Assessing the Impact of Acute Respiratory Illnesses on the Risk of Subsequent Respiratory Illness.

BACKGROUND: Whether acute respiratory illnesses (ARIs), often associated with virus detection, are associated with lower risk for subsequent ARI remains unclear. We assessed the association between symptomatic ARI and subsequent ARI in young children. METHODS: In a prospective cohort of Peruvian children <3 years, we examined the impact of index ARI on subsequent ARI risk. Index ARI were matched with ≤3 asymptomatic observations and followed over 28 days. We compared risk of subsequent ARI between groups using conditional logistic regression adjusting for several covariates, accounting for repeat observations from individual children. RESULTS: Among 983 index ARI, 339 (34%) had an ARI event during follow-up, compared with 876/2826 (31%) matched asymptomatic observations. We found no significant association of index ARI and subsequent ARI risk during follow-up overall (adjusted odds ratio [aOR], 1.10; 95% confidence interval [CI], .98-1.23) or when limited to index ARI with respiratory viruses detected (aOR, 1.03; 95% CI, .86-1.24). Similarly, when the outcome was limited to ARI in which viruses were detected, no significant association was seen (aOR, 1.05; 95% CI, .87-1.27). CONCLUSIONS: ARIs were not associated with short-term protection against subsequent ARI in these children. Additional longitudinal studies are needed to understand drivers of recurrent ARI in young children.

Impact of prior underinsurance on cervical cancer screening among Davidson County, Tennessee, women diagnosed with invasive cervical cancer, 2008-2018.

INTRODUCTION: We sought to investigate the association between insurance coverage history and cervical cancer screening among Davidson County, Tennessee, women diagnosed with incident cervical cancer. METHODS: We reviewed medical records of women diagnosed with invasive cervical cancer from 2008 through 2018 identified via the state's cancer registry and by active surveillance of diagnostic pathology reports for the HPV-IMPACT project. Per 2012 United States Preventive Services Task Force recommended cervical cancer screening guidelines, women were characterized into three screening history categories: "no screening", "no follow-up" and "test/screening failure". Multivariable logistic regression measured the association of prior inadequate insurance (underinsurance) and screening history ("no screening/no follow-up" compared to "test/screening failure"). RESULTS: Of 212 women, most (77%) had not undergone recommended cervical cancer screening or follow-up prior to cancer diagnosis. Overall, 28% of women had history of underinsurance in 5 years prior to diagnosis. In adjusted analyses, underinsured women were more likely to have a "no screening/no follow-up" prior to cancer diagnosis (aOR 4.26; 95% CI 1.15-15.80) compared to "test/screening failure" history. Non-white race (aOR 2.73; 95% CI 0.98-7.61), older age (aOR 1.03 per year; 95% CI 1.00-1.07), and history of smoking (aOR 4.07; 95% CI 1.54-10.74) were also associated with increased likelihood of "no screening/no follow-up". CONCLUSIONS: Previous underinsurance was independently associated with non-adherence to cervical cancer screening and follow-up guidelines among women with incident cervical cancer. Further study of factors contributing to inadequate cervical cancer screening and interventions to increase cervical cancer screening in high-risk populations is needed.

Risk of Death at 1 Year Following Postpartum Opioid Exposure.

