Identifying Cases of Shoulder Injury Related to Vaccine Administration (SIRVA) in the United States: Development and Validation of a Natural Language Processing Method.

BACKGROUND: Shoulder injury related to vaccine administration (SIRVA) accounts for more than half of all claims received by the National Vaccine Injury Compensation Program. However, due to the difficulty of finding SIRVA cases in large health care databases, population-based studies are scarce. OBJECTIVE: The goal of the research was to develop a natural language processing (NLP) method to identify SIRVA cases from clinical notes. METHODS: We conducted the study among members of a large integrated health care organization who were vaccinated between April 1, 2016, and December 31, 2017, and had subsequent diagnosis codes indicative of shoulder injury. Based on a training data set with a chart review reference standard of 164 cases, we developed an NLP algorithm to extract shoulder disorder information, including prior vaccination, anatomic location, temporality and causality. The algorithm identified 3 groups of positive SIRVA cases (definite, probable, and possible) based on the strength of evidence. We compared NLP results to a chart review reference standard of 100 vaccinated cases. We then applied the final automated NLP algorithm to a broader cohort of vaccinated persons with a shoulder injury diagnosis code and performed manual chart confirmation on a random sample of NLP-identified definite cases and all NLP-identified probable and possible cases. RESULTS: In the validation sample, the NLP algorithm had 100% accuracy for identifying 4 SIRVA cases and 96 cases without SIRVA. In the broader cohort of 53,585 vaccinations, the NLP algorithm identified 291 definite, 124 probable, and 52 possible SIRVA cases. The chart-confirmation rates for these groups were 95.5% (278/291), 67.7% (84/124), and 17.3% (9/52), respectively. CONCLUSIONS: The algorithm performed with high sensitivity and reasonable specificity in identifying positive SIRVA cases. The NLP algorithm can potentially be used in future population-based studies to identify this rare adverse event, avoiding labor-intensive chart review validation.

Association Between 2-Dose vs 3-Dose Hepatitis B Vaccine and Acute Myocardial Infarction.

Importance: The 2-dose hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) generated higher seroprotection in prelicensure trials than did a 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant (HepB-alum vaccine; Engerix-B). However, in 1 trial, a higher number of acute myocardial infarction (MI) events were observed among those who received the HepB-CpG vaccine than among those who received the HepB-alum vaccine, an outcome requiring further study. Objective: To compare the rate of acute MI between recipients of HepB-CpG vaccine and HepB-alum vaccine. Design, Setting, and Participants: This prospective cohort noninferiority study was conducted at Kaiser Permanente Southern California (KPSC), an integrated health care system with 15 medical centers and approximately 4.7 million members. The study included 69 625 adults not undergoing dialysis who received at least 1 dose of a hepatitis B vaccine in either family medicine or internal medicine departments at KPSC from August 7, 2018, to October 31, 2019 (November 30, 2020, final follow-up). Exposures: Receipt of HepB-CpG vaccine vs HepB-alum vaccine. The first dose during the study period was the index dose. Main Outcomes and Measures: Individuals were followed up for 13 months after the index dose for occurrence of type 1 acute MI. Potential events were identified using diagnosis codes and adjudicated by cardiologists. The adjusted hazard ratio (HR) of acute MI was estimated comparing recipients of HepB-CpG vaccine with recipients of HepB-alum vaccine, with inverse probability of treatment weighting (IPTW) to adjust for demographic and clinical characteristics. The upper limit of the 1-sided 97.5% CI was compared with a noninferiority margin of 2. Results: Of the 31 183 recipients of HepB-CpG vaccine (median age, 49 years; IQR, 38-56 years), 51.2% (n = 15 965) were men, and 52.7% (n = 16 423) were Hispanic. Of the 38 442 recipients of HepB-alum (median age, 49 years; IQR, 39-56 years), 50.8% (19 533) were men, and 47.1% (n = 18 125) were Hispanic. Characteristics were well-balanced between vaccine groups after IPTW. Fifty-two type 1 acute MI events were confirmed among recipients of HepB-CpG vaccine for a rate of 1.67 per 1000-person-years, and 71 type 1 acute MI events were confirmed among recipients of HepB-alum vaccine for a rate of 1.86 per 1000 person-years (absolute rate difference, -0.19 [95% CI, -0.82 to 0.44]; adjusted HR, 0.92 [1-sided 97.5% CI, ∞ to 1.32], which was below the noninferiority margin; P < .001 for noninferiority). Conclusions and Relevance: In this cohort study, receipt of HepB-CpG vaccine compared with HepB-alum vaccine did not meet the statistical criterion for increased risk of acute myocardial infarction.

