The impact of timing of initiating invasive mechanical ventilation in COVID-19-related respiratory failure.

PURPOSE: Optimal timing of initiating invasive mechanical ventilation (IMV) in coronavirus disease 2019 (COVID-19)-related respiratory failure is unclear. We hypothesized that a strategy of IMV as opposed to continuing high flow oxygen or non-invasive mechanical ventilation each day after reaching a high FiO2 threshold would be associated with worse in-hospital mortality. METHODS: Using data from Kaiser Permanente Northern/Southern California's 36 medical centers, we identified patients with COVID-19-related acute respiratory failure who reached ≥80% FiO2 on high flow nasal cannula or non-invasive ventilation. Exposure was IMV initiation each day after reaching high FiO2 threshold (T0). We developed propensity scores with overlap weighting for receipt of IMV each day adjusting for confounders. We reported relative risk of inpatient death with 95% Confidence Interval. RESULTS: Of 28,035 hospitalizations representing 21,175 patient-days, 5758 patients were included (2793 received and 2965 did not receive IMV). Patients receiving IMV had higher unadjusted mortality (63.6% versus 18.2%, P < 0.0001). On each day after reaching T0 through day >10, the adjusted relative risk was higher for those receiving IMV compared to those not receiving IMV (Relative Risk>1). CONCLUSIONS: Initiation of IMV on each day after patients reach high FiO2 threshold was associated with higher inpatient mortality after adjusting for time-varying confounders. Remaining on high flow nasal cannula or non-invasive ventilation does not appear to be harmful compared to IMV. Prospective evaluation is needed.

Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink.

Importance: Postauthorization monitoring of vaccines in a large population may detect rare adverse events not identified in clinical trials such as Guillain-Barré syndrome (GBS), which has a background rate of 1 to 2 per 100 000 person-years. Objective: To describe cases and incidence of GBS following COVID-19 vaccination and assess the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines. Design, Setting, and Participants: This cohort study used surveillance data from the Vaccine Safety Datalink at 8 participating integrated health care systems in the United States. There were 10 158 003 participants aged at least 12 years. Data analysis was performed from November 2021 to February 2022. Exposures: Ad.26.COV2.S, BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccine, including mRNA vaccine doses 1 and 2, December 13, 2020, to November 13, 2021. Main Outcomes and Measures: GBS with symptom onset in the 1 to 84 days after vaccination, confirmed by medical record review and adjudication. Descriptive characteristics of confirmed cases, GBS incidence rates during postvaccination risk intervals after each type of vaccine compared with the background rate, rate ratios (RRs) comparing GBS incidence in the 1 to 21 vs 22 to 42 days postvaccination, and RRs directly comparing risk of GBS after Ad.26.COV2.S vs mRNA vaccination, using Poisson regression adjusted for age, sex, race and ethnicity, site, and calendar day. Results: From December 13, 2020, through November 13, 2021, 15 120 073 doses of COVID-19 vaccines were administered to 7 894 989 individuals (mean [SE] age, 46.5 [0.02] years; 8 138 318 doses received [53.8%] by female individuals; 3 671 199 doses received [24.3%] by Hispanic or Latino individuals, 2 215 064 doses received [14.7%] by Asian individuals, 6 266 424 doses received [41.4%] by White individuals), including 483 053 Ad.26.COV2.S doses, 8 806 595 BNT162b2 doses, and 5 830 425 mRNA-1273 doses. Eleven cases of GBS after Ad.26.COV2.S were confirmed. The unadjusted incidence rate of GBS per 100 000 person-years in the 1 to 21 days after Ad.26.COV2.S was 32.4 (95% CI, 14.8-61.5), significantly higher than the background rate, and the adjusted RR in the 1 to 21 vs 22 to 42 days following Ad.26.COV2.S was 6.03 (95% CI, 0.79-147.79). Thirty-six cases of GBS after mRNA vaccines were confirmed. The unadjusted incidence rate per 100 000 person-years in the 1 to 21 days after mRNA vaccines was 1.3 (95% CI, 0.7-2.4) and the adjusted RR in the 1 to 21 vs 22 to 42 days following mRNA vaccines was 0.56 (95% CI, 0.21-1.48). In a head-to-head comparison of Ad.26.COV2.S vs mRNA vaccines, the adjusted RR was 20.56 (95% CI, 6.94-64.66). Conclusions and Relevance: In this cohort study of COVID-19 vaccines, the incidence of GBS was elevated after receiving the Ad.26.COV2.S vaccine. Surveillance is ongoing.

