Variation in incidence rates of outcomes relevant to vaccine safety monitoring in a US commercially insured population by case identification algorithm.

BACKGROUND: Large health insurance claims databases can be used to estimate rates of rare safety outcomes. We measured incidence rates of rare outcomes that could be used to contextualize adverse events among people receiving pneumococcal vaccines in clinical trials or clinical practice. However, algorithms used to identify outcomes in administrative databases are subject to error. Using two algorithms for each outcome, we assessed the influence of algorithm choice on the rates of the outcomes. METHODS: We used closed administrative medical and pharmacy claims in the Healthcare Integrated Research DatabaseSM (HIRD) to construct a broad cohort of individuals less than 100 years old (i.e., the target cohort) and a trial-similar cohort of individuals resembling those potentially eligible for a vaccine clinical trial (e.g., for a pneumococcal vaccine). We stratified by age and sex and used specific and sensitive algorithms to estimate rates of 39 outcomes including cardiac/cerebrovascular, metabolic, allergic/autoimmune, neurological, and hematologic outcomes. Specific algorithms intended to reduce false positive errors, while sensitive algorithms intended to reduce false negative errors, thereby providing lower and upper bounds for the "true" rates. RESULTS: We followed approximately 40 million individuals in the target cohort for an average of 3 years. Of 39 outcomes, 14 (36 %) had a rate from the specific algorithm that was less than half the rate from the sensitive algorithm. Rates of cardiac/cerebrovascular outcomes were most consistent (mean ratio of rates from specific algorithms compared to rates from sensitive algorithms = 0.76), while the rates of neurological and hematologic outcomes were the least consistent (mean ratio of rates = 0.33 and 0.36, respectively). CONCLUSIONS: For many cardiac/cerebrovascular outcomes, rates were similar regardless of the algorithm. For other outcomes, rates varied substantially by algorithm. Using multiple algorithms to ascertain outcomes in claims data can be informative about the extent of uncertainty due to outcome misclassification.

Mortality, healthcare resource utilization, and cost among Medicare beneficiaries with Clostridioides difficile infection with and without sepsis.

Objective: To describe mortality, healthcare resource utilization (HRU), and costs among Medicare beneficiaries with primary Clostridioides difficile infection (pCDI) or recurrent CDI (rCDI), with and without sepsis. Methods: We conducted a retrospective observational study of 100% Medicare Fee-for-Service claims from adults aged ⩾ 65 years with ⩾1 CDI episode between 1 January 2009 and 31 December 2017. Patients were continuously enrolled in Medicare Parts A/B/D 12 months before and up to 12 months after pCDI. ICD-9/10 codes defined CDI using ⩾1 inpatient claim, or ⩾1 outpatient claim plus ⩾1 claim for CDI treatment. The pCDI episode ended after 14 days without a CDI claim. rCDI episodes started within 8 weeks from the end of a previous CDI episode. ICD-9/10 codes identified all-cause sepsis over 12 month follow-up. Results: Of 497,489 CDI patients, 41.0% (N = 203,888) had sepsis; 57.7% with sepsis died versus 32.4% without sepsis. Among patients with pCDI only (N = 345,893) or ⩾1 rCDI (N = 151,596), 39.2% and 45.1% suffered sepsis, respectively. All-cause hospitalizations were frequent for all cohorts (range: 81-99%). Among patients who died, those with sepsis versus without had more-frequent intensive care unit (ICU) use (pCDI: 29% versus 15%; rCDI: 65% versus 34%), longer hospital stays (pCDI: 12 versus 10 days; rCDI: 12 versus 9 days), and higher per-patient-per-month costs (pCDI: $34,841 versus $22,753; rCDI: $42,269 versus $25,047). In both cohorts, sepsis patients who survived had higher total costs and all-cause HRU than those without sepsis. All p < 0.001 above. Conclusions: Sepsis was common among Medicare beneficiaries with CDI. CDI patients with sepsis, especially after an rCDI, experienced higher mortality, HRU, and costs compared with those without sepsis.

