Utilization of broad- versus narrow-spectrum antibiotics for the treatment of outpatient community-acquired pneumonia among adults in the United States.

PURPOSE: To characterize antibiotic utilization for outpatient community-acquired pneumonia (CAP) in the United States. METHODS: We conducted a cohort study among adults 18-64 years diagnosed with outpatient CAP and a same-day guideline-recommended oral antibiotic fill in the MarketScan® Commercial Database (2008-2019). We excluded patients coded for chronic lung disease or immunosuppressive disease; recent hospitalization or frequent healthcare exposure (e.g., home wound care, patients with cancer); recent antibiotics; or recent infection. We characterized utilization of broad-spectrum antibiotics (respiratory fluoroquinolone, ß-lactam + macrolide, ß-lactam + doxycycline) versus narrow-spectrum antibiotics (macrolide, doxycycline) overall and by patient- and provider-level characteristics. Per 2007 IDSA/ATS guidelines, we stratified analyses by otherwise healthy patients and patients with comorbidities (coded for diabetes; chronic heart, liver, or renal disease; etc.). RESULTS: Among 263 914 otherwise healthy CAP patients, 35% received broad-spectrum antibiotics (not recommended); among 37 161 CAP patients with comorbidities, 44% received broad-spectrum antibiotics (recommended). Ten-day antibiotic treatment durations were the most common for all antibiotic classes except macrolides. From 2008 to 2019, broad-spectrum antibiotic use substantially decreased from 45% to 19% in otherwise healthy patients (average annual percentage change [AAPC], -7.5% [95% CI -9.2%, -5.9%]), and from 55% to 29% in patients with comorbidities (AAPC, -5.8% [95% CI -8.8%, -2.6%]). In subgroup analyses, broad-spectrum antibiotic use varied by age, geographic region, provider specialty, and provider location. CONCLUSIONS: Real-world use of broad-spectrum antibiotics for outpatient CAP declined over time but remained common, irrespective of comorbidity status. Prolonged duration of therapy was common. Antimicrobial stewardship is needed to aid selection according to comorbidity status and to promote shorter courses.

Comparative Safety and Attributable Healthcare Expenditures Following Inappropriate Versus Appropriate Outpatient Antibiotic Prescriptions Among Adults With Upper Respiratory Infections.

BACKGROUND: Little is known about the clinical and financial consequences of inappropriate antibiotics. We aimed to estimate the comparative risk of adverse drug events and attributable healthcare expenditures associated with inappropriate versus appropriate antibiotic prescriptions for common respiratory infections. METHODS: We established a cohort of adults aged 18 to 64 years with an outpatient diagnosis of a bacterial (pharyngitis, sinusitis) or viral respiratory infection (influenza, viral upper respiratory infection, nonsuppurative otitis media, bronchitis) from 1 April 2016 to 30 September 2018 using Merative MarketScan Commercial Database. The exposure was an inappropriate versus appropriate oral antibiotic (ie, non-guideline-recommended vs guideline-recommended antibiotic for bacterial infections; any vs no antibiotic for viral infections). Propensity score-weighted Cox proportional hazards models were used to estimate the association between inappropriate antibiotics and adverse drug events. Two-part models were used to calculate 30-day all-cause attributable healthcare expenditures by infection type. RESULTS: Among 3 294 598 eligible adults, 43% to 56% received inappropriate antibiotics for bacterial and 7% to 66% for viral infections. Inappropriate antibiotics were associated with increased risk of several adverse drug events, including Clostridioides difficile infection and nausea/vomiting/abdominal pain (hazard ratio, 2.90; 95% confidence interval, 1.31-6.41 and hazard ratio, 1.10; 95% confidence interval, 1.03-1.18, respectively, for pharyngitis). Thirty-day attributable healthcare expenditures were higher among adults who received inappropriate antibiotics for bacterial infections ($18-$67) and variable (-$53 to $49) for viral infections. CONCLUSIONS: Inappropriate antibiotic prescriptions for respiratory infections were associated with increased risks of patient harm and higher healthcare expenditures, justifying a further call to action to implement outpatient antibiotic stewardship programs.