Naloxone Co-Dispensing with Opioids: a Cluster Randomized Pragmatic Trial.

BACKGROUND: Although naloxone prevents opioid overdose deaths, few patients prescribed opioids receive naloxone, limiting its effectiveness in real-world settings. Barriers to naloxone prescribing include concerns that naloxone could increase risk behavior and limited time to provide necessary patient education. OBJECTIVE: To determine whether pharmacy-based naloxone co-dispensing affected opioid risk behavior. Secondary objectives were to assess if co-dispensing increased naloxone acquisition, increased patient knowledge about naloxone administration, and affected opioid dose and other substance use. DESIGN: Cluster randomized pragmatic trial of naloxone co-dispensing. SETTING: Safety-net health system in Denver, Colorado, between 2017 and 2020. PARTICIPANTS: Seven pharmacies were randomized. Pharmacy patients (N=768) receiving opioids were followed using automated data for 10 months. Pharmacy patients were also invited to complete surveys at baseline, 4 months, and 8 months; 325 survey participants were enrolled from November 15, 2017, to January 8, 2019. INTERVENTION: Intervention pharmacies implemented workflows to co-dispense naloxone while usual care pharmacies provided usual services. MAIN MEASURES: Survey instruments assessed opioid risk behavior; hazardous drinking; tobacco, cannabis, and other drug use; and knowledge. Naloxone dispensings and opioid dose were evaluated using pharmacy data among pharmacy patients and survey participants. Intention-to-treat analyses were conducted using generalized linear mixed models accounting for clustering at the pharmacy level. KEY RESULTS: Opioid risk behavior did not differ by trial group (P=0.52; 8-month vs. baseline adjusted risk ratio [ARR] 1.07; 95% CI 0.78, 1.47). Compared with usual care pharmacies, naloxone dispensings were higher in intervention pharmacies (ARR 3.38; 95% CI 2.21, 5.15) and participant knowledge increased (P=0.02; 8-month vs. baseline adjusted mean difference 1.05; 95% CI 0.06, 2.04). There was no difference in other substance use by the trial group. CONCLUSION: Co-dispensing naloxone with opioids effectively increased naloxone receipt and knowledge but did not increase self-reported risk behavior. TRIAL REGISTRATION: Registered at ClinicalTrials.gov ; Identifier: NCT03337100.

Surveillance for Adverse Events After COVID-19 mRNA Vaccination.

Importance: Safety surveillance of vaccines against COVID-19 is critical to ensure safety, maintain trust, and inform policy. Objectives: To monitor 23 serious outcomes weekly, using comprehensive health records on a diverse population. Design, Setting, and Participants: This study represents an interim analysis of safety surveillance data from Vaccine Safety Datalink. The 10 162 227 vaccine-eligible members of 8 participating US health plans were monitored with administrative data updated weekly and supplemented with medical record review for selected outcomes from December 14, 2020, through June 26, 2021. Exposures: Receipt of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccination, with a risk interval of 21 days for individuals after vaccine dose 1 or 2 compared with an interval of 22 to 42 days for similar individuals after vaccine dose 1 or 2. Main Outcomes and Measures: Incidence of serious outcomes, including acute myocardial infarction, Bell palsy, cerebral venous sinus thrombosis, Guillain-Barré syndrome, myocarditis/pericarditis, pulmonary embolism, stroke, and thrombosis with thrombocytopenia syndrome. Incidence of events that occurred among vaccine recipients 1 to 21 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. For a signal, a 1-sided P < .0048 was required to keep type I error below .05 during 2 years of weekly analyses. For 4 additional outcomes, including anaphylaxis, only descriptive analyses were conducted. Results: A total of 11 845 128 doses of mRNA vaccines (57% BNT162b2; 6 175 813 first doses and 5 669 315 second doses) were administered to 6.2 million individuals (mean age, 49 years; 54% female individuals). The incidence of events per 1 000 000 person-years during the risk vs comparison intervals for ischemic stroke was 1612 vs 1781 (RR, 0.97; 95% CI, 0.87-1.08); for appendicitis, 1179 vs 1345 (RR, 0.82; 95% CI, 0.73-0.93); and for acute myocardial infarction, 935 vs 1030 (RR, 1.02; 95% CI, 0.89-1.18). No vaccine-outcome association met the prespecified requirement for a signal. Incidence of confirmed anaphylaxis was 4.8 (95% CI, 3.2-6.9) per million doses of BNT162b2 and 5.1 (95% CI, 3.3-7.6) per million doses of mRNA-1273. Conclusions and Relevance: In interim analyses of surveillance of mRNA COVID-19 vaccines, incidence of selected serious outcomes was not significantly higher 1 to 21 days postvaccination compared with 22 to 42 days postvaccination. While CIs were wide for many outcomes, surveillance is ongoing.

