Long-acting Opioid Use and the Risk of Serious Infections: A Retrospective Cohort Study.

BACKGROUND: Although evidence from animal and human studies indicates opioid analgesics increase susceptibility to infections, it is unclear whether the risk varies by specific opioid. We compared the risk of serious infection among patients initiating long-acting opioid analgesics with and without previously reported immunosuppressive properties. METHODS: We conducted a retrospective cohort study of Tennessee Medicaid enrollees age ≥18 years initiating long-acting opioids (1995-2015). Hospitalizations for serious infection were identified using validated coding algorithms. We used multivariable Poisson regression models to calculate adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) to compare the infection risk among patients using long-acting opioids with known immunosuppressive properties (morphine, fentanyl, methadone) to the infection risk among patients using long-acting opioids without known immunosuppressive properties (oxycodone, oxymorphone, tramadol) accounting for demographics, opioid dose, comorbidities and pain conditions, medication use, frailty indicators, and healthcare encounter history using exposure propensity scores. We further compared users of individual long-acting opioids to long-acting morphine users (considered the prototypical immunosuppressive opioid). RESULTS: Among the 61 240 patients initiating opioids with immunosuppressive properties and 22 811 patients initiating opioids without immunosuppressive properties, we identified 1906 serious infections. Nonimmunosuppressive opioid users had a lower rate of infections than immunosuppressive opioid users (aIRR:0.78 [CI: 0.66-0.91]). Among individual opioids, oxycodone users had a lower rate of infection than morphine users (aIRR:0.73 [CI: 0.60-0.89]). There were no significant differences in the infection risk between other opioids and morphine. CONCLUSION: The risk of serious infections among long-acting opioid users varies by opioid type. Providers should carefully consider the risk of serious infections when making pain management decisions.

Changes in Otitis Media Episodes and Pressure Equalization Tube Insertions Among Young Children Following Introduction of the 13-Valent Pneumococcal Conjugate Vaccine: A Birth Cohort-based Study.

BACKGROUND: The impact of 13-valent pneumococcal conjugate vaccine (PCV13) introduction on the occurrence of first and subsequent otitis media (OM) episodes in early childhood is unclear. We compared the risk of OM episodes among children age <2 years before and after PCV13 introduction, accounting for the dependence between OM episodes. METHODS: We identified consecutive annual (July-June) cohorts of Tennessee Medicaid-enrolled children (2006-2014) from birth through age 2 years. We identified OM episodes using coded diagnoses (we classified diagnoses <21 days apart as the same episode). We modeled adjusted hazard ratios (aHRs) for OM comparing 7-valent pneumococcal conjugate vaccine (PCV7)-era (2006-2010) and PCV13-era (2011-2014) birth cohorts, accounting for risk factors and dependence between first and subsequent episodes. Secondary analyses examined pressure equalization tube (PET) insertions and compared the risk of recurrent OM (≥3 episodes in 6 months or ≥4 episodes in 12 months) between PCV7- and PCV13-era birth cohorts. RESULTS: We observed 618 968 OM episodes and 24 875 PET insertions among 368 063 children. OM and PET insertion rates increased during the PCV7 years and declined after PCV13 introduction. OM and PET insertion risks were lower in the 2013-2014 cohort compared with the 2009-2010 cohort (aHRs [95% confidence interval], 0.92 [.91-.93] and 0.76 [.72-.80], respectively). PCV13 introduction was associated with declines in the risk of first, subsequent, and recurrent OM. CONCLUSIONS: The transition from PCV7 to PCV13 was associated with a decline of OM among children aged <2 years due to a reduction in the risk of both the first and subsequent OM episodes.

Association Between Maternal 2nd Trimester Plasma Folate Levels and Infant Bronchiolitis.