Risk for Shoulder Conditions After Vaccination: A Population-Based Study Using Real-World Data.

BACKGROUND: Although shoulder conditions have been reported as an adverse event after intramuscular vaccination in the deltoid muscle, epidemiologic data on shoulder conditions after vaccination are limited. OBJECTIVE: To estimate the risk for shoulder conditions after vaccination and assess possible risk factors. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Southern California, a large integrated health care organization. PARTICIPANTS: Kaiser Permanente Southern California members aged 3 years or older who had an intramuscular vaccination administered in the deltoid muscle between 1 April 2016 and 31 December 2017. MEASUREMENTS: A natural language processing (NLP) algorithm was used to identify potential shoulder conditions among vaccinated persons with shoulder disorder diagnosis codes. All NLP-identified cases were manually chart confirmed on the basis of our case definition. The characteristics of vaccinated persons with and without shoulder conditions were compared. RESULTS: Among 3 758 764 administered vaccinations, 371 cases of shoulder condition were identified, with an estimated incidence of 0.99 (95% CI, 0.89 to 1.09) per 10 000 vaccinations. The incidence was 1.22 (CI, 1.10 to 1.35) for the adult (aged ≥18 years) and 0.05 (CI, 0.02 to 0.14) for the pediatric (aged 3 to 17 years) vaccinated populations. In the adult vaccinated population, advanced age, female sex, an increased number of outpatient visits in the 6 months before vaccination, lower Charlson Comorbidity Index, and pneumococcal conjugate vaccine were associated with a higher risk for shoulder conditions. Among influenza vaccines, quadrivalent vaccines were associated with an increased risk for shoulder conditions. Simultaneous administration of vaccines was associated with a higher risk for shoulder conditions among elderly persons. LIMITATION: Generalizability to other health care settings, use of administrative data, and residual confounding. CONCLUSION: These population-based data suggest a small absolute risk for shoulder conditions after vaccination. Given the high burden of shoulder conditions, clinicians should pay attention to any factors that may further increase risks. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Causes of Death in End-Stage Kidney Disease: Comparison between the United States Renal Data System and a Large Integrated Health Care System.

INTRODUCTION: Using a large diverse population of incident end-stage kidney disease (ESKD) patients from an integrated health system, we sought to evaluate the concordance of causes of death (CODs) between the underlying COD from the United States Renal Data System (USRDS) registry and CODs obtained from Kaiser Permanente Southern California (KPSC). METHODS: A retrospective cohort study was performed among incident ESKD patients who had mortality records and CODs reported in both KPSC and USRDS databases between January 1, 2007, and December 31, 2016. Underlying CODs reported by the KPSC were compared to the CODs reported by USRDS. Overall and subcategory-specific COD agreements were assessed using Cohen's weighted kappa statistic (95% CI). Proportions of positive and negative agreement were also determined. RESULTS: Among 4,188 ESKD patient deaths, 4,118 patients had CODs recorded in both KPSC and USRDS. The most common KPSC CODs were circulatory system diseases (35.7%), endocrine/nutritional/metabolic diseases (24.2%), genitourinary diseases (12.9%), and neoplasms (9.6%). Most common USRDS CODs were cardiac disease (46.9%), withdrawal from dialysis (12.6%), and infection (10.1%). Of 2,593 records with causes listed NOT as "Other," 453 (17.4%) had no agreement in CODs between the USRDS and the underlying, secondary, tertiary, or quaternary causes recorded by KPSC. In comparing CODs recorded within KPSC to the USRDS, Cohen's weighted kappa (95% CI) was 0.20 (0.18-0.22) with overall agreement of 36.4%. CONCLUSION: Among an incident ESKD population with mortality records, we found that there was only fair or slight agreement between CODs reported between the USRDS registry and KPSC, a large integrated health care system.

Safety of Influenza Vaccination During Orthopaedic Surgery Hospitalizations.

