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This study examined health preference utility weights and utility decrements associated with different types of chronic conditions in the United States.We used the 2010-2015 Medical Expenditure Panel Survey data for persons aged ≥ 18 years with 12-Item Short-Form Survey Physical and Mental Component Summary scores. 12-Item Short-Form Survey scores were converted to Short-Form Six-Dimension (SF-6D) preference scores to measure utilities of different chronic diseases. We used the Clinical Classification Code to identify 30 chronic diseases from 12 categories, such as cardiovascular diseases, cerebrovascular diseases, hypertension, hyperlipidemia, obesity, cancers, musculoskeletal diseases, endocrine or metabolic diseases, oral diseases, respiratory diseases, and mental disorders. A generalized linear model was used to quantify the utility decrements for 30 chronic diseases, controlling for demographic characteristics.We identified 132 737 adults (mean age 47.2 years, 52.2% female, 80% white); 73% had at least one identified chronic disease, and the mean SF-6D was 0.786. Among 30 chronic diseases, the unadjusted mean SF-6D scores of patients with cognitive disorder (0.607) were the lowest, followed by congestive heart failure (0.629), rheumatoid arthritis (0.654), and lung cancer (0.662). After controlling for demographic variables (ie, age, sex) and comorbidities, cognitive disorders (-0.116), mood disorders (-0.099), rheumatoid arthritis (-0.090), liver cancer (-0.078), and stroke (-0.063) showed the highest decrements in the SF-6D scores (P.05).This study provides a nationally representative catalog of utility weights for major chronic diseases in the US general population. The utility decrements will enable researchers to calculate the health utilities of patients with multiple comorbid diseases.

The risk of obstructive sleep apnea (OSA) in patients with resistant hypertension (RH) has not been well-quantified. We sought to evaluate the risk of OSA in patients with RH compared to those with treated but non-resistant hypertension (non-RH) using a time-dependent-exposure analysis. We conducted a retrospective cohort study of patients with treated hypertension (hypertension diagnosis + ≥2 antihypertensive drug claims within 1 year) using the IBM MarketScan® commercial claims database from January 2008 to December 2019. We excluded patients without 12 months of continuous enrollment before the second antihypertensive fill date (index date of cohort entry) and those having the outcome (OSA) in the 12-month pre-index period. We employed Cox proportional hazard regression with OSA as the dependent variable, and time-dependent exposure (non-RH vs. RH) and baseline covariates as independent variables. Of the 1,375,055 patients with treated hypertension, 13,584 patients were categorized as exposed to RH. In the multivariable Cox proportional hazards model, exposure with RH was associated with a 60% increased risk of OSA (adjusted hazard ratio (aHR): 1.60; 95% CI, 1.52–1.68) compared to non-RH exposure. Findings of the study suggest that exposure with RH, compared to non-RH, is associated with a higher risk of incident OSA.

To compare the risk of antihypertensive treatment intensification (TI) and major adverse cardiovascular events (MACE) with the initiation of serotonin norepinephrine reuptake inhibitors compared to selective serotonin reuptake inhibitors (SSRIs) in patients with stable hypertension and depression.Retrospective cohort study.IBM MarketScan® commercial claims database and Medicare Supplemental claims database from 2007 to 2019.Patients aged 18 years or older with stable treated hypertension and depression who newly initiate either serotonin norepinephrine reuptake inhibitors or SSRIs.Serotonin norepinephrine reuptake inhibitors versus SSRIs.The primary outcomes were: (1) TI (first occurrence of antihypertensive regimen augmentation or dose escalation); (2) MACE (first occurrence of stroke or acute myocardial infarction). Baseline risk between the two groups was balanced via 1:1 propensity score (PS) matching. A Cox proportional hazard regression model was used to estimate adjusted hazard ratio (aHR) and 95% confidence intervals (95% CI). After 1:1 PS matching, we included 19,160 patients in the study cohort (mean age: 52 years, 62% females) of which 9580 initiated serotonin norepinephrine reuptake inhibitors and 9580 initiated SSRIs. Patients who initiated serotonin norepinephrine reuptake inhibitors had 15 MACE events (incidence rate per 1000 person-years [IR], 3.9) and 1675 TI events (IR, 540.2), compared with 17 MACE events (IR, 4.0) and 1774 TI events (IR, 518.5) in the SSRI group. The risk of TI (aHR: 1.01, [95% CI: 0.94, 1.08]) and MACE (aHR: 0.98, [95% CI: 0.49, 1.96]) did not differ among patients initiated serotonin norepinephrine reuptake inhibitors versus SSRIs.Among patients with stable hypertension and depression, initiation of serotonin norepinephrine reuptake inhibitors had a similar risk of antihypertensive TI and MACE compared to initiation of SSRIs. Future study with a larger sample size is needed to confirm our findings.

Limited real-world evidence exists for effectiveness and safety of extended oral anticoagulation beyond 6 months of initial treatment in prevention of recurrent venous thromboembolism (VTE) and adverse major bleeding events among patients with VTE. Using MarketScan Commercial and Medicare Supplemental databases (2013-2019), we conducted a retrospective cohort study to compare the risk of recurrent VTE and major bleeding events during extended treatment among patients with VTE who completed the 6-month initial treatment and received extended oral anticoagulant treatment with apixaban, warfarin, or no extended treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards modeling with inverse probability treatment weighting. We identified 14,818 patients with extended treatment of apixaban (n = 4,338), warfarin (n = 5,298), or no extended treatment (n = 5,182). Compared with no extended treatment, apixaban use was associated with decreased risk of recurrent VTE (HR: 0.10, 95% CI: 0.04-0.26) without increased risk of major bleeding events (HR: 1.06, 95% CI: 0.52-2.17); warfarin use was associated with decreased risk of recurrent VTE (HR: 0.23, 95% CI: 0.12-0.44) but with increased risk of major bleeding events (HR: 2.64, 95% CI: 1.51-4.59). Compared with warfarin, apixaban use was associated with decreased risk of major bleeding events (HR: 0.42, 95% CI: 0.22-0.80) but no difference in risk of recurrent VTE (HR: 0.46, 95% CI: 0.15-1.36). In a real-world clinical setting, extended anticoagulation with apixaban or warfarin was associated with decreased risk of recurrent VTE compared with no extended treatment, and apixaban had a better safety profile with fewer major bleeding events compared with warfarin among commercially insured patients with VTE.

