Association of initial opioid prescription duration and an opioid refill by pain diagnosis: Evidence from outpatient settings in ten US health systems.

OBJECTIVE: The Centers for Disease Control and Prevention's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain cautioned that inflexible opioid prescription duration limits may harm patients. Information about the relationship between initial opioid prescription duration and a subsequent refill could inform prescribing policies and practices to optimize patient outcomes. We assessed the association between initial opioid duration and an opioid refill prescription. METHODS: We conducted a retrospective cohort study of adults ≥19 years of age in 10 US health systems between 2013 and 2018 from outpatient care with a diagnosis for back pain without radiculopathy, back pain with radiculopathy, neck pain, joint pain, tendonitis/bursitis, mild musculoskeletal pain, severe musculoskeletal pain, urinary calculus, or headache. Generalized additive models were used to estimate the association between opioid days' supply and a refill prescription. RESULTS: Overall, 220,797 patients were prescribed opioid analgesics upon an outpatient visit for pain. Nearly a quarter (23.5%) of the cohort received an opioid refill prescription during follow-up. The likelihood of a refill generally increased with initial duration for most pain diagnoses. About 1 to 3 fewer patients would receive a refill within 3 months for every 100 patients initially prescribed 3 vs. 7 days of opioids for most pain diagnoses. The lowest likelihood of refill was for a 1-day supply for all pain diagnoses, except for severe musculoskeletal pain (9 days' supply) and headache (3-4 days' supply). CONCLUSIONS: Long-term prescription opioid use increased modestly with initial opioid prescription duration for most but not all pain diagnoses examined.

Management of Neck or Back Pain in Ambulatory Care: Did Visit Mode or the COVID-19 Pandemic Affect Provider Practice or Patient Adherence?

BACKGROUND/OBJECTIVE: In recent years, 2 circumstances have changed provider-patient interactions in ambulatory care: (1) the replacement of virtual for in-person visits and (2) the COVID-19 pandemic. We studied the potential impact of each event on provider practice and patient adherence by comparing the frequency of the association of provider orders, and patient fulfillment of those orders, by visit mode and pandemic period, for incident neck or back pain (NBP) visits in ambulatory care. METHODS: Data were extracted from the electronic health records of 3 Kaiser Permanente regions (Colorado, Georgia, and Mid-Atlantic States) from January 2017 to June 2021. Incident NBP visits were defined from ICD-10 coded as primary or first listed diagnoses on adult, family medicine, or urgent care visits separated by at least 180 days. Visit modes were classified as virtual or in-person. Periods were classified as prepandemic (before April 2020 or the beginning of the national emergency) or recovery (after June 2020). Percentages of provider orders for, and patient fulfillment of orders, were measured for 5 service classes and compared on: virtual versus in-person visits, and prepandemic versus recovery periods. Comparisons were balanced on patient case-mix using inverse probability of treatment weighting. RESULTS: Ancillary services in all 5 categories at each of the 3 Kaiser Permanente regions were substantially ordered less frequently on virtual compared with in-person visits in both the prepandemic and recovery periods (both P ≤ 0.001). Conditional on an order, patient fulfillment within 30 days was high (typically ≥70%) and not likely meaningfully different between visit modes or pandemic periods. CONCLUSIONS: Ancillary services for incident NBP visits were ordered less frequently during virtual than in-person visits in both prepandemic and recovery periods. Patient fulfillment of orders was high, and not significantly different by mode or period.

Did Access to Ambulatory Care Moderate the Associations Between Visit Mode and Ancillary Services Utilization Across the COVID-19 Pandemic Period?

BACKGROUND/OBJECTIVE: In recent years, 2 circumstances changed provider-patient interactions in primary care: the substitution of virtual (eg, video) for in-person visits and the COVID-19 pandemic. We studied whether access to care might affect patient fulfillment of ancillary services orders for ambulatory diagnosis and management of incident neck or back pain (NBP) and incident urinary tract infection (UTI) for virtual versus in-person visits. METHODS: Data were extracted from the electronic health records of 3 Kaiser Permanente Regions to identify incident NBP and UTI visits from January 2016 through June 2021. Visit modes were classified as virtual (Internet-mediated synchronous chats, telephone visits, or video visits) or in-person. Periods were classified as prepandemic [before the beginning of the national emergency (April 2020)] or recovery (after June 2020). Percentages of patient fulfillment of ancillary services orders were measured for 5 service classes each for NBP and UTI. Differences in percentages of fulfillments were compared between modes within periods and between periods within the mode to assess the possible impact of 3 moderators: distance from residence to primary care clinic, high deductible health plan (HDHP) enrollment, and prior use of a mail-order pharmacy program. RESULTS: For diagnostic radiology, laboratory, and pharmacy services, percentages of fulfilled orders were generally >70-80%. Given an incident NBP or UTI visit, longer distance to the clinic and higher cost-sharing due to HDHP enrollment did not significantly suppress patients' fulfillment of ancillary services orders. Prior use of mail-order prescriptions significantly promoted medication order fulfillments on virtual NBP visits compared with in-person NBP visits in the prepandemic period (5.9% vs. 2.0%, P=0.01) and in the recovery period (5.2% vs. 1.6%, P=0.02). CONCLUSIONS: Distance to the clinic or HDHP enrollment had minimal impact on the fulfillment of diagnostic or prescribed medication services associated with incident NBP or UTI visits delivered virtually or in-person; however, prior use of mail-order pharmacy option promoted fulfillment of prescribed medication orders associated with NBP visits.