Mortality, Health Care Use, and Costs of Clostridioides difficile Infections in Older Adults.

OBJECTIVES: Estimate mortality, cost, and health care resource utilization for Medicare beneficiaries aged ≥65 years who suffered a primary Clostridioides difficile infection (CDI) episode only or any recurrent CDI, and understand how outcomes covary with death. DESIGN: Retrospective observational claims analysis. SETTING AND PARTICIPANTS: Patients aged ≥65 years who had an inpatient or outpatient CDI diagnosis claim to Medicare and continuous enrollment in Medicare parts A, B, and D during the 12-month pre- and post-index periods. METHODS: Using 100% Medicare Fee-for-Service claims data for 2009-2017, primary (pCDI, n = 345,893) and recurrent (rCDI: n = 151,596) CDI episodes were identified. Demographic and clinical characteristics, mortality, health care resource utilization, and costs (per patient per month) were summarized for 12 months before and up to 12 months after episode start. Regression models were estimated for hospitalization risk, hospital length of stay (LOS), and cost to adjust for comorbidities. RESULTS: CDI-associated deaths were almost 10 times higher after recurrent CDI (25.4%) than primary CDI (2.7%). Compared with survivors, decedents were older, had higher Charlson Comorbidity Index scores, and were more likely Black. Adjusting for comorbidities, during follow-up, decedents had higher hospitalization rates [pCDI: odds ratio (OR) = 1.83, P < .001; rCDI: OR = 2.58, P < .001], and recurrent CDI decedents had more intensive care unit use (OR = 2.34, P < .001) compared with survivors. Decedents also had a longer length of stay (pCDI: +3.2 days, P < .001; rCDI: +2.6 days, P < .001), and higher total cost (pCDI: +303%, P < .001; rCDI: +297%, P < .001). CONCLUSIONS AND IMPLICATIONS: CDI is an important contributing diagnosis to all-cause mortality, particularly for recurrences. Prior to death, older Medicare beneficiaries who experienced CDI received longer, more intensive, and more costly care compared with survivors. Clinicians should be particularly attentive to prevention, identification, and appropriate treatment of CDI in older adults. Better treatments to reduce primary C difficile infection and recurrences in this vulnerable population can lower both mortality and economic burden.

Relationship of COPD Exacerbation Severity and Frequency on Risks for Future Events and Economic Burden in the Medicare Fee-For-Service Population.

Purpose: To quantify the effects of moderate and/or severe chronic obstructive pulmonary disease (COPD) exacerbations on future exacerbations and healthcare costs in Medicare Fee-For-Service beneficiaries. Patients and Methods: A retrospective cohort study of patients ≥40 years of age, with continuous enrollment from 2015 to 2018, with an index COPD diagnosis defined as first hospitalization, emergency department visit, or first of two outpatient visits (≥30 days apart) in 2015 with a claim for chronic bronchitis, emphysema, or chronic airway obstruction. Patients were stratified by baseline exacerbation categories in year one (YR1) and subsequently evaluated in YR2 and YR3: (A) none; (B) 1 moderate; (C) ≥2 moderate; (D) 1 severe; and (E) ≥2, one being severe. Moderate exacerbations were defined as COPD-related outpatient/ED visits with a corticosteroid/antibiotic claim within ±7 days of the visit and severe exacerbations as hospitalizations with a primary COPD diagnosis. Total all-cause costs for Categories B-E were compared to reference Category A using generalized linear models and inflation adjusted to 2019 dollars. Results: A total of 1,492,108 patients met study criteria with a mean (±SD) age of 70.9±10.9. In YR1, nearly 40% of patients experienced ≥1 moderate and/or severe exacerbations. Patients having multiple exacerbations, regardless of severity were 2-4 times more likely to experience an exacerbation during YR2 and YR3. Adjusted costs ranged between $24,000 and $26,600 for all categories for YR2 and YR3. Adjusted YR2 costs for Category D and E were $1421 and $1548 higher than those without an exacerbation (Category A YR2 $25,084, YR3 $24,282; p<0.0001). The respective YR3 adjusted costs were $2062 and $2117 higher than those without an exacerbation (Category A; p<0.0001), representing an increase of 6-8% and 8-9% for YR2 and YR3. Conclusion: Medicare patients with recent moderate or severe exacerbations, or at least two exacerbations per year are at significant risk for future exacerbations and incur higher all-cause costs.

