Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort.

BACKGROUND: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. METHODS: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). FINDINGS: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. INTERPRETATION: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. FUNDING: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity.

Atypical hemolytic uremic syndrome in the era of terminal complement inhibition: an observational cohort study.

Historically, the majority of patients with complement-mediated atypical hemolytic uremic syndrome (CaHUS) progress to end-stage kidney disease (ESKD). Single-arm trials of eculizumab with a short follow-up suggested efficacy. We prove, for the first time to our knowledge, in a genotype matched CaHUS cohort that the 5-year cumulative estimate of ESKD-free survival improved from 39.5% in a control cohort to 85.5% in the eculizumab-treated cohort (hazard ratio, 4.95; 95% confidence interval [CI], 2.75-8.90; P = .000; number needed to treat, 2.17 [95% CI, 1.81-2.73]). The outcome of eculizumab treatment is associated with the underlying genotype. Lower serum creatinine, lower platelet count, lower blood pressure, and younger age at presentation as well as shorter time between presentation and the first dose of eculizumab were associated with estimated glomerular filtration rate >60 ml/min at 6 months in multivariate analysis. The rate of meningococcal infection in the treated cohort was 550 times greater than the background rate in the general population. The relapse rate upon eculizumab withdrawal was 1 per 9.5 person years for patients with a pathogenic mutation and 1 per 10.8 person years for those with a variant of uncertain significance. No relapses were recorded in 67.3 person years off eculizumab in those with no rare genetic variants. Eculizumab was restarted in 6 individuals with functioning kidneys in whom it had been stopped, with no individual progressing to ESKD. We demonstrated that biallelic pathogenic mutations in RNA-processing genes, including EXOSC3, encoding an essential part of the RNA exosome, cause eculizumab nonresponsive aHUS. Recessive HSD11B2 mutations causing apparent mineralocorticoid excess may also present with thrombotic microangiopathy.

Association Between a National Behavioral Weight Management Program and Veterans Affairs Health Expenditures.

OBJECTIVE: The association between participation in a behavioral weight intervention and health expenditures has not been well characterized. We compared Veterans Affairs (VA) expenditures of individuals participating in MOVE!, a VA behavioral weight loss program, and matched comparators 2 years before and 2 years after MOVE! initiation. METHODS: Retrospective cohort study of Veterans who had one or more MOVE! visits in 2008-2017 who were matched contemporaneously to up to 3 comparators with overweight or obesity through sequential stratification on an array of patient characteristics, including sex. Baseline patient characteristics were compared between the two cohorts through standardized mean differences. VA expenditures in the 2 years before MOVE! initiation and 2 years after initiation were modeled using generalized estimating equations with a log link and distribution with variance proportional to the standard deviation (gamma). RESULTS: MOVE! participants (n=499,696) and comparators (n=1,336,172) were well-matched, with an average age of 56, average body mass index of 35, and similar total VA expenditures in the fiscal year before MOVE! initiation ($9662 for MOVE! participants and $10,072 for comparators, standardized mean difference=-0.019). MOVE! participants had total expenditures that were statistically lower than matched comparators in the 6 months after initiation but modestly higher in the 6 months to 2 years after initiation, though differences were small in magnitude (1.0%-1.6% differences). CONCLUSIONS: The VA's system-wide behavioral weight intervention did not realize meaningful short-term health care cost savings for participants.

Identifying Patterns of Primary Care In-Person and Telemedicine Use in the Veterans Health Administration: A Latent Class Analysis.