One-third of opioid (OPI) overdose deaths involve concurrent benzodiazepine (BZD) use. Little is known about concurrent opioid and benzodiazepine use (OPI-BZD) most associated with overdose risk. We aimed to examine associations between OPI-BZD dose and duration trajectories, and subsequent OPI or BZD overdose in US Medicare.Retrospective cohort study.US Medicare.Using a 5% national Medicare data sample (2013-16) of fee-for-service beneficiaries without cancer initiating OPI prescriptions, we identified 37 879 beneficiaries (age ≥ 65 = 59.3%, female = 71.9%, white = 87.6%, having OPI overdose = 0.3%).During the 6 months following OPI initiation (i.e. trajectory period), we identified OPI-BZD dose and duration patterns using group-based multi-trajectory models, based on average daily morphine milligram equivalents (MME) for OPIs and diazepam milligram equivalents (DME) for BZDs. To label dose levels in each trajectory, we defined OPI use as very low ( 25 MME), low (25-50 MME), moderate (51-90 MME), high (91-150 MME) and very high (150 MME) dose. Similarly, we defined BZD use as very low ( 10 DME), low (10-20 DME), moderate (21-40 DME), high (41-60 DME) and very high ( 60 DME) dose. Our primary analysis was to estimate the risk of time to first hospital or emergency department visit for OPI overdose within 6 months following the trajectory period using inverse probability of treatment-weighted Cox proportional hazards models.We identified nine distinct OPI-BZD trajectories: group A: very low OPI (early discontinuation)-very low declining BZD (n = 10 598; 28.0% of the cohort); B: very low OPI (early discontinuation)-very low stable BZD (n = 4923; 13.0%); C: very low OPI (early discontinuation)-medium BZD (n = 4997; 13.2%); D: low OPI-low BZD (n = 5083; 13.4%); E: low OPI-high BZD (n = 3906; 10.3%); F: medium OPI-low BZD (n = 3948; 10.4%); G: very high OPI-high BZD (n = 1371; 3.6%); H: very high OPI-very high BZD (n = 957; 2.5%); and I: very high OPI-low BZD (n = 2096; 5.5%). Compared with group A, five trajectories (32.3% of the study cohort) were associated with increased 6-month OPI overdose risks: E: low OPI-high BZD [hazard ratio (HR) = 3.27, 95% confidence interval (CI) = 1.61-6.63]; F: medium OPI-low BZD (HR = 4.04, 95% CI = 2.06-7.95); G: very high OPI-high BZD (HR = 6.98, 95% CI = 3.11-15.64); H: very high OPI-very high BZD (HR = 4.41, 95% CI = 1.51-12.85); and I: very high OPI-low BZD (HR = 6.50, 95% CI = 3.15-13.42).Patterns of concurrent opioid and benzodiazepine use most associated with overdose risk among fee-for-service US Medicare beneficiaries initiating opioid prescriptions include very high-dose opioid use (MME 150), high-dose benzodiazepine use (DME 40) or medium-dose opioid with low-dose benzodiazepine use.

BACKGROUND: Patients with substance use disorders (SUD) and chronic hepatitis C virus infection (HCV) have limited access to direct-acting antivirals (DAAs) due to multilevel issues related to providers (eg, concern about reinfection); patients (eg, refusal); payers (eg, prior authorization); and health system structure, although clinical guidelines recommend timely DAA treatment for patients with SUD and HCV. Effects of DAAs on real-world health care utilization and costs among these patients is unknown. OBJECTIVE: To compare changes in medical service utilization and costs related to liver, SUD, and all-cause morbidity in patients with SUD and HCV treated with DAAs (DAA group) vs not treated with DAAs (non-DAA group). METHODS: We conducted a retrospective cohort study using MarketScan Commercial and Medicare Supplemental Claims databases (2012-2018) for newly diagnosed HCV treatment-naive adults with SUD. We used difference-in-differences analyses, stratified by cirrhosis status, to determine the adjusted ratio of rate ratio (RoRR) to assess the difference in the relative changes from the pre- to posttreatment periods between the 2 groups. RESULTS: 6,266 patients with SUD and HCV were identified. Of these patients who also had cirrhosis (n = 607), 49% (n = 298) initiated DAA therapy for HCV, whereas of those without cirrhosis (n = 5,659), 22% (n = 1,219) initiated DAAs. For patients with cirrhosis (n = 607), the liver-related costs decreased by $6,213 (95% CI = -$8,571, -$3,856) for the DAA group and $1,585 (95% CI = -$4,659, $1,490) for the non-DAA group. The relative decreases in the rate of liver-related costs were larger for the DAA group than for the non-DAA group, and the relative changes between groups were significantly different (RoRR = 0.37, 95% CI = 0.19-0.73). There was no difference in the relative changes after DAAs in the rate of SUD-related visits/costs or all-cause costs between the 2 groups. For patients without cirrhosis (n = 5,659), a similar association was observed. Besides, the relative decreases in the rate of SUD-related emergency department (ED) visits (RoRR = 0.54, 95% CI = 0.38-0.77); SUD-related long-term care visits (RoRR = 0.30, 95% CI = 0.13-0.73); all-cause ED visits (RoRR = 0.75, 95% CI = 0.64-0.88); and all-cause long term-care visits (RoRR = 0.36, 95% CI = 0.18-0.72) were larger in the DAA group than in the non-DAA group. CONCLUSIONS: DAAs are associated with a significant decrease in the rate of SUD-related ED visits and liver-related costs without increasing the rate of all-cause costs among patients with SUD and HCV, suggesting that the benefits of DAAs extended beyond liver-related outcomes, especially in this disadvantaged population. DISCLOSURES: Research reported in this publication was supported in part by the National Institute on Drug Abuse of the National Institutes of Health (K01DA045618). The funder did not have a role in the design, the execution, the analyses, the interpretation of the data, or the decision to submit the results of this study. The authors have no potential conflicts of interest.

