vs. 78%) and worry more (72% vs. 65%). CONCLUSIONS: Following implementation, more primary and specialty care clinicians agreed that sharing notes with patients online was beneficial overall. Fewer had concerns about more time needed for office visits or documentation. Most thought patients would worry more and reported being less candid in documentation.

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.

Association of Diabetes and Other Clinical and Sociodemographic Factors With Guideline-concordant Breast Cancer Treatment for Breast Cancer.

BACKGROUND: Women with breast cancer have worse health outcomes with co-occurring type 2 diabetes, possibly due to suboptimal breast cancer treatment. METHODS: We created a cohort of women ages 66 to 85 y with stage I to III breast cancer from 1993 to 2012 from an integrated health care delivery system (n=1612) and fee-for-service Medicare beneficiaries (n=98,915), linked to Surveillance, Epidemiology, and End Results (SEER) data (total n=100,527). We evaluated associations between type 2 diabetes and other factors with undergoing guideline-concordant cancer treatment. We estimated χ tests for univariate analysis and relative risks (RRs) using multivariable log-binomial models for outcomes of (1) overall guideline-concordant treatment, (2) definitive surgical therapy (mastectomy or lumpectomy with radiation), (3) chemotherapy if indicated, and (4) endocrine therapy. RESULTS: Our cohort included 60% of subjects with stage 1 tumors, one quarter below 70 years old, 23% had diabetes, 35% underwent overall guideline-concordant treatment, 24% chemotherapy, and 83% endocrine therapy. Women with diabetes were less likely to undergo overall guideline-concordant treatment (RR: 0.96; 95% confidence interval: 0.94-0.98), and only slightly less likely to undergo guideline-concordant definitive surgical therapy (RR: 0.99; 95% confidence interval: 0.99-1.00). No differences were found for chemotherapy or endocrine therapy. Other factors significantly associated with a lower risk of guideline-concordant care were cancer stages II to III (vs. I; RR=0.47-0.69, P<0.0001), older age (vs. 66 to 69 y; RR=0.56-0.90, P<0.0001), higher comorbidity burden, and Medicaid dual-eligibility. CONCLUSIONS: Diabetes was associated with lower adherence to overall guideline-concordant breast cancer treatment. However, higher stage, older age, higher comorbidity burden, and Medicaid insurance were more strongly associated with lower use of guideline-concordant treatment. Given the heavy burden of breast cancer and diabetes, long-term outcomes analysis should consider guideline-concordant treatment. IMPACT: Other factors besides diabetes are more strongly associated with guideline-concordant breast cancer treatment.

Changes in use of opioid therapy after colon cancer diagnosis: a population-based study.

PURPOSE: To describe patterns of opioid use in cancer survivors. METHODS: In a cohort study of colon cancer patients diagnosed during 1995-2014 and enrolled at two Kaiser Permanente regions, we constructed quarterly measures of opioid use from 1 year before cancer diagnosis through 5 years after diagnosis to examine changes in use. Measures included any use, incident use, regular use (use ≥ 45 days in a 91-day quarter), and average daily dose (converted to morphine milligram equivalent, MME). We also assessed temporal trends of opioid use. RESULTS: Of 2,039 colon cancer patients, 11-15% received opioids in the four pre-diagnosis quarters, 68% in the first quarter after diagnosis, and 15-17% in each subsequent 19 quarters. Regular opioid use increased from 3 to 5% pre-diagnosis to 5-7% post diagnosis. Average dose increased from 15 to 17 MME/day pre-diagnosis to 14-22 MME/day post diagnosis (excluding the quarter in which cancer was diagnosed). Among post-diagnosis opioid users, 73-95% were on a low dose (< 20 MME/day). Over years, regular use of opioids increased in survivorship with no change in dosage. CONCLUSION: Opioid use slightly increased following a colon cancer diagnosis, but high-dose use was rare. Research is needed to differentiate under- versus over-treatment of cancer pain.

Diabetes and differences in detection of incident invasive breast cancer.

Many women diagnosed with breast cancer have chronic conditions such as diabetes that may impact other health behaviors. Our purpose was to determine if breast cancer screening and detection differs among women with and without diabetes. We conducted a cross-sectional analysis of a retrospective cohort of women aged 52-74 years diagnosed with incident stages I-III breast cancer enrolled in an integrated health plan between 1999 and 2014 with linkage to the Surveillance, Epidemiology and End Results registry (n = 2040). Screening data were taken from electronic health records. We used multivariable modified Poisson regression models with robust standard errors to estimate relative risks (RR) and 95% confidence intervals (CI) for outcomes of (i) receipt of screening in the 2 years prior to diagnosis; (ii) symptom-detected breast cancer; and (iii) diagnosis of locally advanced stage III breast cancer. Compared to women without diabetes, women with diabetes were similar with respect to receipt of screening mammography (78% and 77%), symptom-detected breast cancer (46% and 49%), and stage III diagnosis (7% and 7%). In multivariable models adjusting for age and year of diagnosis, race, BMI, Charlson comorbidity score and depression diagnosis no differences were observed in the outcomes by presence of diabetes. Further investigation is warranted to determine how diabetes acts as a mediating factor in adverse breast cancer outcomes.

Risk of second breast cancer events with chronic opioid use in breast cancer survivors.

