Healthcare Costs Across Diabetic Kidney Disease Stages: A Veterans Affairs Study.

Background: In the United States, diabetic kidney disease (DKD) affects about one-third of individuals with type 2 diabetes, causing significant economic burdens on the health care system and affecting patients' quality of life. Objective: The aim of the study was to quantify the burden of care in patients at different stages of DKD and to monitor shifts in healthcare costs throughout these stages. Methods: This study used data from the Veterans Affairs National database, focusing on US veterans diagnosed with DKD between January 2016 and March 2022. Aggregated all-cause health care costs per month were summarized using descriptive statistics. We used a generalized linear model to calculate the cost of DKD patent care based on the stages, dialysis phase, and kidney replacement therapy. Results: The cohort of 685,288 patients with DKD was predominantly male (96.51%), White (74.42%), and non-Hispanic (93.54%). The mean (SD) per-patient per-month costs were $1,597 ($3,178), $1,772 ($4,269), $2,857 ($13,072), $3,722 ($12,134), $5,505 ($14,639), and $6,999 ($16,901) for stages 1, 2, 3a, 3b, 4 and 5 respectively. The average monthly expenditure for patients receiving long-term dialysis was $12,299. Costs peaked sharply during the first month of kidney replacement therapy at $38,359 but subsequently decreased to $6,636 after 1 year. Conclusions: The economic implications of DKD are profound, emphasizing the need for efficient early detection and disease management strategies. Preventing patients from progressing to advanced DKD stage will minimize the economic repercussions of DKD and will assist health care systems in optimizing resource allocation.

Diabetic kidney disease (DKD) places a substantial burden on health care systems in the United States. In part of our effort to close the knowledge gap around the disease burden, care cost analysis for the patients with DKD was performed for US veterans. Along with stage progression, overall care costs per-patient per-month drastically increases from $1,597 (stage 1) to $6,999 (stage 5). Monthly costs exceeded $10,000 once veterans started to receive long-term dialysis. The quantitative summary will help health care systems efficiently allocate resources across various disease sectors.

Factors associated with testing positive for SARS-CoV-2 and evaluation of a recruitment protocol among healthcare personnel in a COVID-19 vaccine effectiveness study.

Objective: The objective of this study was to determine factors associated with testing positive for SARS-CoV-2 among healthcare personnel. Secondary objectives were to assess representativeness of recruited participants and the effectiveness of a multiple-contact protocol for recruiting healthcare personnel in this COVID-19 study. Design: Survey study, conducted as part of an observational test-negative study of COVID-19 vaccine effectiveness. Setting: University of Utah Health system, including both inpatient and outpatient facilities. Participants: Clinical and non-clinical healthcare personnel at University of Utah Health. 1456 were contacted and 503 (34.5%) completed the survey. Cases were all eligible employees testing positive for COVID-19, with 3:1 randomly selected, matched controls (test negative) selected weekly. Methods: Online survey. Results: Significant differences in the demographics of participants and the source population were observed; e.g., nursing staff comprised 31.6% of participants but only 23.3% of the source population. The multiple-contact recruitment protocol increased participation by ten percentage points and ensured equal representation of controls. Potential exposure to illness outside of work was strongly predictive of testing positive for SARS-CoV-2 (OR = 3.74; 95% CI: 2.29, 6.11) whereas potential exposure at work was protective against testing positive (OR: 0.51, 95% CI: 0.29, 0.88). Conclusions: Carefully designed recruitment protocols increase participation and representation of controls, but bias in participant demographics still exists. The negative association between potential workplace exposure and positive test suggests testing bias in the test-negative design. Healthcare personnel's potential exposures to COVID-19 outside of the workplace are important predictors of SARS-CoV-2 seropositivity.

Epidemiology of Diabetic Kidney Disease among US Veterans.