BACKGROUND: Despite national recommendations, influenza vaccination rates during hospitalizations remain low. Inpatient hospitalization for orthopaedic surgery remains a largely missed opportunity for vaccination. To address potential concerns regarding safety, we evaluated whether influenza vaccination during hospitalization for orthopaedic surgery increases evaluations for infection postdischarge because patients and clinicians often cite fear of this potential outcome. METHODS: This was a retrospective cohort study that was conducted among patients of a large integrated healthcare organization aged ≥6 months who were hospitalized for an orthopaedic surgery (defined by International Classification of Diseases, Ninth Revision procedure codes) between September 1 and March 31 from 2011 to 2014. Using propensity score matching (1:1) to adjust for confounding, we assessed the association between influenza vaccination during an inpatient stay for orthopaedic surgery and rates of readmission, emergency department visits, outpatient visits, fever (temperature ≥38.0°C), and evaluations for infections less than 7 days postdischarge. RESULTS: Overall, 2,395 hospitalizations with inpatient vaccination and 21,708 hospitalizations without inpatient vaccination were identified. Following successful balance of covariates (standardized difference <0.1 for all covariates) through 1:1 propensity score matching, we included 2,376 exposed patients and 2,376 unexposed patients in the matched analysis. In adjusted analyses, compared with those who were not vaccinated during hospitalization, those vaccinated during an inpatient stay for orthopaedic surgery had no statistically significant increase in readmission (relative risk [RR] = 1.00, 95% confidence interval [CI]: 0.75 to 1.34), emergency department visits (RR = 1.14, 95% CI: 0.93 to 1.41), fever (RR = 1.31, 95% CI: 0.81 to 2.12), or clinical workups for infection (RR = 1.08, 95% CI: 0.98 to 1.18). A marginally increased risk of outpatient visits in the 7 days postdischarge was detected (RR = 1.13, 95% CI: 1.02 to 1.26). DISCUSSION: There was no evidence of a substantial increased risk of infection-related outcomes associated with influenza vaccination during hospitalization for orthopaedic surgery. Our data support the recommendation of vaccinating orthopaedic surgery patients against influenza perioperatively.

Disparities in Outpatient and Telehealth Visits During the COVID-19 Pandemic in a Large Integrated Health Care Organization: Retrospective Cohort Study.

BACKGROUND: Dramatic decreases in outpatient visits and sudden increases in telehealth visits were observed during the COVID-19 pandemic, but it was unclear whether these changes differed by patient demographics and socioeconomic status. OBJECTIVE: This study aimed to assess the impact of the pandemic on in-person outpatient and telehealth visits (telephone and video) by demographic characteristics and household income in a diverse population. METHODS: We calculated weekly rates of outpatient and telehealth visits by age, sex, race/ethnicity, and neighborhood-level median household income among members of Kaiser Permanente Southern California (KPSC) from January 5, 2020, to October 31, 2020, and the corresponding period in 2019. We estimated the percentage change in visit rates during the early pandemic period (March 22 to April 25, 2020) and the late pandemic period (October 4 to October 31, 2020) from the prepandemic period (January 5 to March 7, 2020) in Poisson regression models for each subgroup while adjusting for seasonality using 2019 data. We examined if the changes in visit rates differed by subgroups statistically by comparing their 95% CIs. RESULTS: Among 4.56 million KPSC members enrolled in January 2020, 15.0% (n=682,947) were ≥65 years old, 51.5% (n=2,345,020) were female, 39.4% (n=1,795,994) were Hispanic, and 7.7% (n=350,721) lived in an area of median household income

Challenges in Phase 4 post-licensure safety studies using real world data in the United States: Hepatitis B vaccine example.

Post-licensure vaccine safety studies are essential to identify adverse events that may not have been detected in pre-licensure clinical trials and to address questions that arose during the pre-licensure phase. These studies are increasingly conducted using real-world data collected as part of routine health care delivery. However, design of post-licensure vaccine safety studies involves many pragmatic and scientific decisions, which must be made while balancing diverse stakeholder opinions. Challenges include selecting exposure and comparison groups, deciding on the most appropriate outcome, determining sample size and length of follow-up time, and other analytic considerations. As an example of this process and to inform other post-licensure vaccine safety studies in real-world settings, we discuss our experience with design of an FDA-required Phase 4 post-licensure safety study of a hepatitis B vaccine in a large integrated health care organization in the United States.

Incidence of pediatric inflammatory bowel disease within the Vaccine Safety Datalink network and evaluation of association with rotavirus vaccination.