Impact of COVID-19 on Trends in Outpatient Clinic Utilization: A Tale of 2 Departments.

BACKGROUND: The COVID-19 pandemic forced many US health care organizations to shift from mostly in-person care to a hybrid of virtual visits (VV) and in-person visits (IPV). While there was an expected and immediate shift to virtual care (VC) early in the pandemic, little is known about trends in VC use after restrictions eased. METHODS: This is a retrospective study using data from 3 health care systems. All completed visits from adult primary care (APC) and behavioral health (BH) were extracted from the electronic health record of adults aged 19 years and older from January 1, 2019 to June 30, 2021. Standardized weekly visit rates were calculated by department and site and analyzed using time series analysis. RESULTS: There was an immediate decrease in APC visits following the onset of the pandemic. IPV were quickly replaced by VV such that VV accounted for most APC visits early in the pandemic. By 2021, VV rates declined, and VC visits accounted for <50% of all APC visits. By Spring 2021, all 3 health care systems saw a resumption of APC visits as rates neared or returned to prepandemic levels. In contrast, BH visit rates remained constant or slightly increased. By April 2020, almost all BH visits were being delivered virtually at each of the 3 sites and continue to do so without changes to utilization. CONCLUSIONS: VC use peaked during the early pandemic period. While rates of VC are higher than prepandemic levels, IPV are the predominant visit type in APC. In contrast, VC use has sustained in BH, even after restrictions eased.

Patient Factors Associated With Use of Adult Primary Care and Virtual Visits During the COVID-19 Pandemic.

BACKGROUND: The delivery of adult primary care (APC) shifted from predominately in-person to modes of virtual care during the COVID-19 pandemic. It is unclear how these shifts impacted the likelihood of APC use during the pandemic, or how patient characteristics may be associated with the use of virtual care. METHODS: A retrospective cohort study using person-month level datasets from 3 geographically disparate integrated health care systems was conducted for the observation period of January 1, 2020, through June 30, 2021. We estimated a 2-stage model, first adjusting for patient-level sociodemographic, clinical, and cost-sharing factors, using generalized estimating equations with a logit distribution, along with a second-stage multinomial generalized estimating equations model that included an inverse propensity score treatment weight to adjust for the likelihood of APC use. Factors associated with APC use and virtual care use were separately assessed for the 3 sites. RESULTS: Included in the first-stage models were datasets with total person-months of 7,055,549, 11,014,430, and 4,176,934, respectively. Older age, female sex, greater comorbidity, and Black race and Hispanic ethnicity were associated with higher likelihood of any APC use in any month; measures of greater patient cost-sharing were associated with a lower likelihood. Conditional on APC use, older age, and adults identifying as Black, Asian, or Hispanic were less likely to use virtual care. CONCLUSIONS: As the transition in health care continues to evolve, our findings suggest that to ensure vulnerable patient groups receive high quality health care, outreach interventions to reduce barriers to virtual care use may be warranted.

Virtual Care and Urinary Tract Infection Management: Comparing Ancillary Service Orders and Patient Order Fulfillments Between Virtual and In-person Encounters During the COVID-19 Pandemic in the United States.

