Exploring social determinants of health and physical activity levels in older adults living with mild cognitive impairment and dementia in the Upper Midwest of the United States.

BACKGROUND: Physical activity can improve physical health for people living with mild cognitive impairment (MCI) and dementia and may have cognitive benefits. Identifying modifiable social factors inhibiting physical activity among this group is needed. We sought to examine the relationship between reported physical activity levels and social determinants of health (SDOH) in a population of older adults living with MCI or dementia. METHODS: This descriptive study included people with a diagnosis of MCI or dementia followed by Community Internal Medicine at Mayo Clinic (Rochester, Minnesota, United States), aged over 55 years, who had a clinic visit between June 1, 2019 and June 30, 2021 and had completed a SDOH questionnaire. We focused on 8 SDOH domains: education, depression, alcohol use, stress, financial resource strain, social connections, food insecurity, and transportation needs. Data were analyzed based on physical activity level (inactive, insufficiently active, sufficiently active). SDOH domains were compared according to physical activity level using the χ2 test and multinomial logistic regression. RESULTS: A total of 3224 persons with MCI (n = 1371) or dementia (n = 1853) who had completed questions on physical activity were included. Of these, 1936 (60%) were characterized as physically inactive and 837 (26%) insufficiently active. Characteristics associated with an increased likelihood of physical inactivity were older age, female sex, obesity, lower education, dementia diagnosis, screening positive for depression and increased social isolation (p < 0.001). CONCLUSIONS: Physical inactivity is common among people living with MCI and dementia. Physical activity levels may be influenced by many factors, highlighting potential areas for intervention.

Identification of sex-specific genetic associations in response to opioid analgesics in a White, non-Hispanic cohort from Southeast Minnesota.

The study of sex-specific genetic associations with opioid response may improve the understanding of inter-individual variability in pain treatments. We investigated sex-specific associations between genetic variation and opioid response. We identified participants in the RIGHT Study prescribed codeine, tramadol, hydrocodone, and oxycodone between 01/01/2005 and 12/31/2017. Prescriptions were collapsed into codeine/tramadol and hydrocodone/oxycodone. Outcomes included poor pain control and adverse reactions within six weeks after prescription date. We performed gene-level and single-variant association analyses stratified by sex. We included 7169 non-Hispanic white participants and a total of 1940 common and low-frequency variants (MAF > 0.01). Common variants in MACROD2 (rs76026520), CYP1B1 (rs1056837, rs1056836), and CYP2D6 (rs35742686) were associated with outcomes. At the gene level, FAAH, SCN1A, and TYMS had associations for men and women, and NAT2, CYP3A4, CYP1A2, and SLC22A2 had associations for men only. Our findings highlight the importance of considering sex in association studies on opioid response.

Implementation of preemptive DNA sequence-based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study.

PURPOSE: The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, rather than genotyping. METHODS: Targeted oligonucleotide-capture sequencing of 77 pharmacogenes was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response-related phenotypes for 13 genes, including CYP2D6 and HLA, affecting 21 drug-gene pairs, were deposited preemptively in the Mayo electronic health record. RESULTS: For the 13 pharmacogenes of interest, the genomes of 79% of participants carried clinically actionable variants in 3 or more genes, and DNA sequencing identified an average of 3.3 additional conservatively predicted deleterious variants that would not have been evident using genotyping. CONCLUSION: Implementation of preemptive rather than reactive and sequence-based rather than genotype-based PGx prescribing revealed nearly universal patient applicability and required integrated institution-wide resources to fully realize individualized drug therapy and to show more efficient use of health care resources.

Systematic review of the evidence on the cost-effectiveness of pharmacogenomics-guided treatment for cardiovascular diseases.