Noninterventional studies in the COVID-19 era: methodological considerations for study design and analysis.

The global COVID-19 pandemic has generated enormous morbidity and mortality, as well as large health system disruptions including changes in use of prescription medications, outpatient encounters, emergency department admissions, and hospitalizations. These pandemic-related disruptions are reflected in real-world data derived from electronic medical records, administrative claims, disease or medication registries, and mobile devices. We discuss how pandemic-related disruptions in healthcare utilization may impact the conduct of noninterventional studies designed to characterize the utilization and estimate the effects of medical interventions on health-related outcomes. Using hypothetical studies, we highlight consequences that the pandemic may have on study design elements including participant selection and ascertainment of exposures, outcomes, and covariates. We discuss the implications of these pandemic-related disruptions on possible threats to external validity (participant selection) and internal validity (for example, confounding, selection bias, missing data bias). These concerns may be amplified in populations disproportionately impacted by COVID-19, such as racial/ethnic minorities, rural residents, or people experiencing poverty. We propose a general framework for researchers to carefully consider during the design and analysis of noninterventional studies that use real-world data from the COVID-19 era.

Utilization of nonguideline concordant antibiotic treatment following acute otitis media in children in the United States.

PURPOSE: Acute otitis media (AOM) is a common indication for antibiotics in children. We sought to characterize the frequency of nonguideline concordant antibiotic therapy for AOM in the United States, by agent and duration. METHODS: Using national administrative claims data (2016-2019), we identified children aged 6 months to 17 years with an oral antibiotic dispensed within 3 days of a new diagnosis of suppurative AOM. Use of nonguideline concordant agents and durations, defined based on national treatment guidelines, were summarized by age, race, rurality, region, and insurance type. Subsequent oral antibiotic dispensing within the year after AOM diagnosis was also evaluated. We created sunburst diagrams to visualize longitudinal patterns of within-person antibiotic utilization for AOM, by agent and duration. RESULTS: We identified 789 424 eligible commercially-insured and 502 239 medicaid-insured children. Among commercially insured children, 35% received nonguideline concordant agents for AOM, including cefdinir (16%), amoxicillin-clavulanate (12%), and azithromycin (7%). Fewer children age <2 years received a nonguideline concordant initial agent (27%) compared to age ≥6 years (41%). More children age <2 years received three or more antibiotics over the following year (34% vs. 3% for children age ≥6 years). The most common treatment duration was 10 days for all ages; treatment duration for the initial antibiotic was nonguideline concordant for 95% and 89% of children age 2-5 years and ≥6 years, respectively. Patterns were similar for medicaid-insured children. CONCLUSIONS: Nonguideline concordant antibiotic use is common when treating AOM in children, including use of broad-spectrum agents and longer-than-recommended antibiotic durations.

The impact of infectious diseases consultation for children with Staphylococcus aureus bacteremia.

BACKGROUND: Despite clear benefit of improved outcomes in adults, the impact of infectious diseases (ID) consultation for Staphylococcus aureus bacteremia in children remains understudied. METHODS: To assess the impact of pediatric ID consultation on management and outcomes, we conducted a cohort study of children with S. aureus bacteremia at St. Louis Children's Hospital from 2011 to 2018. We assessed adherence to six established quality-of-care indicators (QCIs). We applied propensity score methodology to examine the impact of ID consultation on risk of treatment failure, a composite of all-cause mortality or hospital readmission within 90 days. RESULTS: Of 306 patients with S. aureus bacteremia, 193 (63%) received ID consultation. ID consultation was associated with increased adherence to all QCIs, including proof-of-cure blood cultures, indicated laboratory studies, echocardiography, source control, targeted antibiotic therapy, and antibiotic duration. Obtaining proof-of-cure blood cultures and all indicated laboratory studies were associated with improved outcomes. In propensity score-weighted analyses, risk of treatment failure was similar among patients who did and did not receive ID consultation. However, the number of events was small and risk estimates were imprecise. CONCLUSIONS: For children with S. aureus bacteremia, ID consultation improved adherence to QCIs, some of which were associated with improved clinical outcomes. IMPACT: In children with Staphylococcus aureus bacteremia, consultation by an infectious diseases (ID) physician improved adherence to established quality-of-care indicators (QCIs). The current literature regarding ID consultation in pediatric S. aureus bacteremia is sparse. Three prior international studies demonstrated improved quality of care with ID consultation, though results were disparate regarding clinical outcomes. This article impacts the current literature by strengthening the evidence that ID consultation in children improves adherence to QCIs, and demonstrates that adherence to QCIs improves clinical outcomes.