BACKGROUND: During the COVID-19 pandemic, more health care issues were being managed remotely. Urinary tract infections (UTIs) are being managed more often using telehealth although few reports compare the rate of UTI ancillary service orders placed and fulfilled during these visits. OBJECTIVES: We aimed to evaluate and compare the rate of ancillary service orders and order fulfillments in incident UTI diagnoses between virtual and in-person encounters. RESEARCH DESIGN: The retrospective cohort study involved 3 integrated health care systems: Kaiser Permanente (KP) Colorado, KP Georgia, and KP Mid-Atlantic States. SUBJECTS: We included incident UTI encounters from adult primary care data from January 2019 to June 2021. MEASURES: Data were categorized as: prepandemic (January 2019-March 2020), COVID-19 Era 1 (April 2020-June 2020), and COVID-19 Era 2 (July 2020-June 2021). UTI-specific ancillary services included medication, laboratory, and imaging. Orders and order fulfillments were dichotomized for analyses. Weighted percentages for orders and fulfillments were calculated using inverse probability treatment weighting from logistic regression and compared between virtual and in-person encounters using χ2 tests. RESULTS: We identified 123,907 incident encounters. Virtual encounters increased from 13.4% prepandemic to 39.1% in COVID-19 Era 2. Ancillary service orders from virtual encounters were not placed as often as in-person encounters. However, the weighted percentage for ancillary service order fulfillment across all services remained above 65.3% across sites and eras, with many fulfillment percentages above 90%. CONCLUSIONS: Our study reported a high rate of order fulfillment for both virtual and in-person encounters. Health care systems should encourage providers to place ancillary service orders for uncomplicated diagnoses, such as UTI, to provide enhanced access to patient-centered care.

Health-care-Related Practices in Virtual Behavioral Health Treatment for Major Depression Before and During the COVID-19 Pandemic.

BACKGROUND: The abrupt shift to virtual care at the onset of the COVID-19 pandemic had the potential to disrupt care practices in virtual behavioral health encounters. We examined changes over time in virtual behavioral health-care-related practices for patient encounters with diagnoses of major depression. METHODS: This retrospective cohort study utilized electronic health record data from 3 integrated health care systems. Inverse probability of treatment weighting was used to adjust for covariates across 3 time periods, prepandemic (January 2019-March 2020), peak-pandemic shift to virtual care (April 2020-June 2020), and recovery of health care operations (July 2020-June 2021). First virtual follow-up behavioral health department encounters after an incident diagnostic encounter were examined for differences across the time periods in rates of antidepressant medication orders and fulfillments, and completion of patient-reported symptoms screeners in service of measurement-based care. RESULTS: Antidepressant medication orders declined modestly but significantly in 2 of the 3 systems during the peak-pandemic period but rebounded during the recovery period. There were no significant changes in patient fulfillment of ordered antidepressant medications. Completion of symptom screeners increased significantly in all 3 systems during the peak-pandemic period and continued to increase significantly in the subsequent period. CONCLUSIONS: A rapid shift to virtual behavioral health care was possible without compromising health-care-related practices. The transition and subsequent adjustment period have instead been marked by improved adherence to measurement-based care practices in virtual visits, signaling a potential new capacity for virtual health care delivery.

Development of a Common Data Model for a Multisite and Multiyear Study of Virtual Visit Implementation: A Case Study.

BACKGROUND/OBJECTIVE: In multisite studies, a common data model (CDM) standardizes dataset organization, variable definitions, and variable code structures and can support distributed data processing. We describe the development of a CDM for a study of virtual visit implementation in 3 Kaiser Permanente (KP) regions. METHODS: We conducted several scoping reviews to inform our study's CDM design: (1) virtual visit mode, implementation timing, and scope (targeted clinical conditions and departments); and (2) extant sources of electronic health record data to specify study measures. Our study covered the period from 2017 through June 2021. Integrity of the CDM was assessed by a chart review of random samples of virtual and in-person visits, overall and by specific conditions of interest (neck or back pain, urinary tract infection, major depression). RESULTS: The scoping reviews identified a need to address differences in virtual visit programs across the 3 KP regionsto harmonize measurement specifications for our research analyses. The final CDM contained patient-level, provider-level, and system-level measures on 7,476,604 person-years for KP members aged 19 years and above. Utilization included 2,966,112 virtual visits (synchronous chats, telephone visits, video visits) and 10,004,195 in-person visits. Chart review indicated the CDM correctly identified visit mode on>96% (n=444) of visits, and presenting diagnosis on >91% (n=482) of visits. CONCLUSIONS: Upfront design and implementation of CDMs may be resource intensive. Once implemented, CDMs, like the one we developed for our study, provide downstream programming and analytic efficiencies by harmonizing, in a consistent framework, otherwise idiosyncratic temporal and study site differences in source data.

Factor Analysis in Distinguishing Coronavirus Disease 2019 From Other Influenza-like Illness Using a Validated Patient-Reported Outcome Instrument FLU-PRO Plus: A Prospective Real-world Cohort Study.