Rationale: With a large number of patients and high mortality, diabetic kidney disease (DKD) imposes a significant burden on US health care. Although diabetes is the leading cause of chronic kidney disease and complications, the epidemiology of DKD in the contemporary US veteran population is generally unknown. Objective: We aimed to estimate the rate of DKD progression and to measure the general epidemiology of DKD in the United States veteran population. Study Design: We performed a retrospective observational research using electronic health-care records and administrative databases. Setting: The DKD patient cohort was abstracted from the Veterans Health Administration health-record data from January 2016 to March 2022. Participants: We defined DKD patients using the laboratory test data based on Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines. Analytic Approach: Summary statistics include the five-year cumulative incidence of progression to an advanced stage from the DKD stage at the cohort entry date and prevalence at a series of single time points. Results: A total of 685,288 patients (male [96%], mean age 62 years, Caucasian [64%], non-Hispanic [87%]) met our eligibility criteria. The 5-year cumulative incidence of progression to an advanced DKD stage or all-cause death from DKD stages G1 A2/A3, G2 A2/A3, G3a, and G3b were 52.0%, 47.4%, 50.5%, and 60.9%, respectively. In sum, 594,082 patients were classified as moderate or high risk as per KDIGO guidelines in 2021, and stages G3a and G3b accounted for 51.2% and 25.3%, respectively, of cases. Conclusion: More than half of DKD patients underwent a stage progression or death within 5 years. A substantial number of DKD patients at an earlier stage might be left undetermined. The study findings warrant a revision of DKD patient identification and management in US veterans.

Angina Severity, Mortality, and Healthcare Utilization Among Veterans With Stable Angina.

Background Canadian Cardiovascular Society (CCS) angina severity classification is associated with mortality, myocardial infarction, and coronary revascularization in clinical trial and registry data. The objective of this study was to determine associations between CCS class and all-cause mortality and healthcare utilization, using natural language processing to extract CCS classifications from clinical notes. Methods and Results In this retrospective cohort study of veterans in the United States with stable angina from January 1, 2006, to December 31, 2013, natural language processing extracted CCS classifications. Veterans with a prior diagnosis of coronary artery disease were excluded. Outcomes included all-cause mortality (primary), all-cause and cardiovascular-specific hospitalizations, coronary revascularization, and 1-year healthcare costs. Of 299 577 veterans identified, 14 216 (4.7%) had ≥1 CCS classification extracted by natural language processing. The mean age was 66.6±9.8 years, 99% of participants were male, and 81% were white. During a median follow-up of 3.4 years, all-cause mortality rates were 4.58, 4.60, 6.22, and 6.83 per 100 person-years for CCS classes I, II, III, and IV, respectively. Multivariable adjusted hazard ratios for all-cause mortality comparing CCS II, III, and IV with those in class I were 1.05 (95% CI, 0.95-1.15), 1.33 (95% CI, 1.20-1.47), and 1.48 (95% CI, 1.25-1.76), respectively. The multivariable hazard ratio comparing CCS IV with CCS I was 1.20 (95% CI, 1.09-1.33) for all-cause hospitalization, 1.25 (95% CI, 0.96-1.64) for acute coronary syndrome hospitalizations, 1.00 (95% CI, 0.80-1.26) for heart failure hospitalizations, 1.05 (95% CI, 0.88-1.25) for atrial fibrillation hospitalizations, 1.92 (95% CI, 1.40-2.64) for percutaneous coronary intervention, and 2.51 (95% CI, 1.99-3.16) for coronary artery bypass grafting surgery. Conclusions Natural language processing-extracted CCS classification was positively associated with all-cause mortality and healthcare utilization, demonstrating the prognostic importance of anginal symptom assessment and documentation.

Clinical and Economic Outcomes of Ranolazine Versus Conventional Antianginals Users Among Veterans With Chronic Stable Angina Pectoris.