Integrase Strand Transfer Inhibitors Are Associated With Incident Diabetes Mellitus in People With Human Immunodeficiency Virus.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are associated with weight gain in people with HIV (PWH). Less is known about the risk of other metabolic outcomes such as diabetes mellitus and hyperglycemia. METHODS: IBM® MarketScan® databases for commercially and Medicaid-insured adults were used to identify PWH newly initiating antiretroviral therapy (ART). The primary outcome was a composite of new-onset diabetes mellitus/hyperglycemia in the 6 months following ART initiation and was identified using International Classification of Disease, Ninth revision, Clinical Modification (ICD-9-CM) and ICD-10-CM diagnosis and procedure codes and Current Procedural Terminology, 4th Edition (CPT-4) codes. To examine the relationship between INSTI use and the composite outcome, we estimated the risk using Cox proportional hazards models with calendar time-specific standardized mortality ratio weights. RESULTS: Of 42 382 PWH who initiated ART between 1 July 2007 and 30 June 2018, 22 762 (54%) were treated with INSTI-based regimens. Mean age was 38 years, 74% were male, and 19% were Medicaid insured. PWH on INSTIs were 31% more likely to develop new-onset diabetes mellitus/hyperglycemia (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.15-1.48]) compared with those who initiated non-INSTI-based regimens. When examined individually, the highest risk was associated with elvitegravir (HR, 1.54; 95% CI, 1.32-1.97; P < .001) and the lowest risk with raltegravir (HR, 1.19; 95% CI, 1.03-1.37; P = .02). CONCLUSIONS: INSTI use was associated with increased risk of new-onset diabetes mellitus/hyperglycemia in the 6 months following ART initiation.

Association of Inappropriate Outpatient Pediatric Antibiotic Prescriptions With Adverse Drug Events and Health Care Expenditures.

Importance: Nonguideline antibiotic prescribing for the treatment of pediatric infections is common, but the consequences of inappropriate antibiotics are not well described. Objective: To evaluate the comparative safety and health care expenditures of inappropriate vs appropriate oral antibiotic prescriptions for common outpatient pediatric infections. Design, Setting, and Participants: This cohort study included children aged 6 months to 17 years diagnosed with a bacterial infection (suppurative otitis media [OM], pharyngitis, sinusitis) or viral infection (influenza, viral upper respiratory infection [URI], bronchiolitis, bronchitis, nonsuppurative OM) as an outpatient from April 1, 2016, to September 30, 2018, in the IBM MarketScan Commercial Database. Data were analyzed from August to November 2021. Exposures: Inappropriate (ie, non-guideline-recommended) vs appropriate (ie, guideline-recommended) oral antibiotic agents dispensed from an outpatient pharmacy on the date of infection. Main Outcomes and Measures: Propensity score-weighted Cox proportional hazards models were used to estimate hazards ratios (HRs) and 95% CIs for the association between inappropriate antibiotic prescriptions and adverse drug events. Two-part models were used to calculate 30-day all-cause attributable health care expenditures by infection type. National-level annual attributable expenditures were calculated by scaling attributable expenditures in the study cohort to the national employer-sponsored insurance population. Results: The cohort included 2 804 245 eligible children (52% male; median [IQR] age, 8 [4-12] years). Overall, 31% to 36% received inappropriate antibiotics for bacterial infections and 4% to 70% for viral infections. Inappropriate antibiotics were associated with increased risk of several adverse drug events, including Clostridioides difficile infection and severe allergic reaction among children treated with a nonrecommended antibiotic agent for a bacterial infection (among patients with suppurative OM, C. difficile infection: HR, 6.23; 95% CI, 2.24-17.32; allergic reaction: HR, 4.14; 95% CI, 2.48-6.92). Thirty-day attributable health care expenditures were generally higher among children who received inappropriate antibiotics, ranging from $21 to $56 for bacterial infections and from -$96 to $97 for viral infections. National annual attributable expenditure estimates were highest for suppurative OM ($25.3 million), pharyngitis ($21.3 million), and viral URI ($19.1 million). Conclusions and Relevance: In this cohort study of children with common infections treated in an outpatient setting, inappropriate antibiotic prescriptions were common and associated with increased risks of adverse drug events and higher attributable health care expenditures. These findings highlight the individual- and national-level consequences of inappropriate antibiotic prescribing and further support implementation of outpatient antibiotic stewardship programs.