BACKGROUND/OBJECTIVE: InFLUenza Patient-reported Outcome (FLU-PRO Plus) is a 34-item patient-reported outcome instrument designed to capture the intensity and frequency of viral respiratory symptoms. This study evaluates whether FLU-PRO Plus responses could discriminate between symptoms of coronavirus disease 2019 (COVID-19) and influenza-like illness (ILI) with no COVID diagnosis, as well as forecast disease progression. METHODS: FLU-PRO Plus was administered daily for 14 days. Exploratory factor analysis was used to reduce the FLU-PRO Plus responses on the first day to 3 factors interpreted as "symptom clusters." The 3 clusters were used to predict COVID-19 versus ILI diagnosis in logistic regression. Correlation between the clusters and quality of life (QoL) measures was used to assess concurrent validity. The timing of self-reported return to usual health in the 14-day period was estimated as a function of the clusters within COVID-19 and ILI groups. RESULTS: Three hundred fourteen patients completed day 1 FLU-PRO Plus, of which 65% had a COVID-19 diagnosis. Exploratory factor analysis identified 3 symptom clusters: (1)general Body, (2) tracheal/bronchial, and (3) nasopharyngeal. Higher nasopharyngeal scores were associated with higher odds of COVID-19 compared with ILI diagnosis [adjusted odds ratio = 1.61 (1.21, 2.12)]. Higher tracheal/bronchial scores were associated with lower odds of COVID-19 [0.58 (0.44, 0.77)]. The 3 symptom clusters were correlated with multiple QoL measures ( r = 0.14-0.56). Higher scores on the general body and tracheal/bronchial symptom clusters were associated with prolonged time to return to usual health [adjusted hazard ratios: 0.76 (0.64, 0.91), 0.80 (0.67, 0.96)]. CONCLUSION: Three symptom clusters identified from FLU-PRO Plus responses successfully discriminated patients with COVID-19 from non-COVID ILI and were associated with QoL and predicted symptom duration.

Prescription Opioid Dose Reductions and Potential Adverse Events: a Multi-site Observational Cohort Study in Diverse US Health Systems.

BACKGROUND: In response to the opioid crisis in the United States, population-level prescribing of opioids has been decreasing; there are concerns, however, that dose reductions are related to potential adverse events. OBJECTIVE: Examine associations between opioid dose reductions and risk of 1-month potential adverse events (emergency department (ED) visits, opioid overdose, benzodiazepine prescription fill, all-cause mortality). DESIGN: This observational cohort study used electronic health record and claims data from eight United States health systems in a prescription opioid registry (Clinical Trials Network-0084). All opioid fills (excluding buprenorphine) between 1/1/2012 and 12/31/2018 were used to identify baseline periods with mean morphine milligram equivalents daily dose of  ≥ 50 during six consecutive months. PATIENTS: We identified 60,040 non-cancer patients with  ≥ one 2-month dose reduction period (600,234 unique dose reduction periods). MAIN MEASURES: Analyses examined associations between dose reduction levels (1- < 15%, 15- < 30%, 30- < 100%, 100% over 2 months) and potential adverse events in the month following a dose reduction using logistic regression analysis, adjusting for patient characteristics. KEY RESULTS: Overall, dose reduction periods involved mean reductions of 18.7%. Compared to reductions of 1- < 15%, dose reductions of 30- < 100% were associated with higher odds of ED visits (OR 1.14, 95% CI 1.10, 1.17), opioid overdose (OR 1.41, 95% CI 1.09-1.81), and all-cause mortality (OR 1.39, 95% CI 1.16-1.67), but lower odds of a benzodiazepine fill (OR 0.83, 95% CI 0.81-0.85). Dose reductions of 15- < 30%, compared to 1- < 15%, were associated with higher odds of ED visits (OR 1.08, 95% CI 1.05-1.11) and lower odds of a benzodiazepine fill (OR 0.93, 95% CI 0.92-0.95), but were not associated with opioid overdose and all-cause mortality. CONCLUSIONS: Larger reductions for patients on opioid therapy may raise risk of potential adverse events in the month after reduction and should be carefully monitored.

Evaluation of a Natural Language Processing Approach to Identify Social Determinants of Health in Electronic Health Records in a Diverse Community Cohort.

