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OBJECTIVE: Physicians of all specialties experienced unprecedented stressors during the COVID-19 pandemic, exacerbating preexisting burnout. We examine burnouts association with perceived and actionable electronic health record (EHR) workload factors and personal, professional, and organizational characteristics with the goal of identifying levers that can be targeted to address burnout. MATERIALS AND METHODS: Survey of physicians of all specialties in an academic health center, using a standard measure of burnout, self-reported EHR work stress, and EHR-based work assessed by the number of messages regarding prescription reauthorization and use of a staff pool to triage messages. Descriptive and multivariable regression analyses examined the relationship among burnout, perceived EHR work stress, and actionable EHR work factors. RESULTS: Of 1038 eligible physicians, 627 responded (60% response rate), 49.8% reported burnout symptoms. Logistic regression analysis suggests that higher odds of burnout are associated with physicians feeling higher level of EHR stress (odds ratio [OR], 1.15; 95% confidence interval [CI], 1.07-1.25), having more prescription reauthorization messages (OR, 1.23; 95% CI, 1.04-1.47), not feeling valued (OR, 3.38; 95% CI, 1.69-7.22) or aligned in values with clinic leaders (OR, 2.81; 95% CI, 1.87-4.27), in medical practice for ≤15 years (OR, 2.57; 95% CI, 1.63-4.12), and sleeping for

ImportancePrescription drug prices are a leading concern among patients and policy makers. There have been large and sharp price increases for some drugs, but the long-term implications of large drug price increases remain poorly understood.ObjectiveTo examine the association of the large 2010 price increase in colchicine, a common treatment for gout, with long-term changes in colchicine use, substitution with other drugs, and health care use.Design, setting, and participantsThis retrospective cohort study examined MarketScan data from a longitudinal cohort of patients with gout with employer-sponsored insurance from 2007 through 2019.ExposuresThe US Food and Drug Administration's discontinuation of lower-priced versions of colchicine from the market in 2010.Main outcomes and measuresMean price of colchicine; use of colchicine, allopurinol, and oral corticosteroids; and emergency department (ED) and rheumatology visits for gout in year 1 and over the first decade of the policy (through 2019) were calculated. Data were analyzed between November 16, 2021, and January 17, 2023.ResultsA total of 2 723 327 patient-year observations were examined from 2007 through 2019 (mean [SD] age of patients, 57.0 [13.8] years; 20.9% documented as female; 79.1% documented as male). The mean price per prescription of colchicine increased sharply from $11.25 (95% CI, $11.23-$11.28) in 2009 to $190.49 (95% CI, $190.07-$190.91) in 2011, a 15.9-fold increase, with the mean out-of-pocket price increasing 4.4-fold from $7.37 (95% CI, $7.37-$7.38) to $39.49 (95% CI, $39.42-$39.56). At the same time, colchicine use declined from 35.0 (95% CI, 34.6-35.5) to 27.3 (95% CI, 26.9-27.6) pills per patient in year 1 and to 22.6 (95% CI, 22.2-23.0) pills per patient in 2019. Adjusted analyses showed a 16.7% reduction in year 1 and a 27.0% reduction over the decade (P

BACKGROUND: High out-of-pocket prescription drug costs contribute to financial toxicity, medication nonadherence, and adverse cardiovascular (CV) outcomes. Policymakers recently passed the Inflation Reduction Act, which will cap Medicare out-of-pocket drug costs at $2,000/year and expand full low-income subsidies (LIS). It is unclear how these provisions will affect Medicare beneficiaries with CV risk factors and/or conditions. OBJECTIVES: The authors sought to characterize the population of Medicare beneficiaries with CV risk factors/conditions experiencing out-of-pocket prescription drug costs >$2,000/year and estimate their potential savings under the Inflation Reduction Acts spending cap; identify sociodemographic characteristics associated with out-of-pocket costs >$2,000/year; and characterize beneficiaries newly eligible for LIS under the Inflation Reduction Act. METHODS: This was a cross-sectional study of Medicare beneficiaries aged ≥65 years with ≥1 CV risk factor/condition from 2016 to 2019. RESULTS: An annual estimated 34,056,335 ± 855,653 Medicare beneficiaries (mean ± SE) had ≥1 CV risk factor/condition, of whom 1,020,484 ± 77,055 experienced out-of-pocket drug costs >$2,000/year. The likelihood of experiencing out-of-pocket drug costs >$2,000/year was lower among adults ≥75 years vs 65 to 74 years (adjusted OR: 0.67; 95% CI: 0.49-0.93) and for low-income vs higher-income adults. Among beneficiaries currently spending >$2,000/year, estimated median out-of-pocket drug savings would be $855/year and total annual savings $1,723,031,307 ± $91,150,609 under the Inflation Reduction Act. An estimated 1,289,861 beneficiaries would also become newly eligible for LIS. CONCLUSIONS: More than 1 million older adults with CV risk factors and/or conditions spend >$2,000/year out-of-pocket on prescription drugs and will likely benefit from the Inflation Reduction Acts cap, with estimated total out-of-pocket savings of $1.7 billion/year, while another 1.3 million will also become newly eligible for LIS.

ObjectiveTo describe the reported prevalence of cannabis use and co-use with prescription medications among older adult patients attending primary care (PC) clinics in Los Angeles, CA.MethodsWe used electronic health record (EHR) data from sixty PC clinics part of a university-based, urban healthcare system. Patients' ≥50 years of age with an annual physical examination between July 2019 and May 2020 were eligible for inclusion (n = 42,555). Cannabis use was assessed by clinic staff at the time of the visit and recorded in the EHR. We also used EHR data on clinical characteristics including current prescriptions and comorbidities.ResultsThe median age was 63 years (range: 50-101) and 56% were female. Recent cannabis use was reported by 7.6%, which was higher than tobacco use (4.0%; p

BackgroundA study has shown that industry payments to physicians for drugs are associated not only with higher drug prescriptions but also with higher non-drug costs due to additional utilization of healthcare services. However, the association between industry payments to cardiologists for antiplatelet drugs and the costs and number of percutaneous coronary interventions they perform has not been investigated.ObjectiveTo examine the association between industry payments to cardiologists for antiplatelet drugs and the costs and number of percutaneous coronary interventions they perform.DesignUsing the 2016 Open Payments Database linked to the 2017 Medicare Provider Utilization and Payment Data, we examined the association between the value of industry payments related to the antiplatelet drugs prasugrel and ticagrelor and healthcare spending and volume for cardiovascular procedures, adjusted for potential cofounders.SubjectsA total of 7456 cardiologists who performed diagnostic cardiac catheterizations on Medicare beneficiaries in 2017.Main measuresPrimary outcomes included (1) healthcare spending on cardiac procedures, (2) diagnostic cardiac catheterization volumes, and (3) rates of coronary stenting. Secondary outcomes were total expenditures for all drugs and for antiplatelet drugs.Key resultsIndustry payments for antiplatelet drugs were associated with higher healthcare spending on cardiac procedures (adjusted difference, +$50.9 for additional $100 industry payments; 95% CI, +$25.5 to +$76.2; P < 0.001), diagnostic cardiac catheterizations (+0.1 procedures per cardiologist; 95% CI, +0.03 to +0.1; P=0.001), and stent use (+0.5 per 1000 diagnostic cardiac catheterizations per cardiologist; 95% CI, +0.2 to +0.9; P=0.002). Industry payments for antiplatelet drugs were associated with higher total costs for all drugs and antiplatelet drugs.ConclusionsIndustry payments to cardiologists for antiplatelet drugs were associated with both prescribing of antiplatelet drugs and the use of cardiac procedures and stents. Further research is warranted to understand whether the observed associations are causal or reflect a greater propensity for higher volume proceduralists to have relationships with industry.

This cross-sectional study describes the price differences between capsule and tablet or ointment and cream forms of prescription drugs for insured patients.

ImportanceAntidepressant use may be associated with reduced levels of several proinflammatory cytokines suggested to be involved with the development of severe COVID-19. An association between the use of selective serotonin reuptake inhibitors (SSRIs)-specifically fluoxetine hydrochloride and fluvoxamine maleate-with decreased mortality among patients with COVID-19 has been reported in recent studies; however, these studies had limited power due to their small size.ObjectiveTo investigate the association of SSRIs with outcomes in patients with COVID-19 by analyzing electronic health records (EHRs).Design, setting, and participantsThis retrospective cohort study used propensity score matching by demographic characteristics, comorbidities, and medication indication to compare SSRI-treated patients with matched control patients not treated with SSRIs within a large EHR database representing a diverse population of 83 584 patients diagnosed with COVID-19 from January to September 2020 and with a duration of follow-up of as long as 8 months in 87 health care centers across the US.ExposuresSelective serotonin reuptake inhibitors and specifically (1) fluoxetine, (2) fluoxetine or fluvoxamine, and (3) other SSRIs (ie, not fluoxetine or fluvoxamine).Main outcomes and measuresDeath.ResultsA total of 3401 adult patients with COVID-19 prescribed SSRIs (2033 women [59.8%]; mean [SD] age, 63.8 [18.1] years) were identified, with 470 receiving fluoxetine only (280 women [59.6%]; mean [SD] age, 58.5 [18.1] years), 481 receiving fluoxetine or fluvoxamine (285 women [59.3%]; mean [SD] age, 58.7 [18.0] years), and 2898 receiving other SSRIs (1733 women [59.8%]; mean [SD] age, 64.7 [18.0] years) within a defined time frame. When compared with matched untreated control patients, relative risk (RR) of mortality was reduced among patients prescribed any SSRI (497 of 3401 [14.6%] vs 1130 of 6802 [16.6%]; RR, 0.92 [95% CI, 0.85-0.99]; adjusted P = .03); fluoxetine (46 of 470 [9.8%] vs 937 of 7050 [13.3%]; RR, 0.72 [95% CI, 0.54-0.97]; adjusted P = .03); and fluoxetine or fluvoxamine (48 of 481 [10.0%] vs 956 of 7215 [13.3%]; RR, 0.74 [95% CI, 0.55-0.99]; adjusted P = .04). The association between receiving any SSRI that is not fluoxetine or fluvoxamine and risk of death was not statistically significant (447 of 2898 [15.4%] vs 1474 of 8694 [17.0%]; RR, 0.92 [95% CI, 0.84-1.00]; adjusted P = .06).Conclusions and relevanceThese results support evidence that SSRIs may be associated with reduced severity of COVID-19 reflected in the reduced RR of mortality. Further research and randomized clinical trials are needed to elucidate the effect of SSRIs generally, or more specifically of fluoxetine and fluvoxamine, on the severity of COVID-19 outcomes.