The Association between Opioid Discontinuation and Heroin Use: A Nested Case-Control Study.

BACKGROUND: Opioid prescribing guidelines recommend reducing or discontinuing opioids for chronic pain if harms of opioid treatment outweigh benefits. As opioid discontinuation becomes more prevalent, it is important to understand whether opioid discontinuation is associated with heroin use. In this study, we sought to assess the association between opioid discontinuation and heroin use documented in the medical record. METHODS: A matched nested case-control study was conducted in an integrated health plan and delivery system in Colorado. Patients receiving opioid therapy in the study period (January 2006-June 2018) were included. Opioid discontinuation was defined as ≥45 days with no opioids dispensed after initiating opioid therapy. The heroin use onset date represented the index date. Case patients were matched to up to 20 randomly selected patients without heroin use (control patients) by age, sex, calendar time, and time between initiating opioid therapy and the index date. Conditional logistic regression models estimated matched odds ratios (mOR) for the association between an opioid discontinuation prior to the index date and heroin use. RESULTS: Among 22,962 patients prescribed opioid therapy, 125 patients (0.54%) used heroin after initiating opioid therapy, of which 74 met criteria for inclusion in the analysis. The odds of opioid discontinuation were approximately two times higher in case patients (n = 74) than control patients (n = 1045; mOR = 2.19; 95% CI 1.27-3.78). CONCLUSIONS: Among patients prescribed chronic opioid therapy, the observed increased risk for heroin use associated with opioid discontinuation should be balanced with potential benefits.

Adults With Asthma Experience No Increase in Asthma-related Exacerbations When Digital Communication Technology Tools Are Employed to Offset Provider Workload: A Pragmatic Randomized Trial.

BACKGROUND: Challenges to health care efficiency are increasingly addressed with the help of digital communication technology tools (DCTs). OBJECTIVE: The objective of this study was to test whether DCT, compared with Usual Care, can reduce health care clinician burden without increasing asthma-related exacerbations among patients with asthma in a large integrated health care system. RESEARCH DESIGN: The (Breathewell) program was a pragmatic, randomized trial at (Kaiser Permanente Colorado), where asthma nurses screen patients for poor symptom control when beta2-agonist refill requests came within 60 days of previous fill or in the absence of a controller medication fill within 4 months (beta2-agonist overfill). A total of 14,978 adults with asthma were randomized to Usual Care or 1 of 2 DCT intervention groups (Text/Phone call or Email). SUBJECTS: Participants included adults 18 and older with an asthma diagnosis at the time of randomization and no history of chronic obstructive pulmonary disease. MEASURES: Primary outcome measures included asthma-related health care resource utilization (eg, asthma nurse contacts), medication use, and exacerbations. RESULTS: A total of 1933 patients had 4337 events which met beta2-agonist overfill criteria. Of the 2874 events in the intervention arm, 1188 (41%) were resolved by DCT contact and did not require additional clinician contact. Asthma medication use and exacerbations over 12 months did not differ among the 3 groups. CONCLUSIONS: DCT tools can successfully contact adult asthma patients to screen for symptoms and facilitate intervention. The absence of differences in medication fills and health care utilization indicates that the strategic replacement of nursing interventions by digital outreach did not reduce treatment adherence or compromise health care outcomes.

Order of Live and Inactivated Vaccines and Risk of Non-vaccine-targeted Infections in US Children 11-23 Months of Age.

