Burden of Medically Attended Diarrhea and Outpatient Clostridioides difficile Infection Among Persons in 2 Large Integrated Healthcare Settings, 2016-2021.

Background: Identification of Clostridioides difficile infection (CDI) in the community setting is increasing. We describe testing for CDI among patients with medically attended diarrhea (MAD) in the outpatient setting, and the incidence of outpatient CDI. Methods: This was a retrospective cohort study among members ≥18 years of age from Kaiser Permanente Southern California and Kaiser Permanente Northwest from 1 January 2016 through 31 December 2021. MAD was identified by outpatient diarrheal International Classification of Diseases, Tenth Revision diagnosis codes, and CDI through positive laboratory results. Outpatient CDI was defined by no hospitalization ≤7 days after specimen collection. Incidence rates (IRs) of outpatient CDI were stratified by select demographic and clinical variables. Outpatient CDI burden 12 months following index date was measured by CDI-associated healthcare visits, and CDI testing and treatment. Results: We identified 777 533 MAD episodes; 12.1% (93 964/777 533) were tested for CDI. Of those tested, 10.8% (10 110/93 964) were positive. Outpatient CDI IR was 51.0 (95% confidence interval [CI], 49.8-52.2) per 100 000 person-years, decreasing from 58.2 (95% CI, 55.7-60.7) in 2016 to 45.7 (95% CI, 43.7-47.8) in 2021. Approximately 44% (n = 4200) received an antibiotic 30 days prior to index date and 84.1% (n = 8006) CDIs were "community-associated" (no hospitalizations 12 weeks prior to index date). Of outpatient CDIs, 6.7% (n = 526) had a CDI-associated hospitalization ≤12 months. Conclusions: There was a high incidence of outpatient CDI despite infrequent CDI testing among patients with MAD. The majority of those with outpatient CDI had no recent antibiotic use and no recent hospitalization. Further studies are needed to understand the source and management of medically attended outpatient CDI.

Dexamethasone Suppression Testing in a Contemporary Cohort with Adrenal Incidentalomas in Two U.S. Integrated Healthcare Systems.

Autonomous cortisol secretion (ACS) from an adrenal adenoma can increase the risk for comorbidities and mortality. The dexamethasone suppression test (DST) is the standard method to diagnose ACS. A multi-site, retrospective cohort of adults with diagnosed adrenal tumors was used to understand patient characteristics associated with DST completion and ACS. Time to DST completion was defined using the lab value and result date; follow-up time was from the adrenal adenoma diagnosis to the time of completion or censoring. ACS was defined by a DST > 1.8 µg/dL (50 nmol/L). The Cox proportional hazards regression model assessed associations between DST completion and patient characteristics. In patients completing a DST, a logistic regression model evaluated relationships between elevated ACS and covariates. We included 24,259 adults, with a mean age of 63.1 years, 48.1% obese, and 28.7% with a Charlson comorbidity index ≥ 4. Approximately 7% (n = 1768) completed a DST with a completion rate of 2.36 (95% CI 2.35, 2.37) per 100 person-years. Fully adjusted models reported that male sex and an increased Charlson comorbidity index were associated with a lower likelihood of DST completion. Current or former smoking status and an increased Charlson comorbidity index had higher odds of a DST > 1.8 µg/dL. In conclusion, clinical policies are needed to improve DST completion and the management of adrenal adenomas.

Clinical Risk Scores to Predict Nonsusceptibility to Trimethoprim-Sulfamethoxazole, Fluoroquinolone, Nitrofurantoin, and Third-Generation Cephalosporin Among Adult Outpatient Episodes of Complicated Urinary Tract Infection.

Background: Clinical risk scores were developed to estimate the risk of adult outpatients having a complicated urinary tract infection (cUTI) that was nonsusceptible to trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolone, nitrofurantoin, or third-generation cephalosporin (3-GC) based on variables available on clinical presentation. Methods: A retrospective cohort study (1 December 2017-31 December 2020) was performed among adult members of Kaiser Permanente Southern California with an outpatient cUTI. Separate risk scores were developed for TMP-SMX, fluoroquinolone, nitrofurantoin, and 3-GC. The models were translated into risk scores to quantify the likelihood of nonsusceptibility based on the presence of final model covariates in a given cUTI outpatient. Results: A total of 30 450 cUTIs (26 326 patients) met the study criteria. Rates of nonsusceptibility to TMP-SMX, fluoroquinolone, nitrofurantoin, and 3-GC were 37%, 20%, 27%, and 24%, respectively. Receipt of prior antibiotics was the most important predictor across all models. The risk of nonsusceptibility in the TMP-SMX model exceeded 20% in the absence of any risk factors, suggesting that empiric use of TMP-SMX may not be advisable. For fluoroquinolone, nitrofurantoin, and 3-GC, clinical risk scores of 10, 7, and 11 predicted a ≥20% estimated probability of nonsusceptibility in the models that included cumulative number of prior antibiotics at model entry. This finding suggests that caution should be used when considering these agents empirically in patients who have several risk factors present in a given model at presentation. Conclusions: We developed high-performing parsimonious risk scores to facilitate empiric treatment selection for adult outpatients with cUTIs in the critical period between infection presentation and availability of susceptibility results.