ObjectiveTo improve food insecurity interventions, we sought to better understand the hypothesized bidirectional relationship between food insecurity and health care expenditures.Data sourceNationally representative sample of the civilian noninstitutionalized population of the United States (2016-2017 Medical Expenditure Panel Survey [MEPS]).Study designIn a retrospective longitudinal cohort, we conducted two sets of analyses: (a) two-part models to examine the association between food insecurity in 2016 and health care expenditures in 2017; and (b) logistic regression models to examine the association between health care expenditures in 2016 and food insecurity in 2017. We adjusted for demographic and socioeconomic variables as well as 2016 health care expenditures and food insecurity.Data collectionHealth care expenditures, food insecurity, and medical condition data from 10 886 adults who were included in 2016-2017 MEPS.Principal findingsFood insecurity in 2016, compared with being food secure, was associated with both a higher odds of having any health care expenditures in 2017 (OR 1.29, 95% CI: 1.04 to 1.60) and greater total expenditures ($1738.88 greater, 95% CI: $354.10 to $3123.57), which represents approximately 25% greater expenditures. Greater 2016 health care expenditures were associated with slightly higher odds of being food insecure in 2017 (OR 1.007 per $1000 in expenditures, 95% CI: 1.002 to 1.012, P =0.01). Exploratory analyses suggested that poor health status may underlie the relationship between food insecurity and health care expenditures.ConclusionsA bidirectional relationship exists between food insecurity and health care expenditures, but the strength of either direction appears unequal. Higher health care expenditures are associated with a slightly greater risk of being food insecure (adjusted for baseline food insecurity status) but being food insecure is associated with substantially greater subsequent health care expenditures (adjusted for baseline health care expenditures). Interventions to address food insecurity and poor health may be helpful to break this cycle.

A short primer for students entering the health professions, this article provides an overview of the history of therapeutic drugs, from antiquity to modern pharmacology.

An illustrated history of drugs developed for medicinal use from antiquity to modern pharmaceuticals. A primer for health professional students.

Computational models based on recent maps of the RBC proteome suggest that mature erythrocytes may harbor targets for common drugs. This prediction is relevant to RBC storage in the blood bank, in which the impact of small molecule drugs or other xenometabolites deriving from dietary, iatrogenic, or environmental exposures ("exposome") may alter erythrocyte energy and redox metabolism and, in so doing, affect red cell storage quality and posttransfusion efficacy. To test this prediction, here we provide a comprehensive characterization of the blood donor exposome, including the detection of common prescription and over-the-counter drugs in blood units donated by 250 healthy volunteers in the Recipient Epidemiology and Donor Evaluation Study III Red Blood Cell-Omics (REDS-III RBC-Omics) Study. Based on high-throughput drug screenings of 1366 FDA-approved drugs, we report that approximately 65% of the tested drugs had an impact on erythrocyte metabolism. Machine learning models built using metabolites as predictors were able to accurately predict drugs for several drug classes/targets (bisphosphonates, anticholinergics, calcium channel blockers, adrenergics, proton pump inhibitors, antimetabolites, selective serotonin reuptake inhibitors, and mTOR), suggesting that these drugs have a direct, conserved, and substantial impact on erythrocyte metabolism. As a proof of principle, here we show that the antacid ranitidine - though rarely detected in the blood donor population - has a strong effect on RBC markers of storage quality in vitro. We thus show that supplementation of blood units stored in bags with ranitidine could - through mechanisms involving sphingosine 1-phosphate-dependent modulation of erythrocyte glycolysis and/or direct binding to hemoglobin - improve erythrocyte metabolism and storage quality.

BackgroundThe Affordable Care Act expanded Medicaid eligibility allowing low-income individuals greater access to health care. However, the uptake of state Medicaid expansion has been variable. It remains unclear how the Medicaid expansion was associated with the temporal trends in use of evidence-based cardiovascular drugs.MethodsWe used the publicly available Medicaid Drug Utilization and Current Population Survey to extract filled prescription rates per 1000 Medicaid beneficiaries of statins, antihypertensives, P2Y12 inhibitors, and direct oral anticoagulants. We defined expander states as those who expanded Medicaid on or before January 1, 2014, and nonexpander states as those who had not expanded by December 31, 2018. Difference-in-differences (DID) analyses were performed to compare the association of the Medicaid expansion with per-capita cardiovascular drug prescription rates in expander versus nonexpander states.ResultsBetween 2011 and 2018, the total number of prescriptions among all Medicaid beneficiaries increased, with gains of 89.7% in statins (11.0 to 20.8 million), 76% in antihypertensives (35.3 to 62.2 million), and 37% in P2Y12 inhibitors (1.7 to 2.3 million). Medicaid expansion was associated with significantly greater increases in quarterly prescriptions (per 1000 Medicaid beneficiaries) of statins (DID estimate [95% CI]: 22.5 [16.5-28.6], P75% of the expander states had increases in prescription rates of both statins and antihypertensives. In contrast, 44% of nonexpander states saw declines in statins and antihypertensives. The Medicaid expansion was not associated with higher direct oral anticoagulants prescription rates (DID estimate [95% CI] 0.9 [-0.3 to 2.1], P=0.142).ConclusionsThe 2014 Medicaid expansion was associated with a significant increase in per-capita utilization of cardiovascular prescription drugs among Medicaid beneficiaries. These gains in utilization may contribute to long-term cardiovascular benefits to lower-income and previously underinsured populations.

Importance:In 2017, an estimated 7.9% of persons aged 12 to 17 years reported illicit drug use in the past month, and an estimated 50% of adolescents in the US had used an illicit drug by the time they graduated from high school. Young adults aged 18 to 25 years have a higher rate of current illicit drug use, with an estimated 23.2% currently using illicit drugs. Illicit drug use is associated with many negative health, social, and economic consequences and is a significant contributor to 3 of the leading causes of death among young persons (aged 10-24 years): unintentional injuries including motor vehicle crashes, suicide, and homicide. Objective:To update its 2014 recommendation, the USPSTF commissioned a review of the evidence on the potential benefits and harms of interventions to prevent illicit drug use in children, adolescents, and young adults. Population:This recommendation applies to children (11 years and younger), adolescents (aged 12-17 years), and young adults (aged 18-25 years), including pregnant persons. Evidence Assessment:Because of limited and inadequate evidence, the USPSTF concludes that the benefits and harms of primary care-based interventions to prevent illicit drug use in children, adolescents, and young adults are uncertain and that the evidence is insufficient to assess the balance of benefits and harms. More research is needed. Recommendation:The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of primary care-based behavioral counseling interventions to prevent illicit drug use, including nonmedical use of prescription drugs, in children, adolescents, and young adults. (I statement).

Importance:In 2017, an estimated 7.9% of persons aged 12 to 17 years reported illicit drug use in the past month, and an estimated 50% of adolescents in the US had used an illicit drug by the time they graduated from high school. Young adults aged 18 to 25 years have a higher rate of current illicit drug use, with an estimated 23.2% currently using illicit drugs. Illicit drug use is associated with many negative health, social, and economic consequences and is a significant contributor to 3 of the leading causes of death among young persons (aged 10-24 years): unintentional injuries including motor vehicle crashes, suicide, and homicide. Objective:To update its 2014 recommendation, the USPSTF commissioned a review of the evidence on the potential benefits and harms of interventions to prevent illicit drug use in children, adolescents, and young adults. Population:This recommendation applies to children (11 years and younger), adolescents (aged 12-17 years), and young adults (aged 18-25 years), including pregnant persons. Evidence Assessment:Because of limited and inadequate evidence, the USPSTF concludes that the benefits and harms of primary care-based interventions to prevent illicit drug use in children, adolescents, and young adults are uncertain and that the evidence is insufficient to assess the balance of benefits and harms. More research is needed. Recommendation:The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of primary care-based behavioral counseling interventions to prevent illicit drug use, including nonmedical use of prescription drugs, in children, adolescents, and young adults. (I statement).