High costs of direct-acting antivirals (DAAs) have led to their restricted access for patients with hepatitis C virus (HCV).The aim was to assess how HCV treatment access and predictors of HCV treatment changed in the post-DAA period compared with pre-DAA period.A retrospective cohort study using Arizona Medicaid data was conducted for patients with HCV to compare treatment initiation rates between pre-DAA (January 2008-October 2013) and post-DAA (November 2013-December 2018) periods. Multivariable logistic regression was used, controlling for demographic and clinical variables.Twenty-four thousand and ninety and 28,756 patients during the pre-DAA and post-DAA periods were identified. Overall, 12.6% were treated in the post-DAA period compared with 7.8% in the pre-DAA period (P0.001). The relative increase in the HCV treatment initiation rate from the pre-DAA to the post-DAA period was significant greater for Black beneficiaries compared with White beneficiaries (P=0.002). Hispanic beneficiaries were less likely to be treated in the post-DAA period [adjusted odds ratios (aOR): 0.88; CI: 0.79-0.98] compared with White beneficiaries. Those with mental illness (aOR: 0.71; 95% CI: 0.63-0.80) and substance use disorders (aOR: 0.63; 95% CI: 0.58-0.68) were less likely to be treated in the post-DAA period.Although treatment initiation increased and disparities for Black beneficiaries compared with White beneficiaries attenuated in the post-DAA period, only 13% of Arizona Medicaid patients with HCV received DAA treatment. Disparities in DAA access remained among Hispanic patients and those with mental illness and substance use disorders.

BACKGROUND AND AIMS Our aim was to evaluate the impact of direct-acting antivirals (DAAs) on decompensated cirrhosis (DCC) and HCC in patients with chronic HCV and substance use disorder (SUD) compared with those without an SUD. APPROACH AND RESULTS This retrospective cohort study used the MarketScan database (2013-2018) to identify 29,228 patients with chronic HCV, where 22% (n = 6,385) had ≥1 SUD diagnosis. The inverse probability of treatment weighted multivariable Cox proportional hazard models were used to compare the risk of developing DCC and HCC. Among the those who were noncirrhotic, treatment reduced the DCC risk among SUD (adjusted hazard ratio [aHR] 0.13; 95% CI, 0.06-0.30) and non-SUD (aHR 0.11; 95% CI, 0.07-0.18), whereas the risk for HCC was not reduced for the SUD group (aHR 0.91; 95% CI, 0.33-2.48). For those with cirrhosis, compared with patients who were untreated, treatment reduced the HCC risk among SUD (aHR, 0.33; 95% CI, 0.13-0.88) and non-SUD (aHR, 0.40; 95% CI, 0.25-0.65), whereas the risk for DCC was not reduced for the SUD group (aHR, 0.64; 95% CI, 0.37-1.13). Among patients with cirrhosis who were untreated, the SUD group had a higher risk of DCC (aHR, 1.52; 95% CI, 1.03-2.24) and HCC (aHR, 1.69; 95% CI, 1.05-2.72) compared with non-SUD group. CONCLUSIONS Among the HCV SUD group, DAA treatment reduced the risk of DCC but not HCC for those who were noncirrhotic, whereas DAA treatment reduced the risk of HCC but not DCC for those with cirrhosis. Among the nontreated, patients with an SUD had a significantly higher risk of DCC and HCC compared with those without an SUD. Thus, DAA treatment should be considered for all patients with HCV and an SUD while also addressing the SUD.

BACKGROUND: Limited evidence exists regarding long-term effectiveness and safety of aldosterone antagonists (AAs) versus beta blockers (BBs) as fourth-line antihypertensive agents in patients with resistant hypertension (RH). We evaluated the comparative effectiveness and safety of aldosterone AA versus BB. METHODS: We conducted a real-world retrospective cohort study using IBM MarketScan commercial claims and Medicare Supplemental claims (2007–2019). Patients with RH entered the cohort (ie, index date) when they newly initiated either AA or BB. The effectiveness outcome was major adverse cardiovascular events. Safety outcomes were hyperkalemia, gynecomastia, and kidney function deterioration. Potential confounding was addressed by adjustment for baseline characteristics via stabilized inverse probability of treatment weighting (SIPTW) based on propensity scores. Cox proportional hazards regression with SIPTWs were used to estimate adjusted hazard ratio (aHR) and 95% CI comparing risk for outcomes between AA and BB groups. RESULTS: We identified 80 598 patients with RH (mean age: 61 years, 51% males), of which 6626 initiated AA and 73 972 initiated BB as the fourth antihypertensive agent. Among patients with RH, initiation of AA as a fourth-line antihypertensive agent did not significantly reduce major adverse cardiovascular event risk relative to BB initiation (aHR, 0.77 [95% CI, 0.50–1.19]) but did substantially increase the risk of hyperkalemia (aHR, 3.86 [95% CI, 2.78–5.34]), gynecomastia (aHR, 9.51 [95% CI, 5.69–15.89]), and kidney function deterioration (aHR, 1.63 [95% CI, 1.34–1.99]). CONCLUSIONS: Long-term clinical trials powered to assess major adverse cardiovascular events are necessary to understand the risk-benefit trade-off of AA as fourth-line therapy for RH.

BACKGROUND: Florida's House Bill 21 (HB21), implemented into law on July 1, 2018, limited opioid prescriptions for acute pain to a 3-day supply. While the law has been associated with a decrease in opioid prescribing for acute pain, its effect on opioid volume dispensed at the plan level remains unknown. OBJECTIVES: To assess the impact of HB21 on the total volume dispensed of oral Schedule II opioids. We evaluated the change from before to after the law's implementation in (1) total number of opioid units dispensed per month and (2) total morphine milligram equivalent (MMEs) dispensed per month. METHODS: Pharmacy claims from July 2017 to June 2019 were analyzed from a private health plan serving a large Florida employer. We summed the number of units and the total MMEs dispensed for each month per 1,000 enrollees. Units were defined as the total quantity of tablets/capsules dispensed for each Schedule II oral opioid prescription. We used interrupted time series (ITS) models, accounting for autocorrelation, to determine any immediate change after the policy implementation and to estimate trends before and after the policy. RESULTS: We identified 16,226 prescriptions of oral Scheduled II opioids dispensed to 6,315 enrollees over a 2-year period. The HB21 law was associated with an immediate but not statistically significant decrease of 110.25 units dispensed per 1,000 enrollees in the month after implementation (95% CI: -218.84, -1.67; P = 0.06). There was an immediate but not statistically significant decrease of 1,456.29 MMEs dispensed per 1,000 enrollees following HB21 implementation (95% CI: -2,983.87, 71.29; P = 0.07). There were no significant changes in the slopes of the trends for total number of opioid units and total MMEs dispensed after HB21. CONCLUSIONS: Despite substantial lower quantities, there were no significant immediate reductions in total opioid units and MMEs dispensed in the year following the implementation of HB21. Our findings can inform other health plans on the potential effect of such restrictive laws and policies in other states where preexisting declining trends might have a higher impact than restriction policies. Future studies are needed to evaluate long-term intended and unintended consequences, including effects on patients' access to care, resulting from this type of restrictive law. DISCLOSURES: No outside funding supported this study. The authors report no conflicts of interest. Preliminary results of this study were presented at the Virtual ISPOR 2020 Conference held May 18-20, 2020.