BACKGROUND: Recent studies have reported an increase in Inflammatory bowel disease (IBD) incidence in young children, highlighting the need to better understand risk factors for the development of IBD. Licensed for use in infants in 2006, the oral, live-attenuated rotavirus vaccine has biologic plausibility for instigating inflammation of the gut mucosa as a pathway to immune dysregulation. METHODS: Over a ten-year period, we evaluated incidence of IBD within a cohort of children under the age of ten, enrolled in seven integrated healthcare delivery systems. We conducted a nested case-control study to evaluate the association between rotavirus vaccination and IBD using conditional logistic regression. Cases were confirmed via medical record review and matched to non-IBD controls on date of birth, sex, and study site. RESULTS: Among 2.4 million children under the age of 10 years, 333 cases of IBD were identified with onset between 2007 and 2016. The crude incidence of IBD increased slightly over the study period (p-value for trend = 0.046). Of the 333 cases, 227 (68%) were born prior to 2007. Forty-two cases born in 2007 or later, with continuous enrollment since birth were included in the case-control study and matched to 210 controls. The adjusted odds ratio for any rotavirus vaccination in IBD cases, compared to matched controls, was 0.72 (95% confidence interval 0.19-2.65). CONCLUSIONS: Data from this large pediatric cohort demonstrate a small overall increase in IBD incidence in young children over a ten-year period. The data suggest that rotavirus vaccination is not associated with development of IBD.

Physician Compliance to Choosing Wisely® Initiative in Radiographic Imaging of Low Risk Prostate Cancer in an Integrated Health Care System.

INTRODUCTION: We evaluated the adherence of urologists within an integrated health care system to Choosing Wisely®, an initiative aimed at avoiding unnecessary medical tests. In urology, 2 of the guidelines state bone scans and pelvic computerized tomography scans are unnecessary in low risk prostate cancer. METHODS: We performed a retrospective study on patients diagnosed with low risk prostate cancer between January 1, 2010 and December 31, 2017 at Kaiser Permanente Southern California. All demographics and imaging data were obtained. Patients with symptoms concerning for metastatic disease or with other malignancies were excluded by chart review. Statistical analysis was employed to compare the use of bone scans and computerized tomography scans in this population before and after the Choosing Wisely guidelines were published. RESULTS: Of the 6,996 patients, 121 (1.7%) and 96 (1.4%) underwent a bone scan and computerized tomography scan, respectively. A Cochran-Armitage test showed no change after implementation of the statements. Logistic regression analysis revealed that for every point increase in prostate specific antigen, the odds ratio was 1.09 for ordering both a bone scan and computerized tomography scan. When compared to Whites, the odds ratio of having a bone scan and computerized tomography scan were 0.35 and 0.37 for Blacks, 0.30 and 0.38 for Hispanics, and 0.47 and 0.61 for Asians, respectively. CONCLUSIONS: Over the study period, there were low rates of inappropriate imaging for low risk prostate cancer. There was no change in trend after publication of the Choosing Wisely. Higher prostate specific antigen levels and White ethnicity were predictors for ordering inappropriate imaging.

ß-Blocker Use and Risk of Mortality in Heart Failure Patients Initiating Maintenance Dialysis.

RATIONAL & OBJECTIVE: Beta-blockers are recommended for patients with heart failure (HF) but their benefit in the dialysis population is uncertain. Beta-blockers are heterogeneous, including with respect to their removal by hemodialysis. We sought to evaluate whether ß-blocker use and their dialyzability characteristics were associated with early mortality among patients with chronic kidney disease with HF who transitioned to dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults patients with chronic kidney disease (aged≥18 years) and HF who initiated either hemodialysis or peritoneal dialysis during January 1, 2007, to June 30, 2016, within an integrated health system were included. EXPOSURES: Patients were considered treated with ß-blockers if they had a quantity of drug dispensed covering the dialysis transition date. OUTCOMES: All-cause mortality within 6 months and 1 year or hospitalization within 6 months after transition to maintenance dialysis. ANALYTICAL APPROACH: Inverse probability of treatment weights using propensity scores was used to balance covariates between treatment groups. Cox proportional hazard analysis and logistic regression were used to investigate the association between ß-blocker use and study outcomes. RESULTS: 3,503 patients were included in the study. There were 2,115 (60.4%) patients using ß-blockers at transition. Compared with nonusers, the HR for all-cause mortality within 6 months was 0.79 (95% CI, 0.65-0.94) among users of any ß-blocker and 0.68 (95% CI, 0.53-0.88) among users of metoprolol at transition. There were no observed differences in all-cause or cardiovascular-related hospitalization. LIMITATIONS: The observational nature of our study could not fully account for residual confounding. CONCLUSIONS: Beta-blockers were associated with a lower rate of mortality among incident hemodialysis patients with HF. Similar associations were not observed for hospitalizations within the first 6 months following transition to dialysis.