PURPOSE: To examine the evidence on the cost-effectiveness of implementing pharmacogenomics (PGx) in cardiovascular disease (CVD) care. METHODS: We conducted a systematic review using multiple databases from inception to 2018. The titles and abstracts of cost-effectiveness studies on PGx-guided treatment in CVD care were screened, and full texts were extracted. RESULTS: We screened 909 studies and included 46 to synthesize. Acute coronary syndrome and atrial fibrillation were the predominantly studied conditions (59%). Most studies (78%) examined warfarin-CYP2C9/VKORC1 or clopidogrel-CYP2C19. A payer's perspective was commonly used (39%) for cost calculations, and most studies (46%) were US-based. The majority (67%) of the studies found PGx testing to be cost-effective in CVD care, but cost-effectiveness varied across drugs and conditions. Two studies examined PGx panel testing, of which one examined pre-emptive testing strategies. CONCLUSION: We found mixed evidence on the cost-effectiveness of PGx in CVD care. Supportive evidence exists for clopidogrel-CYP2C19 and warfarin-CYP2C9/VKORC1, but evidence is limited in other drug-gene combinations. Gaps persist, including unclear explanation of perspective and cost inputs, underreporting of study design elements critical to economic evaluations, and limited examination of PGx panel and pre-emptive testing for their cost-effectiveness. This review identifies the need for further research on economic evaluations of PGx implementation.

Known-groups validity and responsiveness to change of the Patient Experience with Treatment and Self-management (PETS vs. 2.0): a patient-reported measure of treatment burden.

PURPOSE: The purpose of this study was to test the known-groups validity and responsiveness to change of the Patient Experience with Treatment and Self-management (PETS, vs. 2.0), a measure of treatment burden. METHODS: The PETS and other standard measures were mailed at baseline and 12-month follow-up to adults living with multiple chronic conditions in southeast Minnesota (USA). A sample of 365 people (mean age = 62.1 years) completed both surveys. Baseline, 12-month, and changes in PETS burden scores were examined. Clinical anchors used to test validity included number of diagnoses (2-4 vs. 5+), mental health diagnosis (yes/no), medication adherence and health literacy (suboptimal/optimal), and changes in self-efficacy, global physical, and global mental health (worsening/improving). Independent-samples t-tests were used to compare scores. RESULTS: PETS scales showed good internal consistency (αs ≥ 0.80). There were few differences across number of diagnoses, but having a mental health diagnosis was associated with higher baseline PETS burden scores (Ps < .05). Suboptimal medication adherence and health literacy over time were associated with worse 12-month PETS burden scores (Ps < .05). Compared with improvements, declines over time in self-efficacy, global physical health, and global mental health were each associated with worsening change scores on PETS impact summary, medical expenses, and bother due to medication reliance and medication side effects (Ps < .05). CONCLUSION: Among multi-morbid adults, the PETS demonstrated evidence of known-groups validity and responsiveness to change across both objective (e.g., mental health diagnoses) and subjective anchors (e.g., changes in self-efficacy, global physical, and global mental health).

Correction to: Neighborhood socioeconomic disadvantage is associated with multimorbidity in a geographically-defined community.

An amendment to this paper has been published and can be accessed via the original article.

Neighborhood socioeconomic disadvantage is associated with multimorbidity in a geographically-defined community.

BACKGROUND: Persons with low socioeconomic status may be disproportionately at risk for multimorbidity. METHODS: Adults aged ≥20 years on 4/1/2015 from 7 counties in Minnesota were identified using the Rochester Epidemiology Project (population-based sample). A composite measure of neighborhood socioeconomic disadvantage, the area deprivation index (ADI), was estimated at the census block group level (n = 251). The prevalence of 21 chronic conditions was obtained to calculate the proportion of persons with multimorbidity (≥2 chronic conditions) and severe multimorbidity (≥5 chronic conditions). Hierarchical logistic regression was used to estimate the association of ADI with multimorbidity and severe multimorbidity using odds ratios (OR). RESULTS: Among 198,941 persons (46.7% male, 30.6% aged ≥60 years), the age- and sex-standardized (to the United States 2010 census) median prevalence (Q1, Q3) was 23.4% (21.3%, 25.9%) for multimorbidity and 4.8% (4.0%, 5.7%) for severe multimorbidity. Compared with persons in the lowest quintile of ADI, persons in the highest quintile had a 50% increased risk of multimorbidity (OR 1.50, 95% CI 1.39-1.62) and a 67% increased risk of severe multimorbidity (OR 1.67, 95% CI 1.51-1.86) after adjusting for age, sex, race, and ethnicity. Associations were stronger after further adjustment for individual level of education; persons in the highest quintile had a 78% increased risk of multimorbidity (OR 1.78, 95% CI 1.62-1.96) and a 92% increased risk of severe multimorbidity (OR 1.92, 95% CI 1.72-2.13). There was evidence of interactions between ADI and age, between ADI and sex, and between ADI and education. After age 70 years, no difference in the risk of multimorbidity was observed across quintiles of ADI. The pattern of increasing multimorbidity with increasing ADI was more pronounced in women. Finally, there was less variability across quintiles of ADI for the most highly educated group. CONCLUSIONS: Higher ADI was associated with increased risk of multimorbidity, and the associations were strengthened after adjustment for individual level of education, suggesting that neighborhood context plays a role in health above and beyond individual measures of socioeconomic status. Furthermore, associations were more pronounced in younger persons and women, highlighting the importance of interventions to prevent chronic conditions in younger women, in particular.

