Disease Burden and Health-Related Quality of Life (HRQoL) of Chronic Obstructive Pulmonary Disease (COPD) in the US - Evidence from the Medical Expenditure Panel Survey (MEPS) from 2016-2019.

Purpose: Chronic obstructive pulmonary disease (COPD) is a progressive disease associated with reduced life expectancy, increased morbidity, mortality, and cost. This study characterized the US COPD burden, including socioeconomic and health-related quality of life (HRQoL) outcomes. Study Design and Methods: In this retrospective, cross-sectional study using nationally representative estimates from Medical Expenditures Survey (MEPS) data (2016-2019), adults (≥18 years) living with and without COPD were identified. Adults living without COPD (control cohort) and with COPD were matched 5:1 on age, sex, geographic region, and entry year. Demographics, clinical characteristics, socioeconomic, and generic HRQoL measures were examined to include a race-stratified analysis of people living with COPD. Results: A total of 4,135 people living with COPD were identified; the matched dataset represented a weighted non-institutionalized population of 11.3 million with and 54.2 million people without COPD. Among people living with COPD, 66.3% had ≥1 COPD-related condition; 62.7% had ≥1 cardiovascular condition, compared to 33.5% and 50.5% without COPD. More people living with COPD were unemployed (56.2% vs 45.3%), unable to work due to illness/disability (30.1% vs 12.1%), had problems paying bills (16.1% vs 8.8%), reported poorer perceived health (fair/poor: 36.2% vs 14.4%), missed more working days due to illness/injury per year (median, 2.5 days vs 0.0 days), and had limitations in physical functioning (40.1% vs 19.4%) (all P<0.0001). In race-stratified analyses for people living with COPD, people self-reporting as Black had higher prevalence of cardiovascular-risk conditions, poorer socioeconomic and HRQoL outcomes, and higher healthcare expenses than White or Other races. Conclusion: Adults living with COPD had higher clinical disease burden, lower socioeconomic status, and reduced HRQoL than those without, with greater disparities among Black people living with COPD compared to White and other races. Understanding the characteristics of patients helps address care disparities and access challenges.

Development and validation of a claims-based algorithm to identify moderate exacerbations in patients with asthma treated in the US.

INTRODUCTION: Definitions of moderate asthma exacerbation have been inconsistent, making their economic burden difficult to assess. An algorithm to accurately identify moderate exacerbations from claims data is needed. METHODS: A retrospective cohort study of Reliant Medical Group patients aged ≥18 years, with ≥1 prescription claim for inhaled corticosteroid/long-acting ß2-agonist, and ≥1 medical claim with a diagnosis code for asthma was conducted. The objective was to refine current algorithms to identify moderate exacerbations in claims data and assess the refined algorithm's performance. Positive and negative predictive values (PPV and NPV) were assessed via chart review of 150 moderate exacerbations events and 50 patients without exacerbations. Sensitivity analyses assessed alternative algorithms and compared healthcare resource utilization (HRU) between algorithm-identified patients (claims group) and those confirmed by chart review (confirmed group) to have experienced a moderate exacerbation. RESULTS: Algorithm-identified moderate exacerbations were: visit of ≤1 day with an asthma exacerbation diagnosis OR visit of ≤1 day with selected asthma diagnoses AND ≥1 respiratory pharmacy claim, excluding systemic corticosteroids, within 14 days after the first claim. The algorithm's PPV was 42%; the NPV was 78%. HRU was similar for both groups. CONCLUSION: This algorithm identified potential moderate exacerbations from claims data; however, the modest PPV underscores its limitations in identifying moderate exacerbations, although performance was partially due to identification of previously unidentified severe exacerbations. Application of this algorithm in future claims-based studies may help quantify the economic burden of moderate and severe exacerbations in asthma when an algorithm identifying severe exacerbations is applied first.

Frequency and economic burden of exacerbations in inhaled corticosteroid/long-acting beta-agonist-treated patients with asthma: A retrospective US claims study.