Use of bariatric surgery has increased dramatically in the USA. However, there are growing concerns regarding the safety outcomes of different bariatric procedures. We aim to compare the safety of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), which includes hospital readmissions, emergency room (ER) visits, gastrointestinal bleeding, and revisional surgery.A retrospective cohort analysis was conducted for adults (≥ 18 years) who received SG and RYGB in the USA. We used Truven MarketScan Commercial and Medicare supplemental claims databases from January 1, 2005, to October 1, 2015. To adjust for baseline demographic and clinical characteristics, we used stabilized inverse probability of treatment weighting using propensity score. Cox proportional hazard models was used to compare safety outcomes between SG and RYGB after bariatric surgery.A total of 194,248 patients met inclusion criteria; 79,813 patients (41%) received SG and 114,435 patients (59%) received RYGB. The use of SG was associated with a significantly lower 30-day hospital readmission rate [adjusted hazard ratios (aHRs) 0.77; 95% confidence interval (CI), 0.74-0.81] and ER visits [aHR, 0.82; 95% CI, 0.80-0.83], and decreased risk of gastrointestinal bleeding [aHR, 0.87; 95% CI, 0.78-0.98] compared to RYGB. However, SG was associated with an increased risk of revisional surgery, compared to RYGB [aHR,1.21; 95% CI, 1.08-1.35].Among patients receiving bariatric surgery in a real-world setting, SG was associated with lower complication rate but a higher risk of revisional surgery compared to RYGB. Further longitudinal studies are needed to assess long-term findings.

Medicaid prior authorization (PA) policies for treatment of hepatitis C virus (HCV) with direct‐acting antiviral (DAA) therapy are changing. We aimed to evaluate effects of changes in PA requirements on treatment uptake and to determine the factors associated with DAA treatment among Florida Medicaid beneficiaries with HCV. This is a retrospective cohort analysis of Florida’s Medicaid administrative claims and electronic medical records (2013‐2018). A total of 14,063 newly diagnosed patients with HCV were grouped based on human immunodeficiency virus (HIV) co‐infection and/or a substance use disorder (SUD) (7,735 HCV mono‐infected with a SUD, 5,180 HCV mono‐infected without a SUD, 564 HCV/HIV co‐infected with a SUD, and 584 HCV/HIV co‐infected without a SUD). Although the treatment rate increased three‐fold after June 1, 2016, when a fibrosis‐stage restriction was eliminated, only 8% received DAAs. Compared to HCV mono‐infected without a SUD, HCV mono‐infected with a SUD and HCV/HIV co‐infected with a SUD were 47% (adjusted hazard ratio, 0.53; 95% confidence interval, 0.47‐0.60) and 59% (adjusted hazard ratio, 0.41; 95% confidence interval, 0.28‐0.61) less likely to initiate DAAs. Those with HCV/HIV/SUD did not experience a DAA initiation increase after a fibrosis‐stage restriction was eliminated. Compared with Whites, Blacks were less likely to receive DAAs but were more likely to complete treatment. Use of medication‐assisted therapy was low, despite those on medication‐assisted therapy being 60% more likely to initiate DAA therapy and no more likely to discontinue therapy. Conclusion: Despite changes in Florida’s Medicaid PA requirements for DAA treatment, only 8% received treatment. Disparities in treatment access were found among patients with HIV and a SUD, and who were Black., In our retrospective cohort study analysis using Florida Medicaid claims data (2013‐2018), we examined the effects of prior authorization policy on access to direct‐acting antiviral (DAA) treatment and identified factors associated with disparities among Florida Medicaid patients with hepatitis C virus (HCV). Our work shows that the number of Florida Medicaid patients treated for HCV has increased, but treatment rates are still very low (8%); compared to HCV mono‐infected patients without substance use disorders (SUD), HCV mono‐infected patients with SUD and HCV/HIV patients co‐infected with SUD were 47% and 59% less likely to initiate DAAs, but no difference was observed in HCV/HIV patients co‐infected without SUD. Disparities in access to treatment continue among patients with SUD, blacks, and pregnant women among Medicaid patients with HCV.

Background Little is known about economic and productivity loss by severity of asthma. We investigate health-care utilization, direct medical costs, and indirect costs due to productivity loss from asthma by severity. Methods We conducted a cross-sectional analysis of the Medical Expenditure Panel Survey database (2010-2017) of patients with asthma aged ≥12 years and categorized them into mild, moderate, and severe asthma groups based on symptom control medications. Study outcomes included health-care utilization, direct medical costs, and indirect costs of asthma-related absenteeism. We used zero-inflated Poisson regression models to estimate incremental health-care utilization and generalized linear models to estimate incremental annual direct medical costs compared to patients without asthma. Results An estimated 139 million persons had an asthma diagnosis. Of patients with asthma, 77.1%, 22.2%, and 0.7% had mild, moderate, and severe asthma, respectively. Compared to patients without asthma, patients with asthma had incremental mean differences of 4.16 outpatient visits, 0.18 emergency department visits, and 0.07 hospitalizations per year. Annual direct medical costs were significantly associated with asthma severity ($3305 in mild, $7250 in moderate, and $9175 in severe asthma) (P < 0.05). Patients with mild, moderate, and severe asthma reported 0.76, 2.31, and 7.19 missed work or school days, resulting in $106, $321, and $1000 indirect costs per person per year, respectively. Conclusion Asthma-related direct and indirect costs are significantly associated with asthma severity, with severe asthma medical costs being about three times higher than mild. Controlling asthma symptoms is important to reduce the economic and social burden of asthma.

Background Guidelines assume children with chronic lung disease (CLD) who require medical support within 6 months before the second respiratory syncytial virus (RSV) season remains at high risk of severe RSV disease. We determined the number of days since the last treatment (DSL) when the risk of RSV hospitalization among children with CLD becomes equivalent to the risk for those not qualified for immunoprophylaxis. Methods The study cohort was assembled using Medicaid billing records from 1999 to 2010 linked to Florida and Texas birth certificate records. We developed DSL-trend discrete time logistic regression models within a survival analysis framework, adjusting for use of immunoprophylaxis, to compare the hospitalization risk of CLD infants at 4 age points to that of term infants at 1 month of age with siblings. Results The study cohort included 858 830 healthy term and 5562 preterm infants with CLD. Among 1-month-old term infants, the RSV hospitalization risk averaged across all covariate strata was 14.8 (95% confidence interval [CI], 13.5–16.1) per 1000 patient season-months. Risk for preterm CLD children reached the threshold derived from term infants when DSL was 76 (95% CI, 22–198.5), 52 (95% CI, 6.5–123), 35 (95% CI, 0–93.5), and 12 (95% CI, 0–61.5) at the respective ages of 12, 15, 17.2, and 21 months. Conclusions The 180-day threshold used to define CLD severity at season start can be shortened to 120 days, 90 days, and 60 days for children with CLD at age 15, 17.2, and 21 months, respectively.