Association of Adverse Events With Antibiotic Treatment for Urinary Tract Infection.

BACKGROUND: Little is known about the relative harms of different antibiotic regimens prescribed to treat uncomplicated urinary tract infection (UTI). We sought to compare the risk of adverse events associated with commonly used oral antibiotic regimens for the outpatient treatment of uncomplicated UTI. METHODS: Using data from the IBM® MarketScan® Commercial Database, we identified 1 169 033 otherwise healthy, nonpregnant women aged 18-44 years with uncomplicated UTI who initiated an oral antibiotic with activity against common uropathogens from 1 July 2006 to 30 September 2015. We used propensity score-weighted Kaplan-Meier methods and Cox proportional hazards regression models to estimate the association between antibiotic agent and adverse events. RESULTS: Of 2 first-line agents, trimethoprim-sulfamethoxazole (vs nitrofurantoin) was associated with higher risk of several adverse drug events including hypersensitivity reaction (hazard ratio, 2.62; 95% confidence interval, 2.30-2.98), acute renal failure (2.56; 1.55-4.25), skin rash (2.42; 2.13-2.75), urticaria (1.37; 1.19-1.57), abdominal pain (1.14; 1.09-1.19), and nausea/vomiting (1.18; 1.10-1.28), but a similar risk of potential microbiome-related adverse events. Compared with nitrofurantoin, non-first-line agents were associated with higher risk of several adverse drug events and potential microbiome-related adverse events including non-Clostridium difficile diarrhea, C. difficile infection, vaginitis/vulvovaginal candidiasis, and pneumonia. Treatment duration modified the risk of potential microbiome-related adverse events. CONCLUSIONS: The risks of adverse drug events and potential microbiome-related events differ widely by antibiotic agent and duration. These findings underscore the utility of using real-world data to fill evidentiary gaps related to antibiotic safety.

A Framework for Extension Studies Using Real-World Data to Examine Long-Term Safety and Effectiveness.

Understanding the long-term benefits and risks of treatments, devices, and vaccines is critically important for individual- and population-level healthcare decision-making. Extension studies, or 'roll-over studies,' are studies that allow for patients participating in a parent clinical trial to 'roll-over' into a subsequent related study to continue to observe and measure long-term safety, tolerability, and/or effectiveness. These designs are not new and are often used as an approach to satisfy regulatory post-approval safety requirements. However, designs using traditional clinical trial infrastructure can be expensive and burdensome to conduct, particularly, when following patients for many years post trial completion. Given the increasing availability and access of real-world data (RWD) sources, direct-to-patient technologies, and novel real-world study designs, there are more cost-efficient approaches to conducting extension studies while assessing important long-term outcomes. Here, we describe various fit-for-purpose design options for extension studies, discuss related methodological considerations, and provide scientific and operational guidance on practices when planning to conduct an extension study using RWD. This manuscript is endorsed by the International Society for Pharmacoepidemiology (ISPE).

Estimating the Effectiveness of Rotavirus Vaccine Schedules.