INTRODUCTION: Despite adherence to inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) therapy, many patients with asthma experience moderate exacerbations. Data on the impact of moderate exacerbations on the healthcare system are limited. This study assessed the frequency and economic burden of moderate exacerbations in patients receiving ICS/LABA. METHODS: Retrospective, longitudinal study analyzed data from Optum's de-identified Clinformatics® Data Mart Database recorded between October 1, 2015, and December 31, 2019. Eligibility criteria included patients ≥18 years of age with ≥1 ICS/LABA claim and ≥1 medical claim for asthma in the 12 months pre-index (first ICS/LABA claim). Primary objectives included describing moderate exacerbation frequency, and associated healthcare resource utilization (HRU) and costs. A secondary objective was assessing the relationship between moderate exacerbations and subsequent risk of severe exacerbations. Patients were stratified by moderate exacerbation frequency in the 12 months post index. Moderate exacerbations were identified using a newly developed algorithm. RESULTS: In the first 12 months post index 61.6% of patients experienced ≥1 moderate exacerbation. Mean number of asthma-related visits was 4.1 per person/year and median total asthma-related costs was $3544. HRU and costs increased with increasing exacerbation frequency. Outpatient and inpatient visits accounted for a similar proportion of these costs. Moderate exacerbations were associated with an increased rate and risk of future severe exacerbations (incidence rate ratio, 1.56; hazard ratio, 1.51 [both p < 0.001]). CONCLUSIONS: This study highlighted that a high proportion of patients continue to experience moderate exacerbations despite ICS/LABA therapy and subsequently experience increased economic burden and risk of future severe exacerbations.

Independent and Combined Effects of Prenatal Alcohol Exposure and Prenatal Stress on Fetal HPA Axis Development.

Prenatal alcohol exposure (PAE) and prenatal stress (PS) are highly prevalent conditions known to affect fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis. The objectives of this study were to assess the effect of light PAE, PS, and PAE-PS interaction on fetal HPA axis activity assessed via placental and umbilical cord blood biomarkers. Participants of the ENRICH-2 cohort were recruited during the second trimester and classified into the PAE and unexposed control groups. PS was assessed by the Perceived Stress Scale. Placental tissue was collected promptly after delivery; gene and protein analysis for 11ß-HSD1, 11ß-HSD2, and pCRH were conducted by qPCR and ELISA, respectively. Umbilical cord blood was analyzed for cortisone and cortisol. Pearson correlation and multivariable linear regression examined the association of PAE and PS with HPA axis biomarkers. Mean alcohol consumption in the PAE group was ~2 drinks/week. Higher PS was observed in the PAE group (p < 0.01). In multivariable modeling, PS was associated with pCRH gene expression (ß = 0.006, p < 0.01), while PAE was associated with 11ß-HSD2 protein expression (ß = 0.56, p < 0.01). A significant alcohol-by-stress interaction was observed with respect to 11ß-HSD2 protein expression (p < 0.01). Results indicate that PAE and PS may independently and in combination affect fetal programming of the HPA axis.

Potentially modifiable risk and protective factors affecting mental and emotional wellness in pregnancy.

Introduction: Impaired mental and emotional wellness often co-occurs with prenatal substance use, and both affect infant socio-emotional, cognitive, language, motor, and adaptive behavioral outcomes. Guided by the modified biopsychosocial framework, this study examined the role of common substance exposures during pregnancy (i.e., alcohol and cannabis), socio-cultural factors (social support during pregnancy, adverse childhood experiences), and reproductive health factors on maternal mental health (MMH). Methods: Data were obtained from a prospective cohort study-Ethanol, Neurodevelopment, Infant, and Child Health (ENRICH-2), and included 202 pregnant persons. Alcohol and cannabis exposures were assessed through repeated prospective interviews and a comprehensive battery of drug and ethanol biomarkers. MMH outcomes were evaluated during the third trimester through the Perceived Stress Scale, Edinburgh Depression Scale, Generalized Anxiety Disorders-7, and Post-traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders. Univariate and multivariable linear regression models evaluated significant predictors of MMH. Results: Results of multivariable analysis indicate that both maternal adverse childhood experiences and alcohol exposure, even at low-to-moderate levels, during pregnancy were associated with poorer scores for most MMH measures, while higher level of social support and Spanish as the primary language at home (as a proxy of enculturation) had protective effects (all p's < 0.05). Conclusion: These findings highlight the importance of assessing substance use, including periconceptional alcohol exposure, and mental health in pregnant persons as closely related risk factors which cannot be addressed in isolation. Our findings also emphasize a strong protective effect of socio-cultural factors on maternal mental and emotional wellbeing-a strong precursor to maternal-infant bonding and infant neurodevelopment.

Dose-response effect of prenatal alcohol exposure on perinatal outcomes.

