Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death. Two separate retrospective case–control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first observation in Veterans Affairs Health Care Upstate New York (VISN2) network data system were excluded. Data obtained included use of PPI (Yes/No), demographics, laboratory data, pre-PPI comorbidity variables. A total of 19,311/76,462 patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients receiving PPI were less likely to have vascular disease, COPD, cancer and diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758 died. A prospective logistic analysis of case–control data showed higher odds for development of CKD (OR 1.10 95 % CI 1.05–1.16) and mortality (OR 1.76, 95 % CI 1.67–1.84) among patients taking PPIs versus those not on PPIs. Use of proton pump inhibitors is associated with increased risk of development of CKD and death. With the large number of patients being treated with proton pump inhibitors, healthcare providers need to be better educated about the potential side effects of these medications.

INTRODUCTION: Spontaneous bacterial peritonitis (SBP) bacteriology has changed over time. Reappraisal of primary SBP prophylaxis showed an increased rate of resistance in patients on primary prophylaxis with resultant discontinuation of this prophylaxis throughout the Veterans Affairs (VA). We aimed to re-evaluate the risk-benefit ratio of secondary SBP prophylaxis (SecSBPPr). METHODS: Using validated International Classification of Diseases -9/10 codes, we used the VA Corporate Data Warehouse and the Non-VA National TriNetX database to identify patients in 2 different large US systems who survived their first SBP diagnosis (with chart review from 2 VA centers) between 2009 and 2019. We evaluated the prevalence of SecSBPPr and compared outcomes between those who started on SecSBPPr vs not. RESULTS: We identified 4,673 veterans who survived their index SBP episode; 54.3% of whom were prescribed SecSBPPr. Multivariable analysis showed higher SBP recurrence risk in those on vs off SecSBPPr (hazards ratio 1.63 [1.40–1.91], P < 0.001). This was accompanied by higher fluoroquinolone resistance odds in SecSBPPr patients (odds ratio = 4.32 [1.36–15.83], P = 0.03). In TriNetX, we identified 6,708 patients who survived their index SBP episode; 48.6% were on SecSBPPr. Multivariable analysis similarly showed SecSBPPr increased SBP recurrence risk (hazards ratio 1.68 [1.33–1.80], P < 0.001). Both data sets showed higher SBP recurrence trends over time in SecSBPPr patients. Results remained consistent at 6-month and 2-year timepoints. DISCUSSION: In 2 national data sets of >11,000 patients with SBP, we found that SecSBPPr was prescribed in roughly half of patients. When initiated, SecSBPPr, compared with no prophylaxis after SBP, increased the risk of SBP recurrence in multivariable analysis by 63%–68%, and this trend worsened over time. SecSBPPr should be reconsidered in cirrhosis.

Spontaneous bacterial peritonitis (SBP) is a major cause of mortality. Although SBP primary prophylaxis (SBPPr) with fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX) is often used, resistance could reduce its benefit. Aim: Analyze peritoneal fluid resistance patterns in patients with a first SBP episode with/without SBPPr using the Veterans Health Administration corporate data warehouse and to evaluate national antibiograms. Corporate data warehouse data were extracted using validated International Classification of Disease-9/10 codes, culture, resistance data, and outcomes of 7553 patients who developed their first inpatient SBP between 2009 and 2019 and compared between those with/without SBPPr. Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) sensitivity to ciprofloxacin and TMP-SMX was calculated using 2021 Veterans Health Administration antibiogram data from all states. The most common isolates were E. coli, K. pneumoniae, and Staphylococcus species. Veterans taking ciprofloxacin SBBPr had higher fluoroquinolone resistance (34% vs 14% no SBPPr, p<0.0001); those taking TMP-SMX had higher TMP-SMX resistance (40% vs 14%, p<0.0001). SBPPr patients showed higher culture positivity, greater length of stay, higher second SBP, and higher probability of liver transplant rates versus no SBPPr. Multivariable models showed SBBPr to be the only variable associated with gram-negative resistance, and SBPPr was associated with a trend toward longer length of stay.E. coli ciprofloxacin sensitivity rates were 50%–87% and 43%–92% for TMP-SMX. K. pneumoniae ciprofloxacin sensitivity was 76%–100% and 72%–100% for TMP-SMX. Conclusion: Among patients who developed their first SBP episode, there was a higher prevalence of antibiotic resistance in those on SBPPr, with a high rate of fluoroquinolone resistance across the Veterans Health Administration sites.