Objectives Viral bronchiolitis is the most common cause of infant hospitalization. Folic acid supplementation is important during the periconceptional period to prevent neural tube defects. An area of investigation is whether higher prenatal folate is a risk factor for childhood respiratory illnesses. We investigated the association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Methods We conducted a retrospective cohort analysis in a subset of mother-infant dyads (n = 676) enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study and Tennessee Medicaid. Maternal folate status was determined using 2nd trimester (16-28 weeks) plasma samples. Bronchiolitis diagnosis in the first year of life was ascertained using International Classification of Diagnosis-9 codes from Medicaid administrative data. We used multivariable logistic regression to assess the adjusted association of prenatal folate levels and infant bronchiolitis outcome. Results Half of the women in this lower-income and predominately African-American (84%) study population had high levels of folate (median 2nd trimester level 19.2 ng/mL) and 21% of infants had at least one bronchiolitis healthcare visit. A relationship initially positive then reversing between maternal plasma folate and infant bronchiolitis was observed that did not reach statistical significance (poverall = .112, pnonlinear effect = .088). Additional adjustment for dietary methyl donor intake did not significantly alter the association. Conclusions for Practice Results did not confirm a statistically significant association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Further work is needed to investigate the role of folate, particularly higher levels, in association with early childhood respiratory illnesses.

Opioid Analgesic Use and Risk for Invasive Pneumococcal Diseases: A Nested Case-Control Study.

Background: Although certain opioid analgesics have immunosuppressive properties and increase the risk for infections in animals, the clinical effects of prescription opioid use on infection risk among humans are unknown. Objective: To test the hypothesis that prescription opioid use is an independent risk factor for invasive pneumococcal disease (IPD). Design: Nested case-control study. Setting: Tennessee Medicaid database linked to Medicare and Active Bacterial Core surveillance system databases (1995 to 2014). Patients: 1233 case patients with IPD aged 5 years and older matched to 24 399 control participants by diagnosis date, age, and county of residence. Measurements: Opioid use was measured on the basis of pharmacy prescription fills. Invasive pneumococcal disease was defined by the isolation of Streptococcus pneumoniae from a normally sterile site. The odds of current opioid use were compared between the case and control groups, accounting for known IPD risk factors. Secondary analyses categorized opioid use by opioid characteristics, applied an IPD risk score to assure comparability between exposure groups, and analyzed pneumonia and nonpneumonia IPD cases separately. Results: Persons in the case group had greater odds than control participants of being current opioid users (adjusted odds ratio [aOR], 1.62 [95% CI, 1.36 to 1.92]). Associations were strongest for opioids that were long acting (aOR, 1.87 [CI, 1.24 to 2.82]), of high potency (aOR, 1.72 [CI, 1.32 to 2.25]), or were used at high dosages (50 to 90 morphine milligram equivalents [MME]/d: aOR, 1.71 [CI, 1.22 to 2.39]; ≥90 MME/d: aOR, 1.75 [CI, 1.33 to 2.29]). Results were consistent when the IPD risk score was taken into account and pneumonia and nonpneumonia IPD were analyzed separately. Limitations: Unmeasured confounding and measurement error, although sensitivity analyses suggested that neither was likely to affect results. Actual opioid use and other nonprescription use (such as illicit opioid use) were not measured. Conclusion: Opioid use is associated with an increased risk for IPD and represents a novel risk factor for these diseases. Primary Funding Source: National Institutes of Health.

Effectiveness of Respiratory Syncytial Virus Immunoprophylaxis in Reducing Bronchiolitis Hospitalizations Among High-Risk Infants.

We sought to determine the real-world effectiveness of respiratory syncytial virus (RSV) immunoprophylaxis in a population-based cohort to inform policy. The study population included infants born during 1996-2008 and enrolled in the Kaiser Permanente Northern California integrated health-care delivery system. During the RSV season (November-March), the date of RSV immunoprophylaxis administration and the following 30 days were defined as RSV immunoprophylaxis protected period(s), and all other days were defined as unprotected period(s). Numbers of bronchiolitis hospitalizations were determined using International Classification of Diseases, Ninth Revision, codes during RSV season. We used a proportional hazards model to estimate risk of bronchiolitis hospitalization when comparing infants' protected period(s) with unprotected period(s). Infants who had ever received RSV immunoprophylaxis had a 32% decreased risk of bronchiolitis hospitalization (adjusted hazard ratio = 0.68, 95% confidence interval: 0.46, 1.00) when protected periods were compared with unprotected periods. Infants with chronic lung disease (CLD) had a 52% decreased risk of bronchiolitis hospitalization (adjusted hazard ratio = 0.48, 95% confidence interval: 0.25, 0.94) when protected periods were compared with unprotected periods. Under the new 2014 American Academy of Pediatrics (AAP) guidelines, 48% of infants eligible for RSV immunoprophylaxis on the basis of AAP guidelines in place at birth would no longer be eligible, but nearly all infants with CLD would remain eligible. RSV immunoprophylaxis is effective in decreasing hospitalization. This association is greatest for infants with CLD, a group still recommended for receipt of RSV immunoprophylaxis under the new AAP guidelines.