BACKGROUND: A better understanding of the effects of lower levels of prenatal alcohol exposure (PAE), as a common exposure, is needed. The goal of this study was to examine the effects of mild-moderate PAE and episodic binge drinking on perinatal outcomes. METHODS: The data were obtained from three prospective cohorts with a combined sample of 281 participants: 125 with PAE and 156 without PAE. Alcohol-related measures included the Alcohol Use Disorders Identification Test, timeline follow-back questionnaires (covering the periconceptional period, mid-gestation, and late gestation), and biomarkers. Absolute alcohol per day (AAD) and per drinking day (AADD), number of binge episodes, and maximum number of drinks in a 24-h period were estimated. Perinatal outcomes included gestational age and anthropometric measures. Data were analyzed using correlation and multivariable regression analysis. RESULTS: Among women with PAE, average alcohol consumption across the periconceptional period and pregnancy was 0.37 oz ± 0.74 AA/day (~5 drinks/week). After adjusting for tobacco co-exposure and sociodemographic characteristics, significant associations between all alcohol measures and gestational age at delivery were observed, including cumulative measures of AAD (ß = -0.58; 95% CI: -0.98; -0.17) and AADD (ß = -0.58; 95% CI: -0.90; -0.26) during pregnancy and the periconceptional period. A significant association between the maximum number of drinks in a 24-h period and birth length percentile (ß = -0.70; 95% CI: -1.36; -0.04) was observed in the final model. PAE was associated with lower birth weight percentile in univariate analyses only. CONCLUSIONS: Results of this study demonstrate a negative association between mild-moderate PAE and episodic binge drinking with gestational age at delivery and birth length percentile after controlling for other factors. Robust negative effects of PAE, including in the periconceptional period before pregnancy recognition, on duration of gestation highlight the need for primary prevention efforts aimed at PAE in persons of reproductive age.

Impact of low-level prenatal alcohol exposure and maternal stress on autonomic regulation.

BACKGROUND: Prenatal alcohol exposure (PAE) impacts the neurodevelopment of the fetus, including the infant's ability to self-regulate. Heart rate variability (HRV), that is, the beat-to-beat variability in heart rate, is a non-invasive measurement that can indicate autonomic nervous system (ANS) function/dysfunction. METHODS: The study consisted of a subset of our ENRICH-2 cohort: 80 participants (32 PAE and 48 Controls) who had completed three visits during pregnancy. The participants completed a comprehensive assessment of PAE and other substances throughout pregnancy and assessments for stress, anxiety, and depression in the third trimester. At 24 h of age, infant HRV was assessed in the hospital during the clinically indicated heel lance; 3- to 5-min HRV epochs were obtained during baseline, heel lancing, and recovery episodes. RESULTS: Parameters of HRV differed in infants with PAE compared to Controls during the recovery phase of the heel lance (respiratory sinus arrhythmia (RSA) and high-frequency (HF), p < 0.05). Increased maternal stress was also strongly associated with abnormalities in RSA, HF, and low-frequency / high-frequency (LF/HF, p's < 0.05). CONCLUSIONS: Alterations in ANS regulation associated with PAE and maternal stress may reflect abnormal development of the hypothalamic-pituitary-adrenal axis and have long term implications for infant responsiveness and self-regulation. IMPACT: Previous studies have focused on effects of moderate to heavy prenatal alcohol exposure (PAE) on autonomic dysregulation, but little is known about the effects of lower levels of PAE on infant self-regulation and heart rate variability (HRV). Prenatal stress is another risk factor for autonomic dysregulation. Mild PAE impacts infant self-regulation, which can be assessed using HRV. However, the effect of prenatal stress is stronger than that of mild PAE or other mental health variables on autonomic dysregulation.

National and Local Direct Medical Cost Burden of COPD in the United States From 2016 to 2019 and Projections Through 2029.