BACKGROUND: The Veterans Health Administration increased synchronous telemedicine (video and telephone visits) in primary care in response to the COVID-19 pandemic. OBJECTIVE: Our objective was to determine veteran use patterns of in-person and telemedicine primary care when all modalities were available. DESIGN: A retrospective cohort analysis. We performed a latent class analysis of primary care visits over a 1-year period to identify veteran subgroup (i.e., class) membership based on amount of primary care use and modality used. Then, we used multinomial logistic regression with a categorical outcome to identify patient characteristics associated with class identification. PARTICIPANTS: A random national sample consisting of 564,580 primary care empaneled veterans in June 2021. MAIN MEASURES: Latent class membership. KEY RESULTS: We identified three latent classes: those with few primary care visits that were predominantly telephone-based (45%), intermediate number of visits of all modalities (50%), and many visits of all modalities (5%). In an adjusted model, characteristics associated with the "few" visits class, compared to the intermediate class, were older age, male sex, White race, further driving distance to primary care, higher Gagne, optimal internet speed, and unmarried status (OR 1.002, 1.52, 1.13, 1.004, 1.04, 1.05, 1.06, respectively; p < .05). Characteristics associated with membership in the "many" visits class, compared to the intermediate class, were Hispanic race, higher JEN Frailty Index and Gagne (OR 1.12, 1.11, 1.02, respectively; p < .05), and higher comorbidity by Care Assessment Need score quartile (Q2 1.73, Q3 2.80, Q4 4.12; p < 0.05). CONCLUSIONS: Veterans accessing primary care in-person or via telemedicine do so primarily in three ways: (1) few visits, predominantly telephone; (2) intermediate visits, all modalities, (3) many visits, all modalities. We found no groups of veterans receiving a majority of primary care through video.

Real World Use of Anti-Obesity Medications and Weight Change in Veterans.

BACKGROUND: Anti-obesity medications (AOMs) can be initiated in conjunction with participation in the VA national behavioral weight management program, MOVE!, to help achieve clinically meaningful weight loss. OBJECTIVE: To compare weight change between Veterans who used AOM + MOVE! versus MOVE! alone and examine AOM use, duration, and characteristics associated with longer duration of use. DESIGN: Retrospective cohort study using VA electronic health records. PARTICIPANTS: Veterans with overweight or obesity who participated in MOVE! from 2008-2017. MAIN MEASURES: Weight change from baseline was estimated using marginal structural models up to 24 months after MOVE! initiation. The probability of longer duration of AOM use (≥ 180 days) was estimated via a generalized linear mixed model. RESULTS: Among MOVE! participants, 8,517 (1.6%) used an AOM within 24 months after MOVE! initiation with a median of 90 days of cumulative supply. AOM + MOVE! users achieved greater weight loss than MOVE! alone users at 6 (3.2% vs. 1.6%, p < 0.001), 12 (3.4% vs. 1.4%, p < 0.001), and 24 months (2.7% vs. 1.5%, p < 0.001), and had a greater probability of achieving ≥ 5% weight loss at 6 (38.8% vs. 26.0%, p < 0.001), 12 (43.1% vs. 28.4%, p < 0.001), and 24 months (40.4% vs. 33.3%, p < 0.001). Veterans were more likely to have ≥ 180 days of supply if they were older, exempt from medication copays, used other medications with significant weight-gain, significant weight-loss, or modest weight-loss side effects, or resided in the West North Central or Pacific regions. Veterans were less likely to have ≥ 180 days of AOM supply if they had diabetes or initiated MOVE! later in the study period. CONCLUSIONS: AOM use following MOVE! initiation was uncommon, and exposure was time-limited. AOM + MOVE! was associated with a higher probability of achieving clinically significant weight loss than MOVE! alone.

Defining and Improving Outcomes Measurement for Virtual Care: Report from the VHA State-of-the-Art Conference on Virtual Care.

Virtual care, including synchronous and asynchronous telehealth, remote patient monitoring, and the collection and interpretation of patient-generated health data (PGHD), has the potential to transform healthcare delivery and increase access to care. The Veterans Health Administration (VHA) Office of Health Services Research and Development (HSR&D) convened a State-of-the-Art (SOTA) Conference on Virtual Care to identify future virtual care research priorities. Participants were divided into three workgroups focused on virtual care access, engagement, and outcomes. In this article, we report the findings of the Outcomes Workgroup. The group identified virtual care outcome areas with sufficient evidence, areas in need of additional research, and areas that are particularly well-suited to be studied within VHA. Following a rigorous process of literature review and consensus, the group focused on four questions: (1) What outcomes of virtual care should we be measuring and how should we measure them?; (2) how do we choose the "right" care modality for the "right" patient?; (3) what are potential consequences of virtual care on patient safety?; and (4) how can PGHD be used to benefit provider decision-making and patient self-management?. The current article outlines key conclusions that emerged following discussion of these questions, including recommendations for future research.