Association of Number of Doses With Hepatitis B Vaccine Series Completion in US Adults.

Importance: Receipt of hepatitis B virus vaccine is important to prevent infection. However, adherence to the hepatitis B vaccine series among adults at risk of infection has been low. Objective: To assess whether recipients of a 2-dose hepatitis B vaccine with cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) are more likely to complete their series compared with recipients of a 3-dose vaccine with alum adjuvant (comparator vaccine; Engerix-B [HepB-alum]). Design, Setting, and Participants: This nested cohort study was conducted from August 7 to December 31, 2018, at Kaiser Permanente Southern California, an integrated health care system with a diverse population of approximately 4.6 million members. Adults not receiving dialysis who received a first dose of a hepatitis B vaccine series in family practice or internal medicine departments of 15 Kaiser Permanente Southern California medical centers were followed up through electronic health records for up to 1 year after receipt of the first dose. Data were analyzed from March 16 to September 23, 2020. Exposures: Receipt of a first dose of the HepB-CpG vaccine (2-dose vaccine) vs receipt of a first dose of the HepB-alum vaccine (3-dose vaccine). Main Outcomes and Measures: Series completion within the recommended vaccine schedule plus 3 months (primary outcome) and series completion within 1 year after receipt of the first dose (secondary outcome). Results: Of 4727 individuals who initiated the HepB-CpG vaccine series and 6161 individuals who initiated the HepB-alum vaccine series included in the study, 2876 (60.8%) and 3789 (61.5%), respectively, were ages 40 to 59 years, 2415 (51.1%) and 3113 (50.5%) were male, and 2364 (50.0%) and 2881 (46.8%) were Hispanic. The vaccine series was completed within the recommended schedule plus 3 months for 2111 (44.7%) individuals who initiated the HepB-CpG vaccine series and 1607 (26.1%) individuals who initiated the HepB-alum vaccine series, and within 1 year for 2858 (60.5%) and 1989 (32.3%) individuals, respectively. The individuals who initiated the HepB-CpG vaccine series were significantly more likely to complete the series (adjusted relative risk, 1.77; 95% CI, 1.68-1.87). Results were consistent across clinical and demographic strata. Conclusions and Relevance: In this study, use of the HepB-CpG vaccine was associated with hepatitis B vaccine series completion, but tailored strategies to increase completion of hepatitis B vaccine series are warranted.

Association between hypothyroidism and chronic kidney disease observed among an adult population 55 years and older.

Hypothyroidism and chronic kidney disease (CKD) are highly prevalent conditions with a potential mechanistic link. We sought to determine whether hypothyroidism is associated with CKD among a large diverse community-based cohort.A cross-sectional study was performed (January 1, 1990-December 31, 2017) within a large integrated health system. Individuals age ≥55 years of age with outpatient measurements of thyroid stimulating hormone (TSH) and ≥2 serum creatinine values were included. Hypothyroidism was defined as TSH >4 mIU/L and/or receipt of thyroid hormone replacement and further categorized as hypothyroid status: TSH >4 mcIU/mL and attenuated-hypothyroid status: TSH <4 mcIU/mL with receipt of thyroid hormone replacement. Euthyroidism was defined as TSH <4 mIU/L and no thyroid hormone replacement. Our primary measure was CKD defined as an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m. Multivariable logistic regression adjusting for age, sex, race, and comorbidities was used to estimate odds ratios (OR) for CKD by thyroid status.Among 378,101 individuals, 114,872 (30.4%) had hypothyroidism among whom 31,242 and 83,630 had hypothyroid and attenuated-hypothyroid statuses, respectively. Individuals with hypothyroidism had a CKD OR (95%CI) of 1.25 (1.21-1.29) compared with those with euthyroidism. Granular examination of thyroid statuses showed that hypothyroid and attenuated-hypothyroid statuses had CKD ORs (95% CI) of 1.59 (1.52-1.66) and 1.12 (1.08-1.16), respectively. A similar relationship was observed in analyses that defined CKD as an eGFR <60 L/min/1.73 m.Among individuals 55 years and older, we observed that those with hypothyroidism were more likely to have CKD. A stronger association was found among patients of hypothyroid status compared with attenuated-hypothyroid status suggesting a dose dependent relationship.