BACKGROUND: Despite the significant burden posed by COPD to health care systems, there is a lack of up-to-date information quantifying the general COPD burden, costs, and long-term projections to various stakeholders in the United States. RESEARCH QUESTION: What are the updated state-specific and nationwide estimates of the COPD disease burden and direct costs in 2019, along with projections of COPD-attributable medical costs through 2029? STUDY DESIGN AND METHODS: A cross-sectional, retrospective study design using the 2016 to 2019 Medical Expenditure Panel Survey, 2019 American Community Survey, and 2019 Behavioral Risk Factor Surveillance System data was applied to generate COPD-attributable expenditure estimates. Cost projections for the years 2020 to 2029 were based on 2017 national population projections reported by the US Census Bureau, and all costs were adjusted to 2019 US dollars. RESULTS: In total, 4,135 people living with COPD were included; a higher proportion had other concurrent conditions such as cardiovascular-related conditions compared with people without COPD (n = 86,021). Overall, in 2019, COPD-attributable medical costs after adjusting for demographic characteristics and 19 concurrent conditions (including COPD-related and non-COPD-related conditions) were estimated at $31.3 billion, with state-specific cost estimates reporting wide variation, from $44.8 million in Alaska to $3.1 billion in Florida. Nationwide COPD-attributable medical costs borne by payer type were as follows: private insurance, $11.4 billion; Medicare, $10.8 billion; and Medicaid, $3.0 billion. Projections of national medical costs attributable to COPD are reported to increase to $60.5 billion in 2029. INTERPRETATION: Understanding the current disease and economic burden of COPD in the United States, along with the projected costs attributable to COPD in the next decade, will highlight unmet needs and gaps in care that help inform health care decision-makers in planning future actions to alleviate this disease burden.

The effect of the COVID-19 pandemic on substance use patterns and physiological dysregulation in pregnant and postpartum women.

BACKGROUND: The SARS-CoV-2/COVID-19 pandemic has been associated with increased stress levels and higher alcohol use, including in pregnant and postpartum women. In the general population, alcohol use is associated with dysregulation in the autonomic nervous system (ANS), which is indexed by heart rate variability (HRV). The objectives of this study were to: (1) characterize changes in substance use during the SARS-CoV-2/COVID-19 pandemic via a baseline self-report survey followed by mobile ecological momentary assessment (mEMA) of substance use; and (2) examine the associations between momentary substance use and ambulatory HRV measures in pregnant and postpartum women. METHODS: Pregnant and postpartum women were identified from the ENRICH-2 prospective cohort study. Participants were administered a baseline structured phone interview that included the Coronavirus Perinatal Experiences (COPE) survey and ascertained the prevalence of substance use. Over a 14-day period, momentary substance use was assessed three times daily, and HRV measurements were captured via wearable electronics. Associations between momentary substance use and HRV measures (root mean square of successive differences [RMSSD] and low frequency/high frequency [LF/HF] ratio) were examined using a mixed effects model that included within-subject (WS) and between-subject (BS) effects and adjusted for pregnancy status and participant age. RESULTS: The sample included 49 pregnant and 22 postpartum women. From a combination of a baseline and 14-day mEMA surveys, 21.2% reported alcohol use, 16.9% reported marijuana use, and 8.5% reported nicotine use. WS effects for momentary alcohol use were associated with the RMSSD (ß = -0.14; p = 0.005) and LF/HF ratio (ß = 0.14; p = 0.01) when controlling for pregnancy status and maternal age. No significant associations were observed between HRV measures and instances of marijuana or nicotine use. CONCLUSIONS: These findings highlight the negative effect of the SARS-CoV-2/COVID-19 pandemic on the psychological health of pregnant and postpartum women associated with substance use, and in turn, ANS dysregulation, which potentially puts some women at risk of developing a substance use disorder.

Impulsivity and Alcohol Use during Pregnancy and Postpartum: Insights from Novel Methodological Approaches within the Context of the COVID-19 Pandemic.

Impaired emotion regulation and impulsivity have been linked to substance use. This study evaluated the association between emotion regulation difficulties-specifically impulsivity-and substance use within the context of the COVID-19 pandemic among pregnant (n = 49) and postpartum (n = 20) women. Participants from a prospective cohort ENRICH-2 completed a baseline phone survey of COVID-19-related experiences and impulsivity followed by a 14-day (3x/day) mobile ecological momentary assessment (mEMA) of impulsivity and substance use. Between-subject (BS) and within-subject (WS) associations for baseline impulsivity and momentary impulsivity with respect to substance use were examined using mixed effects models. At the BS level, momentary impulsivity scores that were higher than the overall group average were positively associated with subsequent momentary reports of marijuana use (ß = 1.25; p = 0.04) when controlling for pregnancy status and COVID-19-related stress. At the WS level, momentary impulsivity scores that were higher than an individual's average score were positively associated with subsequent reports of momentary alcohol use (ß = 0.08; p = 0.04). This research supports the idea that impulsivity varies based on individual situations, such as stress associated with the COVID-19 pandemic, and may be an important correlate of substance use in pregnant and postpartum women. Future research might consider investigation of additional factors, which may serve to moderate or mediate the relationship between impulsivity and substance use.

Multiple sclerosis in Indigenous Peoples of the Americas: A systematic review of incidence, prevalence, and outcomes.