Multidrug Resistance of Escherichia coli From Outpatient Uncomplicated Urinary Tract Infections in a Large United States Integrated Healthcare Organization.

Background: Urinary tract infections (UTIs) cause significant disease and economic burden. Uncomplicated UTIs (uUTIs) occur in otherwise healthy individuals without underlying structural abnormalities, with uropathogenic Escherichia coli (UPEC) accounting for 80% of cases. With recent transitions in healthcare toward virtual visits, data on multidrug resistance (MDR) (resistant to ≥3 antibiotic classes) by care setting are needed to inform empiric treatment decision making. Methods: We evaluated UPEC resistance over time by care setting (in-person vs virtual), in adults who received outpatient care for uUTI at Kaiser Permanente Southern California between January 2016 and December 2021. Results: We included 174 185 individuals who had ≥1 UPEC uUTI (233 974 isolates) (92% female, 46% Hispanic, mean age 52 years [standard deviation 20]). Overall, prevalence of UPEC MDR decreased during the study period (13% to 12%) both in virtual and in-person settings (P for trend <.001). Resistance to penicillins overall (29%), coresistance to penicillins and trimethoprim-sulfamethoxazole (TMP-SMX) (12%), and MDR involving the 2 plus ≥1 antibiotic class were common (10%). Resistance to 1, 2, 3, and 4 antibiotic classes was found in 19%, 18%, 8%, and 4% of isolates, respectively; 1% were resistant to ≥5 antibiotic classes, and 50% were resistant to none. Similar resistance patterns were observed over time and by care setting. Conclusions: We observed a slight decrease in both class-specific antimicrobial resistance and MDR of UPEC overall, most commonly involving penicillins and TMP-SMX. Resistance patterns were consistent over time and similar in both in-person and virtual settings. Virtual healthcare may expand access to UTI care.

Impact of a scalable training program on the quality of colonoscopy performance and risk of postcolonoscopy colorectal cancer.

BACKGROUND AND AIMS: Endoscopist adenoma detection rates (ADRs) vary widely and are associated with patients' risk of postcolonoscopy colorectal cancers (PCCRCs). However, few scalable physician-directed interventions demonstrably both improve ADR and reduce PCCRC risk. METHODS: Among patients undergoing colonoscopy, we evaluated the influence of a scalable online training on individual-level ADRs and PCCRC risk. The intervention was a 30-minute, interactive, online training, developed using behavior change theory, to address factors that potentially impede detection of adenomas. Analyses included interrupted time series analyses for pretraining versus posttraining individual-physician ADR changes (adjusted for temporal trends) and Cox regression for associations between ADR changes and patients' PCCRC risk. RESULTS: Across 21 endoscopy centers and all 86 eligible endoscopists, ADRs increased immediately by an absolute 3.13% (95% confidence interval [CI], 1.31-4.94) in the 3-month quarter after training compared with .58% per quarter (95% CI, .40-.77) and 0.33% per quarter (95% CI, .16-.49) in the 3-year pretraining and posttraining periods, respectively. Posttraining ADR increases were higher among endoscopists with pretraining ADRs below the median. Among 146,786 posttraining colonoscopies (all indications), each 1% absolute increase in screening ADR posttraining was associated with a 4% decrease in their patients' PCCRC risk (hazard ratio, .96; 95% CI, .93-.99). An ADR increase of ≥10% versus <1% was associated with a 55% reduced risk of PCCRC (hazard ratio, .45; 95% CI, .24-.82). CONCLUSIONS: A scalable, online behavior change training intervention focused on modifiable factors was associated with significant and sustained improvements in ADR, particularly among endoscopists with lower ADRs. These ADR changes were associated with substantial reductions in their patients' risk of PCCRC.