Risk of Suicide-Related Outcomes After SARS-COV-2 Infection: Results from a Nationwide Observational Matched Cohort of US Veterans.

BACKGROUND: Negative mental health-related effects of SARS-COV-2 infection are increasingly evident. However, the impact on suicide-related outcomes is poorly understood, especially among populations at elevated risk. OBJECTIVE: To determine risk of suicide attempts and other self-directed violence (SDV) after SARS-COV-2 infection in a high-risk population. DESIGN: We employed an observational design supported by comprehensive electronic health records from the Veterans Health Administration (VHA) to examine the association of SARS-COV-2 infection with suicide attempts and other SDV within one year of infection. Veterans with SARS-COV-2 infections were matched 1:5 with non-infected comparators each month. Three periods after index were evaluated: days 1-30, days 31-365, and days 1-365. PARTICIPANTS: VHA patients infected with SARS-COV-2 between March 1, 2020 and March 31, 2021 and matched non-infected Veteran comparators. MAIN MEASURES: Suicide attempt and other SDV events for the COVID-19 and non-infected comparator groups were analyzed using incidence rates per 100,000 person years and hazard ratios from Cox regressions modeling time from matched index date to first event. Subgroups were also examined. KEY RESULTS: 198,938 veterans with SARS-COV-2 (COVID-19 group) and 992,036 comparators were included. Unadjusted one-year incidence per 100,000 for suicide attempt and other SDV was higher among the COVID-19 group: 355 vs 250 and 327 vs 235, respectively. The COVID-19 group had higher risk than comparators for suicide attempts: days 1-30 hazard ratio (HR) = 2.54 (CI:2.05, 3.15), days 31-365 HR = 1.30 (CI:1.19, 1.43) and days 1-365 HR = 1.41 (CI:1.30, 1.54), and for other SDV: days 1-30 HR = 1.94 (CI:1.51, 2.49), days 31-365 HR = 1.32 (CI:1.20, 1.45) and days 1-365 HR = 1.38 (CI:1.26, 1.51). CONCLUSIONS: COVID-19 patients had higher risks of both suicide attempts and other forms of SDV compared to uninfected comparators, which persisted for at least one year after infection. Results support suicide risk screening of those infected with SARS-COV-2 to identify opportunities to prevent self-harm.

Patient Enrollment Growth and Burnout in Primary Care at the Veterans Health Administration.

BACKGROUND: Patient enrollment levels at Veterans Health Administration (VHA) facilities change based on Veteran demand for care, potentially affecting demands on staff. Effects on burnout in the primary care workforce associated with increases or decreases in enrollment are unknown. OBJECTIVE: Estimate associations between patient enrollment and burnout. DESIGN: In this serial cross-sectional study, VHA patient enrollment and workforce data from 2014 to 2018 were linked to burnout estimates for 138 VHA facilities. The VHA's annual All Employee Survey provided burnout estimates. PARTICIPANTS: A total of 82,421 responses to the 2014-2018 All Employee Surveys by primary care providers (PCPs), including physicians, nurse practitioners, and physician assistants; nurses; clinical associates; and administrative clerks were included. Respondents identified as patient-aligned care team members. MAIN MEASURES: Independent variables were (1) the ratio of enrollment to PCPs at VHA facilities and (2) the year-over-year change in enrollment per PCP. Burnout was measured as the annual proportion of staff at VHA facilities who reported emotional exhaustion and/or depersonalization. Each primary care role was analyzed independently. KEY RESULTS: Overall enrollment decreased from 1553 enrollees per PCP in 2014 to 1442 enrollees per PCP in 2018 across VHA facilities. Forty-three facilities experienced increased enrollment (mean of 1524 enrollees/PCP in 2014 to 1668 in 2018) and 95 facilities experienced decreased enrollment (mean of 1566 enrollees/PCP in 2014 to 1339 in 2018). Burnout decreased for all primary care roles. PCP burnout was highest, decreasing from a facility-level mean of 51.7% in 2014 to 43.8% in 2018. Enrollment was not significantly associated with burnout for any role except nurses, for whom a 1% year-over-year increase in enrollment was associated with a 0.2 percentage point increase in burnout (95% CI: 0.1 to 0.3). CONCLUSIONS: Studies assessing changes in organizational-level predictors are rare in burnout research. Patient enrollment predicted burnout only among nurses in primary care.

