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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.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.Cluster randomized pragmatic trial of naloxone co-dispensing.Safety-net health system in Denver, Colorado, between 2017 and 2020.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 pharmacies implemented workflows to co-dispense naloxone while usual care pharmacies provided usual services.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.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.Co-dispensing naloxone with opioids effectively increased naloxone receipt and knowledge but did not increase self-reported risk behavior.Registered at ClinicalTrials.gov ; Identifier: NCT03337100.

ImportanceUncertainty remains about the longer-term benefits and harms of different opioid management strategies, such as tapering and dose escalation. For instance, opioid tapering could help patients reduce opioid exposure to prevent opioid use disorder, but patients may also seek care elsewhere and engage in nonprescribed opioid use.ObjectiveTo evaluate the association between opioid dose trajectories observed in practice and patient outcomes.Design, Setting, and ParticipantsThis retrospective cohort study was conducted in 3 health systems in Colorado and Wisconsin. The study population included patients receiving long-term opioid therapy between 50 and 200 morphine milligram equivalents between August 1, 2014, and July 31, 2017. Follow-up ended on December 31, 2019. Data were analyzed from January 2020 to August 2022.ExposuresGroup-based trajectory modeling identified 5 dosing trajectories over 1 year: 1 decreasing, 1 high-dose increasing, and 3 stable.Main Outcomes and MeasuresPrimary outcomes assessed after the trajectory period were 1-year all-cause mortality, incident opioid use disorder, continued opioid therapy at 1 year, and health plan disenrollment. Associations were tested using Cox proportional hazards regression and log-binomial models, adjusting for baseline covariates.ResultsA total of 3913 patients (mean [SD] age, 59.2 [14.4] years; 2767 White non-Hispanic [70.7%]; 2237 female patients [57.2%]) were included in the study. Compared with stable trajectories, the decreasing dose trajectory was negatively associated with opioid use disorder (adjusted hazard ratio [aHR], 0.40; 95% CI, 0.29-0.55) and continued opioid therapy (site 1: adjusted relative risk [aRR], 0.39; 95% CI, 0.34-0.44), but was positively associated with health plan disenrollment (aHR, 1.66; 95% CI, 1.24-2.22). The decreasing trajectory was not associated with mortality (aHR, 1.28; 95% CI, 0.87-1.86). In contrast, the high-dose increasing trajectory was positively associated with mortality (aHR, 2.19; 95% CI, 1.44-3.32) and opioid use disorder (aHR, 1.81; 95% CI, 1.39-2.37) but was not associated with disenrollment (aHR, 0.90; 95% CI, 0.56-1.42) or continued opioid therapy (site 1: aRR, 0.98; 95% CI, 0.94-1.03).Conclusions and RelevanceIn this cohort study, decreasing opioid dose was associated with reduced risk of opioid use disorder and continued opioid therapy but increased risk of disenrollment compared with stable dosing, whereas the high-dose increasing trajectory was associated with an increased risk of mortality and opioid use disorder. These findings can inform opioid management decision-making.

Introduction Tetanus, diphtheria, and acellular pertussis (Tdap) and influenza vaccines are recommended for pregnant women in each pregnancy, yet uptake is suboptimal. This study tested the efficacy of an online vaccine resource in increasing uptake of Tdap and influenza vaccines among pregnant women. Study design RCT. Setting/participants This study was conducted among women in the third trimester of pregnancy in an integrated healthcare system in Colorado in September 2013–July 2016, with data analysis in 2017–2018. Intervention Women were randomly assigned to 1 of 3 arms: website with vaccine information and interactive social media components, website with vaccine information only, or usual care. Participants in the website with vaccine information and interactive social media components and website with vaccine information only arms had access to the same base vaccine content. The website with vaccine information and interactive social media components also included a blog, discussion forum, and “Ask a Question” portal. Main outcome measures Tdap and influenza vaccination. These outcomes were analyzed separately. Results For influenza (n=289), women in both the website with vaccine information and interactive social media components (OR=2.19, 95% CI=1.06, 4.53) and website with vaccine information only (OR=2.20, 95% CI=1.03, 4.69) arms had higher vaccine uptake than the usual care arm. The proportions of women receiving the influenza vaccine were 57%, 55%, and 36% in the website with vaccine information and interactive social media components, website with vaccine information only, and usual care arms, respectively. For Tdap (n=173), there were no significant differences in vaccine uptake between study arms. The proportions of women receiving Tdap were 71%, 69%, and 68% in the website with vaccine information and interactive social media components, website with vaccine information only, and usual care arms, respectively. Conclusions Web-based vaccination information sent to pregnant women can positively influence maternal influenza vaccine uptake. Because of potential scalability, the impact of robust vaccination information websites should be studied in other settings. Trial registration This study is registered at www.clinicaltrials.gov NCT01873040.

Objective Evidence-based strategies to address vaccine hesitancy are lacking. Personal values are a measurable psychological construct that could be used to deliver personalized messages to influence vaccine hesitancy and behavior. Our objectives were to develop a valid, reliable self-report survey instrument to measure vaccine values based on the Schwartz theory of basic human values, and to test the hypothesis that vaccine values are distinct from vaccine attitudes and are related to vaccine hesitancy and behavior. Methods Parental Vaccine Values (PVV) scale items were generated using formative qualitative research and expert input, yielding 24 items for testing. 295 parents of children aged 14–30 months completed a self-report survey with measures of Schwartz’s global values, the PVV, vaccine attitudes, and vaccine hesitancy. Factor analysis was used to determine vaccine values factor structure. Associations between vaccine values, vaccine attitudes, vaccine hesitancy, and vaccination behavior were assessed using linear and logistic regression models. Late vaccination was assessed from electronic medical records. Results A six-factor structure for vaccine values was determined with good fit (RMSEA = 0.07, Bentler’s CFI = 0.91) with subscales for Conformity, Universalism, Tradition, Self-Direction, Security- Disease Prevention, and Security- Vaccine Risk. Vaccine values were moderately associated with Schwartz global values and vaccine attitudes, indicating discriminant validity from these constructs. Multivariable linear regression showed vaccine hesitancy was associated with vaccine values Conformity (partial R2 = 0.10) and Universalism (0.04) and vaccine attitudes Vaccine Safety (0.52) and Vaccine Benefit (0.16). Multivariable logistic regression showed that late vaccination was associated with vaccine value Self-direction (OR = 1.80, 95% CI: 1.26–2.65) and vaccine attitude of Vaccine Benefit (OR = 0.44, 95% CI: 0.32–0.60). Conclusions The PVV scale had good psychometric properties and appears related to but distinct from Schwartz global values and vaccine attitudes. Vaccine values are associated with vaccine hesitancy and late vaccination and may be useful in tailoring future interventions.