Rochester Epidemiology Project Data Exploration Portal.

INTRODUCTION: The goal of this project was to develop an interactive, web-based tool to explore patterns of prevalence and co-occurrence of diseases using data from the expanded Rochester Epidemiology Project (E-REP) medical records-linkage system. METHODS: We designed the REP Data Exploration Portal (REP DEP) to include summary information for people who lived in a 27-county region of southern Minnesota and western Wisconsin on January 1, 2014 (n = 694,506; 61% of the entire population). We obtained diagnostic codes of the International Classification of Diseases, 9th edition, from the medical records-linkage system in 2009 through 2013 (5 years) and grouped them into 717 disease categories. For each condition or combination of 2 conditions (dyad), we calculated prevalence by dividing the number of persons with a specified condition (numerator) by the total number of persons in the population (denominator). We calculated observed-to-expected ratios (OERs) to test whether 2 conditions co-occur more frequently than would co-occur as a result of chance alone. RESULTS: We launched the first version of the REP DEP in May 2017. The REP DEP can be accessed at http://rochesterproject.org/portal/. Users can select 2 conditions of interest, and the REP DEP displays the overall prevalence, age-specific prevalence, and sex-specific prevalence for each condition and dyad. Also displayed are OERs overall and by age and sex and maps of county-specific prevalence of each condition and OER. CONCLUSION: The REP DEP draws upon a medical records-linkage system to provide an innovative, rapid, interactive, free-of-charge method to examine the prevalence and co-occurrence of 717 diseases and conditions in a geographically defined population.

Participant-perceived understanding and perspectives on pharmacogenomics: the Mayo Clinic RIGHT protocol (Right Drug, Right Dose, Right Time).

PURPOSE: To examine predictors of understanding preemptive CYP2D6 pharmacogenomics test results and to identify key features required to improve future educational efforts of preemptive pharmacogenomics testing. METHODS: One thousand ten participants were surveyed after receiving preemptive CYP2D6 pharmacogenomics test results. RESULTS: Eighty-six percent (n = 869) of patients responded. Of the responders, 98% were white and 55% were female; 57% had 4 years or more of post-secondary education and an average age of 58.9 ± 5.5 years. Twenty-six percent said that they only somewhat understood their results and 7% reported they did not understand them at all. Only education predicted understanding. The most common suggestion for improvement was the use of layperson's terms when reporting results. In addition, responders suggested that results should be personalized by referring to medications that they were currently using. Of those reporting imperfect drug adherence, most (91%) reported they would be more likely to use medication as prescribed if pharmacogenomic information was used to help select the drug or dose. CONCLUSION: Despite great efforts to simplify pharmacogenomic results (or because of them), approximately one-third of responders did not understand their results. Future efforts need to provide more examples and tailor results to the individual. Incorporation of pharmacogenomics is likely to improve medication adherence.Genet Med advance online publication 05 January 2017.

Multidisciplinary model to implement pharmacogenomics at the point of care.