The Appalachian region has been disproportionately impacted by the opioid epidemic. This study, informed by the Health Belief Model (HBM), explored Appalachian community members perspectives on prescription opioid misuse and community-based programs to dispose of unused opioid analgesics. In 2018, we conducted ten focus groups (n=94 participants) in 5 Appalachian counties. Thirteen themes across 5 of the HBM constructs emerged from our analysis. Participants perceived that their communities are susceptible to the harms associated with opioid misuse, these harms are serious, suggesting they could be motivated to change disposal behaviors. Many participants recognized the benefit to disposing of unused prescription opioids including protecting household members from misusing and protecting the home from robbery. Nevertheless, participants identified barriers to proper disposal, including keeping the medications just in case for future ailments and the location of drop boxes near law enforcement (due to deep-seated mistrust of law enforcement agencies). Self-efficacy was difficult to assess as many participants were completely unaware of the presence of dropboxes in the community and also expressed concerns about the inconvenience of proper disposal using dropboxes These findings have implications for developing community-based campaign messages promoting proper disposal of unused opioids.

BackgroundTransporter-mediated drug-nutrient interactions have the potential to cause serious adverse events. However, unlike drug-drug interactions, these drug-nutrient interactions receive little attention during drug development. The clinical importance of drug-nutrient interactions was highlighted when a phase III clinical trial was terminated due to severe adverse events resulting from potent inhibition of thiamine transporter 2 (ThTR-2; SLC19A3).ObjectiveIn this study, we tested the hypothesis that therapeutic drugs inhibit the intestinal thiamine transporter ThTR-2, which may lead to thiamine deficiency.MethodsFor this exploration, we took a multifaceted approach, starting with a high-throughput in vitro primary screen to identify inhibitors, building in silico models to characterize inhibitors, and leveraging real-world data from electronic health records to begin to understand the clinical relevance of these inhibitors.ResultsOur high-throughput screen of 1360 compounds, including many clinically used drugs, identified 146 potential inhibitors at 200 μM. Inhibition kinetics were determined for 28 drugs with half-maximal inhibitory concentration (IC50) values ranging from 1.03 μM to >1 mM. Several oral drugs, including metformin, were predicted to have intestinal concentrations that may result in ThTR-2-mediated drug-nutrient interactions. Complementary analysis using electronic health records suggested that thiamine laboratory values are reduced in individuals receiving prescription drugs found to significantly inhibit ThTR-2, particularly in vulnerable populations (e.g., individuals with alcoholism).ConclusionsOur comprehensive analysis of prescription drugs suggests that several marketed drugs inhibit ThTR-2, which may contribute to thiamine deficiency, especially in at-risk populations.

BackgroundPrescription drug monitoring programs (PDMPs) that collect and distribute information on dispensed controlled substances have been adopted by nearly all US states. We know little about program characteristics that modify PDMP impact on prescription opioid (PO) overdose deaths.MethodsWe measured associations between adoption of any PDMP and changes in fatal PO overdoses in 2002-2016 across 3109 counties in 49 states and D.C. We then measured changes related to the adoption of "proactive PDMPs," which report outlying prescribing/dispensing patterns and provide broader access to PDMP data by law enforcement. Comparisons were made within 3 time intervals that broadly represent the evolution of PDMPs (2002-2004, 2005-2009, and 2010-2016). We modeled overdoses using Bayesian space-time models.ResultsAdoption of electronic PDMP access was associated with 9% lower rates of fatal PO overdoses after three years (rate ratio [RR] = 0.91, 95% credible interval [CI]: 0.88-0.93) with well-supported effects for methadone (RR = 0.86,95% CI: 0.82-0.90) and other synthetic opioids (RR = 0.82, 95% CI: 0.77-0.86). Compared with states with no/weak PDMPs, proactive PDMPs were associated with fewer deaths attributed to natural/semi-synthetic opioids (2002-2004: RR = 0.72 [0.66-0.78]; 2005-2009: RR = 0.93 [0.90-0.97]; 2010-2016: 0.89 [0.86-0.92]) and methadone (2002-2004: RR = 0.77 [0.69-0.85]; 2010-2016: RR = 0.90 [0.86-0.94]). Unintended effects were observed for synthetic opioids other than methadone (2005-2009: RR = 1.29 [1.21-1.38]; 2010-2016: RR = 1.22 [1.16-1.29]).ConclusionsState adoption of PDMPs was associated with fewer PO deaths overall while proactive PDMPs alone were associated with fewer deaths related to natural/semisynthetic opioids and methadone, the specific targets of these programs. See video abstract at, http://links.lww.com/EDE/B619.

Prescription-opioid misus e continues to be a significant health concern in the United States. The relationship between marijuana use and prescription-opioid misuse is not clear from the extant literature. This study examined national trends in prescription-opioid misuse among marijuana users and non-users using the 2007-2017 National Survey on Drug Use and Health. Cochran-Armitage tests were used to assess the statistical significance of changes in the yearly prevalence of prescription-opioid misuse and marijuana use. Multivariable logistic regression was used to examine the association between prescription-opioid and marijuana use adjusting for sociodemographic characteristics. From 2007 to 2017, marijuana use increased, while prescription-opioid misuse declined. Larger declines in prescription-opioid misuse were found among marijuana users than non-users. Marijuana ever-use was significantly associated with prescription-opioid misuse. Specifically, marijuana ever-users had higher odds of prescription-opioid misuse (ever-misuse [OR: 3.04; 95% CI, 2.68-3.43]; past-year misuse [OR: 3.44; 95% CI, 3.00-3.94]; and past-month misuse [OR: 4.50; 95% CI, 3.35-6.05]) compared to marijuana never-users. Similar results were found for the association of past-year and past-month marijuana use with prescription-opioid misuse. This study provides data on trends and associations about opioid misuse among marijuana users and non-users in a changing social environment of drug use in the United States. Future research should consider whether there is a causal relationship between marijuana use and prescription opioid misuse.

ImportanceThe combined 28 years of data of medical aid in dying (MAID) between Oregon (OR) and Washington (WA) are the most comprehensive in North America. No reports to date have compared MAID use in different US states.ObjectiveTo evaluate and compare patterns of MAID use between the states with the longest-running US death with dignity programs.Design, setting, and participantsA retrospective observational cohort study of OR and WA patients with terminal illness who received prescriptions as part of their states' legislation allowing MAID. All published annual reports, from 1998 to 2017 in OR and from 2009 to 2017 in WA, were reviewed. A total of 3368 prescriptions were included.Main outcomes and measuresNumber of deaths from self-administration of lethal medication vs number of prescriptions written.ResultsA combined 3368 prescriptions were written in OR and WA, with 2558 patient deaths from lethal ingestion (76.0%). Of the 2558 patients, most were male (1311 [51.3%]), older than 65 years (1851 [72.4%]), and non-Hispanic white (2426 [94.8%]). The most common underlying illnesses were cancer (1955 [76.4%]), neurologic illness (261 [10.2%]), lung disease (144 [5.6%]), and heart disease (117 [4.6%]). Loss of autonomy (2235 [87.4%]), impaired quality of life (2203 [86.1%]), and loss of dignity (1755 [68.6%]) were the most common reasons for pursuing MAID. Time between drug intake to coma ranged from 1 to 660 minutes and time from drug intake to death ranged from 1 to 6240 minutes. In the 1557 patients for whom rates of complications were reported, 1494 (96.0%) did not experience a complication (592 of 626 [94.6%] in OR and 902 of 931 [96.8%] in WA). Eight patients (

ImportanceThe combined 28 years of data of medical aid in dying (MAID) between Oregon (OR) and Washington (WA) are the most comprehensive in North America. No reports to date have compared MAID use in different US states.ObjectiveTo evaluate and compare patterns of MAID use between the states with the longest-running US death with dignity programs.Design, setting, and participantsA retrospective observational cohort study of OR and WA patients with terminal illness who received prescriptions as part of their states' legislation allowing MAID. All published annual reports, from 1998 to 2017 in OR and from 2009 to 2017 in WA, were reviewed. A total of 3368 prescriptions were included.Main outcomes and measuresNumber of deaths from self-administration of lethal medication vs number of prescriptions written.ResultsA combined 3368 prescriptions were written in OR and WA, with 2558 patient deaths from lethal ingestion (76.0%). Of the 2558 patients, most were male (1311 [51.3%]), older than 65 years (1851 [72.4%]), and non-Hispanic white (2426 [94.8%]). The most common underlying illnesses were cancer (1955 [76.4%]), neurologic illness (261 [10.2%]), lung disease (144 [5.6%]), and heart disease (117 [4.6%]). Loss of autonomy (2235 [87.4%]), impaired quality of life (2203 [86.1%]), and loss of dignity (1755 [68.6%]) were the most common reasons for pursuing MAID. Time between drug intake to coma ranged from 1 to 660 minutes and time from drug intake to death ranged from 1 to 6240 minutes. In the 1557 patients for whom rates of complications were reported, 1494 (96.0%) did not experience a complication (592 of 626 [94.6%] in OR and 902 of 931 [96.8%] in WA). Eight patients (