BACKGROUND: Health care systems in the United States are increasingly interested in measuring and addressing social determinants of health (SDoH). Advances in electronic health record systems and Natural Language Processing (NLP) create a unique opportunity to systematically document patient SDoH from digitized free-text provider notes. METHODS: Patient SDoH status [recorded by Your Current Life Situation (YCLS) Survey] and associated provider notes recorded between March 2017 and June 2020 were extracted (32,261 beneficiaries; 50,722 YCLS surveys; 485,425 provider notes).NLP patterns were generated using a machine learning test statistic (Term Frequency-Inverse Document Frequency). Patterns were developed and assessed in a training, training validation, and final validation dataset (64%, 16%, and 20% of total data, respectively).NLP models analyzed SDoH-specific categories (housing, medical care, and transportation needs) and a combined SDoH metric. Model performance was assessed using sensitivity, specificity, and Cohen κ statistic, assuming the YCLS Survey to be the gold standard. RESULTS: Within the training validation dataset, NLP models showed strong sensitivity and specificity, with moderate agreement with the YCLS Survey (Housing: sensitivity=0.67, specificity=0.89, κ=0.51; Medical care: sensitivity=0.55, specificity=0.73, κ=0.20; Transportation: sensitivity=0.79, specificity=0.87, κ=0.58). Model performance in the training and training validation datasets were comparable.In the final validation dataset, a combined SDoH prediction metric showed sensitivity=0.77, specificity=0.69, κ=0.45. CONCLUSION: This NLP algorithm demonstrated moderate performance in identification of unmet patient social needs. This novel approach may enable improved targeting of interventions, allocation of limited resources and monitoring a health care system's addressing its patients' SDoH needs.

Systematic surveillance of patient-reported symptoms of viral respiratory tract infectious Syndromes in diverse populations.

BACKGROUND: Patient reported outcome measures (PROM) can improve patient care and be crucial for symptom tracking especially during disease outbreaks. FLU-PRO Plus is a validated PROM used to track viral respiratory symptoms. Our study aimed to evaluate the feasibility of using FLU-PRO© Plus, to track symptoms across three healthcare systems. METHODS: The prospective, longitudinal study recruited adults between February-May 2021 from HealthPartners Institute (HP), Kaiser Permanente Georgia (KPGA), and Kaiser Permanente Mid-Atlantic States (KPMAS). Adult members were eligible if they had a positive lab or diagnosis for either COVID-19 or influenza-like illness (ILI) or exhibited 2 + viral respiratory symptoms. Descriptive statistics were calculated to describe the patient characteristics for participants that were eligible for FLU-PRO Plus, successfully contacted, attempted to log in to the FLU-PRO Plus website, and participants who completed FLU-PRO Plus Day 1. Bivariable and multivariable logistic regression using PROC GLIMMIXX investigated the patient characteristics associated with (1) successful contact and (2) FLU-PRO Plus Day 1 completion. RESULTS: We identified a total of 15,650 eligible participants during the enrollment period: 9,582 from HP, 1,740 from KPGA, and 4,328 from KPMAS. Among the total of 409 eligible adults who attempted to participate in FLU-PRO Plus, 317 completed FLU-PRO Plus Day 1. Among the 317 individuals that completed FLU-PRO Plus Day 1, 205 (67.5%) were diagnosed with COVID-19; 112 adults diagnosed with COVID-19 completed FLU-PRO Plus Day 14. Among adults successfully contacted, adults aged 35-64 (OR = 1.40, 95% CI 1.05, 1.87), females (OR = 1.77, 95% CI 1.38, 2.27), and adults diagnosed with COVID-19 (OR = 1.66, 95% CI 1.27, 2.17) had higher odds of completing FLU-PRO Plus Day 1; Asian adults (OR = 0.38, 95% CI 0.19, 0.76) and Black and African American adults (OR = 0.33, 95% CI 0.19, 0.76) had lower odds compared to White adults. CONCLUSION: Our study reports on the feasibility of patients across three integrated healthcare systems utilizing FLU-PRO Plus to monitor their respiratory symptoms. Patient reported outcome measures (PROM) can improve patient care, quality of life, and reduce the strain of limited resources on healthcare systems. Future FLU-PRO Plus studies should develop an implementation strategy to fully integrate FLU-PRO Plus within clinical care and patient management.

Comparative Effectiveness of a Complex Care Program for High-Cost/High-Need Patients: a Retrospective Cohort Study.