INTRODUCTION: The incidence, prevalence and outcomes of multiple sclerosis (MS) are unclear in Indigenous Peoples (IP) who are more likely to be underrepresented in research. We completed a systematic review of MS in IP of the Americas. METHODS: A systematic review was conducted using PubMed, Web of Science, and Cochrane databases as well as references of retrieved papers. Inclusion criteria were: peer-reviewed publications (January 1990- December 2021), incidence, prevalence, or clinical outcome measures of MS in self-identified IP in the Americas. Incidence, prevalence, morbidity and mortality data were summarized and stratified by location and year of publication. Study quality was evaluated by risk of bias or confounding. RESULTS: Out of 416 titles, thirteen studies met inclusion criteria. Four studies evaluated incidence, seven prevalence, three clinical outcomes and one mortality. Most studies were completed in Canada or the United States (US). Incidence rates per 100,000 ranged from 0.48 (in US Indian Health Service records) to 8.15 (First Nations Manitoban Canadians). Prevalence ranged from 0 (Lacandonian Mexicans and Panamanians) to 188.5 (First Nations Manitoban Canadians). Incidence and prevalence are consistently lower in IP than comparator White populations. IP with MS were reported to have higher disability and faster disability progression than non-Indigenous comparators. MS-related mortality is low compared to White people. CONCLUSION: There is an absence of high-quality studies evaluating MS in IP. Available evidence indicates low, but increasing incidence and prevalence of MS in IP of the Americas. IP with MS may have worse disability than non-Indigenous comparators. Future studies should evaluate the factors influencing the increases in incidence and prevalence as well as better characterize possible disparities in MS care among IP.

Preferences for pharmacogenomic testing in polypharmacy patients: a discrete choice experiment.

Aim: To elicit preferences for pharmacogenomic (PGx) testing in polypharmacy patients. Materials & methods: A face-to-face discrete choice experiment survey was designed and administered to adult polypharmacy patients recruited at a local retail pharmacy in Albuquerque (NM, USA). Results: A total of 128 eligible polypharmacy patients completed the discrete choice experiment survey and significantly preferred a PGx test with lower cost, better confidentiality and higher certainty of identifying best medication/dose and side effects and one that can be used to advocate for their treatment needs (all p < 0.01). Conclusion: This is the first study eliciting preferences for PGx testing among polypharmacy patients. The study found most polypharmacy patients were willing to take a PGx test and their preferences were mostly influenced by test cost.

Patients who concurrently take five or more medications are at a higher risk of experiencing side effects related to drug­drug/drug­gene interactions. 'One size doesn't fit all' ­ individuals may respond differently to the same dose of a medication. Pharmacogenomic (PGx) testing identifies individual genetic information that may help explain better or worse outcomes or potential problems with drug therapies and eventually may help optimize patient treatment. The authors conducted a face-to-face survey to assess preferences for PGx testing in polypharmacy patients and found that most polypharmacy patients were willing to take a PGx test and their preferences were mostly influenced by test cost and performance, as well as the confidentiality of test results.

Early developmental trajectory of children with prenatal alcohol and opioid exposure.

BACKGROUND: With significant increases in opioid use/misuse and persistent high prevalence of prenatal alcohol exposure (PAE), identifying infants at risk for long-term developmental sequelae due to these exposures remains an urgent need. This study reports on developmental outcomes in young children from a prospective cohort, ENRICH-1, which recruited pregnant women and followed up maternal-infant pairs. METHODS: Subjects were assigned to four study groups based on prenatal use of medications for opioid use disorder (MOUD), PAE, MOUD+PAE, and unexposed controls (UC). Mixed effects modeling was used to evaluate changes in the Bayley Scales of Infant Development-III (BSID-III) Cognitive, Language, and Motor scores between 6 and 20 months. RESULTS: There was a significant three-way interaction (MOUD-by-PAE-by-Time) with respect to the BSID-III Cognitive (p = 0.045) and Motor (p = 0.033) scales. Significant changes between the two evaluations were observed for MOUD group in Cognitive and Language scores; for PAE group in Cognitive, Language, and Motor scores, and for MOUD+PAE group in Language scores after adjusting for child sex and family socio-economic status. The developmental scores for the UC remained stable. CONCLUSION: Observed decline in neurodevelopmental scores during the first 2 years of life emphasizes the importance of a longitudinal approach when evaluating children with prenatal polysubstance exposure. IMPACT: BSID-III scores were stable during the first 2 years of life for unexposed children. BSID-III scores declined for children with prenatal exposures to alcohol and/or opioids. Standard developmental tests may not be sensitive enough during the first year of life. Findings emphasize the need for repeated evaluations of children who are at high risk.