BACKGROUND: Although medically necessary in some cases, there is growing concern that compounded medications are being overprescribed, leading to questions about safety and necessity for high use and cost. Safety concerns regarding compounded medications were highlighted by the 2013 contamination of steroid injections by the New England Compounding Center, which caused serious infections and other injuries to at least 751 patients and resulted in at least 64 patient deaths. A study contributed to our understanding of compounded medication use and cost, finding in a sample of commercially insured population that the average ingredient cost for compounded medication prescriptions was $710.36, which is 130% higher than for noncompounded medication prescriptions. The literature on use and cost of compounded medications in noncommercially insured populations and related regulations, however, is sparse. The California Workers Compensation System (CAWCS)-the largest U.S. workers compensation system and a public health system experiencing high compounded medication costs-provided an opportunity for additional analysis of these issues. Furthermore, CAWCS data on compounded medication use and cost allow for the exploration of alternative pricing mechanisms that may control costs. OBJECTIVES: To (a) examine use, cost, and billing and reimbursement practices for compounded medications in a public health system-CAWCS- and (b) evaluate regulations and recommend an alternative pricing mechanism that could control costs in California. METHODS: Descriptive statistics for use, cost, and reimbursement patterns of all compounded medication prescriptions included in CAWCSs Workers Compensation Information System claims datasets from 2011 to 2013 were determined. This study coded a unique dataset that (a) identified compounded medications at the ingredient level; (b) grouped compounded medications from ingredient level to compounded medications as a whole; and (c) categorized compounded medications into applicable Colorado pricing categories. T-tests assessed if regulation AB 378, which targets compounded medications, was associated with a difference in mean cost. The Colorado pricing scheme was applied to estimate cost and provide recommendations. RESULTS: Despite the AB 378 requirement for compounded medications to be billed at the ingredient level for reimbursement, 15% of pharmacy-dispensed and 6% of physician-dispensed medications were not billed at the ingredient level. For pharmacy-dispensed compounded medications billed at the ingredient level, mean amount paid (SD) per ingredient was $45.40 (195.97), and for those medications billed at the single compounded medication level, mean amount paid (SD) per medication was $95.20 (326.33) over all years. For physician-dispensed medications billed at the ingredient level, mean amount paid (SD) per ingredient was $75.47 (205.51), and when billed at the single medication level was $204.83 (221.01). T-tests showed a mean increase in compounded medication mean amount paid between pre- and post-AB 378 groups of $12.27 (P < 0.001) for pharmacy-dispensed medications and $11.34 (P < 0.001) for physician-dispensed medications, suggesting that AB 378 did not curb compounded medication mean amount paid. CONCLUSIONS: The average cost of CAWCS pharmacy- and physician-dispensed compounded medications consistently increased. Various factors may have influenced this increase, but AB 378 did not achieve its full regulatory intent to standardize billing and reimbursement and control cost. Grouping of ingredients into compounded medications allowed for application of the Colorado pricing scheme to CAWCS claims data. Adoption of Colorado pricing would save 46% of current compounded medication cost for less complicated medications, while increasing cost for more complicated medications. The analyses recommended a revised Colorado pricing scheme, which would provide improved incentives for accurate billing and lead to savings for CAWCS. DISCLOSURES: Funding for this study was provided by the California Workers Compensation System. The authors had final control regarding study design, study conduct, and writing of the manuscript. The authors report no conflicts of interest.

BackgroundWhile most opioid use disorder (OUD) treatment providers consider opioid abstinence to be the preferred outcome, little is known about the treatment preferences of the larger population of individuals who engage in nonmedical opioid use and have not yet sought treatment. This study sought to descriptively quantify the proportion of out-of-treatment individuals with nonmedical opioid use that have abstinent and nonabstinent recovery goals.MethodsParticipants (N = 235) who engage in nonmedical opioid use and met self-reported criteria for OUD were recruited online and participated in a cross-sectional survey on recovery goals and treatment perceptions. Participants were dichotomized as having either abstinent (70.6%) or nonabstinent (29.4%) recovery goals. Participants were presented with 13 treatment options and asked which treatment they would "try first" and which treatment they thought would be the best option for long-term recovery.ResultsPersons in the nonabstinent group were more likely to want to continue use of prescription opioids as prescribed by a physician compared with the abstinent group (χ[1] = 9.71, P = 0.002). There were no group differences regarding preference for individual OUD treatments. The most frequently endorsed treatments that participants would "try first" were physician visits (23.4%), one-on-one counseling (18.7%), and 12-step groups (13.2%), whereas the most frequently endorsed treatments for long-term recovery were one-on-one counseling (17.4%), residential treatment (16.7%), and buprenorphine (15.3%).ConclusionPublic health initiatives to engage out-of-treatment individuals should take into account recovery goals and treatment preferences to maximize treatment initiation and retention.

Background and aimsIn the US, benzodiazepine overdose deaths increased at an alarming rate in the past two decades. Benzodiazepines were also the most common drugs involved in prescription opioid overdose deaths. Benzodiazepine prescribing has been monitored by Prescription Drug Monitoring Programs (PDMPs), but little was known about whether PDMPs reduced drug overdose deaths involving benzodiazepines.Design and methodsThis study used a difference-in-difference design with state-quarter aggregate data on drug overdose deaths. The primary data source was Mortality Multiple Cause Files in 1999-2016. Three age-adjusted rates of drug overdose deaths were examined, including those involving benzodiazepines, those involving prescription opioids, and those involving both benzodiazepines and prescription opioids. The policy variables included PDMP data access for benzodiazepines and mandatory use of PDMP data for benzodiazepines. Linear multivariable regressions were used to assess the associations of PDMP policies specific to benzodiazepines with drug overdose death rates, controlling for other state-level policy and socioeconomic factors, state and time fixed effects, and state-specific time trends.ResultsNo significant associations were found between PDMP data access for benzodiazepines and changes in drug overdose death rates involving benzodiazepines and/or prescription opioids. Similarly, no significant associations were found between mandatory use of PDMP data for benzodiazepines and changes in drug overdose death outcomes.Discussion and conclusionsThis study suggested no evidence that PDMP policies specific to benzodiazepines were associated with reduction in benzodiazepine overdose death rates. Future research is warranted to examine detailed features of PDMPs and continuously monitor the impacts of PDMP policies on benzodiazepine-related consequences.

BackgroundPeople living with HIV (PLWH) commonly report marijuana use for chronic pain, although there is limited empirical evidence to support its use. There is hope that marijuana may reduce prescription opioid use. Our objective was to investigate whether marijuana use among PLWH who have chronic pain is associated with changes in pain severity and prescribed opioid use (prescribed opioid initiation and discontinuation).MethodsParticipants completed self-report measures of chronic pain and marijuana use at an index visit and were followed up for 1 year in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). Self-reported marijuana use was the exposure variable. Outcome variables were changes in pain and initiation or discontinuation of opioids during the study period. The relationship between exposure and outcomes was assessed using generalized linear models for pain and multivariable binary logistic regression models for opioid initiation/discontinuation.ResultsOf 433 PLWH and chronic pain, 28% reported marijuana use in the past 3 months. Median pain severity at the index visit was 6.3/10 (interquartile range 4.7-8.0). Neither increases nor decreases in marijuana use were associated with changes in pain severity, and marijuana use was not associated with either lower odds of opioid initiation or higher odds of opioid discontinuation.ConclusionsWe did not find evidence that marijuana use in PLWH is associated with improved pain outcomes or reduced opioid prescribing. This suggests that caution is warranted when counseling PLWH about potential benefits of recreational or medical marijuana.

Introduction: Little is known about how repeated exposure to direct-to-consumer prescription drug promotion can impact consumers' retention and perceptions of drug information. The study described here tested the effects of varied ad exposure frequency on these outcomes. Methods: In an in-person experiment, participants with seasonal allergies (n = 616) were randomized to view a mock prescription drug television ad either once, twice, or four times within 1 h of television programming, embedded with six commercial breaks. Respondents then answered a 20-min survey administered via computer. Results: Those who viewed the ad more frequently were better able to recall both risk (X2 = 20.93, p < .001) and benefit information (X2 = 9.34, p = .009) and to recognize risk (F(2,597) = 11.89, p = .001) and benefit information (F(2,597) = 3.17, p = .043) than those who viewed the ad one time. Ad exposure frequency was not associated with perceptions about the magnitude or likelihood of risks or benefits. In general, risk information seemed to require more repetitions than benefit information to be accurately remembered. The recall was mediated by elaborate processing. Discussion: Effects on memory were small; retention of both risks and benefits remained low overall even after four exposures.

Background and aimsPrescription drug monitoring programs (PDMP), defined as state-level databases used in the United States that collect prescribing information when controlled substances are dispensed, have varied substantially between states and over time. Little is known about the combinations of PDMP features that, collectively, may produce the greatest impact on prescribing and overdose. We aimed to (1) identify the types of PDMP models that have developed from 1999 to 2016, (2) estimate whether states have transitioned across PDMP models over time and (3) examine whether states have adopted different types of PDMP models in response to the burden of opioid overdose.MethodsA latent transition analysis of PDMP models based on an adaptation of nine PDMP characteristics classified by prescription opioid policy experts as potentially important determinants of prescribing practices and prescription opioid overdose events.ResultsWe divided the time-period into three intervals (1999-2004, 2005-09, 2010-16), and found three distinct PDMP classes in each interval. The classes in the first and second interval can be characterized as 'no/weak', 'proactive' and 'reactive' types of PDMPs, and in the third interval as 'weak', 'cooperative' and 'proactive'. The meaning of these classes changed over time: until 2009, states in the 'no/weak' class had no active PDMP, whereas states in the 'proactive' class were more likely to proactively provide unsolicited information to PDMP users, provide open access to law enforcement, and require more frequent data reporting than states in the 'reactive' class. In 2010-16, the 'weak' class resembled the 'reactive' class in previous intervals. States in the 'cooperative' class in 2010-16 were less likely than states in the 'proactive' class to provide unsolicited reports proactively or to provide open access to law enforcement; however, they were more likely than those in the 'proactive' class to share PDMP data with other states and to report more federal drug schedules.ConclusionsSince 1999, US states have tended to transition to more robust classes of prescription drug monitoring programs. Opioid overdose deaths in prior years predicted the state's prescription drug monitoring program class but did not predict transitions between prescription drug monitoring program classes over time.