PURPOSE: Despite potential clinical benefits, implementation of pharmacogenomics (PGx) faces many technical and clinical challenges. These challenges can be overcome with a comprehensive and systematic implementation model. METHODS: The development and implementation of PGx were organized into eight interdependent components addressing resources, governance, clinical practice, education, testing, knowledge translation, clinical decision support (CDS), and maintenance. Several aspects of implementation were assessed, including adherence to the model, production of PGx-CDS interventions, and access to educational resources. RESULTS: Between August 2012 and June 2015, 21 specific drug-gene interactions were reviewed and 18 of them were implemented in the electronic medical record as PGx-CDS interventions. There was complete adherence to the model with variable production time (98-392 days) and delay time (0-148 days). The implementation impacted approximately 1,247 unique providers and 3,788 unique patients. A total of 11 educational resources complementary to the drug-gene interactions and 5 modules specific for pharmacists were developed and implemented. CONCLUSION: A comprehensive operational model can support PGx implementation in routine prescribing. Institutions can use this model as a roadmap to support similar efforts. However, we also identified challenges that will require major multidisciplinary and multi-institutional efforts to make PGx a universal reality.Genet Med 19 4, 421-429.

Telephone triage utilization among patients with limited English proficiency.

BACKGROUND: Communication between patients with limited English proficiency (LEP) and telephone triage services has not been previously explored. The purpose of this study was to determine the utilization characteristics of a primary care triage call center by patients with LEP. METHODS: This was a retrospective cohort study of the utilization of a computer-aided, nurse-led telephone triage system by English proficiency status of patients empaneled to a large primary care practice network in the Midwest United States. Interpreter Services (IS) need was used as a proxy for LEP. RESULTS: Call volumes between the 587 adult patients with LEP and an age-frequency matched cohort of English-Proficient (EP) patients were similar. Calls from patients with LEP were longer and more often made by a surrogate. Patients with LEP received recommendations for higher acuity care more frequently (49.4% versus 39.0%; P < 0.0004), and disagreed with recommendations more frequently (30.1% versus 20.9%; P = 0.0004). These associations remained after adjustment for comorbidities. Patients with LEP were also less likely to follow recommendations (60.9% versus 69.4%; P = 0.0029), even after adjusting for confounders (adjusted odds ratio [AOR] = 0.65; 95% confidence interval [CI], 0.49, 0.85; P < 0.001). CONCLUSION: Patients with LEP who utilized a computer-aided, nurse-led telephone triage system were more likely to receive recommendations for higher acuity care compared to EP patients. They were also less likely to agree with, or follow, recommendations given. Additional research is needed to better understand how telephone triage can better serve patients with LEP.

Younger age at initiation of the human papillomavirus (HPV) vaccination series is associated with higher rates of on-time completion.

Vaccination rates for human papillomavirus (HPV) have remained disappointingly low. It is critical to identify methods to increase on-time vaccine series completion rates (before 13 or 15years). To determine whether younger age (9 to 10years of age) at HPV vaccine series initiation was associated with improved on-time completion rates compared to initiation at 11 to 12years, we examined the prevalence of on-time HPV vaccine series completion rates from August 2006 through December 2012 in a large, population-based cohort of children and adolescents (aged 9.5 to 27years) residing in Olmsted County, MN on December 31, 2012 (n=36,223). We compared age at vaccine initiation between individuals who successfully completed both 2 and 3 doses of the vaccination series on-time (before age 13.5 or 15.0years) using multivariate logistic regression. On-time completion of both 2 and 3 doses of the vaccine series by age 13.5 or 15.0years was significantly associated with initiation at 9 to 10years as compared to 11 to 12years after adjusting for sex, race, insurance status, frequent health care visits, and year of first vaccination (all p<.01). Interventions focused on beginning the vaccination series at 9 to 10years of age may result in higher rates of timely series completion.

Emergency department and inpatient health care utilization among patients who require interpreter services.