Real-world outcomes in patients with chronic stable angina treated with ranolazine and other antianginal medications as second- or third-line therapy are limited. In a historical cohort study of veterans with chronic stable angina, we compared time with coronary revascularization procedures, hospitalizations, and 1-year healthcare costs between new-users of ranolazine versus conventional antianginals (i.e., calcium channel blockers, ß blockers, or long-acting nitrates) as second- or third-line. Weighted regression models calculated adjusted hazard ratios (HR) at up to 8-year follow-up, and adjusted incremental costs in the first year. Weighted groups comprised 4,699 ranolazine users and 31,815 conventional antianginal users. Percutaneous coronary intervention (PCI) occurred more often in ranolazine users compared with conventional antianginal users (HR 1.16; 95% confidence intervals [CI] 1.08 to 1.25, p <0.001), and coronary artery bypass grafting occurred less often (HR 0.82; 95% CI 0.68 to 1.00, p <0.046). All-cause and atrial fibrillation (AF) hospitalizations were less common with ranolazine users compared with conventional users (all-cause: HR 0.94; 95% CI 0.90 to 0.99, p <0.010; AF:HR 0.74; 95% CI 0.67 to 0.82, p <0.001), and acute coronary syndrome was more common (HR 1.13; 95% CI 1.00 to 1.27, p <0.042). Adjusted 1-year costs were $24,517 in ranolazine users and $24,798 in conventional users (difference, $-280; 95% CI $-1,742 to $1,181, p = 0.71). In conclusion, ranolazine users had lower rates of coronary artery bypass grafting and all-cause and AF hospitalizations, but higher rates of percutaneous coronary intervention and hospitalizations due to acute coronary syndrome compared with conventional antianginal users. Healthcare costs were similar between ranolazine and conventional antianginal users.

Health Care Costs in a Cohort of HIV-Infected U.S. Veterans Receiving Regimens Containing Tenofovir Disoproxil Fumarate/Emtricitabine.

BACKGROUND: Tenofovir disoproxil fumarate (TDF), a key component in many human immunodeficiency virus (HIV) treatment regimens, is associated with increased renal and bone toxicities. The contributions of such toxicities to treatment costs, as well as the relative differences in treatment costs for various TDF/emtricitabine (FTC) regimens, remains unexplored. OBJECTIVE: To estimate and compare mean overall and renal- and bone-specific costs, including total, inpatient, outpatient, and pharmacy costs in patients treated with TDF/FTC+efavirenz (EFV) compared with several non-EFV-containing TDF/FTC regimens. METHODS: We conducted a national cohort study of treatment-naive HIV-infected U.S. veterans who initiated treatment from 2003 to 2015 with TDF/FTC in combination with EFV, elvitegravir/cobicistat, rilpivirine, or ritonavir-boosted protease inhibitors (atazanavir, darunavir, or lopinavir). Outcomes of interest were quarterly total, inpatient, outpatient, and pharmacy costs using data from the Veterans Health Administration (VHA) electronic medical record and Managerial Cost Accounting System (an activity-based accounting system that allocates VHA expenditures to patient encounters). We controlled for measured confounders using inverse probability of treatment (IPT) weights and assessed differences using standardized mean differences (SMDs). For comparisons where SMDs exceeded 0.1 after IPT weighting, we used the more conservative matching weights in sensitivity analyses. For hypothesis testing, we compared IPT-adjusted differences in quarterly costs between treatment groups using Mann-Whitney U-tests and generalized estimating equation (GEE) regression models. RESULTS: Of 33,048 HIV-positive veterans, 7,222 met eligibility criteria, including 4,172 TDF/FTC + EFV recipients; mean (SD) age of the cohort was 50.0 (10.0) years; 96.7% were male; 60.1% were black; and 30.1% were white. Quarterly periods of exposure to EFV-containing regimens were 22,499 and of exposure to non-EFV-containing regimens were 11,633. After IPT weighting, absolute SMDs were < 0.1 except for a few covariates in the rilpivirine comparison. The per-patient adjusted mean total quarterly costs were $7,145 for EFV versus $8,726 for non-EFV (P < 0.001; Mann-Whitney U-test) and the per-patient adjusted mean difference in total quarterly costs was $1,419 lower for EFV versus all non-EFV combined (P < 0.001; GEE model). Corresponding values for outpatient costs ($2,656 vs. $2,942; P < 0.001; difference, -$254; P = 0.001), inpatient costs ($2,009 vs. $2,614; P < 0.001), radiology costs ($213 vs. $276; P < 0.001), and pharmacy costs ($2,480 vs. $3,170; P < 0.001; difference, -$600; P < 0.001) were all lower for EFV versus all non-EFV combined. Findings based on matching weights were qualitatively similar. Contributions of renal and bone costs to the total costs of treatment were very small, ranging between $52 and $94 per patient per quarter for renal outcomes and between $6 and $114 for bone outcomes. CONCLUSIONS: Among 7,222 HIV-treated veterans over an average follow-up of 1.2 years per patient, those patients receiving TDF/FTC + EFV had lower overall health care costs compared with those receiving non-EFV regimens. DISCLOSURES: This study was funded by Bristol-Myers Squibb. Nelson, Ma, Crook, Knippenberg, Nyman, and LaFleur are employees of the University of Utah, which received a grant from Bristol-Myers Squibb to conduct this study. Nyman also discloses honoraria for consulting from Otsuka and for writing a book chapter from Fresenius. La Fleur reports advisory board and consulting fees from Bristol-Myers Squibb outside of this study. Paul and Esker are employees of, and own stock in, Bristol-Myers Squibb.