OBJECTIVE: Opioids are commonly prescribed to women for acute pain following childbirth. Postpartum prescription opioid exposure is associated with adverse opioid-related morbidities but the association with all-cause mortality is not well studied. This study aimed to examine the association between postpartum opioid prescription fills and the 1-year risk of all-cause mortality among women with live births. METHODS: In a retrospective cohort study of live births among women enrolled in Tennessee Medicaid (TennCare) between 2007 and 2015, we compared women who filled two or more postpartum outpatient opioid prescriptions (up to 41 days of postdelivery discharge) to women who filled one or fewer opioid prescription. Women were followed from day 42 postdelivery discharge through 365 days of follow-up or date of death. Deaths were identified using linked death certificates (2007-2016). We used Cox's proportional hazard regression and inverse probability of treatment weights to compare time to death between exposure groups while adjusting for relevant confounders. We also examined effect modification by delivery route, race, opioid use disorder, use of benzodiazepines, and mental health condition diagnosis. RESULTS: Among 264,135 eligible births, 216,762 (82.1%) had one or fewer maternal postpartum opioid fills and 47,373 (17.9%) had two or more fills. There were 182 deaths during follow-up. The mortality rate was higher in women with two or more fills (120.5 per 100,000 person-years) than in those with one or fewer (57.7 per 100,000 person-years). The risk of maternal death remained higher in participants exposed to two or more opioid fills after accounting for relevant covariates using inverse probability of treatment weighting (adjusted hazard ratio: 1.46 [95% confidence interval: 1.01, 2.09]). Findings from stratified analyses were consistent with main findings. CONCLUSION: Filling two or more opioid prescriptions during the postpartum period was associated with a significant increase in 1-year risk of death among new mothers. KEY POINTS: · Opioid prescribing in the postpartum period is common.. · Prior studies show that >1 postnatal opioid fill is associated with adverse opioid-related events.. · > 1 opioid fill within 42 days of delivery was associated with an increase in 1-year risk of death..

Data and Safety Monitoring of COVID-19 Vaccine Clinical Trials.

To speed the development of vaccines against SARS-CoV-2, the United States Federal Government has funded multiple phase 3 trials of candidate vaccines. A single 11-member data and safety monitoring board (DSMB) monitors all government-funded trials to ensure coordinated oversight, promote harmonized designs, and allow shared insights related to safety across trials. DSMB reviews encompass 3 domains: (1) the conduct of trials, including overall and subgroup accrual and data quality and completeness; (2) safety, including individual events of concern and comparisons by randomized group; and (3) interim analyses of efficacy when event-driven milestones are met. Challenges have included the scale and pace of the trials, the frequency of safety events related to the combined enrollment of over 100 000 participants, many of whom are older adults or have comorbid conditions that place them at independent risk of serious health events, and the politicized environment in which the trials have taken place.

Prevalence of prescription opioid use during pregnancy in eight US health plans during 2001-2014.

PURPOSE: To estimate prevalence of prescription opioid use during pregnancy in eight US health plans during 2001-2014. METHODS: We conducted a cohort study of singleton live birth deliveries. Maternal characteristics were ascertained from health plan and/or birth certificate data and opioids dispensed during pregnancy from health plan pharmacy records. Prevalence of prescription opioid use during pregnancy was calculated for any use, cumulative days of use, and number of dispensings. RESULTS: We examined prevalence of prescription opioid use during pregnancy in each health plan. Tennessee Medicaid had appreciably greater prevalence of use compared to the seven other health plans. Thus, results for the two groups were reported separately. In the seven health plans (n = 587 093 deliveries), prevalence of use during pregnancy was relatively stable at 9%-11% throughout 2001-2014. In Tennessee Medicaid (n = 256 724 deliveries), prevalence increased from 29% in 2001 to a peak of 36%-37% in 2004-2010, and then declined to 28% in 2014. Use for ≥30 days during pregnancy was stable at 1% in the seven health plans and increased from 2% to 7% in Tennessee Medicaid during 2001-2014. Receipt of ≥5 opioid dispensings during pregnancy increased in the seven health plans (0.3%-0.6%) and Tennessee Medicaid (3%-5%) during 2001-2014. CONCLUSION: During 2001-2014, prescription opioid use during pregnancy was more common in Tennessee Medicaid (peak prevalence in late 2000s) compared to the seven health plans (relatively stable prevalence). Although a small percentage of women had opioid use during pregnancy for ≥30 days or ≥ 5 dispensings, they represent thousands of women during 2001-2014.

Increases in Human Papillomavirus Testing Preceding Diagnosis of Cervical Precancer in 5 US States, 2008-2016.