BACKGROUND: Limited English proficiency is associated with health disparities and suboptimal health outcomes. Although Limited English proficiency is a barrier to effective health care, its association with inpatient health care utilization is unclear. The aim of this study was to examine the association between patients with limited English proficiency, and emergency department visits and hospital admissions. METHODS: We compared emergency department visits and hospitalizations in 2012 between patients requiring interpreter services and age-matched English-proficient patients (who did not require interpreters), in a retrospective cohort study of adult patients actively empanelled to a large primary health care network in a medium-sized United States city (n = 3,784). RESULTS: Patients who required interpreter services had significantly more Emergency Department visits (841 vs 620; P ≤ .001) and hospitalizations (408 vs 343; P ≤ .001) than patients who did not require interpreter services. On regression analysis the risk of a first Emergency Department visit was 60% higher for patients requiring interpreter services than those who did not (unadjusted hazard ratio [HR], 1.6; 95% confidence interval (CI), 1.4-1.9; P < .05), while that of a first hospitalization was 50% higher (unadjusted HR, 1.5; 95% CI, 1.2-1.8; P < .05). These findings remained significant after adjusting for age, sex, medical complexity, residency and outpatient health care utilization. CONCLUSIONS: Patients who required interpreter services had higher rates of inpatient health care utilization compared with patients who did not require an interpreter. Further research is required to understand factors associated with this utilization and to develop sociolinguistically tailored interventions to facilitate appropriate health care provision for this population.

Oral fluoroquinolones and the incidence of rhegmatogenous retinal detachment and symptomatic retinal breaks: a population-based study.

OBJECTIVE: To examine whether oral fluoroquinolone antibiotics are associated with an increase in subsequent rhegmatogenous retinal detachment and symptomatic retinal breaks in a large population-based cohort. DESIGN: Population-based cohort study. PARTICIPANTS AND CONTROLS: Adult residents of Olmsted County, Minnesota, who were prescribed oral fluoroquinolone medications from January 1, 2003, to June 30, 2011. Comparison cohorts consisted of patients prescribed oral macrolide and ß-lactam antibiotics during the study period. METHODS: Procedure codes were used to identify retinal detachment repair and prophylaxis procedures occurring within 1 year of prescription dates. Travel clinic, pro re nata, and self-treatment prescriptions were excluded. Patients with tractional retinal detachment, previous retinal detachment repair, endophthalmitis, and necrotizing retinitis were excluded, as were those with intraocular surgery or severe head/eye trauma ≤90 days before the procedure. MAIN OUTCOME MEASURES: Rates of retinal detachment repair and prophylaxis procedures within 7, 30, 90, and 365 days of the first prescription were calculated and compared between antibiotic prescription cohorts using chi-square tests. Retinal detachment repair rates also were compared with the expected Olmsted County, Minnesota, rates using the one-sample log-rank test. RESULTS: Oral fluoroquinolones were prescribed for 38,046 patients (macrolide n = 48,074, ß-lactam n = 69,079) during the study period. Retinal detachment repair procedures were performed within 365 days of the first prescription in 0.03% (95% confidence interval [CI], 0.01-0.06) of the fluoroquinolone cohort, 0.02% (95% CI, 0.01-0.03) of the macrolide cohort, and 0.03% (95% CI, 0.02-0.05) of the ß-lactam cohort (P > 0.05). Retinal detachment prophylaxis procedures for symptomatic retinal breaks were performed within 365 days of the first prescription in 0.01% (95% CI, 0.00-0.03) of the fluoroquinolone cohort, 0.02% (95% CI, 0.01-0.04) of the macrolide cohort, and 0.02% (95% CI, 0.01-0.04) of the ß-lactam cohort (P > 0.05). Similar comparisons of treatment rates within 7, 30, and 90 days of the first prescription were all nonsignificant between cohorts. Post-fluoroquinolone retinal detachment repair rates were similar to expected rates (36.8 per 100,000/year vs. 28.8 per 100,000/year for age- and sex-matched historical rates, P = 0.35). CONCLUSIONS: Oral fluoroquinolone use was not associated with an increased risk of rhegmatogenous retinal detachment or symptomatic retinal breaks in this population-based study.

Changes in U.S. Preventive Services Task Force recommendations: effect on mammography screening in Olmsted County, MN 2004-2013.

OBJECTIVE: We assessed changes in adherence to screening mammography recommendations with the introduction of the new U.S. Preventive Services Task Force (USPSTF) recommendations in 2009. METHODS: Using the Rochester Epidemiology Project data linkage system, we examined mammography screening from 2004 to 2013 in 31,377 women 40years of age and older residing in Olmsted County, MN before and after the 2009 change in recommendations. Chi-square was used to compare screening rates before and after changes in recommendations overall, by age group, and by baseline adherence. RESULTS: Among women 40 years and older, declines in screening were observed: 69% of the population was adherent in 2004-2005, 61% in 2006-2009 and 53% in 2010-2013. Absolute decreases in screening were observed from pre- to post-change for those ages 40-49 (4%), 50-74 (9%), and those 75+ (19%, all p<0.0001). Relative declines in screening rates were observed among women aged 70-74 years who were non-adherent at baseline and among women who were adherent at baseline, overall, and in each age group (all p<.001). CONCLUSIONS: Declines in screening, both absolute and relative, were most pronounced among women who were adherent at baseline. Research is needed to assess factors that influence screening in the context of evolving recommendations.