The internet is an important source of vaccine information for parents. We evaluated and compared the interactive content on an expert moderated vaccine social media (VSM) website developed for parents of children 24 months of age or younger and enrolled in a health care system to a random sample of interactions extracted from publicly available parenting and vaccine-focused blogs and discussion forums. The study observation period was September 2013 through July 2016. Three hundred sixty-seven eligible websites were located using search terms related to vaccines. Seventy-nine samples of interactions about vaccines on public blogs and discussion boards and 61 interactions from the expert moderated VSM website were coded for tone, vaccine stance, and accuracy of information. If information was inaccurate, it was coded as corrected, partially corrected or uncorrected. Using chi-square or Fisher’s exact tests, we compared coded interactions from the VSM website with coded interactions from the sample of publicly available websites. We then identified representative quotes to illustrate the quantitative results. Tone, vaccine stance, and accuracy of information were significantly different (all p < .05). Publicly available vaccine websites tended to be more contentious and have a negative stance toward vaccines. These websites also had inaccurate and uncorrected information. In contrast, the expert moderated website had a more civil tone, minimal posting of inaccurate information, with very little participant-to-participant interaction. An expert moderated, interactive vaccine website appears to provide a platform for parents to gather accurate vaccine information, express their vaccine concerns and ask questions of vaccine experts.

Background As the rates of vaccination decline in children with logistical barriers to vaccination, new strategies to increase vaccination are needed. The goal of this study was to develop and evaluate the effectiveness of the Vaccines For Babies (VFB) intervention, an automated reminder system with online resources to address logistical barriers to vaccination in caregivers of children enrolled in an integrated healthcare system. Effectiveness was evaluated in a randomized controlled trial. Methods Qualitative interviews were conducted with parents of children less than two years old to identify logistical barriers to vaccination that were used to develop the VFB intervention. VFB included automated reminders to schedule the 6- and 12-month vaccine visit linking caregivers to resources to address logistic barriers, sent to the preferred mode of outreach (text, email, and/or phone). Parents of children between 3 and 10 months of age with indicators of logistical barriers to vaccination were randomized to receive VFB or usual well child care (UC). The primary outcome was percentage of days undervaccinated at 2 years of life. A difference in differences analysis was conducted. Results Qualitative interviews with 6 parents of children less than 2 years of age identified transportation, scheduling challenges, and knowledge of vaccine timing as logistical barriers to vaccination. We enrolled 250 participants in the trial, 45% were loss to follow-up. There were no significant differences in vaccination uptake between those enrolled in UC or the VFB intervention (0.51%, p = 0.86). In Medicaid enrolled participants, there was a modest decrease in percentage of days undervaccinated in the VFB intervention compared to UC (6.3%, p = 0.07). Conclusion Automated Reminders and with links to heath system resources was not shown to increase infant vaccination uptake demonstrating additional resources are needed to address the needs of caregivers experiencing logistical barriers to vaccination.

INTRODUCTION: Monitoring the trends in undervaccination, including that because of parental vaccine refusal or delay, can inform public health responses directed at improving vaccine confidence and vaccination coverage. METHODS: A retrospective cohort study was conducted in the Vaccine Safety Datalink. The cohort included all children born in 2004–2017 with ≥3 well-child visits between ages 2 and 23 months. Using electronic health record–based vaccination data, the average days undervaccinated was calculated for each child. Undervaccination patterns were assessed through age 23 months. Temporal trends were inspected for inflection points and were analyzed using linear regression. Nested within the cohort study, a survey was conducted to compare parent reports of vaccine refusal or delay with observed vaccination patterns. Data were analyzed in 2020. RESULTS: The study cohort consisted of 808,170 children. The percentage of children with average days undervaccinated=0 (fully vaccinated, no delays) rose from a nadir of 47.1% for the birth year 2008 to 68.4% for the birth year 2017 (p(trend)

BACKGROUND: To increase vaccine acceptance, we created a Web-based the “Vaccines and Your Baby” intervention (VAYB) that provided new parents with vaccine information messages tailored to vaccine beliefs and values. We evaluated the effectiveness of the VAYB by comparing timely uptake of infant vaccines to an untailored version of the intervention (UT) or usual care intervention (UC) only. METHODS: Between April 2016 and June 2019, we conducted a randomized clinical trial. Pregnant women and new parents were randomly assigned to the VAYB, UT, or UC arms. In the VAYB and UT arms, participants were exposed to interventions at 4 time points from pregnancy until their child was 15 months of age. The primary outcome was up-to-date status for recommended vaccines from birth to 200 days of age. A modified intent-to-treat analysis was conducted. Data were analyzed with logistic regression to generate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We enrolled 824 participants (276 VAYB, 274 UT, 274 UC), 143 (17.4%) of whom were lost to follow-up. The up-to-date rates in the VAYB, UT, and UC arms were 91.44%, 92.86%, and 92.31%, respectively. Infants in the VAYB arm were not more likely to be up to date than infants in the UC arm (OR = 0.89; 95% CI, 0.45–1.76) or in the UT arm (OR = 0.82; 95% CI, 0.42–1.63). The odds of being up to date did not differ between UT and UC arms (OR = 1.08; 95% CI, 0.54–2.18). CONCLUSIONS: Delivering Web-based vaccine messages tailored to parents’ vaccine attitudes and values did not positively impact the timely uptake of infant vaccines.

Coronavirus disease (COVID-19) has spread around the world causing tremendous stress to the US health care system. Knowing the trend of the COVID-19 pandemic is critical for the federal and local governments and health care system to prepare plans. Our aim was to develop an approach and create a SAS macro to estimate the growth rate and doubling time in days if growth rate is positive or half time in days if growth rate is negative. We fit a series of growth curves using a rolling approach. This approach was applied to the hospitalization data of Colorado State during March 13th and April 13th. The growth rate was 0.18 (95% CI=(0.11, 0.24)) and the doubling time was 5 days (95% CI= (4, 7)) for the period of March 13th-March 19th; the growth rate reached to the minimum −0.19 (95% CI= (−0.29, −0.10)) and the half time was 4 days (95% CI= (2, 6)) for the period of April 2nd – April 8th. This approach can be used for regional short-term prediction and monitoring the regional trend of the COVID-19 pandemic.