ObjectivesMedical marijuana use may substitute prescription opioid use, whereas nonmedical marijuana use may be a risk factor of prescription opioid misuse. This study examined the associations between recreational marijuana legalization and prescription opioids received by Medicaid enrollees.MethodsState-level quarterly prescription drug utilization records for Medicaid enrollees during 2010-2017 were obtained from Medicaid State Drug Utilization Data. The primary outcome, opioid prescriptions received, was measured in three population-adjusted variables: number of opioid prescriptions, total doses of opioid prescriptions in morphine milligram equivalents, and related Medicaid spending, per quarter per 100 enrollees. Two difference-in-difference models were used to test the associations: eight states and DC that legalized recreational marijuana during the study period were first compared among themselves, then compared to six states with medical marijuana legalized before the study period. Schedule II and III opioids were analyzed separately.ResultsIn models comparing eight states and DC, legalization was not associated with Schedule II opioid outcomes; having recreational marijuana legalization effective in 2015 was associated with reductions in number of prescriptions, total doses, and spending of Schedule III opioids by 32% (95% CI: (-49%, -15%), p = 0.003), 30% ((-55%, -4.4%), p = 0.027), and 31% ((-59%, -3.6%), p = 0.031), respectively. In models comparing eight states and DC to six states with medical marijuana legalization, recreational marijuana legalization was not associated with any opioid outcome.ConclusionsNo evidence suggested that recreational marijuana legalization increased prescription opioids received by Medicaid enrollees. There was some evidence in some states for reduced Schedule III opioids following the legalization.

Background: Reports indicate a geographic effect of socioeconomic inequalities on the occurrence of opioid-related fatal overdoses. This study aims to (1) estimate the rates of opioid-related overdoses, (2) estimate the association of benzodiazepine co-ingestion with opioid-related deaths, (3) estimate associations between socioeconomic indicators and opioid-related deaths, and (4) map the distribution of fatal overdoses, in Orange County (OC), California. Methods: An ecologic study was conducted of all opioid- related deaths (1205 total) from 2010 to 2014 obtained from the OC Coroner Division database (1065 OC residents, 55 nonresidents, 85 OC homeless) (analyzed 2016-2017). Rates of opioid overdose, benzodiazepine co-ingestion prevalence, and associations with socioeconomic status (SES; education, poverty, median income) using ZIP code analysis in the residential and homeless communities were calculated. Results: Of 1205 deaths, 904 involved prescription-type opioids, 223 involved heroin, 39 involved both, and 39 not stated; 973 were classified unintentional overdoses, 180 suicides, and 52 undetermined; 49% of cases involved benzodiazepines. Prescription-type opioid and heroin death rates for residents were 5.4/ 100,000 person-years (95% confidence interval [CI]: 5.0-5.8) and 1.2/100,000 person-years (95% CI: 1.0-1.4), respectively. Males, age group 45-54, and Caucasian race had the highest rate (13.6/100,000) of opioid mortality. The highest death rates were seen in homeless adults, at 136/100,000 person-years for prescription-type opioids (95% CI: 99.0-185.5) and 156/100,000 person-years for heroin (95% CI: 116.8-209.5). Conclusions: The burden of prescription-type opioid-related deaths in OC affects all demographics and levels of SES; there is a disproportionately high rate of opioid-related deaths in the OC homeless population.

IntroductionCost-related medication nonadherence (CRN) can negatively affect chronic disease prevention and management in an aging population. Limited data are available on the interacting influences among such factors as availability of financial resources, attitudes and beliefs of patients, and CRN. The objective of this study was to examine the causal paths among financial resource availability, patient attitudes and beliefs, and CRN.MethodsWe used a nationally representative sample (n = 4,818) from the 2015 National Health Interview Survey; selected respondents were aged 65 or older, had a diagnosis of hypertension or diabetes or both, and were prescribed medication for at least 1 of these conditions. We performed structural equation modeling to examine whether perceived medication affordability, access to health care, and patient satisfaction influenced the effects of financial resource availability on CRN (skipped doses, took less medicine, or delayed filling a prescription to save money).ResultsSix percent of respondents reported CRN in the previous 12 months. The model showed a good to fair fit, and all paths were significant (P < .05) except for age. The effects of financial resource availability on CRN was mediated through perceived medication affordability, access to health care, and patient satisfaction with health care services.ConclusionThis study suggests that patients' attitudes and beliefs can mediate the effects of financial resource availability on CRN. We call for senior-friendly public health interventions that can address these modifiable barriers to reduce CRN among older adults with chronic conditions.

BACKGROUND:Public attention and recent US Congressional activity has intensified focus on escalating medication prices. However, the actual cost of medication use extends beyond the up-front cost of purchasing medicines. It also encompasses the additional medical costs of morbidity and mortality resulting from nonoptimized medication regimens, including medication nonadherence. OBJECTIVES:Applying the most current nationally representative data sources, our goal was to estimate the cost of prescription drug-related morbidity and mortality in the United States. METHODS:Total costs of nonoptimized prescription drug use and average pathway costs for a patient who experienced a treatment failure (TF), a new medical problem (NMP), or a TF and NMP were modeled in Microsoft Excel (Microsoft Corporation, Redmond, WA) and TreeAge Pro Healthcare, v2014 (TreeAge Software, Inc, Williamstown, MA), respectively. RESULTS:The estimated annual cost of prescription drug-related morbidity and mortality resulting from nonoptimized medication therapy was $528.4 billion in 2016 US dollars, with a plausible range of $495.3 billion to $672.7 billion. The average cost of an individual experiencing TF, NMP, or TF and NMP after initial prescription use were $2481 (range: $2233, $2742), $2610 (range: $2374, $2848) and $2572 (range: $2408, $2751), respectively. CONCLUSIONS:The estimated annual cost of drug-related morbidity and mortality resulting from nonoptimized medication therapy was $528.4 billion, equivalent to 16% of total US health care expenditures in 2016. We propose expansion of comprehensive medication management programs by clinical pharmacists in collaborative practices with physicians and other prescribers as an effective and scalable approach to mitigate these avoidable costs and improve patient outcomes.

BACKGROUND: Sales of medical foods (MFs) and convenience packages (CPs) are projected to exceed $2 billion in the United States, with an annual growth rate of 10%. Several studies have highlighted the rapid growth of MF use within the California Workers Compensation System (CAWCS). To curb this growth, California implemented Assembly Bill 378 (AB 378) in 2012 to regulate physicians incentives to dispense MFs and CPs. AB 378s regulation on only physician-dispensed MFs and CPs and not pharmacy-dispensed MFs and CPs generated a setting for evaluating the differential effect of the bill on MF and CP use and cost. OBJECTIVES: To (a) examine the use and cost of MFs and CPs in the CAWCS that are not for inborn errors of metabolism and (b) evaluate the regulatory effect of AB 378. METHODS: This study adopted a quantitative approach and employed descriptive statistics and t-tests. The analyses used the most recent complete annual claims data from the Workers Compensation Information System dataset to evaluate MF and CP claims frequencies and dollar amounts reimbursed from 2011 to 2013 and to compare the difference between physician-dispensed and pharmacy-dispensed products. RESULTS: Of 151,107 MFs and CPs billed, 95,528 (63.2%) prescriptions were reimbursed. The reimbursed MFs and CPs accounted for approximately $19 million paid to pharmacies and physicians over 3 years. Physician-dispensed MFs, which were regulated by AB 378 in January 2012, experienced a reduction in mean amount reimbursed by $9.95 (P < 0.001)-from $195.64 to $185.68-compared with the mean amount reimbursed in 2011. Conversely, physician-dispensed CPs, as well as pharmacy-dispensed MFs and CPs, did not experience a decrease in mean amount reimbursed. CONCLUSIONS: The results indicated that AB 378 was associated with a statistically significant reduction in physician-dispensed MFs. Concomitantly, the results from t-tests showed no statistically significant difference in mean amount reimbursed for MFs and CPs to pharmacies before and after AB 378. The finding was expected and as hypothesized because AB 378 did not regulate pharmacy-dispensed MFs and CPs. Legislative measures, such as AB 378 in California, may influence rising costs and use of MFs and CPs in general. Other workers compensation systems could adopt similar legislation to affect the behavior of physician prescribing of non-inborn errors of metabolism MFs and further test these findings. DISCLOSURES: Funding for this study was contributed by the California Workers Compensation System. The authors have nothing to disclose.

AIM:To determine the projected impact of a multigene pharmacogenetic (PGx) test on medication prescribing. MATERIALS & METHODS:A retrospective analysis was conducted with 122 cardiac catheterization laboratory patients undergoing angiography for eligibility of potential PGx-guided interventions that could have occurred if multigene PGx information was pre-emptively available at the time of the procedure. Medication data and presence of actionable at-risk genotypes were used to determine eligibility of a PGx intervention. RESULTS:20% of the study population (n = 24) would have qualified for at least one PGx-based medication intervention per US FDA or Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines within 6 months of their cardiac catheterization procedure. Commonly encountered gene-drug pairs for these interventions included: CYP2C19 for clopidogrel and antidepressants, CYP2D6 for antidepressants and codeine, SLCO1B1 for simvastatin, and VKORC1/CYP2C9 for warfarin. CONCLUSION:Pre-emptive use of a multigene PGx test in the cardiac catheterization laboratory offers potential to reduce adverse medication outcomes.