Time trends of antidepressant drug prescriptions in men versus women in a geographically defined US population.

The aim of this work was to study time trends of antidepressant drug (AD) prescriptions in a geographically defined US population between 2005 and 2011 for men and women separately. Using the Rochester Epidemiology Project medical records-linkage system, we identified all Olmsted County, MN residents who received AD outpatient prescriptions between 2005 and 2011 (7 years). We calculated the annual age- and sex-specific prevalence over 7 years and used generalized estimating equation models to test for time trends. The prevalence of subjects receiving at least one AD prescription was approximately two times higher in women than in men consistently across the 7 years of the study. The standardized annual prevalence increased from 10.8 % in 2005 to 14.4 % in 2011 overall, from 7.0 % in 2005 to 9.9 % in 2011 for men, and from 14.4 % in 2005 to 18.6 % in 2011 for women. The absolute percent increase was greater in women (4.2 vs. 2.9 %; standardized); however, the relative percent increase was greater in men (41.4 vs. 29.2 %; standardized). The relative percent increase was greater in the age group 65+ years for both men and women. AD prescriptions are increasing over time, especially in the elderly. Women receive more AD prescriptions than men. However, the relative increase in AD prescriptions over time is greater in men than women.

Social Isolation and Healthcare Utilization in Older Adults Living With Dementia and Mild Cognitive Impairment in the United States.

Background and Objectives: Social isolation is commonly experienced by older people and is associated with adverse health outcomes. Little is known about the influence of social isolation on the risk of acute care utilization among people living with mild cognitive impairment (MCI) or dementia. Our objective was to investigate the impact of social isolation on the risk of death, hospitalization, and emergency department (ED) use among people living with MCI or dementia who are followed in our Community Internal Medicine practice at Mayo Clinic, Rochester, Minnesota. Research Design and Methods: We included people living with MCI or dementia, 55 years and older, who had a clinic visit between June 1, 2019, and June 30, 2021, and who had completed questions about social connections. The risk of death, hospitalization, and ED use was examined by levels of social connection (socially isolated, moderately isolated, moderately integrated, or socially integrated). Results: Of 2,320 people included (1,010 with MCI and 1,310 with dementia), 455 (19.6%) were classified as socially isolated and 591 (25.5%) were moderately isolated. Compared with those who were socially integrated, people who were socially isolated were at higher risk of death, hospitalization, and ED visits (p < .001). Discussion and Implications: Social isolation is associated with an increased risk of acute health care utilization and death in people living with MCI or dementia. Interventions to address social isolation in this population are needed.

Physical Activity and Acute Care Utilization Among Older Adults With Mild Cognitive Impairment and Dementia.

People living with dementia have high rates of hospitalizations. Identifying factors that influence hospitalization is important. This study examines the influence of physical activity levels on risk of hospitalization and emergency department (ED) use among older people living with mild cognitive impairment (MCI) or dementia followed in our primary care practice in Rochester, Minnesota, United States. We included those age 55 years and older, who had a clinic visit between June 1, 2019 and June 30, 2021 and completed a social determinants of health questionnaire about physical activity levels (n = 3090). Physical activity was classified as sufficiently active, insufficiently active, or physically inactive. Risk of hospitalization and ED visits by physical activity levels were examined. People who were physically inactive were at higher risk of hospitalization and ED visits (p < .001) compared with those who were sufficiently active. This highlights an area for health promotion in people living with MCI and dementia.

Multilevel Implementation Strategies for Adolescent Human Papillomavirus Vaccine Uptake: A Cluster Randomized Clinical Trial.