Factors Associated With Firearm Injury Among Pediatric Members of a Large Integrated Healthcare System.

BACKGROUND AND OBJECTIVES: Few studies have tested multiple socio-ecological risk factors assocated with firearm injury among pediatric populations and distinguished self-inflicted from non-self-inflicted injury. To address this gap, the current study examined demographic, individual psychosocial, and neighborhood variables as risk factors for firearm injury among a large cohort of children and adolescents. METHODS: Retrospective cohort study. Data were obtained from the electronic health records of a large integrated healthcare system. The cohort included children <18 years with at least one clinical encounter between January 1, 2010 and December 31, 2018. Poisson regression was used to examine demographic (age, gender, race and ethnicity, Medicaid status), psychosocial (depression, substance use disorder, medical comorbidities), and neighborhood education variables as potential risk factors for non-self-inflicted and self-inflicted firearm injuries. RESULTS: For non-self-inflicted injury, the highest relative risk was found for children age 12-17 years old compared to 0-5 year olds (RR = 37.57); other risk factors included male gender, Black and Hispanic race and ethnicity (compared to White race), being a Medicaid recipient, lower neighborhood education, and substance use disorder diagnosis. For self-inflicted injury, only age 12-17 years old and male gender were associated with increased risk. CONCLUSIONS: These results reinforce the established higher risk for firearm injury among adolescent males, highlight differences between self-inflicted and non-self-inflicted injuries, and the need to consider demographic, psychosocial, and neighborhood variables as risk factors to inform interventions aimed to reduce firearm injuries among children and adolescents.

Cohort profile: pathways to care among people with disorders of sex development (DSD).

PURPOSE: The 'DSD Pathways' study was initiated to assess health status and patterns of care among people enrolled in large integrated healthcare systems and diagnosed with conditions comprising the broad category of disorders (differences) of sex development (DSD). The objectives of this communication are to describe methods of cohort ascertainment for two specific DSD conditions-classic congenital adrenal hyperplasia with 46,XX karyotype (46,XX CAH) and complete androgen insensitivity syndrome (CAIS). PARTICIPANTS: Using electronic health records we developed an algorithm that combined diagnostic codes, clinical notes, laboratory data and pharmacy records to assign each cohort candidate a 'strength-of-evidence' score supporting the diagnosis of interest. A sample of cohort candidates underwent a review of the full medical record to determine the score cutoffs for final cohort validation. FINDINGS TO DATE: Among 5404 classic 46,XX CAH cohort candidates the strength-of-evidence scores ranged between 0 and 10. Based on sample validation, the eligibility cut-off for full review was set at the strength-of-evidence score of ≥7 among children under the age of 8 years and ≥8 among older cohort candidates. The final validation of all cohort candidates who met the cut-off criteria identified 115 persons with classic 46,XX CAH. The strength-of-evidence scores among 648 CAIS cohort candidates ranged from 2 to 10. There were no confirmed CAIS cases among cohort candidates with scores <6. The in-depth medical record review for candidates with scores ≥6 identified 61 confirmed cases of CAIS. FUTURE PLANS: As the first cohort of this type, the DSD Pathways study is well-positioned to fill existing knowledge gaps related to management and outcomes in this heterogeneous population. Analyses will examine diagnostic and referral patterns, adherence to care recommendations and physical and mental health morbidities examined through comparisons of DSD and reference populations and analyses of health status across DSD categories.

Association of Physician Adenoma Detection Rates With Postcolonoscopy Colorectal Cancer.