BACKGROUND: High-cost/high-need (HCHN) adults and the healthcare systems that provide their care may benefit from a new patient-centered model of care involving a dedicated physician and nurse team who coordinate both clinical and social services for a small patient panel. OBJECTIVE: Evaluate the impact of a Complex Care Program (CCP) on likelihood of patient survival and hospital admission in 180 days following empanelment to the CCP. DESIGN: Retrospective cohort study using a quasi-experimental design with CCP patients propensity score matched to a concurrent control group of eligible but unempaneled patients. SETTING: Kaiser Permanente Mid-Atlantic States (KPMAS) during 2017-2018. PARTICIPANTS: Nine hundred twenty-nine CCP patients empaneled January 2017-June 2018, 929 matched control patients for the same period. INTERVENTIONS: The KPMAS CCP is a new program consisting of 8 teams each staffed by a physician and nurse who coordinate care across a continuum of specialty care, tertiary care, and community services for a panel of 200 patients with advanced clinical disease and recent hospitalizations. MAIN OUTCOMES: Time to death and time to first hospital admission in the 180 days following empanelment or eligibility. RESULTS: Compared to matched control patients, CCP patients had prolonged time to death (hazard ratio [HR]: 0.577, 95% CI: 0.474, 0.704), and CCP decedents had longer survival (median days 69.5 vs. 53.0, p=0.03). CCP patients had similar time to hospital admission (HR: 1.081, 95% CI: 0.930, 1.258), with similar results when adjusting for competing risk of death (HR: 1.062, 95% CI: 0.914, 1.084). LIMITATIONS: Non-randomized intervention; single healthcare system; patient eligibility limited to specific conditions. CONCLUSION: The KPMAS CCP was associated with significantly reduced short-term mortality risk for eligible patients who volunteered to participate in this intervention.

Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy.

BACKGROUND: The effect of gender affirming hormone therapy (GAHT) on clinical laboratory parameters, including levels of liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST), is an area of uncertainty in transgender health. AIM: We sought to estimate the distribution parameters of liver enzyme levels among transmasculine (TM) and transfeminine (TF) persons receiving GAHT relative to the corresponding measures in cisgender reference groups, and to evaluate longitudinal changes in these laboratory measures following GAHT initiation. METHODS: The data for this longitudinal study included 624 TF and 438 transmasculine (TM) people as well as 4,090 cisgender males and 4,797 cisgender females enrolled in 3 integrated health systems. Time under observation was divided into 2 intervals: from the first blood test to the date of the first filled GAHT prescription and from GAHT initiation to the most recent ALT or AST measurement. Linear mixed models were used to compare changes in log-transformed ALT and AST values among transgender cohort members before and after GAHT initiation, and relative to the reference groups. The results were expressed as relative differences (in %) and the ratios of these differences (ratios-of-ratios) along with the 95% confidence intervals (CIs). OUTCOMES: Changes in ALT and AST levels among transgender people over time and relative to the corresponding changes in cisgender referents. RESULTS: Among TM study participants, the post GAHT ratios-of-ratios for AST were 1.61 (95% CI: 1.13, 2.31) and 1.57 (95% CI: 1.06, 2.31) relative to cisgender males and females respectively. For ALT, the corresponding comparisons yielded the ratios-of-ratios (95% CIs) of 2.06 (1.67, 2.54) and 1.90 (1.50, 2.40). No statistically significant changes were observed among TF participants. Other factors associated with higher liver enzyme levels included alcohol use/abuse and obesity. CLINICAL IMPLICATIONS: TM persons may experience modest increases in ALT and AST concentrations following testosterone initiation; however, clinical significance of the observed association remains unclear and requires further investigation. By contrast, feminizing GAHT is unlikely to induce appreciable changes in liver enzyme levels. STRENGTH AND LIMITATIONS: The strengths of this study are the longitudinal design and the ability to assemble an unselected cohort nested within large health systems. The main limitations include the lack of information on hormone levels and the inability to take into account GAHT doses and routes of administration. CONCLUSION: The influence of long-term GAHT on ALT and AST levels appears modest and not likely to reflect clinically meaningful changes in liver function. Hashemi L, Zhang Q, Getahun D, et al. Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy. J Sex Med 2021;18:1662-1675.

Physician adjudication of angioedema diagnosis codes in a population of patients with heart failure prescribed angiotensin-converting enzyme inhibitor therapy.

PURPOSE: Our objective was to calculate the positive predictive value (PPV) of the ICD-9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter-rater reliability of physician adjudication. METHODS: Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin-converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included. A team of two physicians per participating site adjudicated possible events using electronic health records for all patients coded for angioedema for a total of five sites. The PPV was calculated as the number of physician-adjudicated cases divided by all cases with the diagnosis code of angioedema (ICD-9-CM code 995.1) meeting the inclusion criteria. The inter-rater reliability of physician teams, or kappa statistic, was also calculated. RESULTS: There were 38 061 adults with heart failure initiating ACEI in the study (21 489 patient-years). Of 114 coded events that were adjudicated by physicians, 98 angioedema events were confirmed for a PPV of 86% (95% CI: 80%, 92%). The kappa statistic based on physician inter-rater reliability was 0.65 (95% CI: 0.47, 0.82). CONCLUSIONS: ICD-9 diagnosis code of 995.1 (angioneurotic edema, not elsewhere classified) is highly predictive of angioedema in adults with heart failure exposed to ACEI.