OBJECTIVE: The aim of the study was to describe trends in human papillomavirus (HPV) testing preceding diagnosis of cervical precancer during a time of changing screening recommendations. MATERIALS AND METHODS: We conducted a cross-sectional analysis of data from active, population-based, laboratory surveillance among 1.5 million residents of 5 areas in the United States. We included women aged 21-39 years diagnosed with cervical intraepithelial neoplasia grades 2, 2/3, or 3 or adenocarcinoma in situ (collectively, CIN2+) during 2008-2016, who had a cytology and/or HPV test before diagnosis (n = 16,359). RESULTS: The proportion of women with an HPV test preceding CIN2+ increased from 42.9% in 2008 to 73.3% in 2016 (p < .01); testing increased in all age groups (21-24 y: 35.3% to 47.6%, 25-29 y: 40.9% to 64.1%, 30-39 y: 51.7% to 85.9%, all p < .01). The HPV testing varied by cytology result and was highest among women with atypical squamous cells of unknown significance (n = 4,310/4,629, 93.1%), negative for intraepithelial lesion or malignancy (n = 446/517, 86.3%), and atypical glandular cells (n = 145/257, 56.4%). By 2016, at least half of all cases in every surveillance area had an HPV test before diagnosis. CONCLUSIONS: During 2008-2016, the proportion of women with an HPV test preceding CIN2+ increased significantly for all age groups, cytology results, and surveillance areas. By 2016, most (85.9%) women aged 30-39 years had an HPV test, consistent with recommendations. Increasing utilization of HPV tests, which have demonstrated improved sensitivity for detecting cervical disease, may in part explain increasing rates of cervical precancer among women 30 years and older.

Cervical adenocarcinoma in situ: Human papillomavirus types and incidence trends in five states, 2008-2015.

Primary prevention through the use of human papillomavirus (HPV) vaccination is expected to impact both cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS). While CIN is well described, less is known about the epidemiology of AIS, a rare cervical precancer. We identified AIS and CIN grade 3 (CIN3) cases through population-based surveillance, and analyzed data on HPV types and incidence trends overall, and among women screened for cervical cancer. From 2008 to 2015, 470 AIS and 6,587 CIN3 cases were identified. The median age of women with AIS was older than those with CIN3 (35 vs. 31 years; p < 0.01). HPV16 was the most frequently detected type in both AIS and CIN3 (57% in AIS; 58% in CIN3), whereas HPV18 was the second most common type in AIS and less common in CIN3 (38% vs. 5%; p < 0.01). AIS lesions were more likely than CIN3 lesions to be positive for high-risk types targeted by the bivalent and quadrivalent vaccines (HPV16/18, 92% vs. 63%; p < 0.01), and 9-valent vaccine (HPV16/18/31/33/45/52/58, 95% vs. 87%; p < 0.01). AIS incidence rates decreased significantly in the 21-24 year age group (annual percent change [APC] overall: -22.1%, 95% CI: -33.9 to -8.2; APC among screened: -16.1%, 95% CI: -28.8 to -1.2), but did not decrease significantly in any older age group. This report on the largest number of genotyped AIS cases to date suggests an important opportunity for vaccine prevention of AIS, and is the first to document a decline in AIS incidence rates among young women during the vaccine era.

Effectiveness of 1, 2, and 3 Doses of Human Papillomavirus Vaccine Against High-Grade Cervical Lesions Positive for Human Papillomavirus 16 or 18.