Importance: Although colonoscopy is frequently performed in the United States, there is limited evidence to support threshold values for physician adenoma detection rate as a quality metric. Objective: To evaluate the association between physician adenoma detection rate values and risks of postcolonoscopy colorectal cancer and related deaths. Design, Setting, and Participants: Retrospective cohort study in 3 large integrated health care systems (Kaiser Permanente Northern California, Kaiser Permanente Southern California, and Kaiser Permanente Washington) with 43 endoscopy centers, 383 eligible physicians, and 735 396 patients aged 50 to 75 years who received a colonoscopy that did not detect cancer (negative colonoscopy) between January 2011 and June 2017, with patient follow-up through December 2017. Exposures: The adenoma detection rate of each patient's physician based on screening examinations in the calendar year prior to the patient's negative colonoscopy. Adenoma detection rate was defined as a continuous variable in statistical analyses and was also dichotomized as at or above vs below the median for descriptive analyses. Main Outcomes and Measures: The primary outcome (postcolonoscopy colorectal cancer) was tumor registry-verified colorectal adenocarcinoma diagnosed at least 6 months after any negative colonoscopy (all indications). The secondary outcomes included death from postcolonoscopy colorectal cancer. Results: Among 735 396 patients who had 852 624 negative colonoscopies, 440 352 (51.6%) were performed on female patients, median patient age was 61.4 years (IQR, 55.5-67.2 years), median follow-up per patient was 3.25 years (IQR, 1.56-5.01 years), and there were 619 postcolonoscopy colorectal cancers and 36 related deaths during more than 2.4 million person-years of follow-up. The patients of physicians with higher adenoma detection rates had significantly lower risks for postcolonoscopy colorectal cancer (hazard ratio [HR], 0.97 per 1% absolute adenoma detection rate increase [95% CI, 0.96-0.98]) and death from postcolonoscopy colorectal cancer (HR, 0.95 per 1% absolute adenoma detection rate increase [95% CI, 0.92-0.99]) across a broad range of adenoma detection rate values, with no interaction by sex (P value for interaction = .18). Compared with adenoma detection rates below the median of 28.3%, detection rates at or above the median were significantly associated with a lower risk of postcolonoscopy colorectal cancer (1.79 vs 3.10 cases per 10 000 person-years; absolute difference in 7-year risk, -12.2 per 10 000 negative colonoscopies [95% CI, -10.3 to -13.4]; HR, 0.61 [95% CI, 0.52-0.73]) and related deaths (0.05 vs 0.22 cases per 10 000 person-years; absolute difference in 7-year risk, -1.2 per 10 000 negative colonoscopies [95%, CI, -0.80 to -1.69]; HR, 0.26 [95% CI, 0.11-0.65]). Conclusions and Relevance: Within 3 large community-based settings, colonoscopies by physicians with higher adenoma detection rates were significantly associated with lower risks of postcolonoscopy colorectal cancer across a broad range of adenoma detection rate values. These findings may help inform recommended targets for colonoscopy quality measures.

Sexually Transmitted Infections Among Men and Transgender Women Using HIV Pre-exposure Prophylaxis in a Large Integrated Health System-A Cohort Study.

BACKGROUND: Sexually transmitted infections (STIs) are common in people using pre-exposure prophylaxis (PrEP). We examined risk and factors associated with STIs in a cohort of PrEP users in an integrated health system in the United States. SETTING: The Kaiser Permanente Southern California is a large integrated health system that provides comprehensive medical services to approximately 4.7 million demographically diverse members. METHODS: We identified men and transgender women initiating PrEP between January 1, 2014, and June 1, 2018, and followed through December 31, 2018. Demographic and clinical factors potentially associated with the risk of bacterial STIs during PrEP use were evaluated using Poisson regression models. RESULTS: Among 5042 individuals tested for STIs with 7198 person-years of follow-up, 1709 (33.9%) had at least one new STI. The estimated incidence of STIs was 48.3 per 100 person-years, and the most common STI was rectal chlamydia. Most repeat STIs (61.4%) occurred <180 days apart. In a multivariable analysis, an history of STIs in the prior 6 months through 7 days after the PrEP initiation was the most prominent risk factor of STIs during PrEP use (adjusted risk ratio: 1.78, 95% confidence intervals: 1.65 to 1.93). Other risk factors included younger age (<35 years), being Hispanic, and having a history of alcohol use disorder or drug use disorder. CONCLUSIONS: Quarterly STI testing and targeted intervention to mitigate STI risk are warranted for young and racial minority PrEP users, particularly for those with prior history of STIs and substance use disorders.

Referral Linkage to Preexposure Prophylaxis Care and Persistence on Preexposure Prophylaxis in an Integrated Health Care System.