PURPOSE: Opioids may increase cancer risk and progression through multiple pathways. Our objective was to estimate the association between chronic opioid use and risk of second breast cancer events (SBCEs). METHODS: Cohort study of women greater than or equal to 18 years, diagnosed with early stage breast cancer between January 1, 1990, and December 31, 2008, and enrolled in a large health plan for 1+ years before and after (unless died) diagnosis. SBCEs were defined as evidence of recurrence or second primary breast cancer in the medical chart. Chronic opioid use was defined as 75+ days of use in any moving 90-day window after breast cancer diagnosis and varied to 150+ days in a 180-day window in a sensitivity analysis. Using Cox proportional hazards models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for SBCE and components of SBCE by chronic opioid use. RESULTS: Almost 10% met the criteria for chronic use and almost a third of users were taking opioids for greater than 3 years. Risk of SBCEs (HR = 1.20; 95% CI, 0.85-1.70), including second primary breast cancer (HR = 1.38; 95% CI, 0.71-2.70), was nonsignificantly higher among chronic users vs nonchronic/nonusers. The HR for recurrence was 1.14 (95% CI, 0.76-2.70). Results of the sensitivity analyses on longer opioid use does support an association with SBCE or recurrence. CONCLUSION: This first US-based study on chronic opioid use and cancer outcomes provides some reassurance on safety. However, the question warrants further exploration in other populations and settings.

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.

Cardiovascular medication use and risks of colon cancer recurrences and additional cancer events: a cohort study.

BACKGROUND: Cardiovascular medications may be associated with cancer development, but little is known about their association with cancer recurrence. Medications such as statins and antihypertensives may be commonly used among colon cancer survivors, who are, on average, diagnosed in their mid-60s. We described the associations between statins and antihypertensive medications and colon cancer recurrence in a large, population-based study. METHODS: We conducted a cohort study among adults with stage I-IIIA colon cancer diagnosed in 1995-2014 in two Kaiser Permanente regions, Colorado and Washington. Statin and antihypertensive use were obtained from electronic pharmacy dispensing data. People were classified as medication users on the date of their first dispensing after cohort entry, which started 90 days after completing cancer treatment, continuing through the earliest of death, health plan disenrollment, or chart abstraction. We collected outcome information from medical record abstraction and tumor registries on colon cancer recurrences and second primary cancers. Using Cox proportional hazards multivariable models, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for colon cancer recurrences and any cancer event (recurrences and new primaries at any anatomic site) comparing medication users to non-users. RESULTS: Among 2039 people, 937 (46%) used statins and 1425 (70%) used antihypertensives at any point during a median of 4.9 years of follow-up; 460 people had any additional cancer event, including 152 with a colon cancer recurrence. Statin use was not associated with colon cancer recurrence (HR = 1.09, 95%CI = 0.65-1.85) or any cancer event (HR = 1.12, 95%CI = 0.85-1.47), nor was antihypertensive use associated with recurrence (HR = 0.73, 95%CI = 0.44-1.21) or any cancer event (HR = 0.93, 95%CI = 0.70-1.24). CONCLUSIONS: Our results suggest no association between cardiovascular medication use and the risk of recurrence or any additional cancer, and may provide reassurance to colon cancer survivors.

Use of antidepressants after colon cancer diagnosis and risk of recurrence.

OBJECTIVE: Prior research examining the association between use of antidepressants after colon cancer diagnosis and risk of recurrence is scant. We evaluated this association among colon cancer patients diagnosed at two integrated health care delivery systems in the United States. METHODS: We conducted a cohort study of stage I to IIIA colon cancer patients diagnosed at greater than or equal to 18 years of age at Kaiser Permanente Colorado and Kaiser Permanente Washington during 1995 to 2014. We used pharmacy records to identify dispensings for antidepressants and tumor registry records and patients' medical charts to identify cancer recurrences. Using Cox proportional hazards models, we estimated the adjusted hazard ratio (HR) of colon cancer recurrence comparing patients who used antidepressants after diagnosis to those who did not. We also evaluated the risk associated with use of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) separately. RESULTS: Among the 1923 eligible colon cancer patients, 807 (42%) used an antidepressant after diagnosis and 139 had a colon cancer recurrence during an average 5.6 years of follow-up. Use of antidepressants after colon cancer diagnosis was not associated with risk of recurrence (HR: 1.14; 95% confidence interval [CI], 0.69-1.87). The HR for use of SSRIs was 1.22 (95% CI, 0.64-2.30), and for TCAs, it was 1.18 (95% CI, 0.68-2.07). CONCLUSIONS: Our findings suggest that use of antidepressants after colon cancer diagnosis was common and not associated with risk of recurrence. Future larger studies with greater power to examine risk associated with individual antidepressants would be valuable additions to the evidence base.

Early Pregnancy Hemoglobin A1C and Pregnancy Outcomes: A Population-Based Study.

OBJECTIVE: Women with prediabetes are identified from screening for overt diabetes in early pregnancy, but the clinical significance of prediabetes in pregnancy is unclear. We examined whether prediabetes in early pregnancy was associated with risks of adverse outcomes. STUDY DESIGN: We conducted a retrospective cohort study of pregnant women enrolled in Kaiser Permanente Washington from 2011 to 2014. Early pregnancy hemoglobin A1C (A1C) values, covariates, and outcomes were ascertained from electronic medical records and state birth certificates. Women with prediabetes (A1C of 5.7-6.4%) were compared with those with normal A1C levels (<5.7%) for risk of gestational diabetes mellitus (GDM) and other outcomes including preeclampsia, primary cesarean delivery, induction of labor, large/small for gestational age, preterm birth, and macrosomia. We used modified Poisson's regression to calculate adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Of 7,020 women, 239 (3.4%) had prediabetes. GDM developed in 48% of prediabetic women compared with 11% of women with normal A1C levels (adjusted RR: 2.8, 95% CI: 2.4-3.3). Prediabetes was not associated with all other adverse maternal and neonatal outcomes. CONCLUSION: Prediabetes in early pregnancy is a risk factor for GDM. Future research is needed to elucidate whether early intervention may reduce this risk.