Changes in Size and Demographic Composition of Transgender and Gender Non-Binary Population Receiving Care at Integrated Health Systems.

OBJECTIVE: To examine temporal changes in the number and demographic composition of transgender/gender non-binary (TGNB) population using data from integrated health care systems. METHODS: Electronic health records from Kaiser Permanente health plans in Georgia and Northern and Southern California were used to identify TGNB individuals, who sought care from January 2006 to December 2014, and the data were analyzed by year, site, age, and sex assigned at birth. RESULTS: In 2006, the number of TGNB people (and corresponding 95% CI) per 100 000 population were 3.5 (1.9, 6.3) in Georgia, 5.5 (4.8, 6.4) in Southern California, and 17 (16, 19) in Northern California. In 2014, these frequencies increased to 38 (32, 45), 44 (42, 46), and 75 (72, 78) per 100 000 population, respectively. When analyzed by age, the most rapid increase was observed among persons 18 to 25 years old, and this increase accelerated after 2010. The ratio of transmasculine to transfeminine persons also changed from 1:1.7 in 2006 to 1:1 in 2014 overall and from 1:1 in 2006 to 1.8:1 in 2014 among persons <18 years of age. CONCLUSION: This analysis confirms previous observations that the proportion of TGNB people is growing, especially among young adults. The composition of the TGNB population is also changing from predominantly transfeminine to roughly 1:1 overall and to predominantly transmasculine in children and adolescents.

Adaptive Validation Design: A Bayesian Approach to Validation Substudy Design With Prospective Data Collection.

An internal validation substudy compares an imperfect measurement of a variable with a gold-standard measurement in a subset of the study population. Validation data permit calculation of a bias-adjusted estimate, which has the same expected value as the association that would have been observed had the gold-standard measurement been available for the entire study population. Existing guidance on optimal sampling for validation substudies assumes complete enrollment and follow-up of the target cohort. No guidance exists for validation substudy design while cohort data are actively being collected. In this article, we use the framework of Bayesian monitoring methods to develop an adaptive approach to validation study design. This method monitors whether sufficient validation data have been collected to meet predefined criteria for estimation of the positive and negative predictive values. We demonstrate the utility of this method using the Study of Transition, Outcomes and Gender-a cohort study of transgender and gender nonconforming people. We demonstrate the method's ability to determine efficacy (when sufficient validation data have accumulated to obtain estimates of the predictive values that fall above a threshold value) and futility (when sufficient validation data have accumulated to conclude the mismeasured variable is an untenable substitute for the gold-standard measurement). This proposed method can be applied within the context of any parent epidemiologic study design and modified to meet alternative criteria given specific study or validation study objectives. Our method provides a novel approach to effective and efficient estimation of classification parameters as validation data accrue.

Visual Conformity With Affirmed Gender or "Passing": Its Distribution and Association With Depression and Anxiety in a Cohort of Transgender People.

BACKGROUND: Visual conformity with affirmed gender (VCAG) or "passing" is thought to be an important, but poorly understood, determinant of well-being in transgender people. VCAG is a subjective measure that is different from having an inner sense of being congruent with one's gender identity. AIM: We examined the frequency and determinants of VCAG and explored its association with mental health outcomes in a cohort of transgender adults. METHODS: The "Study of Transition, Outcomes & Gender (STRONG)" is a cohort of transgender individuals recruited from 3 Kaiser Permanente health plans located in Georgia, Northern California and Southern California. A subset of cohort members completed a survey between 2015 and 2017. VCAG was assessed as the difference between 2 scales: scale 1 reflecting the person's sense of how they are perceived by others, and scale 2 reflecting the person's desire to be perceived. Participants were considered to have achieved VCAG when their scale 1 scores were equal to or exceeded their scale 2 scores. The frequency of VCAG and their independent associations with anxiety and depression symptoms were explored using data from 620 survey respondents including 309 transwomen and 311 transmen. Based on self-described gender identity, none of the participants identified as nonbinary or gender fluid. OUTCOMES: VCAG, depression, and anxiety. RESULTS: VCAG was achieved in 28% of transwomen and 62% of transmen and was more common in persons who reported greater sense of acceptance and pride in their gender identity as measured on the Transgender Congruence Scale. Another factor associated with greater likelihood of VCAG was receipt of gender-affirming surgery, but the association was only evident among transmen. Participants who achieved VCAG had a lower likelihood of depression and anxiety with prevalence ratios (95% confidence intervals) of 0.79 (0.65, 0.96) and 0.67 (0.46, 0.98), respectively. CLINICAL IMPLICATIONS: VCAG may serve as an important outcome measure after gender-affirming therapy. STRENGTHS AND LIMITATIONS: Strengths of this study include a well-defined sampling frame and use of a novel patient-centered outcome of interest. Cross-sectional design and uncertain generalizability of results are the limitations. CONCLUSION: These results, once confirmed by prospective studies, may help better characterize the determinants of well-being in the transgender community, facilitating the design of interventions to improve the well-being and quality of life of this vulnerable population. To M, Zhang Q, Bradlyn A, et al. Visual Conformity With Affirmed Gender or "Passing": Its Distribution and Association With Depression and Anxiety in a Cohort of Transgender People. J Sex Med 2020;17:2084-2092.