Real-World Clinical and Economic Outcomes in Selected Immune-Related Adverse Events Among Patients with Cancer Receiving Immune Checkpoint Inhibitors.

BACKGROUND: With increased use of immune checkpoint inhibitors (ICIs) among patients with cancer, there is substantial interest in understanding clinical and economic outcomes and management of immune-related adverse events (irAEs). PATIENTS, MATERIALS, AND METHODS: A retrospective study was conducted using Premier Healthcare Database, a U.S. national hospital discharge database, from March 1, 2015, through December 31, 2017. The database comprises more than 880 million inpatient and hospital-based outpatient encounters, with more than 200 million unique patients reported by 966 hospitals. Patients with four solid tumors known to benefit from ICI therapy were included. The list of irAEs assessed was defined a priori per American Society of Clinical Oncology clinical guidelines for irAE management. Baseline irAE-related inpatient and outpatient visits were defined as the first inpatient or hospital-based outpatient visit with discharge diagnosis of any irAE of interest following confirmed ICI usage within 90 days prior to the baseline visit. Patients were followed for 90 days after baseline irAE-related inpatient discharge date or outpatient visit date to assess irAE-related inpatient admissions, all-cause in-hospital mortality, ICI reinitiation, and to determine costs and health care resource utilization. RESULTS: Records from 673,957 patients with four tumor types were reviewed for ICI therapy. Of 13,030 patients receiving ICIs, approximately 40% experienced at least one irAE, with a total of 10,121 irAEs occurring within 90 days of the ICI visit. The most frequent (>1,000 events) irAEs were anemia, impaired ventricular function with heart failure and vasculitis, thrombocytopenia, thyroid conditions, and peripheral edema. As might be expected, compared with those with baseline irAE-related outpatient visits, patients with baseline irAE-related inpatient visits had a significantly higher percentage of irAE-related inpatient admissions (23% vs. 14%) and all-cause in-hospital mortality (22% vs. 6%) and lower reinitiation of ICI therapy (31% vs. 71%). Baseline irAE-related inpatient visits had significantly higher mean costs ($29,477 vs. $5,718) with longer hospital stays (12.6 vs. 7.8 days). CONCLUSION: Findings from a U.S. national hospital discharge database suggest that irAEs in patients treated with ICIs are common, occur in multiples and with greater frequency in those with pre-existing comorbidities. Those with inpatient admissions have poorer outcomes. IMPLICATIONS FOR PRACTICE: The present work addressed the knowledge gap in understanding real-world outcomes of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs). Patients who experienced irAEs had significantly higher baseline comorbidities and were more likely to have immune-related or immune-compromised comorbid conditions. Patients with baseline irAE-related hospitalizations were more likely to be rehospitalized and to experience in-hospital mortality and less likely to reinitiate ICI treatment. Real-world patients are more diverse than clinical trials, and clinicians should consider both the efficacy and safety profile of ICI treatments, especially for patients with comorbidity conditions. Close monitoring is needed after patients have experienced an irAE.

Contemporary trend of acute kidney injury incidence and incremental costs among US patients undergoing percutaneous coronary procedures.