ObjectiveTo characterize prescription and other medication use in a geographically and ethnically diverse cohort of women in their first pregnancy.MethodsIn a prospective, longitudinal cohort study of nulliparous women followed through pregnancy from the first trimester, medication use was chronicled longitudinally throughout pregnancy. Structured questions and aids were used to capture all medications taken as well as reasons they were taken. Total counts of all medications taken including number in each category and class were captured. Additionally, reasons the medications were taken were recorded. Trends in medications taken across pregnancy and in the first trimester were determined.ResultsOf the 9,546 study participants, 9,272 (97.1%) women took at least one medication during pregnancy with 9,139 (95.7%) taking a medication in the first trimester. Polypharmacy, defined as taking at least five medications, occurred in 2,915 (30.5%) women. Excluding vitamins, supplements, and vaccines, 73.4% of women took a medication during pregnancy with 55.1% taking one in the first trimester. The categories of drugs taken in pregnancy and in the first trimester include the following: gastrointestinal or antiemetic agents (34.3%, 19.5%), antibiotics (25.5%, 12.6%), and analgesics (23.7%, 15.6%, which includes 3.6%; 1.4% taking an opioid pain medication).ConclusionIn this geographically and ethnically diverse cohort of nulliparous pregnant women, medication use was nearly universal and polypharmacy was common.Clinical trial registrationClinicalTrials.gov, NCT01322529.

BackgroundEarly detection of adverse effects of novel therapies and understanding of their mechanisms could improve the safety and efficiency of drug development. We have retrospectively applied large-scale proteomics to blood samples from ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), a trial of torcetrapib (a cholesterol ester transfer protein inhibitor), that involved 15 067 participants at high cardiovascular risk. ILLUMINATE was terminated at a median of 550 days because of significant absolute increases of 1.2% in cardiovascular events and 0.4% in mortality with torcetrapib. The aims of our analysis were to determine whether a proteomic analysis might reveal biological mechanisms responsible for these harmful effects and whether harmful effects of torcetrapib could have been detected early in the ILLUMINATE trial with proteomics.MethodsA nested case-control analysis of paired plasma samples at baseline and at 3 months was performed in 249 participants assigned to torcetrapib plus atorvastatin and 223 participants assigned to atorvastatin only. Within each treatment arm, cases with events were matched to controls 1:1. Main outcomes were a survey of 1129 proteins for discovery of biological pathways altered by torcetrapib and a 9-protein risk score validated to predict myocardial infarction, stroke, heart failure, or death.ResultsPlasma concentrations of 200 proteins changed significantly with torcetrapib. Their pathway analysis revealed unexpected and widespread changes in immune and inflammatory functions, as well as changes in endocrine systems, including in aldosterone function and glycemic control. At baseline, 9-protein risk scores were similar in the 2 treatment arms and higher in participants with subsequent events. At 3 months, the absolute 9-protein derived risk increased in the torcetrapib plus atorvastatin arm compared with the atorvastatin-only arm by 1.08% (P=0.0004). Thirty-seven proteins changed in the direction of increased risk of 49 proteins previously associated with cardiovascular and mortality risk.ConclusionsHeretofore unknown effects of torcetrapib were revealed in immune and inflammatory functions. A protein-based risk score predicted harm from torcetrapib within just 3 months. A protein-based risk assessment embedded within a large proteomic survey may prove to be useful in the evaluation of therapies to prevent harm to patients.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00134264.

ObjectiveTo identify frequently reported prescription medications and supplements among couples planning pregnancy because there is a lack of descriptive information on these agents in women and men who are trying to conceive.MethodsFive hundred one couples enrolled in the Longitudinal Study of Infertility and the Environment, which took place between 2005 and 2009. Participants reported prescription medications as well as prescription and over-the-counter supplements used through interviews at study enrollment and through daily dairies during the 12-month follow-up. We identified prescription medications and supplements prospectively reported by ≥1% of women and men at baseline and from daily journal information grouped into 3-month preconception follow-up intervals while couples tried for pregnancy.ResultsThe 5 most reported prescription medications among women were levothyroxine (5.8%), cetirizine (2.6%), fluticasone (2.4%), escitalopram (1.8%), and fluoxetine (1.8%) and for men were lisinopril (2.0%), mometasone (2.0%), fexofenadine (1.8%), atorvastatin (1.6%), and montelukast (1.6%). The most reported supplements were multivitamins (63.3%, 43.5%) and fish oil (13.2%, 9.4%) for women and men, respectively, and prenatal vitamins (22.0%) for women. For women during the first 3 months of follow-up, prenatal vitamins (6.0%) and antibiotics (1.2%-2.6%) were among the most frequently started medications. During the next 3 months, clomiphene (4.5%) was the most frequently initiated medication.ConclusionsCouples trying for pregnancy reported a variety of prescription medications and supplements, and they differed by gender. Preconception guidance should address medication and supplement use to avoid potential exposures associated with adverse reproductive and perinatal outcomes.

INTRODUCTION:California's Workers' Compensation System (CAWCS) Department of Industrial Relations questioned the adequacy of the current Medi-Cal fee-schedule pricing and requested analysis of alternatives that maximize price availability and maintain budget neutrality. OBJECTIVES:To compare CAWCS pharmacy-dispensed (PD) drug prices under alternative fee schedules, and identify combinations of alternative benchmarks that have prices available for the largest percentage of PD drugs and that best reach budget neutrality. METHODS:Claims transaction-level data (2011-2013) from CAWCS were used to estimate total annual PD pharmaceutical payments. Medi-Cal pricing data was from the Workman's Compensation Insurance System (WCIS). Average Wholesale Prices (AWP), Wholesale Acquisition Costs (WAC), Direct Prices (DP), Federal Upper Limit (FUL) prices, and National Average Drug Acquisition Costs (NADAC) were from Medi-Span. We matched National Drug Codes (NDCs), pricing dates, and drug quantity for comparisons. We report pharmacy-dispensed (PD) claims frequency, reimbursement matching rate, and paid costs by CAWCS as the reference price against all alternative price benchmarks. RESULTS:Of 12,529,977 CAWCS claims for pharmaceutical products 11.6% (1,462,814) were for PD drugs. Prescription drug cost for CAWCS was over $152M; $63.9M, $47.9M, and $40.6M in 2011-2013. Ninety seven percent of these CAWCS PD claims had a Medi-Cal price. Alternative mechanisms provided a price for fewer claims; NADAC 94.23%, AWP 90.94%, FUL 73.11%, WAC 66.98%, and DP 14.33%. Among CAWCS drugs with no Medi-Cal price in PD claims, AWP, WAC, NADAC, DP, and FUL provided prices for 96.7%, 63.14%, 24.82%, 20.83%, and 15.08% of claims. Overall CAWCS paid 100.52% of Medi-Cal, 60% of AWP, 97% of WAC, 309.53% of FUL, 103.83% of DP, and 136.27% of NADAC. CONCLUSIONS:CAWCS current Medi-Cal fee-schedule price list for PD drugs is more complete than all alternative fee-schedules. However, all reimbursement approaches would require combinations of pricing benchmarks. We suggest keeping primary reimbursement at 100% of Medi-Cal and for drugs without a primary Medi-Cal price calculating the maximum fee as 60% of AWP and then 97% of WAC. Alternatively, we suggest using NADAC as a primary fee-schedule followed by either 60% AWP and 97% WAC or AWP-40% for drugs with no NADAC price. Fee-schedules may not offer the best price and a formulary approach may provide more flexibility.

BackgroundThe use of social media (SM) as a surveillance tool of global illicit drug use is limited. To address this limitation, a systematic review of literature focused on the ability of SM to better recognize illicit drug use trends was addressed.MethodsA search was conducted in databases: PubMed, CINAHL via Ebsco, PsychINFO via Ebsco, Medline via Ebsco, ERIC, Cochrane Library, Science Direct, ABI/INFORM Complete and Communication and Mass Media Complete. Included studies were original research published in peer-reviewed journals between January 2005 and June 2015 that primarily focused on collecting data from SM platforms to track trends in illicit drug use. Excluded were studies focused on purchasing prescription drugs from illicit online pharmacies.ResultsSelected studies used a range of SM tools/applications, including message boards, Twitter and blog/forums/platform discussions. Limitations included relevance, a lack of standardized surveillance systems and a lack of efficient algorithms to isolate relevant items.ConclusionIllicit drug use is a worldwide problem, and the rise of global social networking sites has led to the evolution of a readily accessible surveillance tool. Systematic approaches need to be developed to efficiently extract and analyze illicit drug content from social networks to supplement effective prevention programs.