BMI Trends for Veterans Up to 10 Years After VA Enrollment Following Military Discharge.

BACKGROUND: Obesity (body mass index [BMI]≥30kg/m2) among US adults has tripled over the past 45 years, but it is unclear how this population-level weight change has occurred. OBJECTIVE: We sought to identify distinct long-term BMI trajectories and examined associations with demographic and clinical characteristics. DESIGN: The design was latent trajectory modeling over 10 years of a retrospective cohort. Subgroups were identified via latent class growth mixture models, separately by sex. Weighted multinomial logistic regressions identified factors associated with subgroup membership. PARTICIPANTS: Participants were a retrospective cohort of 292,331 males and 62,898 females enrolled in VA. MAIN MEASURES: The main outcome measure was 6-month average VA-measured BMI over the course of 10 years. Additional electronic health record measures on demographic, clinical, and services utilization characteristics were also used to characterize latent trajectories. KEY RESULTS: Four trajectories were identified for men and for women, corresponding to standard BMI categories "normal weight" (BMI <25), "overweight" (BMI 25-29.99), and "with obesity" (BMI ≥30): "normal weight" and increasing (males: 28.4%; females: 22.8%), "overweight" and increasing (36.4%; 35.6%), "with obesity" and increasing (33.6%; 40.0%), and "with obesity" and stable (males: 1.6%) or decreasing (females: 1.6%). Race, ethnicity, comorbidities, mental health diagnoses, and mental health service utilization discriminated among classes. CONCLUSIONS: BMI in the 10 years following VA enrollment increased modestly. VA should continue prioritizing weight management interventions to the large number of veterans with obesity upon VA enrollment, because the majority remain with obesity.

Impacts of an Electronic Health Record Transition on Veterans Health Administration Health Professions Trainee Experience.

BACKGROUND: Adoption of electronic health care records (EHRs) has proliferated since 2000. While EHR transitions are widely understood to be disruptive, little attention has been paid to their effect on health professions trainees' (HPTs) ability to learn and conduct work. Veterans Health Administration's (VA) massive transition from its homegrown EHR (CPRS/Vista) to the commercial Oracle Cerner presents an unparalleled-in-scope opportunity to gain insight on trainee work functions and their ability to obtain requisite experience during transitions. OBJECTIVE: To identify how an organizational EHR transition affected HPT work and learning at the third VA go-live site. DESIGN: A formative mixed-method evaluation of HPT experiences with VHA's EHR transition including interviews with HPTs and supervisors at Chalmers P. Wylie VA Outpatient Clinic in Columbus, OH, before (~60 min), during (15-30 min), and after (~60 min) go-live (December 2021-July 2022). We also conducted pre- (March 2022-April 2022) and post-go live (May 2022-June 2022) HPT and employee surveys. PARTICIPANTS: We conducted 24 interviews with HPTs (n=4), site leaders (n=2), and academic affiliates (n=2) using snowball sampling. We recruited HPTs in pre- (n=13) and post-go-live (n=10) surveys and employees in pre- (n=408) and post-go-live (n=458) surveys. APPROACH: We conducted interviews using a semi-structured guide and grounded prompts. We coded interviews and survey free text data using a priori and emergent codes, subsequently conducting thematic analysis. We conducted descriptive statistical analysis of survey responses and merged interview and survey data streams. KEY RESULTS: Our preliminary findings indicate that the EHR transition comprehensively affected HPT experiences, disrupting processes from onboarding and training to clinical care contributions and training-to-career retention. CONCLUSIONS: Understanding HPTs' challenges during EHR transitions is critical to effective training. Mitigating the identified barriers to HPT training and providing patient care may lessen their dissatisfaction and ensure quality patient care during EHR transitions.

Design and analysis of outcomes following SARS-CoV-2 infection in veterans.