BACKGROUND: Successful linkage to preexposure prophylaxis (PrEP) and retention in care are important for HIV prevention. We examined gaps in PrEP care following referral and factors associated with PrEP linkage and persistence in an integrated health care system in the United States. METHODS: We identified individuals referred for PrEP from 2014 to 2017 at the Kaiser Permanente Southern California using electronic health records and assessed linkage to care, PrEP prescription orders and fills, and PrEP persistence (medication possession ratio ≥80%) in the year after the first fill. We evaluated demographic and clinical factors potentially associated with PrEP linkage and persistence using a series of multivariable modified Poisson regression models. RESULTS: Of 2995 referred individuals, 74.9% were linked to PrEP care. Nearly all those linked to care were prescribed PrEP and filled a prescription, but only 47.4% of those who filled a prescription were persistent on PrEP. Individuals aged <25 years (vs ≥25 years), female subjects (vs males), and individuals with high-deductible insurance (vs no high deductible) were less likely to be linked to care. Individuals aged <25 years and Hispanics (vs non-Hispanic whites) were less likely to be persistent. Those with alcohol use disorder were more likely to be linked to PrEP care but less likely to be persistent. New HIV diagnoses occurred in 38 individuals, and only 1 had PrEP in possession at diagnosis. CONCLUSIONS: We observed PrEP care gaps and disparities among individuals referred for PrEP. Patient-centered interventions are needed in primary care to address barriers to successful PrEP linkage and persistence.

An automated algorithm using free-text clinical notes to improve identification of transgender people.

Accurate identification of transgender persons is a critical first step in conducting transgender health studies. To develop an automated algorithm for identifying transgender individuals from electronic medical records (EMR) using free-text clinical notes. The development and validation of the algorithm was based on data from an integrated healthcare system that served as a participating site in the multicenter Study of Transition Outcomes and Gender. The training and test datasets each contained a total of 300 individuals identified between 2006 and 2014. Both datasets underwent a full medical record review by experienced research abstractors. The validated algorithm was then implemented to identify transgender individuals in the EMR using all clinical notes of patients that received care between January 1, 2015 and June 30, 2018. Validation of the algorithm against the full chart review demonstrated a high degree of accuracy with 97% sensitivity, 95% specificity, 94% positive predictive value, and 97% negative predictive value. The algorithm classified 7,409 individuals (3.5%) as "Definitely transgender" and 679 individuals (0.3%) as "Probably transgender" out of 212,138 candidates with a total of 378,641 clinical notes. The computerized NLP algorithm can support essential efforts to improve the health of transgender people.

Healthcare Effectiveness Data and Information Set (HEDIS) measures of alcohol and drug treatment initiation and engagement among people living with the human immunodeficiency virus (HIV) and patients without an HIV diagnosis.

Background: Problematic use of alcohol and other drugs (AOD) is highly prevalent among people living with the human immunodeficiency virus (PLWH), and untreated AOD use disorders have particularly detrimental effects on human immunodeficiency virus (HIV) outcomes. The Healthcare Effectiveness Data and Information Set (HEDIS) measures of treatment initiation and engagement are important benchmarks for access to AOD use disorder treatment. To inform improved patient care, we compared HEDIS measures of AOD use disorder treatment initiation and engagement and health care utilization among PLWH and patients without an HIV diagnosis. Methods: Patients with a new AOD use disorder diagnosis documented between October 1, 2014, and August 15, 2015, were identified using electronic health records (EHR) and insurance claims data from 7 health care systems in the United States. Demographic characteristics, clinical diagnoses, and health care utilization data were also obtained. AOD use disorder treatment initiation and engagement rates were calculated using HEDIS measure criteria. Factors associated with treatment initiation and engagement were examined using multivariable logistic regression models. Results: There were 469 PLWH (93% male) and 86,096 patients without an HIV diagnosis (60% male) in the study cohort. AOD use disorder treatment initiation was similar in PLWH and patients without an HIV diagnosis (10% vs. 11%, respectively). Among those who initiated treatment, few engaged in treatment in both groups (9% PLWH vs. 12% patients without an HIV diagnosis). In multivariable analysis, HIV status was not significantly associated with either AOD use disorder treatment initiation or engagement. Conclusions: AOD use disorder treatment initiation and engagement rates were low in both PLWH and patients without an HIV diagnosis. Future studies need to focus on developing strategies to efficiently integrate AOD use disorder treatment with medical care for HIV.

The Be-Well Study: a prospective cohort study of lifestyle and genetic factors to reduce the risk of recurrence and progression of non-muscle-invasive bladder cancer.