Importance Family members are cited as a common source of prescription opioids used for nonmedical reasons. However, the overdose risk associated with exposure to opioids prescribed to family members among adolescents and young adults is not well established. Objective To assess the association of opioids prescribed to family members with pharmaceutical opioid overdose among youth. Design, Setting, and Participants This cohort study included 45 145 family units with a total of 72 040 adolescents and young adults aged 11 to 26 years enrolled in a Kaiser Permanente Colorado health plan in 2006 and observed through June 2018. Exposures Opioid prescriptions and dosage dispensed to family members and youth in the past month. Main Outcomes and Measures Fatal pharmaceutical opioid overdoses identified in vital records and nonfatal pharmaceutical opioid overdoses identified in emergency department and inpatient settings. Time to first overdose was modeled using Cox regression. Results The study population consisted of 72 040 adolescents and young adults (mean [SD] age across follow-up, 19.3 [3.7] years; 36 646 [50.9%] girls and women) nested in 45 145 family units. Youth were more commonly exposed to prescription opioids dispensed to a family member than through their own prescriptions. During follow-up, 26 284 youth (36.5%) filled at least 1 opioid prescription, and 47 461 youth (65.9%) had at least 1 family member with a prescription. Exposure to family members with opioid prescriptions in the past month was associated with increased risk of pharmaceutical opioid overdose (adjusted hazard ratio [aHR], 2.17; 95% CI, 1.24-3.79) independent of opioids prescribed to youth (aHR, 6.62; 95% CI, 3.39-12.91). Concurrent exposure to opioid prescriptions from youth and family members was associated with substantially increased overdose risk (aHR, 12.99; 95% CI, 5.08-33.25). High dosage of total morphine milligram equivalents (MME) prescribed to family members in the past month was associated with youth overdose (0 MME vs >0 to Conclusions and Relevance In this study of youth linked to family members, exposure to family members’ prescribed opioids was associated with increased risk of pharmaceutical opioid overdose, independent of opioids prescribed to youth. Further interventions targeting youth and families are needed, including counseling patients about the risks of opioids to youth in their families.

BackgroundVaccine hesitancy among parents leads to childhood undervaccination and outbreaks of vaccine-preventable disease. As the reasons for vaccine hesitancy are diverse, there is often not enough time during regular clinical visits for medical providers to adequately address all the concerns that parents have. Providing individually tailored vaccine information via the internet before a clinical visit may be a good mechanism for effectively allaying parents’ vaccination concerns while also being time efficient. Including tailoring based on values is a promising, but untested, approach to message creation.ObjectiveThis study aimed to describe the process by which we developed a Web-based intervention that is being used in an ongoing randomized controlled trial aimed at improving the timeliness of infant vaccination by reducing parental vaccine hesitancy.MethodsDevelopment of the intervention incorporated evidence-based health behavior theories. A series of interviews, surveys, and feedback sessions were used to iteratively develop the intervention in collaboration with vaccination experts and potential end users.ResultsIn all, 41 specific content areas were identified to be included in the intervention. User feedback elucidated preferences for specific design elements to be incorporated throughout the website. The tile-based architecture chosen for the website was perceived as easy to use. Creating messages that were two-sided was generally preferred over other message formats. Quantitative surveys identified associations between specific vaccine values and vaccination beliefs, suggesting that values tailoring should vary, depending on the specific belief being endorsed.ConclusionsUsing health behavior theories, qualitative and quantitative data, and significant expert and end user input, we created a novel, Web-based intervention to improve infant vaccination timeliness. The intervention is based on tailoring messages according to each individual’s values and beliefs. This intervention is currently being tested in a controlled randomized clinical trial.

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.

Objective To develop and evaluate a novel Opioid Safety Clinic (OSC) initiative to enhance adherence to guidelines on the assessment and monitoring of patients prescribed chronic opioid therapy (COT). Patients and Methods The OSC was developed at an urban Federally Qualified Health Center to provide guideline-concordant care for COT, standardize workflows, and efficiently use clinic staff. We evaluated the OSC using a matched cohort study. Five hundred thirty-nine patients participated in the clinic between July 1, 2014, and March 31, 2016. Of these, 472 clinic participants were matched to 472 nonparticipants by sex and age on the date of the OSC visit. The OSC was evaluated by its completion rates of standardized pain assessments, urine toxicology, and naloxone dispensings. We conducted logistic regression comparing OSC participants to OSC nonparticipants. Results A total of 539 patients attended an OSC visit, representing approximately 53% of patients in the chronic opioid registry. The OSC participants were more likely than nonparticipants to have completed a pain assessment (adjusted odds ratio [aOR], 169.8; 95% CI, 98.3-293.5), completed a urine toxicology (aOR, 46.1; 95% CI, 30.4-69.9), or had naloxone dispensed (aOR, 2.8; 95% CI, 1.9-4.3) over 12 months of follow-up. Conclusion The OSC model improved adherence to guideline-concordant COT in primary care. Future research is needed to assess the impact of these interventions on pain, quality of life, and adverse events from opioid analgesics.

Introduction Successful strategies are needed to address parental vaccine hesitancy, a significant public health issue. The study objective was to assess whether an Internet-based platform with vaccine information and interactive social media components improved parents’ vaccine-related attitudes. Study design A three-arm RCT. Setting/participants The study was conducted in a large Colorado integrated healthcare organization. Parents were enrolled during September 2013 through October 2015 and followed through November 2016; data were analyzed in 2017. Parents, recruited during pregnancy, were given a survey about vaccine-related attitudes at enrollment (i.e., baseline) and when their child was aged 3–5 months and 12–15 months (Timepoints 1 and 2, respectively). Parental vaccine hesitancy was assessed at baseline. Intervention Study participants were randomized to the following: a study website with vaccine information and social media components (VSM arm); a website with vaccine information only (VI); or usual care. Main outcome measures Change in parental vaccine attitudes over time by baseline degree of vaccine hesitancy. Results Among 1,093 study participants, 945 (86.5%) completed all three surveys. Comparing baseline with Timepoint 1 among vaccine-hesitant parents, the VSM and VI arms were associated with significant improvements in attitudes regarding vaccination benefits compared to usual care (VSM mean change 0.23 on a 5-point scale, 95% CI=0.05, 0.40, VI mean change 0.22, 95% CI=0.04, 0.40). Comparing baseline with Timepoint 2 among hesitant parents, the VSM and VI arms were also associated with significant reductions in parental concerns about vaccination risks compared to usual care (VSM mean change –0.37, 95% CI= –0.60, –0.14, VI mean change –0.31, 95% CI= –0.55, –0.07). Self-efficacy around vaccine decision making also improved among vaccine-hesitant parents. No intervention effect was observed among parents not vaccine-hesitant at baseline. Conclusions Among vaccine-hesitant parents, an Internet-based intervention improved parents’ attitudes about vaccines. Trial registration This study was registered at www.clinicaltrials.gov NCT01873040.