Tenofovir-Associated Bone Adverse Outcomes among a US National Historical Cohort of HIV-Infected Veterans: Risk Modification by Concomitant Antiretrovirals.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF) has been associated with greater incidences of bone complications, which might be modified by some concomitantly administered antiretrovirals, possibly by their effect on tenofovir concentrations. We compared bone adverse outcomes among treatment-naïve HIV-infected US veterans initiating efavirenz (EFV)-containing TDF/emtricitabine (FTC) regimens versus those initiating non-EFV-containing TDF/FTC regimens. METHODS: Using national Veterans Health Administration clinical and administrative data sets, we identified a cohort of treatment-naïve HIV-infected veterans without bone disease who initiated therapy with TDF/FTC plus EFV, rilpivirine, elvitegravir/cobicistat, or ritonavir-boosted protease inhibitors in 2003-2015. The primary composite adverse bone outcome was the unadjusted incidence rate (IR) of osteoporosis, osteopenia, or fragility fracture (any hip, wrist, or spine fracture). To account for selection bias and confounding, we used inverse probability of treatment-weighted Cox proportional hazards regression models to calculate adjusted hazard ratios (HRs) for each outcome associated with EFV + TDF/FTC versus each non-EFV-containing TDF/FTC regimen. RESULTS: Of 33,048 HIV-positive veterans, 7161 initiated a TDF/FTC-containing regimen (mean age, 50 years; baseline CD4 < 200 cells/mm3, 33.3%; HIV-1 RNA > 100,000 copies/ml, 22.3%; mean follow-up, 13.0 months). Of these, 4137 initiated EFV- and 3024 non-EFV-containing regimens. Veterans initiating EFV- versus non-EFV-containing TDF/FTC regimens had a lower IR of the composite bone outcome (29.3 vs. 41.4 per 1000 patient-years), with significant risk reductions for this outcome [HR, 0.69; 95% confidence interval (CI), 0.58-0.83] and fragility fracture (HR, 0.59; 95% CI, 0.44-0.78). CONCLUSION: EFV + TDF/FTC is associated with a lower risk of adverse bone outcomes compared with other TDF-containing regimens in the VHA. FUNDING: Bristol-Myers Squibb.