BACKGROUND: Understanding how SARS-CoV-2 infection impacts long-term patient outcomes requires identification of comparable persons with and without infection. We report the design and implementation of a matching strategy employed by the Department of Veterans Affairs' (VA) COVID-19 Observational Research Collaboratory (CORC) to develop comparable cohorts of SARS-CoV-2 infected and uninfected persons for the purpose of inferring potential causative long-term adverse effects of SARS-CoV-2 infection in the Veteran population. METHODS: In a retrospective cohort study, we identified VA health care system patients who were and were not infected with SARS-CoV-2 on a rolling monthly basis. We generated matched cohorts within each month utilizing a combination of exact and time-varying propensity score matching based on electronic health record (EHR)-derived covariates that can be confounders or risk factors across a range of outcomes. RESULTS: From an initial pool of 126,689,864 person-months of observation, we generated final matched cohorts of 208,536 Veterans infected between March 2020-April 2021 and 3,014,091 uninfected Veterans. Matched cohorts were well-balanced on all 39 covariates used in matching after excluding patients for: no VA health care utilization; implausible age, weight, or height; living outside of the 50 states or Washington, D.C.; prior SARS-CoV-2 diagnosis per Medicare claims; or lack of a suitable match. Most Veterans in the matched cohort were male (88.3%), non-Hispanic (87.1%), white (67.2%), and living in urban areas (71.5%), with a mean age of 60.6, BMI of 31.3, Gagne comorbidity score of 1.4 and a mean of 2.3 CDC high-risk conditions. The most common diagnoses were hypertension (61.4%), diabetes (34.3%), major depression (32.2%), coronary heart disease (28.5%), PTSD (25.5%), anxiety (22.5%), and chronic kidney disease (22.5%). CONCLUSION: This successful creation of matched SARS-CoV-2 infected and uninfected patient cohorts from the largest integrated health system in the United States will support cohort studies of outcomes derived from EHRs and sample selection for qualitative interviews and patient surveys. These studies will increase our understanding of the long-term outcomes of Veterans who were infected with SARS-CoV-2.

A mixed-methods evaluation of why an implementation trial failed to engage veterans with posttraumatic stress disorder in trauma-focused psychotherapy.

An effectiveness trial found that telemedicine collaborative care for posttraumatic stress disorder (PTSD) significantly increased engagement in trauma-focused psychotherapy (TFP) and improved PTSD symptoms. However, in a subsequent implementation trial, very few veterans enrolled in collaborative care initiated TFP. We conducted a mixed-methods evaluation to determine why veterans did not initiate TFP in the implementation trial. After conducting chart reviews of 1,071 veterans with PTSD enrolled in collaborative care, patients were categorized into four mutually exclusive TFP groups: TFP not discussed; TFP discussed, declined; TFP discussed, did not decline; and TFP initiated. We conducted semistructured interviews with 43 unique patients and 58 unique providers (i.e., care managers and mental health specialists). Almost half (48.6%) of the veterans had no documentation of discussing TFP with their care manager; another 28.9% discussed it but declined. Most veterans (77.1%) had an encounter with a mental health specialist, 36.8% of whom never discussed TFP, and 35.7% of whom discussed it but declined. Providers reported that many veterans were not able, willing, or ready to engage in TFP and that non-trauma-focused therapies were better aligned with their treatment goals. Veterans gave numerous reasons for not initiating TFP, including having bad prior experiences with TFP and wanting to avoid thinking about past traumatic experiences. Commonly cited reasons for noninitiation were providers never discussing TFP with veterans and veterans declining TFP after discussing it with their provider. Interventions, such as shared decision-making tools, may be needed to engage providers and patients in informed discussions about TFP.

Full practice authority and burnout among primary care nurse practitioners.

BACKGROUND: Full practice authority (FPA) improves clinical autonomy for nurse practitioners (NPs). Autonomy may reduce burnout. PURPOSE: Estimate the effect of changing from reduced or restricted practice authority to FPA on NP burnout. METHODS: In this quasi-experimental study, we compared NP burnout before (2016) and after (2018) a Veterans Health Administration (VHA) regulation authorized NP FPA. Burnout proportions were estimated for VHA facilities by aggregating responses to the VHA's All Employee Survey from 1,352 primary care NPs. DISCUSSION: Seventy-seven percent of facilities changed to FPA postregulation. Burnout was six points lower among NPs in facilities that changed to FPA compared to facilities that had FPA prior to the regulation; however, this association was not statistically significant. CONCLUSION: NPs are increasingly working under independent practice. While changing to FPA did not reduce NP burnout, this association may vary by health care setting or when burnout is measured for individuals or teams.