Seasonal patterns of Asthma medication fills among diverse populations of the United States.

OBJECTIVE: Nonadherence to controller and overuse of reliever asthma medications are associated with exacerbations. We aimed to determine patterns of seasonal asthma medication use and to identify time period(s) during which interventions to improve medication adherence could reduce asthma morbidity. METHODS: We conducted a retrospective cohort study of asthmatics 4-50 years of age and enrolled in three diverse health insurance plans. Seasonal patterns of medications were reported by monthly prescription fill rates per 1000 individuals with asthma from 1998 to 2013, and stratified by healthcare plan, sex, and age. RESULTS: There was a distinct and consistent seasonal fill pattern for all asthma medications. The lowest fill rate was observed in the month of July. Fills increased in the autumn and remained high throughout the winter and spring. Compared with the month of May with high medication fills, July represented a relative decrease of fills ranging from 13% (rate ratio, RR: 0.87, 95% confidence interval, 95%CI: 0.72-1.04) for the combination of inhaled corticosteroids (ICS) + long acting beta agonists (LABA) to 45% (RR: 0.55, 95%CI: 0.49-0.61) for oral corticosteroids. Such a seasonal pattern was observed each year across the 16-year study period, among healthcare plans, sexes, and ages. LABA containing control medication (ICS+LABA and LABA) fill rates were more prevalent in older asthmatics, while leukotriene receptor antagonists were more prevalent in the younger population. CONCLUSIONS: A seasonal pattern of asthma medication fill rates likely represents a reactive response to a loss of disease control and increased symptoms. Adherence to and consistent use of asthma medications among individuals who use medications in reaction to seasonal exacerbations might be a key component in reducing the risk of asthma exacerbations.

Changes in Childhood Pneumonia Hospitalizations by Race and Sex Associated with Pneumococcal Conjugate Vaccines.

Introduction of pneumococcal conjugate vaccines in the childhood immunization schedule was associated with decreases in all-cause pneumonia hospitalizations among black and white children in Tennessee, USA. Although racial disparities that existed before introduction of these vaccines have been substantially reduced, rates remain higher in boys than in girls among young children.

Socioeconomic Disparities and Influenza Hospitalizations, Tennessee, USA.

We examined population-based surveillance data from the Tennessee Emerging Infections Program to determine whether neighborhood socioeconomic status was associated with influenza hospitalization rates. Hospitalization data collected during October 2007-April 2014 were geocoded (N = 1,743) and linked to neighborhood socioeconomic data. We calculated age-standardized annual incidence rates, relative index of inequality, and concentration curves for socioeconomic variables. Influenza hospitalizations increased with increased percentages of persons who lived in poverty, had female-headed households, lived in crowded households, and lived in population-dense areas. Influenza hospitalizations decreased with increased percentages of persons who were college educated, were employed, and had health insurance. Higher incidence of influenza hospitalization was also associated with lower neighborhood socioeconomic status when data were stratified by race.

Maternal Folic Acid Supplementation During Pregnancy and Early Childhood Asthma.

BACKGROUND: Asthma is one of the most common chronic childhood diseases. While folic acid supplementation around conception helps prevent neural tube defects, an animal model suggests that it may be a risk factor for respiratory diseases, although epidemiologic studies have had conflicting results. We investigated the timing of folic acid-containing prescription filling during pregnancy and child asthma. METHODS: In a retrospective cohort study of 104,428 children, born 1996-2005, and their mothers enrolled in Tennessee Medicaid, we investigated the association of filling folic acid-containing prescriptions during pregnancy and childhood asthma at ages 4.5-6 years. We categorized women into exposure groups based on prescription filling centered around the first trimester: no folic acid prescription exposure, exposure in first trimester only, exposure after first trimester, and exposure in first trimester and beyond. We defined asthma using asthma-specific healthcare visits and medication fills. Using logistic regression models, we investigated the relationship adjusting for potential confounders. RESULTS: Overall 15% of children had asthma. Compared with children born to women with no folic acid prescription exposure, children born to women with exposures in the first trimester only or first trimester and later had increased relative odds of asthma (adjusted odds ratios = 1.2, 95% confidence interval = 1.1, 1.3, and 1.2, 95% confidence interval = 1.2, 1.3); no association was seen in children born to women exposed after the first trimester. CONCLUSION: Timing of folic acid-containing prescription filling during pregnancy was associated with childhood asthma. Our findings contribute to understanding of the role of prenatal nutritional supplements on child respiratory health.