Before 2016, human papillomavirus (HPV) vaccination was recommended on a 3-dose schedule. However, many vaccine-eligible US females received fewer than 3 doses, which provided an opportunity to evaluate the real-world vaccine effectiveness (VE) of 1, 2, and 3 doses. We analyzed data on cervical intraepithelial neoplasia (CIN) grades 2-3 and adenocarcinoma in situ (designated CIN2+) from the HPV Vaccine Impact Monitoring Project (HPV-IMPACT; 2008-2014). Archived tissue from CIN2+ lesions was tested for 37 types of HPV. Women were classified by number of doses received ≥24 months before CIN2+ detection. Using a test-negative design, VE was estimated as 1 minus the adjusted odds ratio from a logistic regression model that compared vaccination history for women whose lesions tested positive for HPV-16/18 (vaccine-type cases) with that for women who had all other CIN2+ lesions (controls). Among 3,300 women with available data on CIN2+, typing results, and vaccine history, 1,561 (47%) were HPV-16/18-positive, 136 (4%) received 1 dose of HPV vaccine, 108 (3%) received 2 doses, and 325 (10%) received 3 doses. Adjusted odds ratios for vaccination with 1, 2, and 3 doses were 0.53 (95% confidence interval (CI): 0.37, 0.76; VE = 47%), 0.45 (95% CI: 0.30, 0.69; VE = 55%), and 0.26 (95% CI: 0.20, 0.35; VE = 74%), respectively. We found significant VE against vaccine-type CIN2+ after 3 doses of HPV vaccine and lower but significant VE with 1 or 2 doses.

Validity of diagnosis and procedure codes for identifying neural tube defects in infants.

PURPOSE: The use of validated criteria to identify birth defects in electronic healthcare databases can avoid the cost and time-intensive efforts required to conduct chart reviews to confirm outcomes. This study evaluated the validity of various case-finding methodologies to identify neural tube defects (NTDs) in infants using an electronic healthcare database. METHODS: This analysis used data generated from a study whose primary aim was to evaluate the association between first-trimester maternal prescription opioid use and NTDs. The study was conducted within the Medication Exposure in Pregnancy Risk Evaluation Program. A broad approach was used to identify potential NTDs including diagnosis and procedure codes from inpatient and outpatient settings, death certificates and birth defect flags in birth certificates. Potential NTD cases were chart abstracted and confirmed by clinical experts. Positive predictive values (PPVs) and 95% confidence intervals (95% CI) are reported. RESULTS: The cohort included 113 168 singleton live-born infants: 55 960 infants with opioid exposure in pregnancy and 57 208 infants unexposed in pregnancy. Seventy-three potential NTD cases were available for the validation analysis. The overall PPV was 41% using all diagnosis and procedure codes plus birth certificates. Restricting approaches to codes recorded in the infants' medical record or to birth certificate flags increased the PPVs (72% and 80%, respectively) but missed a substantial proportion of confirmed NTDs. CONCLUSIONS: Codes in electronic healthcare data did not accurately identify confirmed NTDs. These results indicate that chart review with adjudication of outcomes is important when conducting observational studies of NTDs using electronic healthcare data.

Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America.

Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.

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.

Trends in High-grade Cervical Lesions and Cervical Cancer Screening in 5 States, 2008-2015.

BACKGROUND: We describe changes in rates of cervical intraepithelial neoplasia grades 2, 3 and adenocarcinoma in situ (CIN2+) during a period of human papillomavirus (HPV) vaccine uptake and changing cervical cancer screening recommendations. METHODS: We conducted population-based laboratory surveillance for CIN2+ in catchment areas in 5 states, 2008-2015. We calculated age-specific CIN2+ rates per 100000 women by age groups. We estimated incidence rate ratios (IRR) of CIN2+ for 2-year periods among all women and among screened women to evaluate changes over time. RESULTS: A total of 16572 CIN2+ cases were reported. Among women aged 18-20 and 21-24 years, CIN2+ rates declined in all sites, whereas in women aged 25-29, 30-34, and 35-39 years, trends differed across sites. The percent of women screened annually declined in all sites and age groups. Compared to 2008-2009, rates among screened women were significantly lower for all 3 periods in women aged 18-20 years (2010-2011: IRR 0.82, 95% confidence interval [CI] 0.67-0.99; 2012-2013: IRR 0.63, 95% CI 0.47-0.85; 2014-2015: IRR 0.44, 95% CI 0.28-0.68) and lower for the latter 2 time periods in women aged 21-24 years (2012-2013: IRR 0.86, 95% CI 0.79-0.94; 2014-2015: IRR 0.61, 95% CI 0.55-0.67). CONCLUSIONS: From 2008-2015, both CIN2+ rates and cervical cancer screening declined in women aged 18-24 years. The significant decreases in CIN2+ rates among screened women aged 18-24 years are consistent with a population-level impact of HPV vaccination.