Prospective Study of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma on Waitlist for Liver Transplant.

BACKGROUND AND AIMS: There are no prospective data on stereotactic body radiation therapy (SBRT) as a bridge to liver transplantation for HCC. This study aimed to evaluate the efficacy and safety of SBRT as bridging therapy, with comparison with transarterial chemoembolization (TACE) and high-intensity focused ultrasound (HIFU). APPROACH AND RESULTS: Patients were prospectively enrolled for SBRT under a standardized protocol from July 2015 and compared with a retrospective cohort of patients who underwent TACE or HIFU from 2010. The primary endpoint was tumor control rate at 1 year after bridging therapy. Secondary endpoints included cumulative incidence of dropout, toxicity, and posttransplant survival. During the study period, 150 patients were evaluated (SBRT, n = 40; TACE, n = 59; HIFU, n = 51). The tumor control rate at 1 year was significantly higher after SBRT compared with TACE and HIFU (92.3%, 43.5%, and 33.3%, respectively; P = 0.02). With competing risk analysis, the cumulative incidence of dropout at 1 and 3 years after listing was lower after SBRT (15.1% and 23.3%) compared with TACE (28.9% and 45.8%; P = 0.034) and HIFU (33.3% and 45.1%; P = 0.032). Time-to-progression at 1 and 3 years was also superior after SBRT (10.8%, 18.5% in SBRT, 45%, 54.9% in TACE, and 47.6%, 62.8% in HIFU; P < 0.001). The periprocedural toxicity was similar, without any difference in perioperative complications and patient and recurrence-free survival rates after transplant. Pathological complete response was more frequent after SBRT compared with TACE and HIFU (48.1% vs. 25% vs. 17.9%, respectively; P = 0.037). In multivariable analysis, tumor size <3 cm, listing alpha-fetoprotein <200 ng/mL, Child A, and SBRT significantly reduced the risk of dropout. CONCLUSIONS: SBRT was safe, with a significantly higher tumor control rate, reduced the risk of waitlist dropout, and should be used as an alternative to conventional bridging therapies.

How Did Veterans' Reliance on Veterans Health Administration Outpatient Care Change After Expansion of the Veterans Community Care Program?

BACKGROUND: The Veterans Community Care Program (VCCP) aims to address access constraints in the Veterans Health Administration (VA) by reimbursing care from non-VA community providers. Little existing research explores how veterans' choice of VA versus VCCP providers has evolved as a significant VCCP expansion in 2014 as part of the Veterans Access, Choice, and Accountability Act. OBJECTIVES: We examined changes in reliance on VA for primary care (PC), mental health (MH), and specialty care (SC) among VCCP-eligible veterans. RESEARCH DESIGN: We linked VA administrative data with VCCP claims to retrospectively examine utilization during calendar years 2016-2018. SUBJECTS: 1.78 million veterans enrolled in VA before 2013 and VCCP-eligible in 2016 due to limited VA capacity or travel hardship. MEASURES: We measured reliance as the proportion of total annual outpatient (VA+VCCP) visits occurring in VA for PC, MH, and SC. RESULTS: Of the 26.1 million total outpatient visits identified, 45.6% were for MH, 29.9% for PC, and 24.4% for SC. Over the 3 years, 83.2% of veterans used any VA services, 23.8% used any VCCP services, and 20.0% were dual VA-VCCP users. Modest but statistically significant declines in reliance were observed from 2016-2018 for PC (94.5%-92.2%), and MH (97.8%-96.9%), and a more significant decline was observed for SC (88.5%-79.8%). CONCLUSIONS: Veterans who have the option of selecting between VA or VCCP providers continued using VA for most of their outpatient care in the initial years after the 2014 VCCP expansion.

Identifying and Prioritizing Workplace Climate Predictors of Burnout Among VHA Primary Care Physicians.