Naloxone is a life-saving opioid antagonist. Chronic pain guidelines recommend that physicians co-prescribe naloxone to patients at high risk for opioid overdose. However, clinical tools to efficiently identify patients who could benefit from naloxone are lacking. To develop and validate an overdose predictive model which could be used in primary care settings to assess the need for naloxone. Retrospective cohort. Derivation site was an integrated health system in Colorado; validation site was a safety-net health system in Colorado. We developed a predictive model in a cohort of 42,828 patients taking chronic opioid therapy and externally validated the model in 10,708 patients. Potential predictors and outcomes (nonfatal pharmaceutical and heroin overdoses) were extracted from electronic health records. Fatal overdose outcomes were identified from state vital records. To match the approximate shelf-life of naloxone, we used Cox proportional hazards regression to model the 2-year risk of overdose. Calibration and discrimination were assessed. A five-variable predictive model showed good calibration and discrimination (bootstrap-corrected c-statistic = 0.73, 95% confidence interval [CI] 0.69–0.78) in the derivation site, with sensitivity of 66.1% and specificity of 66.6%. In the validation site, the model showed good discrimination (c-statistic = 0.75, 95% CI 0.70–0.80) and less than ideal calibration, with sensitivity and specificity of 82.2% and 49.5%, respectively. Among patients on chronic opioid therapy, the predictive model identified 66–82% of all subsequent opioid overdoses. This model is an efficient screening tool to identify patients who could benefit from naloxone to prevent overdose deaths. Population differences across the two sites limited calibration in the validation site.

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 usingInternational Classification of Diseases, Ninth RevisionandInternational 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.

Background: Increasing epidemiologic and intervention research is being conducted on opioid overdose, a serious and potentially fatal outcome. However, there is little consensus on how to verify opioid overdose outcomes for research purposes. To ensure reproducibility, minimize misclassification, and permit data harmonization across studies, standardized and consistent overdose definitions are needed. The aims were to develop a case criteria classification scheme based on information commonly available in medical records and to compare it with reviewing physician clinical impression and simple encounter documentation. Methods: In 2 large health systems, we developed a case criteria classification scheme for opioid overdose based on prior literature, expert opinion, and pilot testing with sample medical records. We then identified emergency department and hospital encounters ( n = 259) with at least 1 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code representing a broad range of opioid and non-opioid related poisonings. Physicians conducted structured medical record reviews to identify the proposed case criteria and generate a clinical impression, and trained abstractors verified documentation. We then compared the case criteria classification scheme with clinical impression and encounter documentation. Results: We developed a quantitative opioid overdose case criteria classification scheme that included 3 sets of major criteria and 9 minor criteria (supporting documentation). For the encounters identified using poisoning codes, the proportion verified as opioid overdoses using the case criteria classification scheme, clinical impression, and encounter documentation ranged from 50.4% to 52.7% at one site and 55.5% to 67.2% at the second site. Discrepancies across approaches and sites related to differences in available records and documentation of clinical signs of overdose. Conclusions: We propose a novel case criteria classification scheme for opioid overdose that could be used to rigorously and consistently define overdose across multiple research settings. However, prior to widespread use, further refinement and validation are needed.

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.

Race is often included as an independent variable in health services research, especially in recent studies of racial and ethnic disparities in health care. Although self-reported information on race exists in large electronic health records (EHR) data, these data are sometimes missing. Recently Bayesian Improved Surname Geocoding method (BISG) is used to estimate the probability distribution of race categories for those with missing information on race. The BISG estimated probability distribution has been used in reporting health care measures but not in statistical modellings with dichotomous events as outcomes. We propose two approaches to accommodate available distribution probability of an independent categorical variable (e.g., race) in logistic regression models: 1) a direct substitution approach and 2) a partial information maximum likelihood estimator (PIMLE). In examining the association between race and up-to-date immunization status of children by three years old from an integrated health care organization, 11.3% of 14,903 children have missing self-reported race information but have BISG estimated probability distribution for the six race/ethnicity categories. We employed the direct substitution approach and PIMLE approach to analyze the under vaccination data. Both approaches included all observations and thus yielded smaller standard errors of estimated coefficients compared to the complete data analyses. Our simulation study showed that the direct substitution approach and PIMLE yielded nearly unbiased coefficient estimates and preserved efficiency when the missing rate of the independent categorical variable was up to 30%.

BACKGROUND: Interventions to address vaccine hesitancy and increase vaccine acceptance are needed. This study sought to determine if a Web-based, social media intervention increases early childhood immunization. METHODS: A 3-arm, randomized controlled trial was conducted in Colorado from September 2013 to July 2016. Participants were pregnant women, randomly assigned (3:2:1) to a Web site with vaccine information and interactive social media components (VSM), a Web site with vaccine information (VI), or usual care (UC). Vaccination was assessed in infants of participants from birth to age 200 days. The primary outcome was days undervaccinated, measured as a continuous and dichotomous variable. RESULTS: Infants of 888 participants were managed for 200 days. By using a nonparametric rank-based analysis, mean ranks for days undervaccinated were significantly lower in the VSM arm versus UC (P = .02) but not statistically different between the VI and UC (P = .08) or between VSM and VI arms (P = .63). The proportions of infants up-to-date at age 200 days were 92.5, 91.3, and 86.6 in the VSM, VI, and UC arms, respectively. Infants in the VSM arm were more likely to be up-to-date than infants in the UC arm (odds ratio [OR] = 1.92; 95% confidence interval [CI], 1.07–3.47). Up-to-date status was not statistically different between VI and UC arms (OR = 1.62; 95% CI, 0.87–3.00) or between the VSM and VI arms (OR = 1.19, 95% CI, 0.70–2.03). CONCLUSIONS: Providing Web-based vaccine information with social media applications during pregnancy can positively influence parental vaccine behaviors.

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.