BACKGROUND: Some findings from observational studies have suggested that recent receipt of live vaccines may be associated with decreased non-vaccine-targeted infection risk and mortality. Our objective was to estimate risk of non-vaccine-targeted infections based on most recent vaccine type (live vaccines only, inactivated vaccines only or both concurrently) received in US children 11-23 months of age. METHODS: We conducted a retrospective cohort study within the Vaccine Safety Datalink. We examined electronic health record and immunization data from children born in 2003-2013 who received 3 diphtheria-tetanus-acellular pertussis vaccines before their first birthday. We modeled vaccine type as a time-varying exposure and estimated risk of non-vaccine-targeted infections identified in emergency department and inpatient settings, adjusting for multiple confounders. RESULTS: Among 428,608 children, 48.9% were female, 4.9% had ≥1 immunization visit with live vaccines only and 10.3% had a non-vaccine-targeted infection. In males, lower risk of non-vaccine-targeted infections was observed following last receipt of live vaccines only or live and inactivated vaccines concurrently as compared with last receipt of inactivated vaccines only [live vaccines-only adjusted hazard ratio (aHR) = 0.83, 95% confidence interval (CI): 0.72-0.94; live and inactivated vaccines concurrently aHR: 0.91, 95% CI: 0.88-0.94]. Among females, last receipt of live and inactivated vaccines concurrently was significantly associated with non-vaccine-targeted infection risk (aHR = 0.94, 95% CI: 0.91-0.97 vs. last receipt of inactivated vaccines only). CONCLUSIONS: We observed modest associations between live vaccine receipt and non-vaccine-targeted infections. In this observational study, multiple factors, including healthcare-seeking behavior, may have influenced results.

A primer on quantitative bias analysis with positive predictive values in research using electronic health data.

OBJECTIVE: In health informatics, there have been concerns with reuse of electronic health data for research, including potential bias from incorrect or incomplete outcome ascertainment. In this tutorial, we provide a concise review of predictive value-based quantitative bias analysis (QBA), which comprises epidemiologic methods that use estimates of data quality accuracy to quantify the bias caused by outcome misclassification. TARGET AUDIENCE: Health informaticians and investigators reusing large, electronic health data sources for research. SCOPE: When electronic health data are reused for research, validation of outcome case definitions is recommended, and positive predictive values (PPVs) are the most commonly reported measure. Typically, case definitions with high PPVs are considered to be appropriate for use in research. However, in some studies, even small amounts of misclassification can cause bias. In this tutorial, we introduce methods for quantifying this bias that use predictive values as inputs. Using epidemiologic principles and examples, we first describe how multiple factors influence misclassification bias, including outcome misclassification levels, outcome prevalence, and whether outcome misclassification levels are the same or different by exposure. We then review 2 predictive value-based QBA methods and why outcome PPVs should be stratified by exposure for bias assessment. Using simulations, we apply and evaluate the methods in hypothetical electronic health record-based immunization schedule safety studies. By providing an overview of predictive value-based QBA, we hope to bridge the disciplines of health informatics and epidemiology to inform how the impact of data quality issues can be quantified in research using electronic health data sources.

Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy.

Importance: Attempts to discontinue opioid therapy to reduce the risk of overdose and adhere to prescribing guidelines may lead patients to be exposed to variability in opioid dosing. Such dose variability may increase the risk of opioid overdose even if therapy discontinuation is associated with a reduction in risk. Objective: To examine the association between opioid dose variability and opioid overdose. Design, Setting, and Participants: A nested case-control study was conducted in a large Colorado integrated health plan and delivery system from January 1, 2006, through June 30, 2018. Cohort members were individuals prescribed long-term opioid therapy. Exposures: Dose variability was defined as the SD of the milligrams of morphine equivalents across each patient's follow-up and categorized based on the quintile distribution of the SD in the cohort (0-5.3, 5.4-9.1, 9.2-14.6, 14.7-27.2, and >27.2 mg of morphine equivalents). Main Outcomes and Measures: Opioid overdose cases were identified using International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Each case patient with overdose was matched to up to 20 control patients using risk set sampling. Conditional logistic regression models were used to generate matched odds ratios and 95% CIs, adjusted for age, sex, race/ethnicity, drug or alcohol use disorder, tobacco use, benzodiazepine dispensings, medical comorbidities, mental health disorder, opioid dose, and opioid formulation. Results: In a cohort of 14 898 patients (mean [SD] age, 56.3 [16.0] years; 8988 [60.3%] female) prescribed long-term opioid therapy, 228 case patients with incident opioid overdose were matched to 3547 control patients. The mean (SD) duration of opioid therapy was 36.7 (33.7) months in case patients and 33.0 (30.9) months in control patients. High-dose variability (SD >27.2 mg of morphine equivalents) was associated with a significantly increased risk of overdose compared with low-dose variability (matched odds ratio, 3.32; 95% CI, 1.63-6.77) independent of opioid dose. Conclusions and Relevance: Variability in opioid dose may be a risk factor for opioid overdose, suggesting that practitioners should seek to minimize dose variability when managing long-term opioid therapy.