Association of folic acid supplementation during pregnancy and infant bronchiolitis.

Viral bronchiolitis affects 20%-30% of infants; because there is no known effective treatment, it is important to identify risk factors that contribute to its pathogenesis. Although adequate folate intake during the periconceptional period prevents neural tube defects, animal data suggest that higher supplementation may be a risk factor for child respiratory diseases. Using a population-based retrospective cohort of 167,333 women and infants, born in 1995-2007 and enrolled in the Tennessee Medicaid program, we investigated the association between the filling of folic acid-containing prescriptions and infant bronchiolitis. We categorized women into the following 4 groups in relation to the first trimester: "none" (no prescription filled), "first trimester only," "after first trimester," and "both" (prescriptions filled both during and after the first trimester). Overall, 21% of infants had a bronchiolitis diagnosis, and 5% were hospitalized. Most women filled their first prescriptions after the fifth to sixth weeks of pregnancy, and most prescriptions contained 1,000 µg of folic acid. Compared with infants born to women in the "none" group, infants born to women in the "first trimester only" group had higher relative odds of bronchiolitis diagnosis (adjusted odds ratio = 1.17, 95% confidence interval: 1.11, 1.22) and greater severity (adjusted odds ratio = 1.16, 95% confidence interval: 1.11, 1.22). This study's findings contribute to an understanding of the implications of prenatal nutritional supplement recommendations for infant bronchiolitis.

Declines in pneumonia hospitalizations of children aged <2 years associated with the use of pneumococcal conjugate vaccines - Tennessee, 1998-2012.

The 7-valent pneumococcal conjugate vaccine (PCV7) was added to the U.S. infant immunization schedule in the year 2000. By 2009, PCV7 introduction was associated with a 43% decline in all-cause pneumonia among U.S. children aged <2 years. In 2010, a new 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the infant immunization schedule, expanding protection from seven to 13 pneumococcal serotypes. To examine changes in all-cause pneumonia hospitalizations among children aged <2 years after the switch to PCV13, Tennessee hospital discharge data for 1998-2012 were analyzed. By 2012, all-cause pneumonia hospitalizations in children aged <2 years had declined an additional 27%, relative to the PCV7 years. Pneumonia hospitalizations were estimated to be 4.1 per 1,000 population in 2012, a historically low rate that represents a 72% decline from the rate before PCV7 introduction. Tennessee children aged <2 years experienced about 1,300 fewer pneumonia hospitalizations annually in 2011 and 2012 than in the years before pneumococcal conjugate vaccine (PCV) use. These data attest to the powerful impact of the PCV program on pneumonia in Tennessee children. The observed trend likely represents a major decline in pneumococcal pneumonia, which should stimulate a reassessment of current causes and appropriate management of pneumonia in children.

Personalized Infant Risk Prediction for Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Requiring Intensive Care Unit Admission.

Background: Currently, there are no available tools to identify infants at the highest risk of significant morbidity and mortality from respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) who would benefit most from RSV prevention products. The objective was to develop and internally validate a personalized risk prediction tool for use among all newborns that uses readily available birth/postnatal data to predict RSV LRTI requiring intensive care unit (ICU) admission. Methods: We conducted a population-based birth cohort study of infants born from 1995 to 2007, insured by the Tennessee Medicaid Program, and who did not receive RSV immunoprophylaxis during the first year of life. The primary outcome was severe RSV LRTI requiring ICU admission during the first year of life. We built a multivariable logistic regression model including demographic and clinical variables available at or shortly after birth to predict the primary outcome. Results: In a population-based sample of 429 365 infants, 713 (0.2%) had severe RSV LRTI requiring ICU admission. The median age of admission was 66 days (interquartile range, 37-120). Our tool, including 19 variables, demonstrated good predictive accuracy (area under the curve, 0.78; 95% confidence interval, 0.77-0.80) and identified infants who did not qualify for palivizumab, based on American Academy of Pediatrics guidelines, but had higher predicted risk levels than infants who qualified (27% of noneligible infants with >0.16% predicted probabilities [lower quartile for eligible infants]). Conclusions: We developed a personalized tool that identified infants at increased risk for severe RSV LRTI requiring ICU admission, expected to benefit most from immunoprophylaxis.