Sodium-Glucose Cotransporter 2 Inhibitor Use Among Individuals Age <65 with Type 2 Diabetes and Heart Failure with Reduced Ejection Fraction: A Cost-Benefit Analysis.

Background: Type 2 diabetes (T2D) patients face increased risk of heart failure (HF) as they age. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) have demonstrated effectiveness in reducing HF hospitalizations in patients with T2D and HF with reduced ejection fraction (HFrEF). Diabetes guidelines recommend SGLT-2i therapy for patients with HFrEF; however, SGLT-2i cost is high. Objective: Study objectives were to assess SGLT-2i utilization and HF hospitalization rates in commercially insured adults (age <65) with T2D and heart failure with reduced ejection fraction (HFrEF) taking metformin with/without SGLT-2i use and conduct a cost-benefit analysis of SGLT-2i use from payer and societal perspectives. Methods: Economic models included HF hospitalization rates from real-world data (RWD) and hospitalization rate reductions from RWD and SGLT-2i clinical trials. Real-world HF hospitalization rates were obtained from claims data (MarketScan Commercial Database, years 2013-2018). Societal perspective analyses included indirect costs. Sensitivity analyses were conducted on key parameters. Results: Among adults with T2D and HFrEF age 30-64, SGLT-2i use increased (1.1% to 17.4%) between 2013 and 2018. The HF hospitalization rate without SGLT-2i use vs with was 15.5% vs 11.0% (absolute risk reduction of 4.5%). Base case scenario net-benefit was negative across all payer perspective models, while positive for societal-perspective. Payer perspective overall net-benefit in 30-64 population: -$1,725,758 (-$4106 per person). Societal perspective net-benefit in 30-64 population: $5,996,851 ($14,269 per person). In sensitivity analyses, estimated per person base case societal net-benefit of $14,269 was most sensitive to changes in baseline HF hospitalization rates, post-discharge mortality rates, and readmission rates. Lowering SGLT-2i prescription costs 50% and 80% resulted in per person net-benefit increases of $1737 and $4004, respectively. Conclusion: SGLT-2i utilization has steadily increased, with lower HF hospitalization rates observed among SGLT-2i users. Societal benefits of SGLT-2i use in this population are substantive; payer benefits are negative unless SGLT-2i cost is drastically reduced.

Frailty Among Older Individuals with and without COPD: A Cohort Study of Prevalence and Association with Adverse Outcomes.

Rationale: Frailty prevalence estimates among individuals with COPD have varied widely, and few studies have investigated relationships between frailty and adverse outcomes in a COPD population. Objectives: Describe frailty prevalence among individuals with and without COPD and examine associations between frailty and mortality and other adverse outcomes in the next two years. Methods: This was an observational cohort study using Health and Retirement Study data (2006-2018) of community living individuals ages 50-64 and ≥65 with and without COPD (non-COPD). Frailty (Fried phenotype [5 items], and a modified Frailty Index-Comprehensive Geriatric Assessment [Enhanced FI-CGA] [37 items], and debility (modified BODE Index [4 items]) were assessed. Two-year post-assessment outcomes (mortality, ≥1 inpatient stay, home health and skilled nursing facility (SNF) use) were reviewed in a population matched 3:1 (non-COPD: COPD) on age, sex, race, and year using univariate and multivariate logistic regression (adjusted for morbidities). Area-under-the-curve (AUC) was used to evaluate regressions. Results: The study included 18,979 survey observations for age 50-64, and 24,162 age ≥65; 7.8% and 12.0% respectively reporting a diagnosis of COPD. Fried phenotype frailty prevalence for age ≥65 was 23.1% (COPD) and 9.4% (non-COPD), and for the Enhanced FI-CGA, 45.9% (COPD) and 22.4% (non-COPD). Two-year mortality for COPD was more than double non-COPD for age 50-64 (95% CI: 3.8-5.9% vs 0.7-1.3%) and age ≥65 (95% CI: 11.9-14.3% vs 5.6-6.6%). Inpatient utilization, home health care use, or at least temporary SNF placement were also more frequent for COPD. Measures were predictive of adverse outcomes. In adjusted models, the Fried phenotype and modified BODE score performed similarly, and both performed better than the Enhanced FI-CGA index. AUC values were higher for morality regressions. Conclusion: Frailty prevalence among individuals with COPD in this national survey is substantially greater than without COPD, even at pre-retirement (50-64 years). These measures identify patients with increased risk of poor outcomes.