Nasopharyngeal Pneumococcal Density during Asymptomatic Respiratory Virus Infection and Risk for Subsequent Acute Respiratory Illness.

Increased nasopharyngeal pneumococcal (Streptococcus pneumoniae) colonization density has been associated with invasive pneumococcal disease, but factors that increase pneumococcal density are poorly understood. We evaluated pneumococcal densities in nasopharyngeal samples from asymptomatic young children from Peru and their association with subsequent acute respiratory illness (ARI). Total pneumococcal densities (encompassing all present serotypes) during asymptomatic periods were significantly higher when a respiratory virus was detected versus when no virus was detected (p<0.001). In adjusted analyses, increased pneumococcal density was significantly associated with the risk for a subsequent ARI (p<0.001), whereas asymptomatic viral detection alone was associated with lower risk for subsequent ARI. These findings suggest that interactions between viruses and pneumococci in the nasopharynx during asymptomatic periods might have a role in onset of subsequent ARI. The mechanisms for these interactions, along with other potentially associated host and environmental factors, and their role in ARI pathogenesis and pneumococcal transmission require further elucidation.

Estimated Number of Cases of High-Grade Cervical Lesions Diagnosed Among Women - United States, 2008 and 2016.

Human papillomavirus (HPV) causes approximately 30,000 cancers in the United States annually (1). HPV vaccination was introduced in 2006 to prevent HPV-associated cancers and diseases (1). Cervical cancer is the most common HPV-associated cancer in women (1). Whereas HPV-associated cancers typically take decades to develop, screen-detected high-grade cervical lesions (cervical intraepithelial neoplasia grades 2 [CIN2], 3 [CIN3], and adenocarcinoma in situ, collectively CIN2+) develop within a few years after infection and have been used to monitor HPV vaccine impact (1-3). CDC analyzed data from the Human Papillomavirus Vaccine Impact Monitoring Project (HPV-IMPACT), a population-based CIN2+ surveillance system, to describe rates of CIN2+ among women aged ≥18 years during 2008-2016. Age-specific rates were applied to U.S. population data to estimate the total number of CIN2+ cases diagnosed in the United States in 2008* and in 2016. From 2008 to 2016, the rate of CIN2+ per 100,000 women declined significantly in women aged 18-19 years and 20-24 years and increased significantly in women aged 40-64 years. In the United States in 2008, an estimated 216,000 (95% confidence interval [CI] = 194,000-241,000) CIN2+ cases were diagnosed, 55% of which were in women aged 18-29 years; in 2016, an estimated 196,000 (95% CI = 176,000-221,000) CIN2+ cases were diagnosed, 36% of which were in women aged 18-29 years. During 2008 and 2016, an estimated 76% of CIN2+ cases were attributable to HPV types targeted by the vaccine currently used in the United States. These estimates of CIN2+ cases likely reflect changes in CIN2+ detection resulting from updated cervical cancer screening and management recommendations, as well as primary prevention through HPV vaccination. Increasing coverage of HPV vaccination in females at the routine age of 11 or 12 years and catch-up vaccination through age 26 years will contribute to further reduction in cervical precancers.

Evaluation of weight change and hypoglycaemia as mediators in the association between insulin use and death.