Traditional definition of healthcare-associated influenza underestimates cases associated with other healthcare exposures in a population-based surveillance system.

OBJECTIVE: To provide comprehensive population-level estimates of the burden of healthcare-associated influenza. DESIGN: Retrospective cross-sectional study. SETTING: US Influenza Hospitalization Surveillance Network (FluSurv-NET) during 2012-2013 through 2018-2019 influenza seasons. PATIENTS: Laboratory-confirmed influenza-related hospitalizations in an 8-county catchment area in Tennessee. METHODS: The incidence of healthcare-associated influenza was determined using the traditional definition (ie, positive influenza test after hospital day 3) in addition to often underrecognized cases associated with recent post-acute care facility admission or a recent acute care hospitalization for a noninfluenza illness in the preceding 7 days. RESULTS: Among the 5,904 laboratory-confirmed influenza-related hospitalizations, 147 (2.5%) had traditionally defined healthcare-associated influenza. When we included patients with a positive influenza test obtained in the first 3 days of hospitalization and who were either transferred to the hospital directly from a post-acute care facility or who were recently discharged from an acute care facility for a noninfluenza illness in the preceding 7 days, we identified an additional 1,031 cases (17.5% of all influenza-related hospitalizations). CONCLUSIONS: Including influenza cases associated with preadmission healthcare exposures with traditionally defined cases resulted in an 8-fold higher incidence of healthcare-associated influenza. These results emphasize the importance of capturing other healthcare exposures that may serve as the initial site of viral transmission to provide more comprehensive estimates of the burden of healthcare-associated influenza and to inform improved infection prevention strategies.

The Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Otitis Media-Related Antibiotic Use Among Young Children in Tennessee, USA.

Otitis media (OM) is a leading cause of pediatric antibiotic use. Introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) led to reductions in OM among US children, though its impact on OM-related antibiotic use remains unclear. Among 499 683 Tennessee children <2 years of age, the OM-related antibiotic fill rate was stable after PCV13 introduction.

Human Papillomavirus Vaccine Impact on Cervical Precancers in a Low-Vaccination Population.

INTRODUCTION: Demonstrating human papillomavirus vaccine impact is critical for informing guidelines to increase vaccination and decrease human papillomavirus‒related outcomes, particularly in states with suboptimal vaccination coverage, such as Tennessee. This study examines the trends in high-grade cervical lesion incidence among Tennessee Medicaid-enrolled women aged 18-39 years and the subset of women who were screened for cervical cancer. METHODS: Using a validated claims-based model to identify incident cervical intraepithelial neoplasia Grades 2 or 3 or adenocarcinoma in situ events, annual age group‒specific incidence rates from Tennessee Medicaid billing data, 2008-2018, were calculated. Significant trends were determined by Joinpoint. Analyses were conducted in 2020. RESULTS: From 2008 to 2018, high-grade cervical lesion incidence significantly declined in women aged 18-20 years (average annual percentage change= -31.9, 95% CI= -38.6, -24.6), 21-24 years (average annual percentage change= -12.9, 95% CI= -22.3, -2.4), and 25-29 years (average annual percentage change= -6.4, 95% CI= -8.1, -4.6). Among screened women, rates significantly declined for ages 18-20 years (average annual percentage change= -20.3, 95% CI= -25.3, -15.0), 21-24 years (average annual percentage change= -10.2, 95% CI= -12.6, -7.8), and 25-29 years (average annual percentage change= -2.6, 95% CI= -3.9, -1.2). Trends from 2008 to 2018 were stable for older age groups (30-34 and 35-39 years). CONCLUSIONS: Results show reductions in high-grade cervical lesion incidence among ages most likely to have benefited from the human papillomavirus vaccine. Declines among young, screened women suggest causes other than reduction in screening. Evidence of vaccine impact in populations with low-vaccination coverage, such as Tennessee, is promising.