Brief Report: Tenofovir-Associated Nephrotoxicity Among a US National Historical Cohort of HIV-Infected Veterans: Risk Modification by Concomitant Antiretrovirals.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been associated with renal complications. The third agent in TDF-containing antiretroviral regimens may modify that risk. We compared renal adverse outcomes among treatment-naive HIV-infected patients initiating TDF-containing regimens including efavirenz (EFV) or other agents. SETTING: This population-based historical cohort study used national Veterans Health Administration (VHA) clinical and administrative data sets to identify treatment-naive HIV-infected veterans initiating antiretroviral therapy with TDF/emtricitabine (FTC) + EFV, rilpivirine (RPV), elvitegravir/cobicistat (EVG/c), or ritonavir (RTV)-boosted protease inhibitors (PIs) from 2003 to 2015. METHODS: Unadjusted incidence rates (IRs) for each regimen and covariate-adjusted hazard ratios [ using Cox proportional hazards models and inverse probability of treatment weighting] for between-regimen comparisons were calculated for renal outcomes including confirmed proteinuria, defined as 2 consecutive protein-to-creatinine ratios >150 mg/g or albumin-to-creatinine ratios >30 mg/g occurring ≥90 days apart; chronic kidney disease (CKD), defined as 2 consecutive estimated glomerular filtration rate measurements <60 mL·min·1.73 m occurring ≥90 days apart; and kidney dialysis. RESULTS: Of 33,048 HIV-positive veterans, 4172 received EFV + TDF/FTC, 234 EVG/c/TDF/FTC, 173 RPV/TDF/FTC, and 2651 RTV-boosted PIs + TDF/FTC. Confirmed proteinuria and CKD IRs were numerically lower with EFV + TDF/FTC versus non-EFV + TDF/FTC (dialysis IRs were rare and comparable). After inverse probability of treatment weighting adjustment, EFV + TDF/FTC was associated with lower CKD risk versus non-EFV + TDF/FTC (hazard ratio, 0.62; 95% confidence interval, 0.53 to 0.72), EVG/c/TDF/FTC (0.75; 0.59 to 0.95), RPV/TDF/FTC (0.20; 0.17 to 0.24), and RTV-boosted PIs + TDF/FTC (0.62; 0.53 to 0.72). CONCLUSIONS: EFV + TDF/FTC was associated with significantly lower risk of CKD versus other TDF-containing regimens in the Veterans Health Administration.

Cardiovascular outcomes among HIV-infected veterans receiving atazanavir.

OBJECTIVE: Patients with HIV infection have an increased risk of cardiovascular disease compared with uninfected individuals. Antiretroviral therapy with atazanavir (ATV) delays progression of atherosclerosis markers; whether this reduces cardiovascular disease event risk compared with other antiretroviral regimens is currently unknown. DESIGN: Population-based, noninterventional, historical cohort study conducted from 1 July 2003 through 31 December 2015. SETTING: Veterans Health Administration hospitals and clinics throughout the United States. PARTICIPANTS: Treatment-naive patients with HIV infection (N = 9500). ANTIRETROVIRAL EXPOSURES: Initiating antiretroviral regimens containing ATV, other protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTIs), or integrase strand transfer inhibitors (INSTIs). MAIN OUTCOME/EFFECT SIZE MEASURES: Incidence rates of myocardial infarction (MI), stroke, and all-cause mortality within each regimen. ATV versus other protease inhibitor, NNRTI, or INSTI covariate-adjusted hazard ratios by using Cox proportional hazards models and inverse probability of treatment weighting. RESULTS: Incidence rates for MI, stroke, and all-cause mortality with ATV-containing regimens (5.2, 10.4, and 16.0 per 1000 patient-years, respectively) were lower than with regimens containing other protease inhibitors (10.2, 21.9, and 23.3 per 1000 patient-years), NNRTIs (7.5, 15.9, and 17.5 per 1000 patient-years), or INSTIs (13.0, 33.1, and 21.5 per 1000 patient-years). After inverse probability of treatment weighting, adjusted hazard ratios (95% confidence intervals) for MI, stroke, and all-cause mortality with ATV-containing regimens versus all non-ATV-containing regimens were 0.59 (0.41-0.84), 0.64 (0.50-0.81), and 0.90 (0.73-1.11), respectively. CONCLUSION: Among treatment-naive HIV-infected patients in the Veterans Health Administration initiating ATV-containing regimens, risk of both MI and stroke were significantly lower than in those initiating regimens containing other protease inhibitors, NNRTIs, or INSTIs.