OBJECTIVE: Burnout, or job-related stress, affects more than half of all US physicians, with primary care physicians (PCPs) experiencing some of the highest rates in medicine. Our study analyzes national survey data to identify and prioritize workplace climate predictors of burnout among PCPs within a large integrated health system. DESIGN: Observational study of annual survey data from the Veterans Health Administration (VHA) All Employee Survey (AES) for 2013-2017. AES response rate ranged from 56 to 60% during the study period. Independent and dependent variables were measured from separate random samples. In total, 8,456 individual-level responses among PCPs at 110 VHA practice sites were aggregated at the facility level by reporting year. We used the semi-automated LASSO procedure to identify workplace climate measures that were more influential in predicting burnout and assessed relative importance using the Shapely value decomposition. PARTICIPANTS: VHA employees that self-identify as PCPs. MAIN MEASURES: Dependent variables included two dichotomous measures of burnout: emotional exhaustion and depersonalization. Independent measures included 30 survey measures related to dimensions of workplace climate (e.g., workload, leadership, satisfaction). RESULTS: We identified seven influential workplace climate predictors of emotional exhaustion and nine predictors of depersonalization. With few exceptions, higher agreement/satisfaction scores for predictors were associated with a lower likelihood of burnout. The majority of explained variation in emotional exhaustion was attributable to perceptions of workload (32.6%), organization satisfaction (28.2%), and organization support (19.4%). The majority of explained variation in depersonalization was attributable to workload (25.3%), organization satisfaction (22.9%), and connection to VHA mission (20.7%). CONCLUSION: Identifying the relative importance of workplace climate is important for the allocation of health organization resources to mitigate and prevent burnout within the PCP workplace. In a context of limited resources, efforts to reduce perceived workload and improve organization satisfaction may represent the biggest leverage points for health organizations to address physician burnout.

Paraneoplastic cast nephropathy associated with malignant prolactinoma: A case report and literature review.

Malignant prolactinomas are very rare and are diagnosed when a prolactin-producing pituitary adenoma has metastasized. We report on a 54-year-old man with a history of macroprolactinoma transforming into a pituitary carcinoma secreting both prolactin and growth hormone with metastases to the stomach, bone, lungs, retroperitoneum, and kidney. Reviewing the literature, this case is the first reporting of a pituitary carcinoma with biopsy-proven paraneoplastic cast nephropathy. Symptoms and renal function improved following a course of palliative chemotherapy and radiotherapy. After 2 years, his disease progressed requiring further palliative treatment that was complicated by severe chest sepsis. He was not fit for further chemotherapy, receiving symptomatic relief in a hospice, and died soon after. The case highlights the importance of considering a patient's past medical history in the context of persistent unexplained renal impairment and systemic metastases when unexplained systemic symptoms and multi-organ involvement is present. The importance of renal biopsy for definitive diagnosis and before using potentially nephrotoxic chemotherapy is also highlighted. Renal diagnosis helped inform the decision to give chemotherapy, with the importance of this evidenced by an improvement in renal function following chemotherapy.

Large-Scale Whole-Genome Sequencing Reveals the Genetic Architecture of Primary Membranoproliferative GN and C3 Glomerulopathy.

BACKGROUND: Primary membranoproliferative GN, including complement 3 (C3) glomerulopathy, is a rare, untreatable kidney disease characterized by glomerular complement deposition. Complement gene mutations can cause familial C3 glomerulopathy, and studies have reported rare variants in complement genes in nonfamilial primary membranoproliferative GN. METHODS: We analyzed whole-genome sequence data from 165 primary membranoproliferative GN cases and 10,250 individuals without the condition (controls) as part of the National Institutes of Health Research BioResource-Rare Diseases Study. We examined copy number, rare, and common variants. RESULTS: Our analysis included 146 primary membranoproliferative GN cases and 6442 controls who were unrelated and of European ancestry. We observed no significant enrichment of rare variants in candidate genes (genes encoding components of the complement alternative pathway and other genes associated with the related disease atypical hemolytic uremic syndrome; 6.8% in cases versus 5.9% in controls) or exome-wide. However, a significant common variant locus was identified at 6p21.32 (rs35406322) (P=3.29×10-8; odds ratio [OR], 1.93; 95% confidence interval [95% CI], 1.53 to 2.44), overlapping the HLA locus. Imputation of HLA types mapped this signal to a haplotype incorporating DQA1*05:01, DQB1*02:01, and DRB1*03:01 (P=1.21×10-8; OR, 2.19; 95% CI, 1.66 to 2.89). This finding was replicated by analysis of HLA serotypes in 338 individuals with membranoproliferative GN and 15,614 individuals with nonimmune renal failure. CONCLUSIONS: We found that HLA type, but not rare complement gene variation, is associated with primary membranoproliferative GN. These findings challenge the paradigm of complement gene mutations typically causing primary membranoproliferative GN and implicate an underlying autoimmune mechanism in most cases.