Background In 2008, a diphtheria, tetanus, acellular pertussis, and inactivated poliovirus combined vaccine (DTaP–IPV) was licensed for use in children 4 through 6 years of age. While pre-licensure studies did not demonstrate significant safety concerns, the number vaccinated in these studies was not sufficient to examine the risk of uncommon but serious adverse events. Objective To assess the risk of serious adverse events following DTaP–IPV vaccination. Methods The study was conducted from January 2009 through September 2012 in the Vaccine Safety Datalink (VSD) project. In the VSD, electronic vaccination and encounter data are updated and aggregated weekly as part of ongoing surveillance activities. Based on previous reports and biologic plausibility, eight potential adverse events were monitored: meningitis/encephalitis; seizures; stroke; Guillain–Barre syndrome; Stevens–Johnson syndrome; anaphylaxis; serious allergic reactions other than anaphylaxis; and serious local reactions. Adverse event rates in DTaP–IPV recipients were compared to historical incidence rates in the VSD population prior to 2009. Sequential probability ratio testing was used to analyze the data on a weekly basis. Results During the study period, 201,116 children received DTaP–IPV vaccine. Ninety-seven percent of DTaP–IPV recipients also received other vaccines on the same day, typically measles–mumps–rubella and varicella vaccines. There was no statistically significant increased risk of any of the eight pre-specified adverse events among DTaP–IPV recipients when compared to historical incidence rates. Conclusions In this safety surveillance study of more than 200,000 DTaP–IPV vaccine recipients, there was no evidence of increased risk for any of the pre-specified adverse events monitored. Continued surveillance of DTaP–IPV vaccine safety may be warranted to monitor for rare adverse events, such as Guillain–Barre syndrome.

This study examines incident treatment patterns for attention-deficit/hyperactivity disorder (ADHD) in children seen in eight integrated healthcare delivery systems and identifies factors associated with adherence to Healthcare Effectiveness Data and Information Set (HEDIS) quality measures developed by the National Committee for Quality Assurance (NCQA).A retrospective cohort analysis using electronic healthcare data from children aged 3 through 17 years with newly diagnosed ADHD between January 1, 2009 and December 31, 2010 was conducted. NCQA quality definitions for initiation and for continuation and maintenance (CM) of ADHD medications were expanded to include preschoolers and adolescents. Poisson regression models with robust error variance were used to evaluate the association between NCQA HEDIS adherence measures, provider type, patient characteristics and care process measures.Of 6864 children aged 3-17 years old qualifying for incident treatment analyses, 5538 (80.7%) were started on ADHD medication within a year of diagnosis. Adherence to NCQA HEDIS measures was 49.8% for initiation and 45.8% for CM, with adherence rates higher for mental health than non-mental health providers, school-aged children than adolescents, and for patients concurrently on other psychotropic medications than those who were not. Of those started on ADHD medication, 62.3% were not eligible for CM analyses according to HEDIS guidelines, because they did not receive continuous (210 of 300 days) ADHD medication treatment, with adolescents less likely than school-aged children to persist with medications.Study limitations must be considered, including reliance on electronic medical record data, absence of patient race and sociodemographic data, and limited generalizability to other care contexts. Nevertheless, findings suggest novel strategies are needed to improve the quality of ADHD care processes for children of all ages, because even within integrated delivery systems less than half of children with ADHD received care consistent with NCQA HEDIS standards for initiation and CM care. RESULTS suggest the need to refine quality measures by including follow-up care in those children not receiving or discontinuing medication treatment, a considerable quality concern not currently captured in NCQA HEDIS standards.

IntroductionIncreasing numbers of children are failing to receive many recommended vaccines, which has led to significant outbreaks of vaccine-preventable diseases in the USA and worldwide. A major driver of undervaccination is parental vaccine hesitance. Prior research demonstrates that mothers are the primary decision maker for infant vaccination, and that their vaccination attitudes form primarily during pregnancy and early in their infant’s life.Methods and analysisThis manuscript describes the protocol for an ongoing three-armed randomised controlled trial done at Kaiser Permanente Colorado (KPCO). The trial aims to test the efficacy of provided tailored, individualised information via the Internet to pregnant and new mothers versus untailored information versus usual care on the timeliness of infant vaccination. The primary outcome to be assessed is vaccination status, which is a dichotomous outcome (up to date vs not) assessed at age 200 days, reflecting the time when infants should have completed the first set of vaccine provided (at age 2, 4 and 6 months). Infants with one or more age-appropriate recommended vaccines at least 30 days delayed are categorised as not up to date whereas all other infants are considered up to date. Secondary outcomes include vaccination status at age 489 days, reflecting receipt of recommended vaccines at age 12–15 months, as well as vaccination attitudes, hesitancy and intention. Vaccination data will be derived from the electronic medical record and the state immunisation registry. Other secondary outcomes will be assessed by online surveys.Ethics and disseminationThe study activities were approved by the Institutional Review Boards of the University of Colorado, KPCO and the University of Michigan. Results will be disseminated through peer-reviewed manuscripts and conference presentations.Trial registration numberNCT02665013; Pre-results.

To describe parental vaccine decision making behaviors and characterize trust in physician advice among parents with varying childhood vaccination behaviors.Between 2008 and 2011, a mixed methods study was conducted with parents of children aged4 years who were members of Kaiser Permanente Colorado health plan. Seven focus groups were conducted with vaccine-hesitant parents. On the basis of findings from the focus groups, a survey was developed, pilot tested, and mailed to a stratified sample of 854 parents who accepted (n = 500), delayed (n = 227), or refused (n = 127) vaccinations for one of their children. Survey results were analyzed by chi-square tests and multivariable logistic regression.Several themes emerged from the focus groups, including: 1) the vaccine decision-making process begins prenatally, 2) vaccine decision making is an evolving process, and 3) there is overall trust in the pediatrician but a lack of trust in the information they provided about vaccines. The survey response rate was 52% (n = 443). Parents who refused or delayed vaccines were 2 times more likely to report that they began thinking about vaccines before their child was born and 8 times more likely to report that they constantly reevaluate their vaccine decisions than parents who accepted all vaccines. Although parents tended to report trusting their pediatrician's advice on nutrition, behavior, and the physical examination, they did not believe their pediatrician provided "balanced" information on both the benefits and risks of vaccination.These results have implications for future interventions to address parental vaccination concerns. Such interventions may be more effective if they are applied early (during pregnancy) and often (pregnancy through infancy), and cover both the risks and benefits of vaccination.

Preinfluenza periods have been used to test for uncontrolled confounding in studies of influenza vaccine effectiveness, but some authors have claimed that confounding differs in preinfluenza and influenza periods. We tested this claim by comparing estimates of the vaccine-mortality association during the 2009/2010 influenza year, when there was essentially no circulation of seasonal influenza in the United States, and 2007/2008, a typical influenza year. We pooled data on seniors (adults aged ≥65 years) from 7 US managed care organizations that participated in the Vaccine Safety Datalink Project. We defined influenza vaccination, all-cause mortality, and potential confounders from administrative databases. We quantified the vaccine-mortality association using Cox regression. During 2007/2008, the adjusted hazard ratio was 0.44 prior to influenza season, 0.62 during influenza season, and 0.71 after influenza season. A similar pattern was observed during 2009/2010, when any effect of seasonal influenza vaccine observed during all time periods must have resulted from confounding: 0.65 during the autumn, 0.80 during the winter, and 0.84 during the summer. In a year with minimal seasonal influenza, we found no evidence that confounding in autumn preinfluenza periods is qualitatively different from confounding in winter. This supports the use of preinfluenza periods as control time periods in studies of influenza vaccine effectiveness.