Prenatal opioid-exposed infant extracellular miRNA signature obtained at birth predicts severity of neonatal opioid withdrawal syndrome.

Prenatal opioid exposure (POE) is commonly associated with neonatal opioid withdrawal syndrome (NOWS), which is characterized by a broad variability in symptoms and severity. Currently there are no diagnostic tools to reliably predict which infants will develop severe NOWS, while risk stratification would allow for proactive decisions about appropriate clinical monitoring and interventions. The aim of this prospective cohort study was to assess if extracellular microRNAs (miRNAs) in umbilical cord plasma of infants with POE could predict NOWS severity. Participants (n = 58) consisted of pregnant women receiving medications for opioid use disorder and their infants. NOWS severity was operationalized as the need for pharmacologic treatment and prolonged hospitalization (≥ 14 days). Cord blood miRNAs were assessed using semi-quantitative qRT-PCR arrays. Receiver operating characteristic curves and area under the curve (AUC) were estimated. The expression of three miRNAs (miR-128-3p, miR-30c-5p, miR-421) predicted need for pharmacologic treatment (AUC: 0.85) and prolonged hospitalization (AUC: 0.90). Predictive validity improved after two miRNAs (let-7d-5p, miR-584-5p) were added to the need for pharmacologic treatment model (AUC: 0.94) and another two miRNAs (let-7b-5p, miR-10-5p) to the prolonged hospitalization model (AUC: 0.99). Infant cord blood extracellular miRNAs can proactively identify opioid-exposed neonates at high-risk for developing severe NOWS.

CONSIDER New Mexico: Effects of naloxone training among pharmacists and pharmacy technicians.

BACKGROUND: Pharmacists serve a critical role in providing health care, especially in medically underserved areas. Despite the opioid crisis and legislation in most states allowing pharmacists to dispense naloxone without a prescription from another provider, pharmacists face multiple barriers to dispensing naloxone. OBJECTIVE: This study tested the effectiveness of CONSIDER New Mexico, an innovative educational initiative designed to increase naloxone dispensing by pharmacies. METHODS: A quasi-experimental study was conducted in New Mexico in 2019-2020. Community pharmacists and pharmacy technicians were recruited from a purposive sample of pharmacies. Data were collected through pre- and postintervention surveys with 65 pharmacists and 44 technicians from 49 pharmacies. Data analysis included hybrid fixed-effects regression models of variables associated with pre-post intervention change in intent to dispense naloxone and generalized least squares with maximum likelihood estimation for pre-post intervention change in naloxone dispensing. RESULTS: Positive intervention effects were observed for measures of normative beliefs, self-efficacy, and intent to dispense naloxone (P < 0.05). Changes in normative beliefs and self-efficacy were associated with greater intent to offer naloxone to patients (P < 0.05). In addition, the median number of naloxone prescriptions dispensed per month increased 3.5 times after intervention. A statistically significant positive association was observed between the intervention and naloxone dispensing after adjusting for other factors (P < 0.001). Pharmacies providing more than 4 additional health services were more likely to increase naloxone dispensing postintervention than pharmacies offering not more than 2 services (P < 0.01). This difference averaged 19 naloxone prescriptions per month. Estimated change in dispensing postintervention was statistically significantly lower at independent, clinic-based, and other pharmacies where an average of 36 fewer naloxone prescriptions were dispensed per month compared with chain drug stores (P = 0.03). CONCLUSION: The CONSIDER New Mexico intervention effectively increased self-efficacy, intent to dispense, and naloxone dispensing. Findings will inform future research examining widespread dissemination and implementation of the intervention and the sustainability of intervention effects.