Long-term outcomes and response to treatment in diacylglycerol kinase epsilon nephropathy.

Recessive mutations in diacylglycerol kinase epsilon (DGKE) display genetic pleiotropy, with pathological features reported as either thrombotic microangiopathy or membranoproliferative glomerulonephritis (MPGN), and clinical features of atypical hemolytic uremic syndrome (aHUS), nephrotic syndrome or both. Pathophysiological mechanisms and optimal management strategies have not yet been defined. In prospective and retrospective studies of aHUS referred to the United Kingdom National aHUS service and prospective studies of MPGN referred to the National Registry of Rare Kidney Diseases for MPGN we defined the incidence of DGKE aHUS as 0.009/million/year and so-called DGKE MPGN as 0.006/million/year, giving a combined incidence of 0.015/million/year. Here, we describe a cohort of sixteen individuals with DGKE nephropathy. One presented with isolated nephrotic syndrome. Analysis of pathological features reveals that DGKE mutations give an MPGN-like appearance to different extents, with but more often without changes in arterioles or arteries. In 15 patients presenting with aHUS, ten had concurrent substantial proteinuria. Identified triggering events were rare but coexistent developmental disorders were seen in six. Nine with aHUS experienced at least one relapse, although in only one did a relapse of aHUS occur after age five years. Persistent proteinuria was seen in the majority of cases. Only two individuals have reached end stage renal disease, 20 years after the initial presentation, and in one, renal transplantation was successfully undertaken without relapse. Six individuals received eculizumab. Relapses on treatment occurred in one individual. In four individuals eculizumab was withdrawn, with one spontaneously resolving aHUS relapse occurring. Thus we suggest that DGKE-mediated aHUS is eculizumab non-responsive and that in individuals who currently receive eculizumab therapy it can be safely withdrawn. This has important patient safety and economic implications.

Events Associated With Changes in Reliance on the Veterans Health Administration Among Medicare-eligible Veterans.

OBJECTIVES: We can learn something about how Veterans value the Veterans Health Administration (VHA) versus community providers by observing Veterans' choices between VHA and Medicare providers after they turn 65. For a cohort of Veterans who were newly age-eligible for Medicare, we estimated the change in VHA reliance (VHA outpatient visits divided by total VHA and Medicare visits) associated with specific events: receiving a life-threatening diagnosis, having a Medicare-paid hospitalization, or moving further from the VHA. RESEARCH DESIGN: A longitudinal cohort study of VHA and Medicare administrative data. SUBJECTS: A total of 5932 VHA users who completed a health survey in 1999 and became age-eligible for Medicare from 1998 to 2000 were followed through 2016. PRINCIPAL FINDINGS: More Veterans chose to rely on the VHA than Medicare (64% vs. 36.%). For a VHA-reliant Veteran, a Medicare-paid hospital stay was associated with a decrease of 7.8 percentage points (pps) (P<0.001) in VHA reliance in the subsequent 12 months, but by 36 months reliance increased to near prehospitalization levels (-1.5 pps; P=0.138). Moving further from the VHA, or receiving a diagnosis of cancer, heart failure, or renal failure had no significant association with subsequent VHA reliance; however, a diagnosis of dementia was associated with a decrease in VHA reliance (-8.6 pps; P=0.026). CONCLUSIONS: A significant majority of newly Medicare-eligible VHA users voted with their feet in favor of sustaining the VHA as a provider of comprehensive medical care for Veterans. These VHA-reliant Veterans maintained their reliance even after receiving a life-threatening diagnosis, and after experiencing Medicare-provided hospital care.