It is not clear from prior studies whether trauma exposure predicts substance use problems independent of psychiatric comorbidities. Most prior studies were cross-sectional in nature, and none focused on prescription drug problems. To address this gap in the literature, the current article is a secondary analysis of veterans from the Mind Your Heart prospective cohort study. The primary research question is whether trauma exposure predicts prescription drug problems even after controlling for major psychiatric symptoms, such as post-traumatic stress disorder and depression. Multinomial logistic regression was used to assess whether the 10-item lifetime Brief Trauma Questionnaire (e.g., serious car accidents, war traumas, life-threatening illness, natural disasters, physical, or sexual abuse) predicts prescription drug problems as determined by a self-report categorical question (three answer choices) over a 4-year follow-up time period (n = 661 [100%] at year 1; 83.4% at year 2; 85.9% at year 3; and 78.2% at year 4). Trauma exposure was positively associated with prescription drug problems in unadjusted and age-, sex-, and race-adjusted analyses at follow-up. After accounting for post-traumatic stress disorder (PTSD Checklist-17 Civilian Version) and depression (Patient Health Questionnaire-9) symptoms, trauma exposure was no longer associated with prescription drug problems at all time points (relative risk ratios range 0.91-1.47). These results were robust to different missing data strategies. Trauma exposure was not associated with prescription drug problems over a 4-year follow-up in a prospective cohort study of veterans. Future directions include detailed measures of prescription drug problems and recruitment from community sites.

ImportanceMedication adherence is essential to diabetes care. Patient-physician language barriers may affect medication adherence among Latino individuals.ObjectiveTo determine the association of patient race/ethnicity, preferred language, and physician language concordance with patient adherence to newly prescribed diabetes medications.Design, setting, and participantsThis observational study was conducted from January 1, 2006, to December 31, 2012, at a large integrated health care delivery system with professional interpreter services. Insured patients with type 2 diabetes, including English-speaking white, English-speaking Latino, or limited English proficiency (LEP) Latino patients with newly prescribed diabetes medication.ExposuresPatient race/ethnicity, preferred language, and physician self-reported Spanish-language fluency.Main outcomes and measuresPrimary nonadherence (never dispensed), early-stage nonpersistence (dispensed only once), late-stage nonpersistence (received ≥2 dispensings, but discontinued within 24 months), and inadequate overall medication adherence (>20% time without sufficient medication supply during 24 months after initial prescription).ResultsParticipants included 21 878 white patients, 5755 English-speaking Latino patients, and 3205 LEP Latino patients with a total of 46 131 prescriptions for new diabetes medications. Among LEP Latino patients, 50.2% (n = 1610) had a primary care physician reporting high Spanish fluency. For oral medications, early adherence varied substantially: 1032 LEP Latino patients (32.2%), 1565 English-speaking Latino patients (27.2%), and 4004 white patients (18.3%) were either primary nonadherent or early nonpersistent. Inadequate overall adherence was observed in 1929 LEP Latino patients (60.2%), 2975 English-speaking Latino patients (51.7%), and 8204 white patients (37.5%). For insulin, early-stage nonpersistence was 42.8% among LEP Latino patients (n = 1372), 34.4% among English-speaking Latino patients (n = 1980), and 28.5% among white patients (n = 6235). After adjustment for patient and physician characteristics, LEP Latino patients were more likely to be nonadherent to oral medications and insulin than English-speaking Latino patients (relative risks from 1.11 [95% CI, 1.06-1.15] to 1.17 [95% CI, 1.02-1.34]; P  .28).Conclusions and relevanceNonadherence to newly prescribed diabetes medications is substantially greater among Latino than white patients, even among English-speaking Latino patients. Limited English proficiency Latino patients are more likely to be nonadherent than English-speaking Latino patients independent of the Spanish-language fluency of their physicians. Interventions beyond access to interpreters or patient-physician language concordance will be required to improve medication adherence among Latino patients with diabetes.

This article examines whether California Medicare beneficiaries with HIV/AIDS choose Part D prescription drug plans that minimize their expenses. Among beneficiaries without low-income supplementation, we estimate the excess cost, and the insurance policy and beneficiary characteristics responsible, when the lowest cost plan is not chosen. We use a cost calculator developed for this study, and 2010 drug use data on 1453 California Medicare beneficiaries with HIV who were taking antiretroviral medications. Excess spending is defined as the difference between projected total spending (premium and cost sharing) for the beneficiary's current drug regimen in own plan vs spending for the lowest cost alternative plan. Regression analyses related this excess spending to individual and plan characteristics. We find that beneficiaries pay more for Medicare Part D plans with gap coverage and no deductible. Higher premiums for more extensive coverage exceeded savings in deductible and copayment/coinsurance costs. We conclude that many beneficiaries pay for plan features whose costs exceed their benefits.

Inaccurate self-reported data on medication exposure lead to less reliable study findings. From 2013 to 2015, we assessed the validity of information on medication use collected via a mailed medication inventory among 223 Women's Health Initiative participants who were members of a health-care delivery system. Self-reported information on medication use was compared with pharmacy records for statins, calcium channel blockers, β-blockers, and bisphosphonates. We assessed sensitivity, specificity, and positive predictive value (PPV) for current medication use. We assessed agreement on duration of use (

Objective. To evaluate first-year pharmacy students' ability to identify medication errors involving the top 100 prescription medications. Design. In the first quarter of a 3-quarter pharmacy self-care course, a didactic lecture on the most common prescribing and dispensing prescription errors was presented to first-year pharmacy students (P1) in preparation for a prescription review simulation done individually and as a group. In the following quarter, they were given a formal prescription review workshop before a second simulation involving individual and group review of a different set of prescriptions. Students were evaluated based on the number of correctly checked prescriptions and a self-assessment of their confidence in reviewing prescriptions. Assessment. All 63 P1 students completed the prescription review simulations. The individual scores did not significantly change, but group scores improved from 79 (16.2%) in the fall quarter to 98.6 (4.7%) in the winter quarter. Students perceived improvement of their prescription checking skills, specifically in their ability to fill a prescription on their own, identify prescribing and dispensing errors, and perform pharmaceutical calculations. Conclusion. A prescription review module consisting of a didactic lecture, workshop and simulation-based methods to teach prescription analysis was successful at improving first year pharmacy students' knowledge, confidence, and application of these skills.

BackgroundThe Centers for Medicare & Medicaid Services (CMS) Medicare Health Plan Quality and Performance Ratings program, or Star Ratings program, includes 3 medication adherence outcome measures (Medication Adherence for Diabetes Medications, Medication Adherence for Hypertension, and Medication Adherence for Cholesterol), which contribute to approximately 31% of a Medicare Advantage prescription drug (MA-PD) plan's Part D summary rating and 12% of its overall star rating (a weighted summary of a plan's Part C and Part D ratings). MA-PD plans have been increasing their adherence intervention efforts as an approach to improving beneficiaries' medication adherence and the plan's quality performance ratings. However, few evaluations have examined the effects of these interventions on medication adherence and performance ratings.ObjectiveTo assess the impact of a quasi-experimental multichannel adherence intervention on beneficiaries' medication adherence and health plan quality performance measures for 2 MA-PD plans. The intervention included a daily prescriber-directed 90-day retail refill component and a weekly member-directed refill reminder component.MethodsMembers filling 1 or more medications assessed by the 3 CMS star ratings adherence measures (oral antidiabetics [DM], antihypertensives [HTN], and statins [CHOL]) were identified for a 2-component intervention starting in April 2013. The retail-based 90-day refill component sent populated 90-day prescription letters via fax to prescribers of members who had filled a 30-day prescription. One fax per member-medication instance was sent and included the option to fax approval of a new 90-day prescription. For prescribers who approved, members were notified that a 90-day refill was available at their retail pharmacies. The refill reminder component used weekly scans of pharmacy claims to identify members' refill patterns. Reminder letters were sent to members 7 days late to refill. An intent-to-treat approach was used to assess intervention effectiveness. Pharmacy claims and health plan enrollment data were used to calculate adherence among members enrolled 1 year pre- and postintervention start (April 2013) for the intervention group and a comparator group that consisted of 4 MA-PD plans not implementing an adherence intervention. Adherence was estimated by the proportion of days covered (PDC) and generalized linear models were fit to calculate difference-in-difference (DID) estimators to control for demographics, comorbidity, and changes in adherence over the study period. To estimate the impact of the intervention on health plan quality performance, 2013 and 2014 CMS star ratings for the respective 2012 and 2013 measurement years were compared by group.ResultsDuring the first year of the intervention, 1,344 prescribers representing 6,701 members were faxed 15,284 populated prescription letters. Prescriber response rate was 53.7% and approval rate (approved letters of total sent) was 47.3%. An average of 539 refill reminder letters were sent per week. DID estimators showed positive influence of the intervention on adherence to HTN and CHOL. For the intervention group, adherence increased 2.0 percentage points (P < 0.001) for HTN and 1.8 percentage points (P < 0.001) for CHOL, relative to the control group. The odds of achieving adherence (PDC ≥ 80%) were greater in the intervention group compared with control for HTN (ratio of odds ratio [ROR] = 1.334; 95% CI = 1.203-1.479) and for CHOL (ROR = 1.247; 95% CI = 1.132-1.374). For the 2 plans implementing the intervention, CMS-published adherence rates for DM, HTN, and CHOL increased from 2012 to 2013 by an average 5.5, 6.0, and 7.0 percentage points, respectively, compared with the control group (3.5, 2.0, and 1.8 percentage points, respectively).ConclusionsThis study found increases in adherence to HTN and CHOL in 2 MA-PD plans implementing a combined prescriber and patient-directed intervention. MA-PD plans can use broad multichannel interventions to address common adherence barriers and as an approach to improving members' adherence to maintenance medications and CMS quality performance ratings.DisclosuresNo funding was received in return for conducting this research. Leslie is an employee of MedImpact Healthcare Systems. The authors report no conflicts of interest. Study concept was developed primarily by Leslie, along with Gilmer. Leslie took the lead in data collection, while data interpretation was performed by Leslie, Natarajan, and Gilmer. The manuscript was written primarily by Leslie, along with Gilmer and assisted by Hovell. Leslie, Gilmer, and Hovell revised the manuscript, with assistance from Natarajan.