Development and evaluation of a record linkage protocol for Utah's Controlled Substance Database.

Utah's Controlled Substance Database prescription registry does not include master identifiers to link records for individual patients. We describe and evaluate a linkage protocol for Utah's Controlled Substance Database. Prescriptions (N = 22,401,506) dated 2005-2009 were linked using The Link King software and patient identifiers (e.g. names, dates of birth) for 2,232,725 patients. Review of 998 randomly selected record pairs classified 46 percent as definitely correct links and 54 percent as probably correct links. A correct link could not be confirmed for <1 percent. None were classified as probably incorrect links or definitely incorrect links. Record set reviews (N = 100 patients/set for 10 set sizes, randomly selected) classified 27-49 percent as definitely correct links and 39-63 percent as probably correct links. Fewer had too little information to confirm a link (5%-22%) or were probably incorrect (0%-6%). None were definitely incorrect. Overall, results suggest that Utah's Controlled Substance Database records were correctly linked. These data may be useful for cross-sectional and longitudinal studies of patient-controlled substance prescription histories.

Unintentional prescription opioid-related overdose deaths: description of decedents by next of kin or best contact, Utah, 2008-2009.

BACKGROUND: Little is known about the characteristics that may predispose an individual to being at risk for fatal overdose from prescription opioids. OBJECTIVE: To identify characteristics related to unintentional prescription opioid overdose deaths in Utah. DESIGN: Interviews were conducted (October 2008-October 2009) with a relative or friend most knowledgeable about the decedent's life. SUBJECTS: Analyses involved 254 decedents aged 18 or older, where cause of death included overdose on at least one prescription opioid. KEY RESULTS: Decedents were more likely to be middle-aged, Caucasian, non-Hispanic/Latino, less educated, not married, or reside in rural areas than the general adult population in Utah. In the year prior to death, 87.4 % were prescribed prescription pain medication. Reported potential misuse prescription pain medication in the year prior to their death was high (e.g., taken more often than prescribed [52.9 %], obtained from more than one doctor during the previous year [31.6 %], and used for reasons other than treating pain [29.8 %, almost half of which "to get high"]). Compared with the general population, decedents were more likely to experience financial problems, unemployment, physical disability, mental illness (primarily depression), and to smoke cigarettes, drink alcohol, and use illicit drugs. The primary source of prescription pain medication was from a healthcare provider (91.8 %), but other sources (not mutually exclusive) included: for free from a friend or relative (24 %); from someone without their knowledge (18.2 %); purchase from a friend, relative, or acquaintance (16.4 %); and purchase from a dealer (not a pharmacy) (11.6 %). CONCLUSIONS: The large majority of decedents were prescribed opioids for management of chronic pain and many exhibited behaviors indicative of prescribed medication misuse. Financial problems, unemployment, physical disability, depression, and substance use (including illegal drugs) were also common.

Studying adverse events related to prescription opioids: the Utah experience.

BACKGROUND: Epidemiologists at the Utah Department of Health (UDOH) began to study prescription drug-related harm in 2004. We have analyzed several types of data including vital statistics, medical examiner records, emergency department diagnoses, and the state prescription registry to estimate the scope and correlates of prescription drug-related harm. OBJECTIVES: To describe data sets analyzed in Utah related to the problem of prescription drug-related harm with the goal of designing interventions to reduce the burden of adverse events and death. RESULTS: Prescription drug-related harm in Utah primarily involved opioids and can be examined with secondary analysis of administrative databases, although each database has limitations. CONCLUSIONS: More analyses, likely from cohort studies, are needed to identify risky prescribing patterns and individual-level risk factors for opioid-related harm. Combining data sets via linkage procedures can generate individual-level drug exposure and outcome histories, which may be useful to simulate a prospective cohort.