Optimizing number and timing of appointment reminders: a randomized trial.

OBJECTIVES: To compare missed appointment rates for patients receiving a single reminder either 3 days prior to a primary care visit, 1 day prior to the visit, or both 3 days and 1 day prior to the visit. STUDY DESIGN: Three-armed randomized controlled trial. METHODS: Text messages or interactive voice response calls were sent to patients with appointments at 25 primary care clinics in an integrated delivery system. A multivariable prediction model was developed to identify patients at high risk of missing appointments, based on prior appointment-keeping history and other variables from electronic health records. RESULTS: Among 54,066 randomized patients, those who received reminders both 3 days and 1 day prior to the visit were less likely to miss their appointment than those who received only a 3-day or 1-day reminder (4.4% vs 5.8% vs 5.3%, respectively; P <.001). In patients at high risk, 20.5% of those who received 2 reminders missed their visit, compared with 25.0% and 24.2% of those with only 3-day or 1-day reminders, respectively (P <.001). Visit satisfaction was unaffected by providing an additional reminder. CONCLUSIONS: Two automated reminders were more effective than 1 in reducing missed appointments and did not reduce visit satisfaction. A predictive model based on clinical characteristics and prior appointment history can accurately identify patients who are at highest risk of missing appointments. These individuals may benefit more from multiple reminders, but additional strategies are necessary to further reduce their rates of missed appointments.

Bias from outcome misclassification in immunization schedule safety research.

PURPOSE: The Institute of Medicine recommended conducting observational studies of childhood immunization schedule safety. Such studies could be biased by outcome misclassification, leading to incorrect inferences. Using simulations, we evaluated (1) outcome positive predictive values (PPVs) as indicators of bias of an exposure-outcome association, and (2) quantitative bias analyses (QBA) for bias correction. METHODS: Simulations were conducted based on proposed or ongoing Vaccine Safety Datalink studies. We simulated 4 studies of 2 exposure groups (children with no vaccines or on alternative schedules) and 2 baseline outcome levels (100 and 1000/100 000 person-years), with 3 relative risk (RR) levels (RR = 0.50, 1.00, and 2.00), across 1000 replications using probabilistic modeling. We quantified bias from non-differential and differential outcome misclassification, based on levels previously measured in database research (sensitivity > 95%; specificity > 99%). We calculated median outcome PPVs, median observed RRs, Type 1 error, and bias-corrected RRs following QBA. RESULTS: We observed PPVs from 34% to 98%. With non-differential misclassification and true RR = 2.00, median bias was toward the null, with severe bias (median observed RR = 1.33) with PPV = 34% and modest bias (median observed RR = 1.83) with PPV = 83%. With differential misclassification, PPVs did not reflect median bias, and there was Type 1 error of 100% with PPV = 90%. QBA was generally effective in correcting misclassification bias. CONCLUSIONS: In immunization schedule studies, outcome misclassification may be non-differential or differential to exposure. Overall outcome PPVs do not reflect the distribution of false positives by exposure and are poor indicators of bias in individual studies. Our results support QBA for immunization schedule safety research.

Predicting the 6-month risk of severe hypoglycemia among adults with diabetes: Development and external validation of a prediction model.

AIMS: To develop and externally validate a prediction model for the 6-month risk of a severe hypoglycemic event among individuals with pharmacologically treated diabetes. METHODS: The development cohort consisted of 31,674 Kaiser Permanente Colorado members with pharmacologically treated diabetes (2007-2015). The validation cohorts consisted of 38,764 Kaiser Permanente Northwest members and 12,035 HealthPartners members. Variables were chosen that would be available in electronic health records. We developed 16-variable and 6-variable models, using a Cox counting model process that allows for the inclusion of multiple 6-month observation periods per person. RESULTS: Across the three cohorts, there were 850,992 6-month observation periods, and 10,448 periods with at least one severe hypoglycemic event. The six-variable model contained age, diabetes type, HgbA1c, eGFR, history of a hypoglycemic event in the prior year, and insulin use. Both prediction models performed well, with good calibration and c-statistics of 0.84 and 0.81 for the 16-variable and 6-variable models, respectively. In the external validation cohorts, the c-statistics were 0.80-0.84. CONCLUSIONS: We developed and validated two prediction models for predicting the 6-month risk of hypoglycemia. The 16-variable model had slightly better performance than the 6-variable model, but in some practice settings, use of the simpler model may be preferred.