Background Clinical guidelines increasingly recommended ambulatory blood pressure monitoring (ABPM) for hypertension diagnosis and management. Yet, ABPM is used infrequently in the United States, possibly because of low insurance coverage and high patient costs. We sought to analyze out-of-pocket payments (OPPs) for ABPM among privately insured patients. Methods We conducted a retrospective analysis using IBM® MarketScan® commercial claims of beneficiaries aged ≥18 years receiving ABPM from January 2012 to December 2018. The date of first ABPM claim (Healthcare Common Procedure Coding System codes 93784, 93786, 93788, or 93790) was considered the index date. Patients with 12 months of continuous enrollment preindex and 30-day postindex were included. Per beneficiary OPP was calculated by aggregating all ABPM-related OPPs within the 30-day postindex window (ABPM episode). Results Of 22,317 beneficiaries receiving ABPM, 62% had $0 OPP and 38% had OPP >$0. Among the latter, median OPP per beneficiary for an ABPM episode was $23 (interquartile range [IQR], $14, $32), driven primarily by full ABPM claims (median, $22; IQR, $14, $24). Among individual components, scan analysis and report claims (median, $25; IQR, $13, $49) had the greatest OPP. The median OPP per ABPM episode did not change substantively from 2012 through 2018. Conclusions Among commercially insured in the United States, nearly 4-in-10 have an OPP for ABPM. Though most OPPs are relatively modest, some patients incur substantial OPP. Our findings highlight the need for policymakers to ensure adequate ABPM coverage in the commercial insurance marketplace.

Purpose Compared with conventional therapy (enoxaparin followed by warfarin), the direct-acting oral anticoagulant apixaban is thought to offer similar protection against recurrent venous thromboembolism (VTE) with lower bleeding risk. However, evidence regarding the heterogeneity of treatment effect from real-world data is lacking. The study described here aimed to compare the effectiveness and safety of use of apixaban versus warfarin in patients with VTE. Methods We conducted a retrospective cohort analysis of commercial and Medicare supplemental databases (data coverage period, 2014-2017) among patients with a diagnosis of VTE who were new users of apixaban or warfarin. We controlled for confounding using propensity score [PS] 1:4 matching. Cox proportional hazard models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). Heterogeneity of treatment effect was assessed among patients with provoked VTE versus unprovoked VTE. Results After PS matching, a total of 36,907 patients were included in the cohort (n = 8,094 apixaban users and n = 28,813 warfarin users). In Cox regression models, the use of apixaban versus warfarin was associated with lower risks of recurrent VTE (HR, 0.54; 95% CI, 0.45-0.65) and major bleeding events (HR, 0.67; 95% CI, 0.54-0.84); these results remained consistent in patients with provoked VTE and those with unprovoked VTE. Conclusion This population-based analysis of patients with VTE extends results of randomized clinical trials indicating lower risks of development of recurrent VTE and major bleeding events with use of apixaban versus warfarin in real-world settings. The observed benefits of apixaban extended to selected subgroups of the VTE population, including patients with provoked VTE.

The optimal dose of apixaban therapy to prevent asecondary venous thromboembolism (VTE) event remains unconfirmed. To investigate the effects of extended phase use of apixaban (2.5 vs. 5 mg twice daily) beyond 6 months of initial treatment on the risk of recurrent VTE and major bleeding events among patients with a history of VTE.A retrospective cohort analysis of two large national insurance claims databases was conducted for patients diagnosed with VTE. Cox proportional hazard models after propensity score matching were used to compare the risk of recurrent VTE and major bleeding.There were no detected differences in recurrent VTE or major bleeding events between patients prescribed low versus full dose apixaban.This study provides evidence that apixaban 2.5 mg twice daily is an alternative option for extended phase therapy for risk reduction of VTE recurrence compared to apixaban 5 mg twice daily.

The objective of this study was to estimate the economic impact of providing universal hepatitis C virus testing in commercially insured middle-aged persons who inject drugs in the U.S.This study developed a dynamic 10-year economic model to project the clinical and economic outcomes associated with hepatitis C virus testing among middle-aged adult persons who inject drugs, from a payer's perspective. Costs related to hepatitis C virus testing, direct-acting antiviral, and liver-related outcomes between the (1) current hepatitis C virus testing rate (i.e., 8%) and (2) universal hepatitis C virus testing rate (i.e., 100%) were compared. Among patients testing positive, 21% of those without cirrhosis and 48% of those with cirrhosis were assumed to initiate direct-acting antivirals. Sensitivity analyses were performed to identify variables (e.g., direct-acting antiviral drug costs, hepatitis C virus testing costs, direct-acting antiviral treatment rate) influencing this study's conclusion.The model predicts that during the 10-year period, universal hepatitis C virus testing will cost an additional $242 per person who injects drugs to the payers' healthcare budgets compared with the current scenario. Sensitivity analyses showed values ranging from $1,656 additional costs to $1,085 cost savings across all varied parameters and scenarios. A total of 80% of the current direct-acting antiviral costs indicated that cost savings will be $383 per person who injects drugs.Universal hepatitis C virus testing among persons who inject drugs would not achieve cost savings within 10 years, with the cost of direct-acting antivirals contributing the most to the spending. To promote universal hepatitis C virus testing among persons who inject drugs, decreasing direct-acting antiviral costs and sustainable funding streams for hepatitis C virus testing should be considered.