Development and Validation of a Healthcare Utilization-Based Algorithm to Identify Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Introduction: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are important events that may precipitate other adverse outcomes. Accurate AECOPD event identification in electronic administrative data is essential for improving population health surveillance and practice management. Objective: Develop codified algorithms to identify moderate and severe AECOPD in two US healthcare systems using administrative data and electronic medical records, and validate their performance by calculating positive predictive value (PPV) and negative predictive value (NPV). Methods: Data from two large regional integrated health systems were used. Eligible patients were identified using International Classification of Diseases (Ninth Edition) COPD diagnosis codes. Two algorithms were developed: one to identify potential moderate AECOPD by selecting outpatient/emergency visits associated with AECOPD-related codes and antibiotic/systemic steroid prescriptions; the other to identify potential severe AECOPD by selecting inpatient visits associated with corresponding codes. Algorithms were validated via patient chart review, adjudicated by a pulmonologist. To estimate PPV, 300 potential moderate AECOPD and 250 potential severe AECOPD events underwent review. To estimate NPV, 200 patients without any AECOPD identified by the algorithms (100 patients each without moderate or severe AECOPD) during the two years following the index date underwent review to identify AECOPD missed by the algorithm (false negatives). Results: The PPVs (95% confidence interval [CI]) for both moderate and severe AECOPD were high: 293/298 (98.3% [96.1-99.5]) and 216/225 (96.0% [92.5-98.2]), respectively. NPV was lower for moderate AECOPD (75.0% [65.3-83.1]) than for severe AECOPD (95.0% [88.7-98.4]). Results were consistent across both healthcare systems. Conclusion: This study developed healthcare utilization-based algorithms to identify moderate and severe AECOPD in two separate healthcare systems. PPV for both algorithms was high; NPV was lower for the moderate algorithm. Replication and consistency of results across two healthcare systems support the external validity of these findings.

Post-discharge healthcare utilization in infants with neonatal opioid withdrawal syndrome.

The opioid epidemic in the United States has led to a significant increase in the incidence of neonatal opioid withdrawal syndrome (NOWS); however, the understanding of long-term consequences of NOWS is limited. The objective of this study was to evaluate post-discharge healthcare utilization in infants with NOWS and examine the association between NOWS severity and healthcare utilization. A retrospective cohort design was used to ascertain healthcare utilization in the first year after birth-related discharge using the CERNER Health Facts® database. ICD-9/ICD-10 diagnostic codes were used to identify live births and to classify infants into two study groups: NOWS and uncomplicated births (a 25% random sample). Evaluated outcomes included rehospitalization, emergency department (ED) visits within 30-days and one-year after discharge, and a composite one-year utilization event (either hospitalization or emergency department visit during that year). NOWS severity was operationalized as pharmacologic treatment, length of hospitalization, and medical conditions often associated with NOWS. In 3,526 infants with NOWS (restricted to gestational age ≥ 33 weeks), NOWS severity was associated with an increase in composite one-year utilization (OR: 1.1; 95% CI: 1.04-1.2) after adjusting for prematurity, sepsis, jaundice, use of antibiotics, infant sex, insurance status, race, hospital bed size, year of birth, and census division. In a subset of full-term infants (3008 with NOWS and 88,452 uncomplicated births), having a NOWS diagnosis was associated with higher odds of a 30-day (OR: 1.6; 95% CI: 1.03-2.4) and one-year rehospitalization (OR: 1.6; 95% CI: 1.1-2.4) after adjusting for infant sex, race, type of medical insurance, hospital location, census division, year of primary encounter, hospital bed size, and medical conditions. This study found higher healthcare utilization during the first year of life in infants diagnosed with NOWS, especially those with severe NOWS. Findings suggest a need for closer post-discharge follow-up and management of infants with NOWS.

Real-World Evidence: Bridging Gaps in Evidence to Guide Payer Decisions.

Randomized controlled trials (RCTs) are preferred by payers for health technology assessments and coverage decisions. However, the inclusion of a highly selective patient population and the rigorously controlled conditions in RCTs may not be reflective of real-world clinical practice. Real-world evidence (RWE) obtained from an analysis of real-world data (RWD) from observational studies can bridge gaps in evidence not addressed by RCTs and is thus valuable to public and private payers for decision-making. Through a broad literature search to obtain insights into payers' experience, we found that payers have concerns about real-world studies with respect to data quality, poor internal validity, potential bias, and lack of meaningful endpoints. However, they valued RWE to fill evidence gaps not addressed by RCTs, such as high-quality, real-world, long-term effectiveness and safety data; head-to-head drug comparisons; cost analyses for tiering formulary placement; medication use and adherence patterns; identification of relevant responder and non-responder patient subpopulations; and patient-reported outcomes (PROs). RWE can be used to assess clinically meaningful endpoints and gauge the impact of interventions on the quality of healthcare. Here, we review how payers use or can use RWD on the comparative effectiveness and safety of treatments, PROs, medication adherence and persistence, prescribing patterns, healthcare resource utilization, and patient characteristics and/or biomarkers associated with treatment response when making health technology assessments and payer coverage decisions across therapeutic areas.