BACKGROUND: Important questions exist regarding the comparative effectiveness of alternative childhood vaccine schedules; however, optimal approaches to studying this complex issue are unclear. METHODS: We applied methods for studying dynamic treatment regimens to estimate the comparative effectiveness of different rotavirus vaccine (RV) schedules for preventing acute gastroenteritis-related emergency department (ED) visits or hospitalization. We studied the effectiveness of six separate protocols: one- and two-dose monovalent rotavirus vaccine (RV1); one-, two-, and three-dose pentavalent rotavirus vaccine (RV5); and no RV vaccine. We used data on all infants to estimate the counterfactual cumulative risk for each protocol. Infants were censored when vaccine receipt deviated from the protocol. Inverse probability of censoring-weighted estimation addressed potentially informative censoring by protocol deviations. A nonparametric group-based bootstrap procedure provided statistical inference. RESULTS: The method yielded similar 2-year effectiveness estimates for the full-series protocols; weighted risk difference estimates comparing unvaccinated children to those adherent to either full-series (two-dose RV1, three-dose RV5) corresponded to four fewer hospitalizations and 12 fewer ED visits over the 2-year period per 1,000 children. We observed dose-response relationships, such that additional doses further reduced risk of acute gastroenteritis. Under a theoretical intervention to fully vaccinate all children, the 2-year risk differences comparing full to observed adherence were 0.04% (95% CI = 0.03%, 0.05%) for hospitalizations and 0.17% (95% CI = 0.14%, 0.19%) for ED visits. CONCLUSIONS: The proposed approach can generate important evidence about the consequences of delaying or skipping vaccine doses, and the impact of interventions to improve vaccine schedule adherence.

Risk of antibiotic treatment failure in premenopausal women with uncomplicated urinary tract infection.

PURPOSE: Acute uncomplicated urinary tract infections (UTIs) are among the most common indications for antibiotic prescriptions in otherwise healthy women. We compared the risk of treatment failure of antibiotic regimens for outpatient treatment of UTI in real-world practice. METHODS: We identified non-pregnant, premenopausal women diagnosed with uncomplicated, lower tract UTI and prescribed an oral antibiotic with activity against common uropathogens. We used propensity score-weighted Kaplan-Meier functions to estimate 30-day risks and risk differences (RD) for pyelonephritis and UTI-related antibiotic prescription switch. RESULTS: Of 1 140 602 patients, the distribution of index prescriptions was 44% fluoroquinolones (non-first-line), 28% trimethoprim-sulfamethoxazole (TMP/SMX) (first-line), 24% nitrofurantoin (first-line), 3% narrow-spectrum ß-lactams (non-first-line), 1% broad-spectrum ß-lactams (non-first-line), and 1% amoxicillin/ampicillin (non-recommended). Compared to the risk of pyelonephritis for nitrofurantoin (0.3%), risks were higher for TMP/SMX (RD, 0.2%; 95% CI, 0.2%-0.2%) and broad-spectrum ß-lactams (RD, 0.2%; 95% CI, 0.1%-0.4%). Compared to the risk of prescription switch for nitrofurantoin (12.7%), the risk was higher for TMP/SMX (RD 1.6%; 95% CI 1.3%-1.7%) but similar for broad-spectrum ß-lactams (RD -0.7%; 95% CI -1.4%-0.1%) and narrow-spectrum ß-lactams (RD -0.3%; 95% CI -0.8%-0.2%). Subgroup analyses suggest TMP/SMX treatment failure may be due in part to increasing uropathogen resistance over time. CONCLUSIONS: The risk of treatment failure differed by antibiotic agent, with higher risk associated with TMP/SMX versus nitrofurantoin, and lower or similar risk associated with broad- versus narrow-spectrum ß-lactams. Given serious safety warnings for fluoroquinolones, these results suggest that nitrofurantoin may be preferable as the first-line agent for outpatient treatment of uncomplicated UTI.

Rural-urban differences in antibiotic prescribing for uncomplicated urinary tract infection.