ObjectiveTo characterize patent and proprietary medicine vendors and shops in Nigeria and to assess their ability to help improve access to high-quality, primary health-care services.MethodsIn 2013 and 2014, a census of patent and proprietary medicine shops in 16 states of Nigeria was carried out to determine: (i) the size and coverage of the sector; (ii) the basic characteristics of shops and their staff; and (iii) the range of products stocked for priority health services, particularly for malaria, diarrhoea and family planning. The influence of the medical training of people in charge of the shops on the health-care products stocked and registration with official bodies was assessed by regression analysis.FindingsThe number of shops per 100,000 population was higher in southern than in northern states, but the average percentage of people in charge with medical training across local government areas was higher in northern states: 52.6% versus 29.7% in southern states. Shops headed by a person with medical training were significantly more likely to stock artemisinin-based combination therapy, oral rehydration salts, zinc, injectable contraceptives and intrauterine contraceptive devices. However, these shops were less likely to be registered with the National Association of Patent and Proprietary Medicine Dealers and more likely to be registered with the regulatory body, the Pharmacist Council of Nigeria.ConclusionMany patent and proprietary medicine vendors in Nigeria were medically trained. With additional training and oversight, they could help improve access to basic health-care services. Specifically, vendors with medical training could participate in task-shifting interventions.

BackgroundThe Centers of Disease Control and Prevention have declared prescription drug abuse an epidemic in the United States. However, demographic data correlating prescription-related deaths with actual prescriptions written is not well described. The purpose of this study is to compare toxicology reports on autopsy for prescription-related deaths with Prescription Drug Monitor Program (PDMP) data.MethodsThis is a retrospective analysis comparing 2013 San Diego Medical Examiner data on 254 unintentional prescription-related deaths obtained for 12 months before death with data from the California PDMP. Data were analyzed on age, sex, whether there was information on the PDMP, types and quantities of prescribed medications, number of pharmacies and providers involved, and whether there was a match between the Medical Examiner toxicology report and data from the PDMP.ResultsIn 2013, there were 254 unintentional prescription-related deaths; 186 patients (73%) had PDMP data 12 months before death. Ingesting prescription medications with illicit drugs, alcohol, and/or over-the-counter medications accounted for 40% of the unintentional deaths. Opioids were responsible for the majority of single medication deaths (36; 70.6%). The average number of prescriptions was 23.5 per patient, and the average patient used 3 pharmacies and had 4.5 providers. Chronic prescription use was found in 68.8% of patients with PDMP data.ConclusionsThe PDMP data highlight important patterns that can provide valuable insight to clinicians making decisions regarding types and amounts of medications they prescribe. Although there is no guaranteed solution to prevent prescription-related deaths, PDMP data can be useful to prevent coprescribing and medication interaction and by following best clinical practices.

ObjectiveTo characterize the 20 most common prescription medications and the 10 most common prescription medications classified in the former U.S. Food and Drug Administration categories D or X dispensed to pregnant women enrolled in the U.S. Medicaid program.MethodsWe conducted a cohort study of 1,106,757 pregnant women with live births using 2000-2007 Medicaid Analytic eXtract data. We used outpatient pharmacy records to identify medication dispensings and reported the proportion of pregnancies that were dispensed at least one prescription medication. Maternal age and race and ethnicity-stratified estimates were compared using prevalence ratios and 95% confidence intervals (CIs).ResultsDuring pregnancy, 82.5% of the cohort had a dispensing for one or more prescription medication. The most commonly dispensed medications during pregnancy included nitrofurantoin (21.6%), metronidazole (19.4%), amoxicillin (18.0%), azithromycin (16.9%), and promethazine (13.5%). Proportions were highest among younger women for several medications; eg, nitrofurantoin (23.9% compared with 15.4%; prevalence ratio 1.55, CI 1.52-1.58), metronidazole (20.7% compared with 12.0%; prevalence ratio 1.73, CI 1.69-1.77), and azithromycin (21.1% compared with 11.0%; prevalence ratio 1.93, CI 1.89-1.97) were more common among women younger than 20 years than among women aged 35 years or older. Proportions were highest among white women with some exceptions; eg, compared with white women, metronidazole was more common among black women (29.8% compared with 14.4%; prevalence ratio 2.07, CI 2.05-2.09). Excluding fertility treatments, 42.0% had at least one dispensing for a D or X medication during pregnancy. Codeine (11.9%) and hydrocodone (10.2%) were the most common D medications.ConclusionMedications used to treat infections were the most commonly dispensed prescription medications. Dispensing of commonly used prescription medications during pregnancy varied by maternal age and race-ethnicity.Level of evidenceII.

BackgroundYouth and adolescent non-medical use of prescription medications (NUPM) has become a national epidemic. However, little is known about the association between promotion of NUPM behavior and access via the popular social media microblogging site, Twitter, which is currently used by a third of all teens.ObjectiveIn order to better assess NUPM behavior online, this study conducts surveillance and analysis of Twitter data to characterize the frequency of NUPM-related tweets and also identifies illegal access to drugs of abuse via online pharmacies.MethodsTweets were collected over a 2-week period from April 1-14, 2015, by applying NUPM keyword filters for both generic/chemical and street names associated with drugs of abuse using the Twitter public streaming application programming interface. Tweets were then analyzed for relevance to NUPM and whether they promoted illegal online access to prescription drugs using a protocol of content coding and supervised machine learning.ResultsA total of 2,417,662 tweets were collected and analyzed for this study. Tweets filtered for generic drugs names comprised 232,108 tweets, including 22,174 unique associated uniform resource locators (URLs), and 2,185,554 tweets (376,304 unique URLs) filtered for street names. Applying an iterative process of manual content coding and supervised machine learning, 81.72% of the generic and 12.28% of the street NUPM datasets were predicted as having content relevant to NUPM respectively. By examining hyperlinks associated with NUPM relevant content for the generic Twitter dataset, we discovered that 75.72% of the tweets with URLs included a hyperlink to an online marketing affiliate that directly linked to an illicit online pharmacy advertising the sale of Valium without a prescription.ConclusionsThis study examined the association between Twitter content, NUPM behavior promotion, and online access to drugs using a broad set of prescription drug keywords. Initial results are concerning, as our study found over 45,000 tweets that directly promoted NUPM by providing a URL that actively marketed the illegal online sale of prescription drugs of abuse. Additional research is needed to further establish the link between Twitter content and NUPM, as well as to help inform future technology-based tools, online health promotion activities, and public policy to combat NUPM online.

BackgroundThe association between the Medicare Part D low-income subsidy (LIS), gap coverage, and outcomes such as medical expenditures, prescription fills, and medication adherence is not well understood. The purpose of this study was to examine the relationship between the LIS and these measures for patients within a large, national Part D plan in the United States.MethodsIn this cross-sectional, retrospective analysis, we compared total and plan expenditures, out-of-pocket costs, and medication fills and adherence for three categories of Medicare beneficiaries: non-LIS beneficiaries without gap coverage (non-LIS/non-GC), non-LIS beneficiaries with gap coverage (non-LIS/GC), and LIS beneficiaries (LIS).ResultsLIS beneficiaries, relative to non-LIS/non-GC and non-LIS/GC beneficiaries, had higher total expenditures ($1,887 vs. $1,360 vs. $1,341); lower out-of-pocket costs ($148 vs. $546 vs. $570); more expenditures exceeding the gap threshold (27.6% vs. 18.4% vs. 16.9%); and slightly higher adherence to blood pressure (65.6% vs. 64.2% vs. 62.4%); diabetes (62.5% vs. 57.7 vs. 57.4%); and lipid-lowering (59.6% vs. 57.0 vs. 55.6%) medications.ConclusionLIS beneficiaries had higher total expenditures, lower out-of-pocket costs, and modestly better adherence to diabetes medications than non-LIS/non-GC and non-LIS/GC beneficiaries.

There is little or no data examining the association between either pain or the use or misuse of opioid analgesic with adherence to antiretroviral medications (ARVs) among HIV-infected adults. We interviewed a community-based cohort of HIV-infected indigent adults prescribed antiretroviral medications (ARVs) quarterly to examine the association between (1) pain, (2) receipt of opioid analgesics, and (3) opioid analgesic misuse with self-reported ARV adherence. Of 281 participants, most (82.5 %) reported severe or moderate pain, half (52.4 %) received a prescription for opioids, and one quarter (24.6 %) misused opioid analgesics. Most (71.9 %) reported >90 % ARV adherence. In a GEE model, neither pain (unadjusted OR 1.14, CI 0.90–1.45) nor prescription of opioid analgesics (unadjusted OR 1.11, CI 0.84–1.49) were significantly associated with ARV adherence. Misuse of opioid analgesics was associated with incomplete adherence (AOR 1.42, CI 1.09–1.86). Individuals who misuse opioid analgesics, like those who use illicit substances, may have difficulty adhering to medication regimens.