PURPOSE: Bladder cancer is one of the top five cancers diagnosed in the U.S. with a high recurrence rate, and also one of the most expensive cancers to treat over the life-course. However, there are few observational, prospective studies of bladder cancer survivors. METHODS: The Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study) is a National Cancer Institute-funded, multi-center prospective cohort study of non-muscle-invasive bladder cancer (NMIBC) patients (Stage Ta, T1, Tis) enrolled from the Kaiser Permanente Northern California (KPNC) and Southern California (KPSC) health care systems, with genotyping and biomarker assays performed at Roswell Park Comprehensive Cancer Center. The goal is to investigate diet and lifestyle factors in recurrence and progression of NMIBC, with genetic profiles considered, and to build a resource for future NMIBC studies. RESULTS: Recruitment began in February 2015. As of 30 June 2018, 1,281 patients completed the baseline interview (774 KPNC, 511 KPSC) with a recruitment rate of 54%, of whom 77% were male and 23% female, and 80% White, 6% Black, 8% Hispanic, 5% Asian, and 2% other race/ethnicity. Most patients were diagnosed with Ta (69%) or T1 (27%) tumors. Urine and blood specimens were collected from 67% and 73% of consented patients at baseline, respectively. To date, 599 and 261 patients have completed the 12- and 24-month follow-up questionnaires, respectively, with additional urine and saliva collection. CONCLUSIONS: The Be-Well Study will be able to answer novel questions related to diet, other lifestyle, and genetic factors and their relationship to recurrence and progression among early-stage bladder cancer patients.

Colorectal Cancer Screening Participation Among Asian Americans Overall and Subgroups in an Integrated Health Care Setting with Organized Screening.

BACKGROUND: Screening reduces colorectal cancer deaths, but <50% of Asian Americans are screening up-to-date according to surveys, with variability across Asian subgroups. We examined colorectal cancer screening participation among Asian Americans overall and Asian subgroups in a large integrated health care system with organized screening. METHODS: Data were electronically accessed to characterize screening in 2016 for Asians overall and subgroups relative to the National Colorectal Cancer Roundtable target of ≥80% screening and compared with non-Hispanic whites. Screening up-to-date was defined as a colonoscopy with 10 years, a sigmoidoscopy within 5 years, or a fecal immunochemical test (FIT) completed in 2016. RESULTS: Among 436,398 patients, 69,826 (16.0%) were Asian, of whom 79.8% were screening up-to-date vs. 77.6% of non-Hispanic whites (p < 0.001). Almost all subgroups met the 80% target: Chinese (83.3%), Vietnamese (82.4%), Korean (82.1%), other Asian (80.3%), Filipino (78.7%), Asian Indian (79.6%), and Japanese (79.0%). Among Asians overall and non-Hispanic whites, 50.6% and 48.4% of members were up-to-date with screening by colonoscopy, and 28.0% and 28.2% were up-to-date by FIT, respectively. Across Asian subgroups, colonoscopy most frequently accounting for being screening up-to-date (range: 47.4-59.7%), followed by FIT (range: 21.6-31.5%). CONCLUSIONS: In an organized screening setting, there were minimal differences in screening participation among Asian subgroups and almost all met the 80% screening target, despite differences in language preference. Screening test type differences across subgroups suggest possible preferences in screening modality, which can inform future research into tailored education or outreach.

Influence of Varying Quantitative Fecal Immunochemical Test Positivity Thresholds on Colorectal Cancer Detection: A Community-Based Cohort Study.

Background: The fecal immunochemical test (FIT) is commonly used for colorectal cancer (CRC) screening. Despite demographic variations in stool hemoglobin concentrations, few data exist regarding optimal positivity thresholds by age and sex. Objective: To identify programmatic (multitest) FIT performance characteristics and optimal FIT quantitative hemoglobin positivity thresholds in a large, population-based, screening program. Design: Retrospective cohort study. Setting: Kaiser Permanente Northern and Southern California. Participants: Adults aged 50 to 75 years who were eligible for screening and had baseline quantitative FIT results (2013 to 2014) and 2 years of follow-up. Nearly two thirds (411 241) had FIT screening in the previous 2 years. Measurements: FIT programmatic sensitivity for CRC and number of positive test results per cancer case detected, overall and by age and sex. Results: Of 640 859 persons who completed a baseline FIT and were followed for 2 years, 481 817 (75%) had at least 1 additional FIT and 1245 (0.19%) received a CRC diagnosis. Cancer detection (programmatic sensitivity) increased at lower positivity thresholds, from 822 in 1245 (66.0%) at 30 µg/g to 925 (74.3%) at 20 µg/g and 987 (79.3%) at 10 µg/g; the number of positive test results per cancer case detected increased from 43 at 30 µg/g to 52 at 20 µg/g and 85 at 10 µg/g. Reducing the positivity threshold from 20 to 15 µg/g would detect 3% more cancer cases and require 23% more colonoscopies. At the conventional FIT threshold of 20 µg/g, programmatic sensitivity decreased with increasing age (79.0%, 73.4%, and 68.9% for ages 50 to 59, 60 to 69, and 70 to 75 years, respectively; P = 0.009) and was higher in men than women (77.0% vs. 70.6%; P = 0.011). Limitation: Information on advanced adenoma was lacking. Conclusion: Increased cancer detection at lower positivity thresholds is counterbalanced by substantial increases in positive tests. Tailored thresholds may provide screening benefits that are more equal among different demographic groups, depending on local resources. Primary Funding Source: National Cancer Institute.