OBJECTIVE: To examine rural-urban differences in temporal trends and risk of inappropriate antibiotic use by agent and duration among women with uncomplicated urinary tract infection (UTI). DESIGN: Observational cohort study. METHODS: Using the IBM MarketScan Commercial Database (2010-2015), we identified US commercially insured women aged 18-44 years coded for uncomplicated UTI and prescribed an oral antibiotic agent. We classified antibiotic agents and durations as appropriate versus inappropriate based on clinical guidelines. Rural-urban status was defined by residence in a metropolitan statistical area. We used modified Poisson regression to determine the association between rural-urban status and inappropriate antibiotic receipt, accounting for patient- and provider-level characteristics. We used multivariable logistic regression to estimate trends in antibiotic use by rural-urban status. RESULTS: Of 670,450 women with uncomplicated UTI, a large proportion received antibiotic prescriptions for inappropriate agents (46.7%) or durations (76.1%). Compared to urban women, rural women were more likely to receive prescriptions with inappropriately long durations (adjusted risk ratio 1.10, 95% CI, 1.10-1.10), which was consistent across subgroups. From 2011 to 2015, there was slight decline in the quarterly proportion of patients who received inappropriate agents (48.5% to 43.7%) and durations (78.3% to 73.4%). Rural-urban differences varied over time by agent (duration outcome only), geographic region, and provider specialty. CONCLUSIONS: Inappropriate antibiotic prescribing is quite common for the treatment of uncomplicated UTI. Rural women are more likely to receive inappropriately long antibiotic durations. Antimicrobial stewardship interventions are needed to improve outpatient UTI antibiotic prescribing and to reduce unnecessary exposure to antibiotics, particularly in rural settings.

Comparative safety of high-dose versus standard-dose influenza vaccination in patients with end-stage renal disease.

BACKGROUND: High-dose influenza vaccine (HDV) is an alternative vaccination strategy in patients with end-stage renal disease (ESRD), though the safety of HDV has not been evaluated in this population. The objective of this study was to estimate the relative occurrence of adverse vaccine reactions in patients with ESRD following vaccination with HDV compared with standard-dose influenza vaccine (SDV). METHODS: Using data from the United States Renal Data System, we identified patients with ESRD aged ≥ 65 years at influenza vaccination during yearly influenza seasons from 2010 through 2016. Patients were followed after vaccination to observe serious (anaphylaxis, angioedema, seizure, encephalopathy, Guillain-Barré syndrome [GBS], and short-term, all-cause mortality) and milder (urticaria/hives, rash, pain in limb, cellulitis, myalgia/myositis, fever, nausea and vomiting, diarrhea, and syncope) adverse events. Propensity score-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) for HDV versus SDV were estimated with Cox proportional hazards models. RESULTS: Of 520,876 vaccinations observed (mean age = 74.7 years at vaccination; 63% white race), 7.4% were HDV. For serious events, the weighted HRs were null for seizure, encephalopathy, and mortality and inestimable due to too few cases for anaphylaxis, angioedema, and GBS. For milder vaccine reactions, the weighted HRs demonstrated generally increased risks in the HDV group, including rash (HR = 1.86; 95% CI, 1.34-2.57), diarrhea (HR = 1.26; 95% CI, 1.07-1.50), pain in limb (HR = 1.23; 95% CI, 1.12-1.34), and myalgia/myositis (HR = 1.16; 95% CI, 1.04-1.30). CONCLUSIONS: The risks of serious adverse events were low and similar between treatment groups; however, HDV recipients had increased risks of several milder adverse events compared with SDV recipients, consistent with clinical trial findings in the general population of older adults. These results add important information to inform the risk-benefit tradeoff of the use of HDV versus SDV in patients with ESRD.

A qualitative study examining pediatric clinicians' perceptions of delayed vaccine schedules.