Evaluating changes in ambient ozone and respiratory-related healthcare utilization in the Washington, DC metropolitan area.

Ozone pollution is a known respiratory irritant, yet we do not fully understand the magnitude or timing of respiratory effects based on short-term exposure. We investigated the associations between ambient ozone concentrations and respiratory symptoms as measured by healthcare utilization events. We used comprehensive electronic health records to identify respiratory responses to changes in ambient ozone levels. We constructed a dataset from Kaiser Permanente Mid-Atlantic States (KPMAS) that included information on 2013 and 2014 daily utilization rates for a broad range of healthcare utilization - nurse calls/emails, provider visits, emergency department and urgent care visits (ED/UC) and hospital admissions - by census block. We used 8-h average ozone concentrations collected from 48 air monitoring stations in the region via the Air Data database of the USEPA. We estimated the association between changes in ambient ozone (exposure windows of current day, 1-day lag and 3-day moving average) and changes in healthcare utilization using linear regression controlling for census tract-level socioeconomic indicators and temperature. Increases in ozone were associated with increases in three of the four utilization event types. A 10 ppb increase in 1-day ozone was associated with a 2.95% (95% CI: 1.93%, 3.96%) increase in calls/emails, a 1.56% (95% CI: 0.38%, 2.74%) increase in ED/UC visits and a 1.10% (95% CI: 0.48%, 1.73%) increase in provider visits. We did not find associations between ozone and hospital admissions. Proportionally, highest effects were found for nurse calls/emails possibly indicating a high number of mild effects that may be underreported in studies that examine only ED visits or hospital admissions.

Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons: A Cohort Study.

Background: Venous thromboembolism (VTE), ischemic stroke, and myocardial infarction in transgender persons may be related to hormone use. Objective: To examine the incidence of these events in a cohort of transgender persons. Design: Electronic medical record-based cohort study of transgender members of integrated health care systems who had an index date (first evidence of transgender status) from 2006 through 2014. Ten male and 10 female cisgender enrollees were matched to each transgender participant by year of birth, race/ethnicity, study site, and index date enrollment. Setting: Kaiser Permanente in Georgia and northern and southern California. Patients: 2842 transfeminine and 2118 transmasculine members with a mean follow-up of 4.0 and 3.6 years, respectively, matched to 48 686 cisgender men and 48 775 cisgender women. Measurements: VTE, ischemic stroke, and myocardial infarction events ascertained from diagnostic codes through the end of 2016 in transgender and reference cohorts. Results: Transfeminine participants had a higher incidence of VTE, with 2- and 8-year risk differences of 4.1 (95% CI, 1.6 to 6.7) and 16.7 (CI, 6.4 to 27.5) per 1000 persons relative to cisgender men and 3.4 (CI, 1.1 to 5.6) and 13.7 (CI, 4.1 to 22.7) relative to cisgender women. The overall analyses for ischemic stroke and myocardial infarction demonstrated similar incidence across groups. More pronounced differences for VTE and ischemic stroke were observed among transfeminine participants who initiated hormone therapy during follow-up. The evidence was insufficient to allow conclusions regarding risk among transmasculine participants. Limitation: Inability to determine which transgender members received hormones elsewhere. Conclusion: The patterns of increases in VTE and ischemic stroke rates among transfeminine persons are not consistent with those observed in cisgender women. These results may indicate the need for long-term vigilance in identifying vascular side effects of cross-sex estrogen. Primary Funding Source: Patient-Centered Outcomes Research Institute and Eunice Kennedy Shriver National Institute of Child Health and Human Development.