Reducing Missed Primary Care Appointments in a Learning Health System: Two Randomized Trials and Validation of a Predictive Model.

BACKGROUND: Collaborations between clinical/operational leaders and researchers are advocated to develop "learning health systems," but few practical examples are reported. OBJECTIVES: To describe collaborative efforts to reduce missed appointments through an interactive voice response and text message (IVR-T) intervention, and to develop and validate a prediction model to identify individuals at high risk of missing appointments. RESEARCH SUBJECTS AND DESIGN: Random assignment of 8804 adults with primary care appointments to a single IVR-T reminder or no reminder at an index clinic (IC) and 7497 at a replication clinic (RC) in an integrated health system in Denver, CO. MEASURES: Proportion of missed appointments; demographic, clinical, and appointment-specific predictors of missed appointments. RESULTS: Patients receiving IVR-T had a lower rate of missed appointments than those receiving no reminder at the IC (6.5% vs. 7.5%, relative risk=0.85, 95% confidence interval, 0.72-1.00) and RC (8.2% vs. 10.5%, relative risk=0.76, 95% confidence interval, 0.65-0.89). A 10-variable prediction model for missed appointments demonstrated excellent discrimination (C-statistic 0.90 at IC, 0.89 at RC) and calibration (P=0.99 for Osius and McCullagh tests). Patients in the 3 lowest-risk quartiles missed 0.4% and 0.4% of appointments at the IC and RC, respectively, whereas patients in the highest-risk quartile missed 24.1% and 28.9% of appointments, respectively. CONCLUSIONS: A single IVR-T call reduced missed appointments, whereas a locally validated prediction model accurately identified patients at high risk of missing appointments. These rigorous studies promoted dissemination of the intervention and prompted additional research questions from operational leaders.

Timely versus delayed early childhood vaccination and seizures.

BACKGROUND: Little is known regarding the timing of childhood vaccination and postvaccination seizures. METHODS: In a cohort of 323 247 US children from the Vaccine Safety Datalink born from 2004 to 2008, we analyzed the association between the timing of childhood vaccination and the first occurrence of seizure with a self-controlled case series analysis of the first doses of individual vaccines received in the first 2 years of life. RESULTS: In infants, there was no association between the timing of infant vaccination and postvaccination seizures. In the second year of life, the incident rate ratio (IRR) for seizures after receipt of the first measles-mumps-rubella vaccine (MMR) dose at 12 to 15 months was 2.65 (95% confidence interval [CI] 1.99-3.55); the IRR after an MMR dose at 16 to 23 months was 6.53 (95% CI 3.15-13.53). The IRR for seizures after receipt of the first measles-mumps-rubella-varicella vaccine (MMRV) dose at 12 to 15 months was 4.95 (95% CI 3.68-6.66); the IRR after an MMRV dose at 16 to 23 months was 9.80 (95% CI 4.35 -22.06). CONCLUSIONS: There is no increased risk of postvaccination seizure in infants regardless of timing of vaccination. In year 2, delaying MMR vaccine past 15 months of age results in a higher risk of seizures. The strength of the association is doubled with MMRV vaccine. These findings suggest that on-time vaccination is as safe with regard to seizures as delayed vaccination in the first year of life, and that delayed vaccination in the second year of life is associated with more postvaccination seizures than on-time vaccination.

Automating assessment of lifestyle counseling in electronic health records.