Kaiser Permanente Colorado has been responding to the financial challenges of its members by providing a medical financial assistance (MFA) program since 1992. However, there have been no evaluations of the effect of this program on members' use of health services or their health outcomes.A prospective cohort study of 308 MFA program members who were enrolled between May 16, 2008, and May 16, 2009, examined changes in their use of health services, costs, and self-reported physical and mental health after enrollment in the MFA program. Use of services was analyzed with multiple regression, and costs of services with generalized linear models.MFA increased members' access to health services. There were no changes in physical or mental health status. For each health care visit before the MFA award, patients used the health care system 0.23 visits less. The MFA amount was not associated with an increase or decrease in use. There was no significant difference in total overall cost. Hospital costs were lower, but costs for clinic visits, pharmacy services, phone calls, and radiology services were significantly higher, resulting in service cost neutrality, possibly because financial barriers before MFA award led to accumulated demand for services.Use of services decreased after MFA was received. There was no significant change in total service cost. MFA improved members' ability to pay for medical services and increased their satisfaction with health services.

BACKGROUND: In 2013 the Institute of Medicine suggested that the Vaccine Safety DataLink (VSD) should broaden its population by including data of more patients from low income and racially and ethnically diverse backgrounds. In response, Kaiser Permanente Colorado (KPCO) partnered with Denver Health (DH), an integrated safety net health care system, to explore the integration of DH data. METHODS: We compared three different methods (reference date of September 1, 2013): “Empanelment” (any patient who has had a primary care visit in the past 18 months), “Proxy-enrollment” (two health care visits in 3 years separated by 90 days), and “Enrollment” in a managed care plan. For each of these methods, we compared cohort size, vaccination rates, socio-demographic characteristics, and health care utilization. RESULTS: The empaneled population at DH provided the best comparison to KPCO. DH’s empaneled population was 111,330 (57,173 adults; 54,157 children), while KPCO had 436,290 empaneled patients (336,462 adults; 99,828 children). Vaccination rates in both health care systems for empaneled patients were comparable. Two year-old up-to-date coverage rates were 83.2% (KPCO) and 86.9% (DH); rates for adolescent Tdap and MCV4 were 85.5% (KPCO) and 90.6% (DH). There were significant differences in the two populations in age, gender, race, preferred language, and % Federal Poverty Level (FPL) (DH 70.7% < 100% FPL; KPCO 17.4%), as well as in healthcare utilization – for example pediatric emergency department utilization was twice as high at DH. CONCLUSIONS: Using a cohort of “empaneled” patients, it is possible to integrate data from a safety net health care system that does not have a uniform managed care population into the VSD, and to compare vaccination rates, socio-demographic characteristics, and health care utilization across the two systems. The KPCO-DH collaboration may serve as a model for incorporating data from a safety net healthcare system into the VSD.

Purpose An association between the influenza antiviral medication oseltamivir and neuropsychiatric events has been suggested by post-marketing case reports in Japan. This possible association was not supported by cohort studies in the U.S. conducted prior to the 2009 influenza A (H1N1) pandemic, when usage rates were comparatively low. We assessed oseltamivir safety before and during the pandemic using biologically plausible risk intervals, particularly focusing on psychiatric events. Methods Outpatients with influenza episodes from January 2007 through June 2010 were identified using diagnosis codes and positive tests at eight health care systems (sites) in the Vaccine Safety Datalink Project. Oseltamivir-treated and untreated patients were matched according to calendar week, age, sex, site, and propensity for treatment. Within this matched cohort, conditional logistic regression models were used to estimate the risk of four neuropsychiatric and five other adverse events (AEs) during pre-specified risk intervals. Results Among 27,684 matched pairs, no associations were identified between oseltamivir treatment and any pre-defined AE. The absolute risks of incident psychiatric events in the 1-7 day risk interval were 0.126% for oseltamivir-treated and 0.105% for untreated patients (odds ratio = 1.21, 95% confidence interval [CI]: 0.74, 1.97; risk difference = 0.022%, 95% CI: -0.035%, 0.078%); the most common diagnosis was unspecified anxiety state. Results were similar for 1-14 and 1-2 day risk intervals and for pediatric/adolescent subgroups. Conclusions Consistent with prior U.S. cohort studies, no evidence was identified for an increased risk of neuropsychiatric or other AEs following oseltamivir treatment. Safety should be prospectively monitored to inform antiviral medication usage recommendations.

Importance Some parents are concerned that multiple vaccines in early childhood could weaken their child’s immune system. Biological data suggest that increased vaccine antigen exposure could increase the risk for infections not targeted by vaccines. Objective To examine estimated cumulative vaccine antigen exposure through the first 23 months of life in children with and without non–vaccine-targeted infections from 24 through 47 months of age. Design, Setting, and Participants A nested case-control study was conducted in 6 US health care organizations participating in the Vaccine Safety Datalink. Cases were identified byInternational Classification of Diseases codes for infectious diseases in the emergency department and inpatient medical settings and then validated by medical record review. Cases of non–vaccine-targeted infection were matched to controls by age, sex, health care organization site, and chronic disease status. Participants were children ages 24 through 47 months, born between January 1, 2003, and September 31, 2013, followed up until December 31, 2015. Exposures Cumulative vaccine antigen exposure, estimated by summing the number of antigens in each vaccine dose received from birth through age 23 months. Main Outcomes and Measures Non–vaccine-targeted infections, including upper and lower respiratory infections and gastrointestinal infections, from 24 through 47 months of age, and the association between these infections and estimated cumulative vaccine exposure from birth through 23 months. Conditional logistic regression was used to estimate matched odds ratios representing the odds of non–vaccine-targeted infections for every 30-unit increase in estimated cumulative number of antigens received. Results Among the 944 patients (193 cases and 751 controls), the mean (SD) age was 32.5 (6.3) months, 422 (45%) were female, and 61 (7%) had a complex chronic condition. Through the first 23 months, the estimated mean (SD) cumulative vaccine antigen exposure was 240.6 (48.3) for cases and 242.9 (51.1) for controls. The between-group difference for estimated cumulative antigen exposure was −2.3 (95% CI, −10.1 to 5.4;P = .55). Among children with vs without non–vaccine-targeted infections from 24 through 47 months of age, the matched odds ratio for estimated cumulative antigen exposure through age 23 months was not significant (matched odds ratio, 0.94; 95% CI, 0.84 to 1.07). Conclusions and Relevance Among children from 24 through 47 months of age with emergency department and inpatient visits for infectious diseases not targeted by vaccines, compared with children without such visits, there was no significant difference in estimated cumulative vaccine antigen exposure through the first 23 months of life.