Importance: Despite availability of a safe and effective vaccine, an estimated 36 500 new cancers in the US result from human papillomavirus (HPV) annually. HPV vaccine uptake falls short of national public health goals and lags other adolescent vaccines. Objective: To evaluate the individual and combined impact of 2 evidence-based interventions on HPV vaccination rates among 11- and 12-year-old children. Design, Setting, and Participants: The study team conducted a cluster randomized clinical trial with a stepped-wedge factorial design at 6 primary care practices affiliated with Mayo Clinic in southeastern Minnesota. Using block randomization to ensure balance of patient volumes across interventions, each practice was allocated to a sequence of four 12-month steps with the initial baseline step followed by 2 intermediate steps (none, 1, or both interventions) and a final step wherein all practices implemented both interventions. Each month, all eligible children who turned 11 or 12 years in the 2 months prior were identified and followed until the end of the step. Data were analyzed from April 2018 through March 2019. Participants included children who turned 11 or 12 years old and were due for a dose of the HPV vaccine. Interventions: Parents of eligible patients were mailed reminder/recalls following their child's birthdays. Health care professionals received confidential audit/feedback on their personal in-office success with HPV vaccine uptake via intra-campus mail. These 2 interventions were assessed separately and in combination. Main Outcomes and Measures: Eligible patients' receipt of any valid dose of HPV vaccine during the study step. Results: The cohort was comprised of 9242 11-year-olds (5165 [55.9%]) and 12-year-olds (4077 [44.1%]), and slightly more males (4848 [52.5%]). Parent reminder/recall resulted in 34.6% receiving a dose of HPV vaccine, health care professional audit/feedback, 30.4%, both interventions together resulted in 39.7%-all contrasted to usual care, 21.9%. Compared with usual care, the odds of HPV vaccination were higher for parent reminder/recall (odds ratio [OR], 1.56; 95% CI, 1.23-1.97) and for the combination of parent reminder/recall and health care professional audit/feedback (OR, 2.03; 95% CI, 1.44-2.85). Health care professional audit/feedback alone did not differ significantly from usual care (OR, 1.19; 95% CI, 0.94-1.51). Conclusions and Relevance: In this cluster randomized trial, the combination of parent reminder/recall and health care professional audit/feedback increased the odds of HPV vaccination compared with usual care. These findings underscore the value of simultaneous implementation of evidence-based strategies to improve HPV vaccination.

Emergency department visits and hospitalizations attributable to recent Epstein-Barr virus infection.

OBJECTIVE: Infectious mononucleosis (IM) or mono is typically caused by primary infection with Epstein-Barr virus (EBV) and may have a months-long, complicated course. We utilized population-based data to add to the limited literature on health care utilization following EBV infection. METHODS: The Rochester Epidemiology Project includes medical records for ∼60% of residents living in 27 counties of Minnesota (MN) and Wisconsin (WI). Persons meeting a case definition of recent EBV infection from 1 January 1998 to 31 December 2021 were compared to three persons not meeting the definition, matched on case's sex, age, and index date. Emergency department (ED) visits and hospitalizations in the two groups were compared during 5-years' follow-up divided into three periods (short-term ≤3 months, mid-term >3 months-1 year, long-term >1-5 years). Adjusted hazard ratios (AHR) were estimated to account for the potential influence of confounding variables. RESULTS: In total, 6,423 persons had a recent EBV infection and were matched to 19,269 comparators. The risk of an ED visit was significantly higher among cases in the short-term period (24.3% vs referents: 7.6%, p <.001; AHR = 3.71, 95% CI = 3.41-4.03). Cases also had an increased risk of hospitalization in the short-term (5.2% vs 1.6%: referents, p <.001; AHR = 3.53, 95% CI = 2.94-4.24). For ED visits but not hospitalization, the excess risk persisted into the mid-term follow-up period. Persons without a concurrent clinical diagnosis of IM continued to have an increased risk of hospitalizations up to 1 year after index date (AHR = 1.45, 95% CI = 1.09-1.91) and an increased risk of ED visits up to 5 years after the index date (AHR = 1.29, 95% CI = 1.14-1.46). CONCLUSION: There is a substantial short- and mid-term increased risk of serious health care encounters associated with recent EBV infection. Mid- and long-term risks are increased in patients who do not have a concomitant diagnosis of IM.