Background:COVID-19 sequelae among veterans need evaluation. Design: Propensity-score-matched retrospective cohort study. Participants: A total 778,738 veterans, who were tested for COVID-19 at VA facilities between 20 February 2020–27 March 2021. Main Outcomes: Development of new physical and mental health conditions (incidence) during the follow-up period of 7 days to 3 months after the diagnosis of COVID-19. Results: Out of 778,738 veterans, 149,205 (19.2%) were inpatients and 629,533 (80.8%) were outpatients. 123,757 (15.9%) diagnosed with COVID-19. Mean age was 61 ± 15.4, mostly men (89%) who were White (68%) and non-Hispanic (88%). In hospitalized patients, COVID-19 is associated with significantly higher incidences of physical conditions (venous thromboembolism (5.8% vs. 2.9%, p < 0.001), pulmonary circulation disorder (5.1% vs. 2.9%, p < 0.001), chronic lung disease (8.4% vs. 4.3%, p < 0.001), acute kidney injury (16.4% vs. 9.3%, p < 0.001), chronic kidney disease (6.5% vs. 4.8%, p < 0.001), cardiac arrhythmia (15.2% vs. 10.9%, p < 0.001), complicated hypertension (12% vs. 8.5%, p < 0.001), coagulopathy (6.1% vs. 2.6%, p < 0.001), fluid/electrolyte disorders (24.4% vs. 12.6%, p < 0.001) and neurological disorders (7.1% vs. 3.8%, p < 0.001)) and mental health conditions (depressive episode (6.6% vs. 4.3%, p < 0.001), adjustment disorder (2.5% vs. 1.7%, p < 0.001), insomnia (4.9% vs. 3.2%, p < 0.001) and dementia (3.0% vs. 1.9%, p < 0.001)) compared to propensity-matched hospitalized COVID-19 negative patients. In outpatient settings, COVID-19 diagnosis is associated with smaller increase in the incidences of the physical sequelae. Conclusions: In this propensity-score-matched analysis of US veterans, COVID-19 survivors, especially those who were hospitalized, developed new physical and mental health sequelae at a significantly higher rate than those without COVID-19.

INTRODUCTION: Antibiotic overuse and subsequent antibiotic resistance lead to worse infection outcomes in cirrhosis. Secondary spontaneous bacterial peritonitis prophylaxis (SecSBBPr) is associated with higher SBP recurrence, but impact on non-SBP infections is unclear. METHODS: We studied patients with cirrhosis and SBP who were given SecSBPPr or not between 2009 and 2019 in 2 complementary national cohorts (Veterans Affairs Corporate Data Warehouse [VA-CDW] and non-VA TriNetX). Development of total non-SBP infections and specifically urinary tract infections (UTIs), bacteremia, pneumonia, and C. difficile using validated codes over 2 years was compared between those on SecSBPPr vs not. Multivariable regression for non-SBP infections was performed. RESULTS: VA-CDW: Of 4,673 veterans with index SBP, 2,539 (54.3%) were started on SecSBPPr. In total, 1,406 (30.1%) developed non-SBP infections (13.5% UTI, 12.4% pneumonia, 8.5% bacteremia, and 6.8% C. difficile). On multivariable regression, SecSBPPr was significantly associated with any non-SBP infection (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.10–1.44, P < 0.0001) and UTI (OR 1.21, 95% CI 1.01–1.45, P = 0.036). TriNetX: Of 6,708 patients with index SBP, 3,261 (48.6%) were started on SecSBPPr. In total, 1,932 (28.8%) patients developed non-SBP infections (13.4% UTI, 12.9% pneumonia, 8.6% bacteremia, and 5.9% C. difficile). On multivariable regression, SecSBPPr was significantly associated with any non-SBP infection (OR 1.33, 95% CI 1.12–1.59, P < 0.0001), UTI (OR 1.35, 95% CI 1.07–1.71, P = 0.010), pneumonia (OR 1.35, 95% CI 1.06–1.72, P = 0.017), and bacteremia (OR 1.47, 95% CI 1.10–1.97, P = 0.009). DISCUSSION: In 2 diverse US-based national cohorts of patients with cirrhosis and SBP, use of SecSBPPr was associated with a higher risk of non-SBP infections, especially urinary tract infections.

Despite negative outcomes, hepatic encephalopathy (HE) is not included in the Model for End-Stage Liver Disease (MELD) scores, including MELD 3.0. In a National Veterans Affairs database, we studied the additive mortality predictive impact of a documented inpatient overt HE diagnosis on MELD 3.0 and MELD-sodium (MELD-Na) scores in 75,327 veterans (26.8% with HE, 22% 90-day and 37% 1-year mortality). The addition of HE to MELD 3.0 and MELD-Na significantly improved their mortality prediction with interactions at 90 days and 1 year on multivariable regression. A documented inpatient HE episode is additive to the mortality prediction of MELD 3.0 by 4–5 extra points and could enhance future MELD iterations.