Identifying Patients with Rare Disease Using Electronic Health Record Data: The Kaiser Permanente Southern California Membranous Nephropathy Cohort.

INTRODUCTION: Developing a reliable means to identify and study real-world populations of patients with membranous nephropathy (MN) using electronic health records (EHRs) would help advance glomerular disease research. Identifying MN cases using EHRs is limited by the need for manual reviews of biopsy reports. OBJECTIVE: To evaluate the accuracy of identifying patients with biopsy-proven MN using the EHR in a large, diverse population of an integrated health system. METHODS: A retrospective cohort study was performed between June 28, 1999, and June 25, 2015, among patients with kidney biopsy results (N = 4723), which were manually reviewed and designated as MN or non-MN. The sensitivity, specificity, and positive predictive value (PPV) of International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes were determined using 2 approaches: 1) clinical (MN-specific codes 581.1, 582.1, or 583.1) and 2) agnostic/data-derived (codes selected from supervised learning at the highest predictive performance). RESULTS: One year after biopsy, the sensitivity and specificity of an MN diagnosis were 86% and 76%, respectively, but the PPV was 26%. The data-driven approach detected that using only 2 codes (581.1 or 583.1) improved specificity to 94% and PPV to 58%, with a small decrease in sensitivity to 83%. When any code was reported at least 3 times, specificity was 98%; PPV, 78%; and sensitivity, 64%. DISCUSSION: Our findings suggest that ICD-9 diagnosis codes might be a convenient tool to identify patients with MN using EHR and/or administrative claims information. Codes selected from supervised learning achieved better overall performance, suggesting the potential of developing data-driven methods.

Sex-Specific Trends in Acute Myocardial Infarction Within an Integrated Healthcare Network, 2000 Through 2014.

BACKGROUND: In recent decades, the rates of incident acute myocardial infarction (AMI) have declined in the United States, yet disparities by sex remain. In an integrated healthcare delivery system, we examined temporal trends in incident AMI among women and men. METHODS: We identified hospitalized AMI among members ≥35 years of age in Kaiser Permanente Southern California. The first hospitalization for AMI overall, and for ST-segment-elevation MI and non-ST-segment-elevation MI was identified by International Classification of Diseases, Ninth Revision, Clinical Modification primary discharge diagnosis codes in each calendar year from 2000 through 2014. Age- and sex-standardized incidence rates per 100 000 person-years were calculated by using direct adjustment to the 2010 US Census population. Average annual percent changes (AAPCs) and period percent changes were calculated, and trend tests were conducted using Poisson regression. RESULTS: We identified 45 331 AMI hospitalizations between 2000 and 2014. Age- and sex-standardized incidence rates of AMI declined from 322.4 (95% CI, 311.0-333.9) in 2000 to 174.6 (95% CI, 168.2-181.0) in 2014, representing an AAPC of -4.4% (95% CI, -4.2 to -4.6) and a period percent change of -46.6%. The AAPC for AMI in women was -4.6% (95% CI, -4.1 to -5.2) between 2000 and 2009 and declined to -2.3% (95% CI, -1.2 to -3.4) between 2010 and 2014. The AAPC for AMI in men was stable over the study period (-4.7% [95% CI, -4.4 to -4.9]). The AAPC for ST-segment-elevation MI hospitalization overall was -8.3% (95% CI, -8.0% to -8.6%).The AAPC in ST-segment-elevation MI changed among women in 2009 (2000-2009: -10.2% [95% CI, -9.3 to -11.1] and in 2010-2014: -5.2% [95% CI, -3.1 to -7.3]) while remaining stable among men (-8.0% [95% CI, -7.6 to -8.4]). The AAPC for non-ST-segment-elevation MI hospitalization was smaller than for ST-segment-elevation MI among both women and men (-1.9% [95% CI, -1.5 to -2.3] and -2.8% [95% CI, -2.5 to -3.2], respectively). CONCLUSIONS: These results suggest that the incidence of hospitalized AMI declined between 2000 and 2014; however, declines in AMI have slowed among women in comparison with men in recent years. Determining unmet care needs among women may reduce these sex-based AMI disparities.