AIM: To evaluate whether weight change or hypoglycaemia mediates the association between insulin use and death. MATERIALS AND METHODS: In a retrospective cohort of veterans who filled a new prescription for metformin and added insulin or sulphonylurea (2001-2012), we assessed change in body mass index (BMI) and hypoglycaemia during the first 12 months of treatment intensification. Cox proportional hazards models compared the risk of death between treatment groups. Using the difference method, we estimated the indirect effect and proportion mediated through each mediator. A sensitivity analysis assessed mediators in the first 6 months of intensified therapy. RESULTS: Among 28 892 patients surviving 12 months, deaths per 1000 person-years were 15.4 for insulin users and 12.9 for sulphonylurea users (HR 1.20, 95% CI 0.87, 1.64). Change in BMI and hypoglycaemia mediated 13% (-98, 98) and -1% (-37, 71) of this association, respectively. Among 30 214 patients surviving 6 months, deaths per 1000 person-years were 34.8 for insulin users and 21.3 for sulphonylurea users (HR 1.66, 95% CI 1.28, 2.15). Change in BMI and hypoglycaemia mediated 9% (1, 23) and 0% (-9, 4) of this association, respectively. CONCLUSIONS: We observed an increased risk of death among metformin users intensifying treatment with insulin versus sulphonylurea and surviving 6 months of intensified therapy, but not among those surviving 12 months. This association was mediated in part by weight change.

A comparison of two algorithms to identify sudden cardiac deaths in computerized databases.

PURPOSE: Two previously validated algorithms to identify sudden cardiac death using administrative data showed high positive predictive value. We evaluated the agreement between the algorithms using data from a common source population. METHODS: We conducted a cross-sectional study to assess the percent agreement between deaths identified by two sudden cardiac death algorithms using Tennessee Medicaid and death certificate data from 2007 through 2014. The source population included all deceased patients aged 18 to 64 years with Medicaid enrollment in the 6 months prior to death. To identify sudden cardiac deaths, algorithm 1 used only hospital/emergency department (ED) claims from encounters at the time of death, and algorithm 2 required death certificates and used claims data for specific exclusion criteria. RESULTS: We identified 34 107 deaths in the source population over the study period. The two algorithms identified 4372 potential sudden cardiac deaths: Algorithm 1 identified 3117 (71.3%) and algorithm 2 identified 1715 (39.2%), with 460 (10.5%) deaths identified by both algorithms. Of the deaths identified by algorithm 1, 1943 (62.3%) had an underlying cause of death not specified in algorithm 2. Of the deaths identified by algorithm 2, 1053 (61.4%) had no record of a hospital or ED encounter at the time of death, and 202 (11.8%) had a discharge diagnosis code not specified in algorithm 1. CONCLUSIONS: We found low agreement between the two algorithms for identification of sudden cardiac deaths because of differences in sudden cardiac death definitions and data sources.

Accuracy of a composite event definition for hypoglycemia.

PURPOSE: To evaluate the accuracy of a composite definition for the identification of hypoglycemia events that used both administrative claims and laboratory data in a cohort of patients. METHODS: We reviewed medical records in a sample of presumed hypoglycemia events among patients who received care at the Veterans Health Administration Tennessee Valley Healthcare System in 2001 to 2012. A hypoglycemia event was defined as a hospitalization or emergency department visit judged by the treating clinician to be due to hypoglycemia, or an outpatient laboratory or point-of-care blood glucose measurement <60 mg/dL. Based on medical record review, each event was classified as true positive (severe, documented symptomatic, documented asymptomatic) or false positive (probable symptomatic, not hypoglycemia). The positive predictive values (PPV) of the individual event types (hospitalization, emergency department, and outpatient) were estimated. RESULTS: Of 2250 events identified through the composite definition, 321 events (15 hospitalizations, 103 emergency department visits, and 203 outpatient events) were reviewed. The PPVs were 80% for hospitalization events, 48% for emergency department events, and 96% for outpatient events. The emergency department definition included a nonspecific diagnosis code for diabetic complications which captured many false positive events. Excluding this code from the definition improved the PPV for emergency department events to 70% and missed one true event. CONCLUSIONS: Our composite definition for hypoglycemia performed moderately well in a cohort of Veterans. Further evaluation of the emergency department events may be needed.

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.