OBJECTIVE: To explore pediatric clinicians' attitudes, beliefs, and perceived social norms about the impact of delayed vaccine schedules on the clinical management of their patients. METHODS: We conducted 30 semi-structured qualitative interviews with academic (Infectious Diseases, Emergency Medicine) and community pediatric clinicians (General Pediatrics) to explore clinicians' perspectives on how delayed schedules influence their clinical management of patients. The interview guide was based on the Theory of Planned Behavior. We analyzed interview transcripts using both an inductive and deductive thematic approach. RESULTS: The pediatric clinicians in our study overwhelmingly supported the recommended schedule, sought guidance on approaches to navigating conversations with vaccine hesitant families, and desired more evidence to effectively promote on-time vaccination. Clinicians described how delayed schedules have consequences for sick children (e.g., increased antibiotics, laboratory tests, emergency department visits) and healthy children (e.g., increased vaccine visits, out-of-pocket costs, fears among children receiving frequent shots). Clinicians stated that delayed schedules also negatively impact pediatric practices (e.g., increased time counseling patients, staff burden, clogged clinic space, unpredictable vaccine utilization, costs). CONCLUSIONS: Pediatric clinicians perceive that delayed vaccine schedules negatively affect patients, pediatric practices, the healthcare system, and society. Future research should quantify the consequences of delayed schedules and identify strategies that promote vaccine adherence. Results from future studies can better support clinician-parent conversations about vaccine hesitancy, guide decision-makers about practice-level approaches to vaccine schedules, and advise payors and policymakers regarding vaccine-related policies.

Brief Report: Integrase Strand Transfer Inhibitors Are Associated With Lower Risk of Incident Cardiovascular Disease in People Living With HIV.

BACKGROUND: Several antiretroviral therapy (ART) classes have been associated with increased myocardial infarction (MI) risk. Cardiovascular disease in people living with HIV (PLWH) on integrase strand transfer inhibitors (INSTI) has not been examined. Here we aim to examine this. SETTING: Retrospective cohort design study. METHODS: We used the IBMMarketScan databases for U.S. commercially insured and Medicaid covered adults to identify PLWH newly initiated on ART between January 1, 2008 and December 30, 2015. Major adverse cardiac event (MACE), a composite of acute MI, ischemic stroke, coronary artery bypass grafting, and percutaneous coronary intervention was the primary outcome. We used calendar time-specific probability-weighted Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for the association between INSTI use and MACE. We used propensity score weighting methods to account for potential confounding. RESULTS: Twenty thousand two hundred forty-two new ART initiators were identified. 5069 (25%) PLWH initiated INSTI-based regimens. 203 MACE events occurred; acute MI 16 (0.32%) vs 66 (0.43%), stroke 24 (0.47%) vs 54 (0.36), coronary artery bypass grafting 2 (0.04%) vs 9 (0.06%), percutaneous coronary intervention 7 (0.14%) vs 25 (0.16%) of INSTI users vs non-users. INSTI-based ART was associated with significantly lower risk of MACE events (hazard ratios 0.79; 95% confidence intervals: 0.64 to 0.96) compared with non-INSTI-based regimens. CONCLUSION: In this cohort, INSTI-based regimens were associated with a 21% decreased risk of incident cardiovascular disease. These finding require validation in other cohorts and with longer follow-up.

Association of State Legislation of Human Papillomavirus Vaccination with Vaccine Uptake Among Adolescents in the United States.

We assessed the association of state legislation with adolescent human papillomavirus (HPV) vaccination rates in states that legislated information dissemination or administration of HPV vaccination. Using insurance claims, we calculated monthly HPV vaccination rates (November 2009-December 2017) among adolescents in states that passed HPV vaccination legislation during that period: Missouri (July 2010), Kentucky (February 2012), Indiana (March 2013), Oregon (June 2013). We used segmented regression to estimate levels and trends of HPV vaccination rates, comparing pre-legislation to post-legislation segments, adjusting for seasonal vaccination patterns and changes to the vaccination recommendation among males during the study period. Indiana's legislation allowed pharmacists to administer HPV vaccination; legislation in Kentucky, Missouri, and Oregon included provisions HPV and cervical cancer education. No statistically significant increases in HPV vaccination levels or trends were observed in the post-legislation segments among adolescents overall; however, a significant post-legislation increase in vaccination trends was observed among boys in Missouri (ß = 0.16, p = 0.03). Evidence for a positive impact of legislation on HPV vaccination rates is limited. The scarcity of policies that directly facilitate or promote HPV vaccination, and the breadth of exemptions to school vaccination requirements, may limit the effectiveness of these policies. Continuing efforts to introduce and pass legislation that directly facilitates HPV vaccination, combined with promoting existing evidence-based interventions, can provide opportunities to identify the most effective strategies to increase adolescent HPV vaccination rates.