Sub-acute hyponatraemia more than chronic hyponatraemia is associated with serious falls and hip fractures.

BACKGROUND: Falls and hip fractures among older people are associated with high morbidity and mortality. Hyponatraemia may be a risk for falls/hip fractures, but the effect of hyponatraemia duration is not well understood. AIMS: To evaluate individuals with periods of sub-acute and chronic hyponatraemia on subsequent risk for serious falls and/or hip fractures. METHODS: Retrospective cohort study in the period 1 January 1998 to 14 June 2016 within an integrated health system of individuals aged ≥55 years with ≥2 outpatient serum sodium measurements. Hyponatraemia was defined as sodium <135 mEq/L with sub-acute (<30 days) and chronic (≥30 days) analysed as a time-dependent exposure. Multivariable Cox proportional-hazards modelling was used to estimate hazard ratios (HR) for serious falls/hip fractures based on sodium category. RESULTS: Among 1 062 647 individuals totalling 9 762 305 sodium measurements, 96 096 serious falls/hip fracture events occurred. Incidence (per-1000-person-years) of serious falls/hip fractures were 11.5, 27.9 and 19.8 for normonatraemia, sub-acute and chronic hyponatraemia. Any hyponatraemia duration compared to normonatraemia had a serious falls/hip fractures HR (95%CI) of 1.18 (1.15, 1.22), with sub-acute and chronic hyponatraemia having HR of 1.38 (1.33, 1.42) and 0.91 (0.87, 0.95), respectively. Examined separately, the serious falls HR was 1.37 (1.32, 1.42) and 0.92 (0.88, 0.96) in sub-acute and chronic hyponatraemia, respectively. Hip fracture HR were 1.52 (1.42, 1.62) and 1.00 (0.92, 1.08) for sub-acute and chronic hyponatraemia, respectively, compared to normonatraemia. CONCLUSIONS: Our findings suggest that early/sub-acute hyponatraemia appears more vulnerable and associated with serious falls/hip fractures. Whether hyponatraemia is a marker of frailty or a modifiable risk factor for falls remains to be determined.

Secular trends in the incidence and prevalence of rheumatoid arthritis within members of an integrated health care delivery system.

The study objective was to estimate secular trends in the overall incidence rate (IR) and prevalence rate (PR) of rheumatoid arthritis (RA); and subgroup-specific IR and PR by race, ethnicity, and sex in a multi-ethnic population of a large integrated health care delivery system. An ecological study was conducted within the adult population of Kaiser Permanente Southern California health plan. From January 1995 up to and including December 2014, annual IR and PR were calculated separately by race, ethnicity, sex and pooled overall. Depending on the stationarity of each ecological series, annual percentage change in IR and PR was evaluated using auto-regressive integrated moving average models. Average overall IR was 53 [95% confidence interval (CI) 46, 61] per 100,000 person-years. The overall as well as subgroup-specific annual IR of RA were unchanged from 1995 to 2014. In 1995, the overall PR of RA was 59 (44, 74) per 100,000 person-years which increased by 14% (7%, 21%) annually thereafter. The increase in PR in Caucasians was lower as compared to African American, Asian and other race (13% vs 15%, 15%, and 18%, respectively). Compared to non-Hispanic ethnicity, the increase in PR among Hispanic was higher (17% vs 14%). Over the past 2 decades, while the incidence of RA was unchanged, the prevalence had increased significantly overall as well as within every subgroup of race, ethnicity, and sex.

Dialysis Provider and Outcomes among United States Veterans Who Transition to Dialysis.