We aimed to develop and validate machine learning algorithms to predict direct-acting antiviral (DAA) treatment failure among patients with hepatitis C virus (HCV) infection. We used HCV-TARGET registry data to identify HCV-infected adults receiving all-oral DAA treatment and having virologic outcome. Potential pre-treatment predictors (n=179) included sociodemographic, clinical characteristics, and virologic data. We applied multivariable logistic regression (MLR) as well as elastic net (EN), random forest (RF), gradient boosting machine (GBM), and feedforward neural network (FNN) machine learning algorithms to predict DAA treatment failure. Training (n=4,894) and validation (n=1,631) patient samples had similar sociodemographic and clinical characteristics (mean age, 57 years; 60% male; 66% White; 36% with cirrhosis). Of 6525 HCV-infected adults, 95.3% achieved sustained virologic response, whereas 4.7% experienced DAA treatment failure. In the validation sample, machine learning approaches performed similarly in predicting DAA treatment failure (C statistic [95% CI]: GBM, 0.69 [0.64–0.74]; RF, 0.68 [0.63–0.73]; FNN, 0.66 [0.60–0.71]; EN, 0.64 [0.59–0.70]), and all four outperformed MLR (0.51 [0.46–0.57]). Using the Youden index to identify the balanced risk score threshold, GBM had 66.2% sensitivity and 65.1% specificity, and 12 individuals were needed to evaluate to identify one DAA treatment failure. Over 55% of patients with treatment failure were classified by the GBM in the top three risk decile subgroups (positive predictive value: 6% to 14%). The top 10 GBM-identified predictors included albumin, liver enzymes (aspartate aminotransferase, alkaline phosphatase), total bilirubin levels, sex, HCV viral loads, sodium level, hepatocellular carcinoma, platelet levels, and tobacco use. CONCLUSIONS: Machine learning algorithms performed effectively for risk prediction and stratification of DAA treatment failure.

Background: Little is known about anticoagulation medication nonadherence patterns impacting effectiveness and safety outcomes in clinical practice. Objective: We identified adherence trajectories of extended therapy with direct-acting oral anticoagulants (DOACs) and warfarin after 6 months initial anticoagulant therapy among Medicare beneficiaries with venous thromboembolism (VTE). We further assessed the associated recurrent VTE and major bleeding risks. Methods: Using group-based trajectory models, this retrospective cohort study identified distinct beneficiary subgroups with similar adherence patterns of extended-phase anticoagulant treatment (DOACs or warfarin) for patients with VTE who completed 6 months of initial anticoagulant treatment. We examined associations between adherence trajectories and risks of recurrent VTE and major bleeding using inverse probability treatment weighted Cox proportional hazards models. Results: Compared with no extended treatment, consistently high DOAC adherence was associated with decreased recurrent VTE risk (hazard ratio [HR] = 0.33, 95% confidence interval [CI] = 0.21-0.51) without increased major bleeding risk, and consistently high warfarin adherence was associated with decreased recurrent VTE risk (HR = 0.62, 95% CI = 0.40-0.95) and increased major bleeding risk (HR = 1.64, 95% CI = 1.12-2.41). Gradually declining adherence to DOACs (HR = 1.80, 95% CI = 1.07-3.03) or warfarin (HR = 2.34, 95% CI = 1.57-3.47) was associated with increased bleeding risk with no change in recurrent VTE risk. Conclusion and relevance: This real-world evidence suggests persistently adhering to extended DOAC therapy is associated with lower recurrent VTE risk without increasing major bleeding among Medicare beneficiaries with VTE. Persistently adhering to extended warfarin therapy was associated with lower recurrent VTE risk but higher major bleeding risk.

We examined the prevalence trends of non-human immunodeficiency virus (HIV) sexually transmitted infections (STI) and associated patient characteristics in U.S. ambulatory-care settings from 2005–2016. We conducted a retrospective repeated cross-sectional analysis using data from the National Ambulatory Medical Care Survey (NAMCS) for individuals aged 15–64 with a non-HIV STI-related visit. Data were combined into three periods (2005–2008, 2009–2012, and 2013–2016) to obtain reliable estimates. Logistic regression was used for analysis. A total of 19.5 million weighted, non-HIV STI-related ambulatory visits from 2005–2016 were identified. STI-related visits per 100,000 ambulatory care visits increased significantly over the study period: 206 (95% CI = 153–259), 343 (95% CI = 279–407), and 361 (95% CI = 277–446) in 2005–2008, 2009–2012, and 2013–2016, respectively (Ptrend = 0.003). These increases were mainly driven by increases in HPV-related visits (56 to 163 per 100,000 visits) from 2005–2008 to 2009–2012, followed by syphilis- or gonorrhea-related visits (30 to 67 per 100,000 visits) from 2009–2012 to 2013–2016. Higher odds of having STI-related visit were associated with younger age (aged 15–24: aOR = 4.45; 95% CI = 3.19–6.20 and aged 25–44: aOR = 3.59; 95% CI = 2.71–4.77) vs. 45–64-year-olds, Black race (aOR = 2.41; 95% CI = 1.78–3.25) vs. White, and HIV diagnosis (aOR = 10.60; 95% CI = 5.50–20.27) vs. no HIV diagnosis. STI-related office visits increased by over 75% from 2005–2016, and were largely driven by HPV-related STIs and syphilis- or gonorrhea-related STIs.

PURPOSE: US Food and Drug Administration approvals of immune checkpoint inhibitors and targeted therapies revolutionized the treatment of metastatic melanoma. Our aim was to assess health care resource utilization and costs for patients with metastatic melanoma treated with systemic therapies in first line between January 2012 and December 2017. METHODS: We conducted a retrospective cohort study of patients with metastatic melanoma using MarketScan data. We included patients diagnosed with melanoma and secondary malignant neoplasm who used pembrolizumab, nivolumab, ipilimumab, ipilimumab plus nivolumab, BRAF-inhibitor (BRAF-i) plus MEK inhibitor (MEK-i), BRAF-i or MEK-i monotherapy, or chemotherapy in first line. We compared health care utilization and costs per patient per month (PPPM) using two-part and generalized linear models. RESULTS: We identified 1,870 patients, including 185 pembrolizumab, 103 nivolumab, 689 ipilimumab, 185 nivolumab plus ipilimumab, 214 BRAF-i plus MEK-i, 240 BRAF-i or MEK-i monotherapy, and 254 chemotherapy users. Highest PPPM rates of hospitalizations, emergency room visits, and outpatient visits were observed in patients with ipilimumab plus nivolumab therapy (adjusted difference v pembrolizumab [aDiff], 0.18, 0.12, and 0.88, respectively; all P < .001). Ipilimumab monotherapy users (aDiff, 0.07 and 0.93; all P < .001) and chemotherapy users (aDiff, 0.10 and 2.63; all P < .001) showed higher PPPM rates of hospitalizations and outpatient visits compared with pembrolizumab users, respectively. Utilization rates in nivolumab, BRAF-i plus MEK-i, and BRAF-i or MEK-i groups were similar to the pembrolizumab group. Highest PPPM total costs and drug-related costs were observed in the ipilimumab group ($80,139 US dollars [USD] and $70,051 USD; all P < .001), followed by the ipilimumab plus nivolumab ($71,689 USD and $56,217 USD; all P < .001) and the BRAF-i plus MEK-i group ($31,184 USD and $19,648 USD; all P < .001). PPPM costs in the nivolumab group were similar to the pembrolizumab group. CONCLUSION: Significant differences in health care resource utilization and costs were found across first-line metastatic melanoma regimens. Utilization rates were highest in patients using ipilimumab-containing therapies. High drug costs constituted a major fraction of total PPPM health care costs.