Comparative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccine Among Patients Receiving Maintenance Hemodialysis.

RATIONALE & OBJECTIVE: Studies of patients on maintenance dialysis therapy suggest that standard-dose influenza vaccine (SDV) may not prevent influenza-related outcomes. Little is known about the comparative effectiveness of SDV versus high-dose influenza vaccine (HDV) in this population. STUDY DESIGN: Cohort study using data from the US Renal Data System. SETTING & PARTICIPANTS: 507,552 adults undergoing in-center maintenance hemodialysis between the 2010 to 2011 and 2014 to 2015 influenza seasons. EXPOSURES: SDV and HDV. OUTCOMES: All-cause mortality, hospitalization due to influenza or pneumonia, and influenza-like illness during the influenza season. ANALYTIC APPROACH: Patients were eligible for inclusion in multiple yearly cohorts; thus, our unit of analysis was the influenza patient-season. To examine the relationship between vaccine dose and effectiveness outcomes, we estimated risk differences and risk ratios using propensity score weighting of Kaplan-Meier functions, accounting for a wide range of patient- and facility-level characteristics. For nonmortality outcomes, we used competing-risk methods to account for the high mortality rate in the dialysis population. RESULTS: Within 225,215 influenza patient-seasons among adults 65 years and older, 97.4% received SDV and 2.6% received HDV. We observed similar risk estimates for HDV and SDV recipients for mortality (risk difference, -0.08%; 95% CI, -0.85% to 0.80%), hospitalization due to influenza or pneumonia (risk difference, 0.15%; 95% CI, -0.69% to 0.93%), and influenza-like illness (risk difference, 0.00%; 95% CI, -1.50% to 1.08%). Our findings were similar among adults younger than 65 years, as well as within other subgroups defined by influenza season, age group, dialysis vintage, month of influenza vaccination, and vaccine valence. LIMITATIONS: Residual confounding and outcome misclassification. CONCLUSIONS: The HDV does not appear to provide additional protection beyond the SDV against all-cause mortality or influenza-related outcomes for adults undergoing hemodialysis. The additional cost and side effects associated with HDV should be considered when offering this vaccine. Future studies of HDV and other influenza vaccine strategies are warranted.

The Role Of Social Risk Factors In Dialysis Facility Ratings And Penalties Under A Medicare Quality Incentive Program.

Medicare's End-Stage Renal Disease Quality Incentive Program is a mandatory pay-for-performance program for US dialysis facilities, in which facilities are penalized up to 2 percent of their total Medicare payments based on their performance on quality metrics. While analyses of similar programs in other settings have shown performance to be related to social risk factors, it is unknown whether this program displays similar patterns. In this national study, facilities located in low-income ZIP codes and with high proportions of patients who were black or dually enrolled in Medicaid had lower performance scores and higher rates of penalization under the program. Independent (versus chain) status, large facility size, and urban location were also associated with penalties. Further study is needed to determine the degree to which these patterns reflect low-quality care delivery versus patient factors beyond providers' control. In the meantime, the impact of these penalties on providers serving vulnerable populations should be tracked closely.

Variation in rotavirus vaccination coding in state US Medicaid data.

Differences in state Medicaid policies and practices may result in variation in the recording of individual-level vaccination claims, which may present challenges for vaccination research using state Medicaid data. We describe differences in procedure coding for rotavirus vaccination in four states' Medicaid programs by identifying rotavirus vaccine-specific codes and oral vaccine administration codes. The proportion of vaccinated children with vaccine-specific and oral vaccine administration codes differed substantially across states: two states used vaccine-specific codes almost exclusively (95.9% and 99.0%); one had exclusively oral vaccine administration codes (>99.9%); another had a mixture (32.1% vaccine-specific codes, 40.0% oral vaccine administration codes, and 27.9% both). Depending on the research question, studies using Medicaid data in states without (or with incomplete) vaccine-specific coding may be infeasible. Prior to initiating research, investigators should carefully evaluate state Medicaid policies and patterns of vaccination uptake, as vaccine reimbursement policies and availability of vaccine claims may vary.