Background Tetanus-diphtheria-acellular pertussis (Tdap) and influenza (flu) vaccines are recommended for all pregnant women in each pregnancy. However, vaccination uptake is suboptimal. Our objective was to test of the efficacy of an online vaccine and social media resource in increasing uptake of Tdap and flu vaccines. Methods The RCT was conducted in an integrated health care system in Colorado from September 2013 to July 2016. Participants were pregnant women in the third trimester of pregnancy. Participants were randomly assigned to a website with vaccine information and interactive social media components (VSM), a website with vaccine information only (VI), or usual care (UC). To facilitate interaction on the VSM site, women were randomized 3:2:1 across the VSM:VI:UC arms. The interventions were designed and pilot tested using focus groups, individual interviews, surveys, and usability testing with vaccine-hesitant parents and pregnant women and included content on maternal and infant vaccination. Participants in the VSM and VI arms had access to the same base vaccine content. The VSM site also included a blog, discussion forum, chat room, and “Ask a Question” portal. After randomization, women in the VSM and VI arms were sent a website link. While they were encouraged to use the vaccine website, it was not required. Tdap and flu vaccination outcomes were analyzed separately. Women were included in each analysis if they had no record of vaccination for the relevant vaccine at enrollment and were >2 weeks from delivery. Results For Tdap (n = 172), there were no significant differences in uptake between study arms (VSM: 71%, VI: 69%, UC: 68%, P = .95). For flu (n = 284), women in both the VSM and VI arms had higher rates of uptake compared with UC, although the intervention arms were not significantly different from each other (VSM: 57%, VI: 55%, UC: 38%, P = .09). Women receiving any intervention (VSM or VI) had significantly higher uptake of flu vaccine compared with UC (VSM/VI: 56%, UC: 38%, P = .03). Conclusion Web-based vaccination information which is sent to pregnant women, with or without social media components, can positively influence maternal flu vaccine uptake. Because of the potential for scalability, the impact of robust vaccination information websites should be studied in other settings and with women in earlier stages of pregnancy. Disclosures All authors: No reported disclosures.

Objective. Describe a process for designing, building, and evaluating a theory-driven social media intervention tool to help reduce parental concerns about vaccination. Method. We developed an interactive web-based tool using quantitative and qualitative methods (e.g., survey, focus groups, individual interviews, and usability testing). Results. Survey results suggested that social media may represent an effective intervention tool to help parents make informed decisions about vaccination for their children. Focus groups and interviews revealed four main themes for development of the tool: Parents wanted information describing both benefits and risks of vaccination, transparency of sources of information, moderation of the tool by an expert, and ethnic and racial diversity in the visual display of people. Usability testing showed that parents were satisfied with the usability of the tool but had difficulty with performing some of the informational searches. Based on focus groups, interviews, and usability evaluations, we made additional revisions to the tool’s content, design, functionality, and overall look and feel. Conclusion. Engaging parents at all stages of development is critical when designing a tool to address concerns about childhood vaccines. Although this can be both resource- and time-intensive, the redesigned tool is more likely to be accepted and used by parents. Next steps involve a formal evaluation through a randomized trial.

Importance Undervaccination is an increasing trend that potentially places children and their communities at an increased risk for serious infectious diseases. Objective To examine the association between undervaccination and pertussis in children 3 to 36 months of age. Design Matched case-control study with conditional logistic regression analysis. Setting Eight managed care organizations of the Vaccine Safety Datalink between 2004 and 2010. Participants Each laboratory-confirmed case of pertussis (72 patients) was matched to 4 randomly selected controls (for a total of 288 controls). The case patients were matched to controls by managed care organization site, sex, and age at the index date. The index date was defined as the date of pertussis diagnosis for the case patients. Exposure Undervaccination for the diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccine. Undervaccination was defined as the number of doses of DTaP vaccine that was either missing or delayed by the index date. Case patients and controls could be undervaccinated by 0, 1, 2, 3, or 4 doses of DTaP vaccine. Children undervaccinated by 0 doses were considered age-appropriately vaccinated by the index date. Main Outcome and Measure Pertussis. Results Of the 72 case patients with pertussis, 12 (16.67%) were hospitalized, and 34 (47.22%) were undervaccinated for DTaP vaccine by the date of pertussis diagnosis. Of the 288 matched controls, 64 (22.22%) were undervaccinated for DTaP vaccine. Undervaccination was strongly associated with pertussis. Children undervaccinated for 3 or 4 doses of DTaP vaccine were 18.56 (95% CI, 4.92-69.95) and 28.38 (95% CI, 3.19-252.63) times more likely, respectively, to have received a diagnosis of pertussis than children who were age-appropriately vaccinated. Conclusions and Relevance Undervaccination with DTaP vaccine increases the risk of pertussis among children 3 to 36 months of age.

Background The primary prevention measure for influenza infection has been the use of influenza vaccines. However, even when the vaccine and circulating strains are well-matched, some healthy children do not respond to the vaccine, likely due to a genetic basis for immune hyporesponsiveness. The primary objective of this study was to identify HLA class II genes associated with clinical hyporesponsiveness after trivalent inactivated influenza vaccine (TIV) in children. Methods We conducted a case–control study nested within a retrospective cohort of children that were screened at birth for HLA-DR,DQ genotypes by the Diabetes Autoimmunity Study in the Young (DAISY) and were subsequently followed for up to 8 years by Kaiser Permanente, Colorado (KPCO). Hyporesponsiveness was clinically defined as the occurrence of influenza or influenza-like illness (ILI) in peak influenza weeks in children fully vaccinated with TIV. Each child with clinical hyporesponse ( n = 252) was matched to 4 randomly selected controls ( n = 1006) by age and season. Children with clinical hyporesponse to TIV were identified using the Kaiser electronic clinical and immunization databases. Fully vaccinated children within the KPCO-DAISY cohort who did not have a diagnosis of ILI during the entire influenza season were eligible to be controls for that season. Class II HLA-DRB1 and HLA-DQB1 genes were the primary exposure variables. We used conditional logistic regression to calculate the matched odds ratios. Results In non-Hispanic white children, HLA-DR7/4,DQB1*0302 genotype was significantly associated (OR = 5.15; 95% CI = 1.94, 13.67; p = 0.001), while in Hispanic children, HLA-DRB1*15 or 16 allele (OR = 0.31; 95% CI = 0.14, 0.69; p = 0.004) and HLA-DR7/Y (DRB1*11, DRB1*13 and DRB1*14) genotype (OR = 5.84; 95% CI = 1.68, 20.28; p = 0.006) were significantly associated with clinical hyporesponsiveness after TIV. Conclusions HLA class II genes are associated with clinical hyporesponsiveness to TIV. This finding is important as it may help identify a group of children who are not protected by the commonly used TIV and may require alternative preventive strategies.