Testing for Coccidioidomycosis among Community-Acquired Pneumonia Patients, Southern California, USA1.

We conducted a cohort study to identify characteristics associated with testing for, and testing positive for, coccidioidomycosis among patients with community-acquired pneumonia in southern California, USA. Limited and delayed testing probably leads to underdiagnosis among non-Hispanic black, Filipino, or Hispanic patients and among high-risk groups, including persons in whom antimicrobial drug therapy has failed.

TREATMENT PATTERNS AND 2-YEAR VISION OUTCOMES WITH BEVACIZUMAB IN DIABETIC MACULAR EDEMA: An Analysis From a Large U.S. Integrated Health Care System.

PURPOSE: To assess health care utilization and vision outcomes over 2 years in patients receiving bevacizumab treatment in clinical practice for diabetic macular edema. METHODS: Patients with newly diagnosed diabetic macular edema who received an intravitreal bevacizumab injection within 12 months of initial diagnosis were identified from Kaiser Permanente's 350,000 patients with diabetes mellitus treated between 2008 and 2013. Snellen best-corrected visual acuity (BCVA), number of intravitreal injections, and patient characteristics were abstracted from the electronic record. The main outcome measure was change in BCVA. RESULTS: Three hundred and nine patients met the inclusion criteria and had 2 years of follow-up after their first bevacizumab injection. These patients had a mean of 3.1 injections (range, 1-17) during the 2-year follow-up. Mean BCVA improvement was 5.4 letters at 12 months and 5.3 letters at 24 months. Only 29.8% of patients demonstrated ≥3 lines of vision improvement from baseline, whereas 12.3% had ≥3 lines of vision loss from baseline at 24 months. CONCLUSION: This is the largest U.S. clinical practice-based study of bevacizumab use in diabetic macular edema. Consistent with national studies, the frequency of injection was low. Average BCVA improvement was lower than in anti-vascular endothelial growth factor trials. Significant BCVA improvement was achieved in approximately 30% of patients with newly diagnosed diabetic macular edema.

Cohort profile: Study of Transition, Outcomes and Gender (STRONG) to assess health status of transgender people.

PURPOSE: The Study of Transition, Outcomes and Gender (STRONG) was initiated to assess the health status of transgender people in general and following gender-affirming treatments at Kaiser Permanente health plans in Georgia, Northern California and Southern California. The objectives of this communication are to describe methods of cohort ascertainment and data collection and to characterise the study population. PARTICIPANTS: A stepwise methodology involving computerised searches of electronic medical records and free-text validation of eligibility and gender identity was used to identify a cohort of 6456 members with first evidence of transgender status (index date) between 2006 and 2014. The cohort included 3475 (54%) transfeminine (TF), 2892 (45%) transmasculine (TM) and 89 (1%) members whose natal sex and gender identity remained undetermined from the records. The cohort was matched to 127 608 enrollees with no transgender evidence (63 825 women and 63 783 men) on year of birth, race/ethnicity, study site and membership year of the index date. Cohort follow-up extends through the end of 2016. FINDINGS TO DATE: About 58% of TF and 52% of TM cohort members received hormonal therapy at Kaiser Permanente. Chest surgery was more common among TM participants (12% vs 0.3%). The proportions of transgender participants who underwent genital reconstruction surgeries were similar (4%-5%) in the two transgender groups. Results indicate that there are sufficient numbers of events in the TF and TM cohorts to further examine mental health status, cardiovascular events, diabetes, HIV and most common cancers. FUTURE PLANS: STRONG is well positioned to fill existing knowledge gaps through comparisons of transgender and reference populations and through analyses of health status before and after gender affirmation treatment. Analyses will include incidence of cardiovascular disease, mental health, HIV and diabetes, as well as changes in laboratory-based endpoints (eg, polycythemia and bone density), overall and in relation to gender affirmation therapy.