High asthma prevalence and increased morbidity among rural children in a Medicaid cohort.

BACKGROUND: Urban children represent a group at high risk for asthma development and adverse asthma outcomes. Although rural children also encounter sociodemographic disparities that might be expected to worsen asthma, asthma in the rural United States is poorly studied. OBJECTIVES: To determine rural-urban differences in childhood asthma diagnosis and morbidity. METHODS: We studied a statewide population of 117,080 children continuously enrolled in Tennessee Medicaid from birth through the sixth year of life, using linked Tennessee Medicaid, vital records, and pharmacy claims databases to determine asthma diagnosis and residence. RESULTS: The cohort was 45% urban, 23% suburban, and 33% rural. Compared with urban children, rural children were more likely to be white, have a history of bronchiolitis, and have mothers who smoked. Eleven percent of urban, 12% of suburban, and 13% of rural children met study criteria for asthma diagnosis (adjusted odds ratio for rural children, 1.16; 95% confidence interval, 1.09-1.24; adjusted odds ratio for suburban children, 1.22; 95% confidence interval, 1.14-1.30; with urban as the referent; P < .001). Rural children had greater use of outpatient asthma care, whereas urban children had greater use of inhaled corticosteroids. Compared with urban children, rural children had fewer asthma emergency department visits but were hospitalized for asthma at similar rates and had similar use of asthma rescue medications. CONCLUSION: In this pediatric Medicaid population, rural children had increased asthma prevalence and similar asthma morbidity compared with urban children but differences in patterns of asthma care and resource use, suggesting that optimal interventions for asthma may differ in rural compared with urban populations.

The risk of serious opioid-related events associated with common opioid prescribing regimens in the postpartum period after cesarean delivery.

BACKGROUND: Opioid analgesics are commonly prescribed to women after cesarean delivery. There is a growing effort to prescribe opioids judiciously; however, the risk of serious opioid-related events associated with specific prescribing patterns after cesarean delivery remains unclear. OBJECTIVE: We examined the association between the dosage of the first opioid prescription filled after cesarean delivery and the risk of serious opioid-related events. STUDY DESIGN: We identified opioid-naïve women with a cesarean delivery enrolled in Tennessee Medicaid (2007-2014). Pharmacy prescription fill data characterized opioids filled within 5 days after delivery. Patients were followed up from day 5 after delivery to the earliest of the following: serious opioid-related event (persistent opioid use, evidence of opioid use disorder [diagnosis or methadone or buprenorphine fill], overdose, or opioid-related death), non-opioid-related death, enrollment loss, or 365th day. We estimated the adjusted hazard ratios and 95% confidence intervals for the serious opioid-related event outcomes based on the dosage (morphine milligram equivalents) of the first filled opioid prescription, adjusting for baseline sociodemographic characteristics, delivery complications, multiple deliveries, comorbidities, and medication use. Secondary analyses examined the role of commonly prescribed opioid strengths and quantities. RESULTS: The overall incidence rate of serious opioid-related events among women after cesarean delivery was 3.0 per 100 person-years. Compared with women who did not fill an opioid prescription, the rate of serious opioid-related events was higher among women who filled an opioid prescription, although only significantly higher among women who filled a total dosage of ≥100 morphine milligram equivalents (97.1% of opioid prescriptions). In the secondary analyses, women with a low prescribed daily opioid dosage and women with a low prescribed number of oxycodone (5 mg) tablets (<10 tablets) were not at increased risk of serious opioid-related events compared with women who did not fill an opioid prescription. CONCLUSION: Opioid-naïve women who filled a postpartum opioid prescription at commonly prescribed doses after cesarean delivery had an increased risk of serious opioid-related events compared to women who did not fill a postpartum opioid prescription. Low opioid doses were not associated with a significant increase in the risk of serious opioid-related events.

Improving Cervical Precancer Surveillance: Validity of Claims-Based Prediction Models in ICD-9 and ICD-10 Eras.