An association between the influenza antiviral medication oseltamivir and neuropsychiatric events has been suggested by post-marketing case reports in Japan. This possible association was not supported by cohort studies in the U.S. conducted prior to the 2009 influenza A (H1N1) pandemic, when usage rates were comparatively low. We assessed oseltamivir safety before and during the pandemic using biologically plausible risk intervals, particularly focusing on psychiatric events.Outpatients with influenza episodes from January 2007 through June 2010 were identified using diagnosis codes and positive tests at eight health care systems (sites) in the Vaccine Safety Datalink Project. Oseltamivir-treated and untreated patients were matched according to calendar week, age, sex, site, and propensity for treatment. Within this matched cohort, conditional logistic regression models were used to estimate the risk of four neuropsychiatric and five other adverse events (AEs) during pre-specified risk intervals.Among 27,684 matched pairs, no associations were identified between oseltamivir treatment and any pre-defined AE. The absolute risks of incident psychiatric events in the 1-7 day risk interval were 0.126% for oseltamivir-treated and 0.105% for untreated patients (odds ratio = 1.21, 95% confidence interval [CI]: 0.74, 1.97; risk difference = 0.022%, 95% CI: -0.035%, 0.078%); the most common diagnosis was unspecified anxiety state. Results were similar for 1-14 and 1-2 day risk intervals and for pediatric/adolescent subgroups.Consistent with prior U.S. cohort studies, no evidence was identified for an increased risk of neuropsychiatric or other AEs following oseltamivir treatment. Safety should be prospectively monitored to inform antiviral medication usage recommendations.

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). Conclusions: This large cohort study did not find an association of influenza vaccination and hospitalization for sickle cell crises in children with sickle cell anemia.

To evaluate the safety of trivalent inactivated influenza vaccine (TIV) in children aged 24 to 59 months and to evaluate the risk of medically attended events (MAEs) in a subcohort of children who had multiple annual doses of TIV over their lifetimes.Self-controlled screening study.Seven US managed care organizations from October 1, 2002, to March 31, 2006.Children aged 24 to 59 months who received at least 1 TIV dose (66 283 children and 91 692 TIV doses).Vaccination with TIV.Medically attended events in inpatient and emergency department settings in one of the following risk windows: 0 to 2, 1 to 14, or 1 to 42 days after vaccination. All MAEs that met the screening criteria of incidence rate ratios (IRRs) exceeding 1.0 and P ≤ .05 or IRRs exceeding 2.0 and P.20 underwent medical record review. A secondary analysis examined the risk of MAEs in children who had multiple annual lifetime TIV doses.Nine diagnoses met the screening criteria. After medical record review, gastrointestinal tract symptoms (IRR, 1.18; 95% confidence interval [CI], 1.10-1.25), gastrointestinal tract disorders (7.70; 1.11-53.52), and fever (1.71; 1.64-1.80) remained significantly associated with vaccination. None of the events seemed to be serious, and none had complications. In the secondary analysis, there was an apparent dose response for vaccine and allergic reactions in the 1- to 3-day risk window.There was no evidence of serious MAEs following vaccination with TIV among children aged 24 to 59 months. Further studies are warranted to evaluate the risk of MAEs in children with multiple lifetime TIV doses.

An increasing number of parents are choosing to decline immunizations for their children. This study examined the association between the parental decision to decline pneumococcal conjugate (PCV7) vaccinations and the risk of hospitalization due to pneumococcal disease or lobar pneumonia in children.We conducted a case-control study nested within a cohort of children enrolled in the Kaiser Permanente Colorado (KPCO) health plan between 2004 and 2009. Each child hospitalized with pneumococcal disease or lobar pneumonia (n=106) was matched to 4 randomly selected controls (n=401). Cases were matched to controls by age, sex, high-risk status, calendar time, and length of enrollment in KPCO. Disease status and parental vaccination decisions were validated with medical record review. Cases and controls were classified as vaccine decliners or vaccine acceptors.Among 106 cases, there were 6 (6%) PCV7 vaccine decliners; among 401 controls, there were 4 (1%) vaccine decliners. Children of parents who declined PCV7 immunization were 6.5 times (OR=6.5; 95% CI=1.7, 24.5) more likely to be hospitalized for invasive pneumococcal disease or lobar pneumonia than vaccinated children.Parental decline of pneumococcal vaccination apparently increases the risk for hospitalization due to pneumococcal disease or lobar pneumonia in children. Providers can use this information when helping parents weigh the benefits and risks of immunizing their children.

Background/Aims: KPCO continuously checks our electronic health data for unexpected values. These values may be errors or legitimate reflections of clinical procedures and data collection rules. Rigorous data analysis requires an understanding of these unexpected values as well as methods to address them. We do not yet have an organized way to document unexpected data values. Methods: We followed a multi-phase plan to develop a database that describes data issues from HMORN data partners. In Phase 1 (Requirements), we met with stakeholders at KPCO to determine needs. For Phase 2 (Design), we drafted a data collection survey and built an initial prototype of the database. In Phase 3 (Development), we improved upon multiple versions of the database and documented procedures to enter new data items, create reports, and review the accuracy of existing data items. When the database framework was sufficiently developed, members of the Analytic Team at KPCO entered issues based on their experience with HMORN studies. In Phase 4 (Testing), we evaluated our documentation and ran sample reports against the new data content. We also assessed the degree of overlap with the VDW Issue Tracker. During Phase 5 (Implementation), we presented the database to key stakeholders at KPCO and began discussions to build similar databases at other HMORN sites and/or enhance the Issue Tracker as a multi-site centralized database. Results: The Analytic Team at KPCO recorded a wide range of data issues occurring in projects from 2010-2013. Data items came from general VDW quality assessments as well as study-specific data checks. Database content included data errors as well as real phenomena attributable to clinical practice or data collection. Conclusions: Analysts can better anticipate problems and nuances in electronic health data with a database that describes the past data anomalies and methods for using the data.

Background/Aims Effective communication during cancer care is critical for good health outcomes. Understanding what information patients look for and from whom is necessary to ensure their information needs are met. This study examined health information seeking behavior of KPCO members diagnosed with cancer and explored how ethnicity, race, age, cancer type, gender, and educational level are related to choices of health information content, sources, and format.