Association Between Time to Colonoscopy After a Positive Fecal Test Result and Risk of Colorectal Cancer and Cancer Stage at Diagnosis.

IMPORTANCE: The fecal immunochemical test (FIT) is commonly used for colorectal cancer screening and positive test results require follow-up colonoscopy. However, follow-up intervals vary, which may result in neoplastic progression. OBJECTIVE: To evaluate time to colonoscopy after a positive FIT result and its association with risk of colorectal cancer and advanced-stage disease at diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study (January 1, 2010-December 31, 2014) within Kaiser Permanente Northern and Southern California. Participants were 70 124 patients aged 50 through 70 years eligible for colorectal cancer screening with a positive FIT result who had a follow-up colonoscopy. EXPOSURES: Time (days) to colonoscopy after a positive FIT result. MAIN OUTCOMES AND MEASURES: Risk of any colorectal cancer and advanced-stage disease (defined as stage III and IV cancer). Odds ratios (ORs) and 95% CIs were adjusted for patient demographics and baseline risk factors. RESULTS: Of the 70 124 patients with positive FIT results (median age, 61 years [IQR, 55-67 years]; men, 52.7%), there were 2191 cases of any colorectal cancer and 601 cases of advanced-stage disease diagnosed. Compared with colonoscopy follow-up within 8 to 30 days (n = 27 176), there were no significant differences between follow-up at 2 months (n = 24 644), 3 months (n = 8666), 4 to 6 months (n = 5251), or 7 to 9 months (n = 1335) for risk of any colorectal cancer (cases per 1000 patients: 8-30 days, 30; 2 months, 28; 3 months, 31; 4-6 months, 31; and 7-9 months, 43) or advanced-stage disease (cases per 1000 patients: 8-30 days, 8; 2 months, 7; 3 months, 7; 4-6 months, 9; and 7-9 months, 13). Risks were significantly higher for examinations at 10 to 12 months (n = 748) for any colorectal cancer (OR, 1.48 [95% CI, 1.05-2.08]; 49 cases per 1000 patients) and advanced-stage disease (OR, 1.97 [95% CI, 1.14-3.42]; 19 cases per 1000 patients) and more than 12 months (n = 747) for any colorectal cancer (OR, 2.25 [95% CI, 1.89-2.68]; 76 cases per 1000 patients) and advanced-stage disease (OR, 3.22 [95% CI, 2.44-4.25]; 31 cases per 1000 patients). CONCLUSIONS AND RELEVANCE: Among patients with a positive fecal immunochemical test result, compared with follow-up colonoscopy at 8 to 30 days, follow-up after 10 months was associated with a higher risk of colorectal cancer and more advanced-stage disease at the time of diagnosis. Further research is needed to assess whether this relationship is causal.

Health-related quality of life outcomes from a contemporary prostate cancer registry in a large diverse population.

OBJECTIVE: To assess the health-related quality of life (HRQoL) of patients with prostate cancer up to 24 months after treatment in a contemporary large diverse population. PATIENTS AND METHODS: Patients with newly diagnosed prostate cancer from March 2011 to January 2014 in our healthcare system were included. The Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire was administered before treatment, and at 1, 3, 6, 12, 18, and 24 months after treatment up to November 2014 for all methods of treatment. The Kruskall-Wallis test was used to compare the distribution of each EPIC-26 domain score at each time point, and mixed models were used to assess the overall scores over the period after treatment. RESULTS: In all, 5 727 patients were included. There were data for 3 422, 2 329, 2 017, 1 922, 1 772, 1 260, and 837 patients before treatment, and at 1, 3, 6, 12, 18, and 24 months after treatment, respectively. At 1 month, bowel scores were the lowest for patients that had had radiation therapy, and urinary irritative symptoms were the lowest for those who had had brachytherapy. There were sexual function declines for all the treatment methods, with surgery having the steepest decline; open radical prostatectomy (ORP) had a greater decline than robot-assisted laparoscopic prostatectomy (RALP). Patients who underwent RALP had a better return of sexual function, approaching that of brachytherapy and radiation therapy at 24 months. Urinary incontinence (UI) also declined the most in surgical patients, with RALP patients improving slightly more than ORP patients at 12-24 months. CONCLUSIONS: Patients' HRQoL after prostate cancer treatment varies by treatment method. Notably, sexual function recovers most for RALP patients. UI remains worse at 24 months after surgery, compared to other methods of prostate cancer treatment.