BACKGROUND: Numerous population-based surveys indicate that overweight and obese patients can benefit from lifestyle counseling during routine clinical care. PURPOSE: To determine if natural language processing (NLP) could be applied to information in the electronic health record (EHR) to automatically assess delivery of weight management-related counseling in clinical healthcare encounters. METHODS: The MediClass system with NLP capabilities was used to identify weight-management counseling in EHRs. Knowledge for the NLP application was derived from the 5As framework for behavior counseling: Ask (evaluate weight and related disease), Advise at-risk patients to lose weight, Assess patients' readiness to change behavior, Assist through discussion of weight-loss methods and programs, and Arrange follow-up efforts including referral. Using samples of EHR data between January 1, 2007, and March 31, 2011, from two health systems, the accuracy of the MediClass processor for identifying these counseling elements was evaluated in postpartum visits of 600 women with gestational diabetes mellitus (GDM) compared to manual chart review as the gold standard. Data were analyzed in 2013. RESULTS: Mean sensitivity and specificity for each of the 5As compared to the gold standard was at or above 85%, with the exception of sensitivity for Assist, which was 40% and 60% for each of the two health systems. The automated method identified many valid Assist cases not identified in the gold standard. CONCLUSIONS: The MediClass processor has performance capability sufficiently similar to human abstractors to permit automated assessment of counseling for weight loss in postpartum encounter records.

Geographic variation in cardiovascular procedure use among Medicare fee-for-service vs Medicare Advantage beneficiaries.

IMPORTANCE: Little is known about how different financial incentives between Medicare Advantage and Medicare fee-for-service (FFS) reimbursement structures influence use of cardiovascular procedures. OBJECTIVE: To compare regional cardiovascular procedure rates between Medicare Advantage and Medicare FFS beneficiaries. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of Medicare beneficiaries older than 65 years between 2003-2007 comparing rates of coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery across 32 hospital referral regions in 12 states. MAIN OUTCOMES AND MEASURES: Rates of coronary angiography, PCI, and CABG surgery. RESULTS: We evaluated a total of 878,339 Medicare Advantage patients and 5,013,650 Medicare FFS patients. Compared with Medicare FFS patients, Medicare Advantage patients had lower age-, sex-, race-, and income-adjusted procedure rates per 1000 person-years for angiography (16.5 [95% CI, 14.8-18.2] vs 25.9 [95% CI, 24.0-27.9]; P < .001) and PCI (6.8 [95% CI, 6.0-7.6] vs 9.8 [95% CI, 9.0-10.6]; P < .001) but similar rates for CABG surgery (3.1 [95% CI, 2.8-3.5] vs 3.4 [95% CI, 3.1-3.7]; P = .33). There were no significant differences between Medicare Advantage and Medicare FFS patients in the rates per 1000 person-years of urgent angiography (3.9 [95% CI, 3.6-4.2] vs 4.3 [95% CI, 4.0-4.6]; P = .24) or PCI (2.4 [95% CI, 2.2-2.7] vs 2.7 [95% CI, 2.5-2.9]; P = .16). Procedure rates varied widely across hospital referral regions among Medicare Advantage and Medicare FFS patients. For angiography, the rates per 1000 person-years ranged from 9.8 to 40.6 for Medicare Advantage beneficiaries and from 15.7 to 44.3 for Medicare FFS beneficiaries. For PCI, the rates ranged from 3.5 to 16.8 for Medicare Advantage and from 4.7 to 16.1 for Medicare FFS. The rates for CABG surgery ranged from 1.5 to 6.1 for Medicare Advantage and from 2.5 to 6.0 for Medicare FFS. Across regions, we found no statistically significant correlation between Medicare Advantage and Medicare FFS beneficiary utilization for angiography (Spearman r = 0.19, P = .29) and modest correlations for PCI (Spearman r = 0.33, P = .06) and CABG surgery (Spearman r = 0.35, P = .05). Among Medicare Advantage beneficiaries, adjustment for additional cardiac risk factors had little influence on procedure rates. CONCLUSIONS AND RELEVANCE: Although Medicare beneficiaries enrolled in capitated Medicare Advantage programs had lower angiography and PCI procedure rates than those enrolled in Medicare FFS, the degree of geographic variation in procedure rates was substantial among Medicare Advantage beneficiaries and was similar in magnitude to that observed among Medicare FFS beneficiaries.

A population-based cohort study of undervaccination in 8 managed care organizations across the United States.