Background: Human papillomavirus vaccine (HPV) impact on cervical precancer (cervical intraepithelial neoplasia grades 2+ [CIN2+]) is observable sooner than impact on cancer. Biopsy-confirmed CIN2+ is not included in most US cancer registries. Billing codes could provide surrogate metrics; however, the International Classification of Diseases, ninth (ICD-9) to tenth (ICD-10) transition disrupts trends. We built, validated, and compared claims-based models to identify CIN2+ events in both ICD eras. Methods: A database of Davidson County (Nashville), Tennessee, pathology-confirmed CIN2+ from the HPV Vaccine Impact Monitoring Project (HPV-IMPACT) provided gold standard events. Using Tennessee Medicaid 2008-2017, cervical diagnostic procedures (N = 8549) among Davidson County women aged 18-39 years were randomly split into 60% training and 40% testing sets. Relevant diagnosis, procedure, and screening codes were used to build models from CIN2+ tissue diagnosis codes alone, least absolute shrinkage and selection operator (LASSO), and random forest. Model-classified index events were counted to estimate incident events. Results: HPV-IMPACT identified 983 incident CIN2+ events. Models identified 1007 (LASSO), 1245 (CIN2+ tissue diagnosis codes alone), and 957 (random forest) incident events. LASSO performed well in ICD-9 and ICD-10 eras: 77.3% (95% confidence interval [CI] = 72.5% to 81.5%) vs 81.1% (95% CI = 71.5% to 88.6%) sensitivity, 93.0% (95% CI = 91.9% to 94.0%) vs 90.2% (95% CI = 87.2% to 92.7%) specificity, 61.3% (95% CI = 56.6% to 65.8%) vs 60.3% (95% CI = 51.0% to 69.1%) positive predictive value, 96.6% (95% CI = 95.8% to 97.3%) vs 96.3% (95% CI = 94.1% to 97.8%) negative predictive value, 91.0% (95% CI = 89.9% to 92.1%) vs 88.8% (95% CI = 85.9% to 91.2%) accuracy, and 85.1% (95% CI = 82.9% to 87.4%) vs 85.6% (95% CI = 81.4% to 89.9%) C-indices, respectively; performance did not statistically significantly differ between eras (95% confidence intervals all overlapped). Conclusions: Results confirmed model utility with good performance across both ICD eras for CIN2+ surveillance. Validated claims-based models may be used in future CIN2+ trend analyses to estimate HPV vaccine impact where population-based biopsies are unavailable.

Prescription Opioid Dose After Vaginal Delivery and the Risk of Serious Opioid-Related Events: A Retrospective Cohort Study.

PURPOSE: Postpartum opioid use remains common among women with uncomplicated vaginal delivery and may increase the risk of serious opioid-related events. Therefore, we examined the association between the dose of the first filled opioid prescription after vaginal delivery and the subsequent risk of serious opioid-related events. METHODS: We conducted a retrospective cohort study among women enrolled in Tennessee Medicaid with a vaginal delivery (2007-2015). We used Cox proportional hazards regression to model adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for serious opioid-related events after delivery according to the dose (morphine milligram equivalents [MME]) of the first postpartum opioid prescription, accounting for comorbidities, medication use, parity, and delivery complications. Serious opioid-related events were defined as the occurrence of persistent opioid use, a methadone or buprenorphine fill, opioid use disorder diagnosis, opioid overdose, or opioid-related death. We used filled pharmacy data to characterize the dose of the first postpartum opioid prescription filled within 4 days after delivery. RESULTS: More than one-half of women (53.2%; n = 147,598) filled an opioid prescription within 4 days of a vaginal delivery. After accounting for baseline risk factors, filling a postpartum opioid prescription was associated with an increased risk of serious opioid-related events across all dose categories, compared with women filling none (aHR 1-99 MME, 1.52; 95% CI, 1.33-1.74; aHR 100-149 MME, 1.41; 95% CI, 1.26-1.58; aHR 150-199 MME, 1.40; 95% CI, 1.26-1.57: and aHR ≥200 MME, 1.60; 95% CI, 1.43-1.78). CONCLUSIONS: Filling a postpartum opioid prescription after a vaginal delivery was associated with an increased risk of serious opioid-related events, regardless of dose. Prescribing guidelines should discourage the routine prescribing of opioids after vaginal delivery.