BACKGROUND AND OBJECTIVES: Veterans with ESKD initiate dialysis under the Veterans Health Administration (VHA), an integrated health system, or are outsourced to non-VHA providers. It is unknown whether outcomes differ according to their dialysis provider at initiation. We sought to evaluate the association between dialysis provider and mortality and hospitalization among United States veterans initiating dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 68,727 United States veterans who initiated dialysis in 2007-2014, we examined the association of dialysis provider (VHA versus non-VHA) at initiation with mortality and hospitalization rates in the first 12 months post-initiation. Associations were examined across adjusted models, accounting for demographics and comorbidities. RESULTS: Patients were 72±11 years, 5% were women, 24% were black, and 10% (n=7584) initiated at VHA dialysis centers. VHA dialysis center patients were younger, more likely to be black, had fewer cardiovascular comorbidities, and lower eGFR at dialysis initiation. VHA provider patients were more likely to be hospitalized in the first 12 months (adjusted incidence rate ratio, 1.10; 95% confidence interval, 1.07 to 1.14), but had lower all-cause mortality risk (adjusted hazard ratio, 0.87; 95% confidence interval, 0.83 to 0.93) in fully adjusted models. CONCLUSIONS: Veteran patients initiating dialysis with a VHA dialysis provider appear to have a lower mortality risk but higher hospitalization rates than veterans initiating dialysis at non-VHA dialysis units.

The Use of 5-Alpha Reductase Inhibitors to Manage Benign Prostatic Hyperplasia and the Risk of All-cause Mortality.

OBJECTIVE: To compare the risk of mortality among men treated for benign prostatic hyperplasia (BPH) with 5 alpha-reductase inhibitors (5ARI) to those treated with alpha-blockers (AB) in community practice settings. METHODS: We employed a retrospective matched cohort study in 4 regions of an integrated healthcare system. Men aged 50 years and older who initiated pharmaceutical treatment for BPH and/or lower urinary tract symptoms between 1992 and 2008 and had at least 3 consecutive prescriptions that were eligible and followed through 2010 (N = 174,895). Adjusted hazard ratios were used to estimate the risk of mortality due to all-causes associated with 5ARI use (with or without concomitant ABs) as compared to AB use. RESULTS: In this large and diverse sample with 543,523 person-years of follow-up, 35,266 men died during the study period, 18.9% of the 5ARI users and 20.4% of the AB users. After adjustment for age, medication initiation year, race, region, prior AB history, Charlson score, and comorbidities, 5ARI use was not associated with an increased risk of mortality when compared to AB use (Adjusted hazard ratios: 0.64, 95% confidence interval: 0.62, 0.66). CONCLUSION: Among men receiving medications for BPH in community practice settings, 5ARI use was not associated with an increased risk of mortality when compared to AB use. These data provide reassurance about the safety of using 5ARIs in general practice to manage BPH and/or lower urinary tract symptoms.

End-Stage Renal Disease and Mortality Outcomes Across Different Glomerulonephropathies in a Large Diverse US Population.

OBJECTIVE: To compare renal function decline, incident end-stage renal disease (ESRD), and mortality among patients with 5 common glomerular diseases in a large diverse population. PATIENTS AND METHODS: A retrospective cohort study (between January 1, 2000, and December 31, 2011) of patients with glomerulonephropathy using the electronic health record of an integrated health system was performed. Estimated glomerular filtration rate (eGFR) change, incident ESRD, and mortality were compared among patients with biopsy-proven focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MN), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), and lupus nephritis (LN). Competing risk models were used to estimate hazard ratios for different glomerulonephropathies for incident ESRD, with mortality as a competing outcome after adjusting for potential confounders. RESULTS: Of the 2350 patients with glomerulonephropathy (208 patients [9%] younger than 18 years) with a mean follow-up of 4.5±3.6 years, 497 (21%) progressed to ESRD and 195 (8%) died before ESRD. The median eGFR decline was 1.0 mL/min per 1.73 m2 per year but varied across different glomerulonephropathies (P<.001). The highest ESRD incidence (per 100 person-years) was observed in FSGS 8.72 (95% CI, 3.93-16.72) followed by IgAN (4.54; 95% CI, 1.37-11.02), LN (2.38; 95% CI, 0.37-7.82), MN (2.15; 95% CI, 0.29-7.46), and MCD (1.67; 95% CI, 0.15-6.69). Compared with MCD, hazard ratios (95% CIs) for incident ESRD were 3.43 (2.32-5.08) and 2.35 (1.46-3.81), 1.28 (0.79-2.07), and 1.02 (0.62-1.68) for FSGS, IgAN, LN, and MN, respectively. No significant association between glomerulonephropathy types and mortality was detected (P=.24). CONCLUSION: Our findings from a real-world clinical environment revealed significant differences in eGFR decline and ESRD risk among patients with 5 glomerulonephropathies. These variations in presentation and outcomes warrant different management strategies and expectations.