OBJECTIVES To examine patterns and trends of undervaccination in children aged 2 to 24 months and to compare health care utilization rates between undervaccinated and age-appropriately vaccinated children. DESIGN Retrospective matched cohort study. SETTING Eight managed care organizations of the Vaccine Safety Datalink. PARTICIPANTS Children born between 2004 and 2008. MAIN EXPOSURE Immunization records were used to calculate the average number of days undervaccinated. Two matched cohorts were created: 1 with children who were undervaccinated for any reason and 1 with children who were undervaccinated because of parental choice. For both cohorts, undervaccinated children were matched to age-appropriately vaccinated children by birth date, managed care organization, and sex. MAIN OUTCOME MEASURES Rates of undervaccination, specific patterns of undervaccination, and health care utilization rates. RESULTS Of 323 247 children born between 2004 and 2008, 48.7% were undervaccinated for at least 1 day before age 24 months. The prevalence of undervaccination and specific patterns of undervaccination increased over time (P < .001). In a matched cohort analysis, undervaccinated children had lower outpatient visit rates compared with children who were age-appropriately vaccinated (incidence rate ratio [IRR], 0.89; 95% CI, 0.89- 0.90). In contrast, undervaccinated children had increased inpatient admission rates compared with age-appropriately vaccinated children (IRR, 1.21; 95% CI, 1.18-1.23). In a second matched cohort analysis, children who were undervaccinated because of parental choice had lower rates of outpatient visits (IRR, 0.94; 95% CI, 0.93-0.95) and emergency department encounters (IRR, 0.91; 95% CI, 0.88-0.94) than age-appropriately vaccinated children. CONCLUSIONS Undervaccination appears to be an increasing trend. Undervaccinated children appear to have different health care utilization patterns compared with age-appropriately vaccinated children.

Interventional radiologic treatment of hepatocellular carcinoma-a cost analysis from the payer perspective.

PURPOSE: To determine whether there is a cost advantage for one of the three commonly performed interventional radiology (IR) procedures (chemoembolization, selective internal radiation therapy [SIRT], radiofrequency ablation [RFA]) in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A cost analysis from the payer perspective was performed. Primary data were collected from a university hospital, and sensitivity testing was done by comparing coding information obtained at two other tertiary care medical facilities. Medicare allowable reimbursements were used to estimate costs. Decision analytic models using decision tree analysis and Monte Carlo simulations were used to compare alternatives. Simulations were performed comparing all three procedures, followed by a two-way comparison of chemoembolization and SIRT. RESULTS: Simple decision tree analyses showed that RFA was less expensive compared with chemoembolization and SIRT. Monte Carlo simulations showed average reimbursements for each of the three procedures that was largely dependent on the number of repeat procedures required ($9,362 vs $30,107 vs $35,629 for RFA, chemoembolization, and SIRT; P < .001). When comparing only chemoembolization and SIRT, chemoembolization was the lower cost strategy in most scenarios, but SIRT was lower in cost in more than one-third of the simulations. CONCLUSIONS: RFA was the least costly of the three IR strategies in nearly all scenarios studied in these models. Although chemoembolization was less expensive than SIRT in most instances, Monte Carlo simulation showed a preference for SIRT in more than one-third of all scenarios. Sensitivity analyses showed that the most important variables assessed were the need for repeat procedures.

Trivalent inactivated influenza vaccine is not associated with sickle cell crises in children.

BACKGROUND AND OBJECTIVES: Children with sickle cell disease are considered at high risk for complications from influenza infection and are recommended to receive annual influenza vaccination. However, data on the safety of influenza vaccination in children with sickle cell anemia are sparse. METHODS: Using a retrospective cohort of children aged 6 months to 17 years in 8 managed care organizations that comprise the Vaccine Safety Datalink and who had a diagnosis of sickle cell anemia from 1999 to 2006, we conducted matched case-control and self-controlled case series studies to examine the association of trivalent inactivated influenza vaccination with hospitalization for sickle cell crisis in the 2 weeks after vaccination. RESULTS: From an original pool of 1085 pediatric subjects with a diagnosis of sickle cell anemia, we identified 179 children with at least 1 sickle cell crisis during any influenza season (October 1-March 31). In the matched case-control study (matching on age category, gender, Vaccine Safety Datalink site, and season), the odds ratio of hospitalization for a crisis in vaccinated compared with unvaccinated children was not significant: 1.3 (95% confidence interval 0.8-2.2). In the self-controlled case series study of hospitalized cases, the incident rate ratio for hospitalization with sickle cell crisis in the 2 weeks after trivalent inactivated influenza vaccination was also not significant: 1.2 (95% confidence interval 0.75-1.95). CONCLUSION: This large cohort study did not find an association of influenza vaccination and hospitalization for sickle cell crises in children with sickle cell anemia.