Ambulatory blood pressure monitoring (ABPM) is increasingly recommended for confirming hypertension diagnosis and ongoing hypertension monitoring. However, reimbursement in the United States is variable and low compared with other advanced health care systems. We examined the reimbursement of ABPM and factors associated with successful reimbursement. A retrospective analysis of IBM MarketScan® commercial claims database was conducted for patients ≥18 years with ≥1 ABPM claim from January 2012 to December 2016. The date of first the ABPM claim was used as the index date. Per-beneficiary ABPM episode reimbursements were calculated by aggregating all ABPM-related reimbursements within a 30-day post-index window, considered as an ABPM episode. Multivariable logistic regression was used to identify predictors of successful reimbursement. Of 20 875 beneficiaries with ABPM claims, 16 920 (81.0%) were reimbursed. The median reimbursement per beneficiary for an ABPM episode was $89 (Inter Quartile Range [IQR], $62, $132), driven primarily by reimbursement for the full procedure (median, $86; IQR, $66, $110). Comparing benefit plan types, consumer-directed health plans provided the highest median reimbursement ($96; IQR, $61, $175). Successful reimbursement was associated with female patient sex (adjusted OR [aOR], 1.20; 95% CI, 1.11-1.28), having a health maintenance organization (aOR 2.11; 95% CI, 1.82-2.43) or point of service (aOR 2.08; 95% CI, 1.74-2.49) as benefit plan types, claim filing by a specialist (aOR 1.26; 95% CI, 1.14-1.40) and services provided at an outpatient hospital (aOR 1.17; 95% CI, 1.01-1.35). Among commercially insured Americans, our data suggest significant variability in successful reimbursement. Accordingly, more uniform criteria for ABPM reimbursement may facilitate greater use of guideline-recommended monitoring.

Background The completeness of medical encounters capture among Medicaid enrollees in comprehensive managed care (CMC) has been shown to vary across states and years. CMC penetration has grown, and CMC encounter capture specific to pregnancy care is understudied. Objectives To compare the completeness of encounter data for pregnant beneficiaries in CMC versus traditional fee-for-service (FFS) in Texas and Florida between 2007 and 2010. Methods Using Medicaid Analytic eXtract (MAX) data linked to Florida and Texas birth certificate records, for each state and study year, we compared proportions using seven themes: (a) delivery; (b) prenatal visits; (c) dispensed prescriptions during pregnancy; (d) gestational diabetes and blood glucose testing; (e) antidiabetics and diagnosis of diabetes mellitus; (f) antibiotics for urinary tract infection and outpatient encounter; and (g) bacterial vaginosis and dispensing for metronidazole or clindamycin. We considered CMC data to be acceptable if proportions were no less than 10% below the corresponding (2007 to 2010) FFS control values. Results Pregnancy-related characteristics of FFS vs CMC denominators were comparable. Proportions for the seven measures among FFS controls ranged from 26% to 98%. In Texas, CMC encounter data met the thresholds for all measures between 2007 and 2010. Florida had usable CMC encounter data starting from 2009 with incomplete medical and pharmacy records in 2007 and 2008. Conclusions The quality of CMC encounter data in MAX files for pregnant women varied in Florida and Texas and improved over time. Use of pregnancy-specific measures can aid researchers in selecting states and years with acceptable encounter data quality.

Liver cirrhosis is a substantial health burden in the USA, but population-based data regarding the trend and medical expenditure are limited and outdated. We investigated the trends of inpatient admissions, costs, and inpatient mortality from 2005 to 2015 among cirrhotic patients. A retrospective analysis was conducted using the National Inpatient Sample database. We adjusted the costs to 2015 US dollars using a 3% inflation rate. National estimates of admissions were determined using discharge weights. We identified 1,627,348 admissions in cirrhotic patients between 2005 and 2015. From 2005 to 2015, the number of weighted admissions in cirrhotic patients almost doubled (from 505,032 to 961,650) and the total annual hospitalization cost in this population increased three times (from 5.8 to 16.3 billion US dollars). Notably, admission rates varied by liver disease etiology, decreasing from 2005 to 2015 among patients with hepatitis C virus (HCV)-related cirrhosis while increasing (almost tripled) among patients with nonalcoholic fatty liver disease (NAFLD)-related cirrhosis. The annual inpatient mortality rate per 1000 admissions overall decreased from 63.8 to 58.2 between 2005 and 2015 except for NAFLD (27.2 to 35.8) (P

Purpose Few studies have reported an association between proton pump inhibitor (PPI) use and tuberculosis. Tuberculosis incidence is relatively high in Asian people, and an increase in PPI prescriptions has been reported in South Korea. Thus, we investigated the association between PPI use and tuberculosis development. Methods We conducted a case-control study on 25 672 newly diagnosed tuberculosis patients using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database (2002-2013). We selected a control group without tuberculosis using 1:1 exact matching based on age, sex, index year, insurance type, and income level. We investigated PPI exposure 2 years prior to the index date and classified the subjects into nonuser, continuous user, recent user, and former user groups. Odds ratios (ORs) and 95% confidence intervals (CIs) for tuberculosis development were calculated using conditional logistic regression. Results A total of 51 344 cases and controls were analyzed. Recent PPI use (adjusted odds ratio [aOR], 1.28; 95% CI, 1.18-1.39) and continuous PPI use (aOR, 1.13; 95% CI 1.10-1.28) were significantly associated with tuberculosis development, compared with nonuse of PPIs. An increased tuberculosis incidence was not observed in the former use group compared with the nonuse group (aOR 1.05, 95% CI 0.95-1.17). Conclusions In this case-control study, we found that recent PPI use and continuous PPI use were associated with increased tuberculosis development. Although further investigation is needed, the tuberculosis risk accompanying PPI treatment should be considered.