OBJECTIVES: To assess national trends of acute kidney injury (AKI) incidence, incremental costs, risk factors, and readmissions among patients undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) during 2012-2017. BACKGROUND: AKI remains a serious complication for patients undergoing CAG/PCI. Evidence is lacking in contemporary AKI trends and its impact on hospital resource utilization. METHODS: Patients who underwent CAG/PCI procedures in 749 hospitals were identified from Premier Healthcare Database. AKI was defined by ICD-9/10 diagnosis codes (584.9/N17.9, 583.89/N14.1, 583.9/N05.9, E947.8/T50.8X5) during 7 days post index procedure. Multivariable regression models were used to adjust for confounders. RESULTS: Among 2,763,681 patients, AKI incidence increased from 6.0 to 8.4% or 14% per year in overall patients; from 18.0 to 28.4% in those with chronic kidney disease (CKD) and from 2.4 to 4.2% in those without CKD (all p < .001). Significant risk factors for AKI included older age, being uninsured, inpatient procedures, CKD, anemia, and diabetes (all p < .001). AKI was associated with higher 30-day in-hospital mortality (ORadjusted = 2.55; 95% CI: 2.40, 2.70) and readmission risk (ORadjusted = 1.52; 95% CI: 1.50, 1.55). The AKI-related incremental cost during index visit and 30-day readmissions were estimated to be $8,416 and $580 per inpatient procedure and $927 and $6,145 per outpatient procedure. Overall excess healthcare burden associated with AKI was $1.67 billion. CONCLUSIONS: AKI incidence increased significantly in this large, multifacility sample of patients undergoing CAG/PCI procedures and was associated with substantial increase in hospital costs, readmissions, and mortality. Efforts to reduce AKI risk in US healthcare system are warranted.

Epidemiology of Serratia Bloodstream Infections Among Hospitalized Children in the United States, 2009-2016.

Serratia can cause serious bloodstream infections (BSIs). This retrospective cohort study identified 5,312 pediatric inpatient encounters with BSIs from 2009 to 2016, of which 82 (0.01%) had Serratia BSIs. The rate among hospitalized patients increased significantly from 0.4 in 2009 to 1.0 in 2016 per 10,000 admissions. Risk factors differed and outcomes were worse for Serratia BSIs compared with non-Serratia BSIs.

Risk-Set Matching to Assess the Impact of Hospital-Acquired Bloodstream Infections.

Hospital-acquired bloodstream infections have a definite impact on patient encounters and cause increased length of stay, costs, and mortality. However, methods for estimating these effects are potentially biased, especially if the time of infection is not incorporated into the estimation strategy. We focused on matching patient encounters in which a hospital-acquired infection occurred to comparable encounters in which an infection did not occur. This matching strategy is susceptible to a selection bias because inpatients that stay longer in the hospital are more likely to acquire an infection and thus also are more likely to have longer and more costly stays. Instead, we have proposed risk-set matching, which matches infected encounters to similar encounters still at risk for infection at the corresponding time of infection. Matching on the one-dimensional propensity score can create comparable pairs for a large number of characteristics; an analogous propensity score is described for risk-set matching. We have presented dramatically different estimates using these 2 approaches with data from a pediatric cohort from the Premier Healthcare Database, United States, 2009-2016. The results suggest that estimates that did not incorporate time of infection exaggerated the impact of hospital-acquired infections with regard to attributed length of stay and costs.

Assessment of Risk Factors Associated With Hospital-Acquired Pressure Injuries and Impact on Health Care Utilization and Cost Outcomes in US Hospitals.

Hospital-acquired pressure injuries (HAPI) are a societal burden and considered potentially preventable. Data on risk factors and HAPI burden are important for effective prevention initiatives. This study of the 2009-2014 US Premier Healthcare Database identified HAPI risk factors and compared outcomes after matching HAPI to non-HAPI patients. The cumulative incidence of HAPI was 0.28% (47 365 HAPI among 16 967 687 total adult inpatients). Among the matched sample of 110 808 patients (27 702 HAPI), the strongest risk factors for HAPI were prior PI (odds ratio [OR] = 12.52, 95% confidence interval [CI] = 11.93-13.15), prior diabetic foot ulcer (OR = 3.43, 95% CI = 3.20-3.68), and malnutrition (OR = 3.11, 95% CI = 3.02-3.20). HAPI patients had longer adjusted length of stay (3.7 days, P < .0001), higher total hospitalization cost ($8014, P < .0001), and greater odds of readmissions through 180 days (OR = 1.60, 95% CI = 1.55-1.65). This study demonstrates how big data may help quantify HAPI burden and improve internal hospital processes by identifying high-risk patients and informing best practices for prevention.