Approved treatment for hepatitis C virus (HCV) with all-oral direct-acting antivirals (DAA) therapy is now entering into its fourth year; however, little has been reported on the real-world clinical (decompensated cirrhosis [DCC] and hepatocellular carcinoma [HCC]) and economic outcomes. A retrospective cohort analysis of the Truven Health MarketScan Database (2012-2016) was conducted. In a cohort of 26,105 patients with newly diagnosed HCV, 30% received all-oral DAA therapy (DAA group) and 70% were not treated (untreated group). Multivariate Cox proportional hazards models were used to compare the risk of developing HCC and DCC, stratified by cirrhosis status. Among patients with cirrhosis (n = 2157), DAA therapy was associated with a 72% and a 62% lower incidence of HCC (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.15-0.52) and DCC (HR, 0.38; 95% CI, 0.26-0.56). Similarly, DAA therapy was associated with a 57% and a 58% lower incidence of HCC (HR, 0.43; 95% CI, 0.26-0.71) and DCC (HR, 0.42; 95% CI, 0.30-0.58) in patients with noncirrhotic HCV (n = 23,948). A propensity score-matched cohort of 8064 HCV-infected patients who had at least a 12-month follow-up after HCV treatment was included for economic analysis. For patients with cirrhosis in the DAA group, the mean adjusted liver-related costs ($1749 vs. $4575; P < 0.001) and all-cause medical costs ($19,300 vs. $33,039; P < 0.001) were significantly lower compared with those in the untreated group. The mean adjusted costs were not statistically different between the two groups among patients without cirrhosis. Conclusion: In the short term, all-oral DAA treatment for HCV infection was associated with a decreased risk of developing HCC and DCC, resulting in decreased health care costs, especially in patients with cirrhosis. A longitudinal study is necessary to confirm our findings.

Introduction Hepatitis C virus testing is recommended for people at high risk for infection, including those with substance use disorders. Little is known about the cascade of hepatitis C virus care (including testing, diagnosis, and treatments) among patients with substance use disorders in real-world clinical practice. This study aims to characterize the hepatitis C virus cascade of care and identify the factors associated with hepatitis C virus testing and diagnosis among Florida Medicaid beneficiaries with substance use disorders. Methods A retrospective cohort analysis of Florida Medicaid data (2013–2018) was conducted in 2020 for patients aged 18–64 years with newly diagnosed substance use disorders (year 2012 was used to ascertain 1-year previous enrollment). A generalized estimating equation identified the factors associated with hepatitis C virus testing; a multivariable logistic model identified the factors associated with hepatitis C virus diagnosis. Results Of the 156,770 patients with substance use disorders, 18% were tested for hepatitis C virus at least once. Among the tested patients, 8% had hepatitis C virus diagnoses. Among the 2,177 patients having a hepatitis C virus diagnosis, 11% initiated hepatitis C virus treatments, and 96% of them completed the hepatitis C virus treatments. Factors associated with being less likely to receive hepatitis C virus testing included being male (AOR=0.73, 95% CI=0.71, 0.75) and White (AOR=0.85, 95% CI=0.83, 0.87), whereas individuals who were male (AOR=1.49, 95% CI=1.35, 1.66) and White (AOR=2.71, 95% CI=2.38, 3.08) were more likely to be diagnosed with hepatitis C virus. The odds of receiving hepatitis C virus testing significantly increased annually (AOR=1.06, 95% CI=1.05, 1.07). Conclusions Future studies are warranted to investigate the barriers to access hepatitis C virus testing and treatment among Florida Medicaid beneficiaries with substance use disorders, especially for White male individuals.

STUDY OBJECTIVE To assess the effectiveness of sacubitril/valsartan versus angiotensin receptor antagonist therapy for prevention of heart failure (HF)-related hospitalization and all-cause hospitalization in a large cohort of patients with heart failure with reduced ejection fraction (HFrEF). DESIGN Retrospective cohort study. DATA SOURCE IBM® MarketScan® research databases (2014-2018). PATIENTS Patients aged 18 years or older with their first HFrEF hospitalization on or after January 1, 2015, who initiated sacubitril/valsartan or angiotensin receptor antagonist after hospital discharge. INTERVENTION Sacubitril/Valsartan versus Angiotensin receptor antagonist. MEASUREMENTS AND MAIN RESULTS The index date was the first sacubitril/valsartan or angiotensin receptor antagonist fill date. After 1 up to 3 propensity score matching, Cox proportional hazards regression was used with robust variance estimators to compare HF-related and all-cause hospitalizations between treatments. Subgroup and sensitivity analyses were conducted to assess the robustness of the main analysis. After propensity score matching, 1,088 sacubitril/valsartan and 2,839 angiotensin receptor antagonist new users were included. The crude incidence of HF-related hospitalization was 13 per 100 person-years for sacubitril/valsartan users and 18 per 100 person-years for angiotensin receptor antagonist users. Compared with angiotensin receptor antagonist use, sacubitril/valsartan use was associated with 27% lower risk of HF-related hospitalization (adjusted hazard ratio, 0.73; 95% confidence interval, 0.58-0.91; p = 0.006) and 31% lower risk of all-cause hospitalization (adjusted hazard ratio, 0.69; 95% confidence interval, 0.61-0.79; p < 0.001). Subgroup analyses revealed no significant heterogeneity, including subpopulations with chronic kidney disease or coronary artery disease. CONCLUSIONS Compared with angiotensin receptor antagonists, sacubitril/valsartan was associated with lower risk of HF-related and all-cause hospitalizations. Our data suggest that, when added sequentially, sacubitril/valsartan should be the preferred initial agent over angiotensin receptor antagonists.

Guidelines recommend palivizumab immunoprophylaxis for children with CLD in their second year of life if they continue to need treatment within 6 months before the RSV season. The utilization patterns of treatment (chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) are not well understood. We examined variations in CLD treatment for ten consecutive 20-day segments preceding RSV season onset. Among infants and children with CLD (n = 19,026), 35.2% received one or more medical treatments for CLD any time within 200 days before entering the second RSV season: 8.6%, 3.2%, and 29.7% received oxygen, diuretics, and corticosteroids, respectively. Utilization decreased as infants’ age increased with corticosteroids surpassing oxygen and diuretics. To avoid the capture of intermittent use of corticosteroids for acute infections, we found a minimum of 45 days cumulative exposure was necessary to determine chronic use.