Outcomes and Costs in Patients with Immune Thrombotic Thrombocytopenic Purpura Receiving Front-Line Versus Delayed Caplacizumab: A US Hospital Database Study.

European real-world data indicate that front-line treatment with caplacizumab is associated with improved clinical outcomes compared with delayed caplacizumab treatment. The objective of the study was to describe the characteristics, treatment patterns, and outcomes in hospitalized patients with an immune-mediated thrombotic thrombocytopenic purpura (iTTP) episode treated with front-line versus delayed caplacizumab in the US. This retrospective cohort analysis of a US hospital database included adult patients (≥18 years) with an acute iTTP episode (a diagnosis of thrombotic microangiopathy and ≥1 therapeutic plasma exchange [TPE] procedure) from January 21, 2019, to February 28, 2021. Unadjusted baseline characteristics, treatment patterns, healthcare resource utilization, and costs were compared between patients who received front-line versus delayed (<2 vs ≥2 days after TPE initiation) caplacizumab treatment. Out of 39 patients, 16 (41.0%) received front-line and 23 (59.0%) received delayed treatment with caplacizumab. Baseline characteristics and symptoms were similar between the two groups. Patients who received front-line caplacizumab treatment had significantly fewer TPE administrations (median: 5.0 vs 12.0); and a significantly shorter hospital stay (median: 9.0 days vs 16.0 days) than patients receiving delayed caplacizumab therapy. Both of these were significantly lower in comparison of means (t-test P < .01). Median inpatient costs (inclusive of caplacizumab costs) were 54% higher in the delayed treated patients than in the front-line treated patients (median: $112 711 vs $73 318). TPE-specific cost was lower in the front-line treated cohort (median: $6 989 vs $10 917). In conclusion, front-line treatment with caplacizumab had shorter hospitalizations, lower healthcare resource utilization, and lower costs than delayed caplacizumab treatment after TPE therapy.

Buprenorphine Out-of-Pocket Costs and Discontinuation in Privately Insured Adults With Opioid Use Disorder.

This cohort study examined the association between out-of-pocket costs for an initial buprenorphine prescription and its discontinuation among commercially insured US adults with opioid use disorder.

GEnZ explorer: a tool for visualizing agroclimate to inform research and regulatory risk assessment.

Confined field trials (CFT) of genetically engineered (GE) crops are used to generate data to inform environmental risk assessments (ERA). ERAs are required by regulatory authorities before novel GE crops can be released for cultivation. The transportability of CFT data to inform risk assessment in countries other than those where the CFT was conducted has been discussed previously in an analysis showing that the primary difference between CFT locations potentially impacting trial outcomes is the physical environment, particularly the agroclimate. This means that data from trials carried out in similar agroclimates could be considered relevant and sufficient to satisfy regulatory requirements for CFT data, irrespective of the country where the CFTs are conducted. This paper describes the development of an open-source tool to assist in determining the transportability of CFT data. This tool provides agroclimate together with overall crop production information to assist regulators and applicants in making informed choices on whether data from previous CFTs can inform an environmental risk assessment in a new country, as well as help developers determine optimal locations for planning future CFTs. The GEnZ Explorer is a freely available, thoroughly documented, and open-source tool that allows users to identify the agroclimate zones that are relevant for the production of 21 major crops and crop categories or to determine the agroclimatic zone at a specific location. This tool will help provide additional scientific justification for CFT data transportability, along with spatial visualization, to help ensure regulatory transparency.

An assessment of the relation between metal contaminated sediment and freshwater mussel populations in the Big River, Missouri.

The Big River in southeast Missouri drains the largest historical lead mining area in the United States. Ongoing releases of metal contaminated sediments into this river are well documented and are suspected of suppressing freshwater mussel populations. We characterized the spatial extent of metal contaminated sediments and evaluated its relationship with mussel populations in the Big River. Mussels and sediments were collected at 34 sites with potential metal effects and 3 reference sites. Analysis of sediment samples showed that lead (Pb) and zinc (Zn) concentrations were 1.5 to 65 times greater than background concentrations in the reach extending 168 km downstream from Pb mining releases. Mussel abundance decreased acutely downstream from these releases where sediment Pb concentrations were highest and increased gradually as Pb sediment concentrations attenuated downstream. We compared current species richness with historical survey data from three reference rivers with similar physical habitat characteristics and human effects, but without Pb-contaminated sediment. Big River species richness was on average about one-half that expected based on reference stream populations and was 70-75 % lower in reaches with high median Pb concentrations. Sediment Zn and cadmium, and particularly Pb, had significant negative correlations with species richness and abundance. The association of sediment Pb concentrations with mussel community metrics in otherwise high-quality habitat indicates that Pb toxicity is likely responsible for depressed mussel populations observed within the Big River. We used concentration-response regressions of mussel density verses sediment Pb to determine that the Big River mussel community is adversely affected when sediment Pb concentrations are above 166 ppm, the concentration associated with 50 % decreases in mussel density. Based on this assessment of metals concentrations sediment and mussel fauna, our findings indicate that sediment in approximately 140 km of the Big River with suitable habitat has a toxic effect to mussels.

Healthcare utilisation and costing for decompensated chronic liver disease hospitalisations at a Victorian network.

BACKGROUND: The economic burden of decompensated chronic liver disease (CLD) on Australian healthcare services is poorly characterised. AIMS: To evaluate the in-patient healthcare utilisation costs associated with decompensated CLD at Monash Health, an Australian tertiary healthcare service. METHODS: The current retrospective cost analysis examined patients with decompensated CLD admitted between 1 January 2012 and 31 December 2018. Hospitalisations were identified using CLD-specific International Classification of Diseases, Tenth Revision, codes. Cost measures were estimated using the Victorian Weighted Inlier Equivalent Separation funding data based on the Australian Refined Diagnosis Related Groups cost weights. RESULTS: There were 707 hospitalisations in 435 adult patients. The mean age was 56.7 ± 11.7 years and the mean length of stay was 10.28 ± 11.2 days. Median survival was 31 months (interquartile range, 2-94 months) and 177 (40.8%) patients died within 1 year of admission. The cost of admission varied according to decompensation: hepatorenal syndrome ($20 162 AUD), variceal bleed ($16 630 AUD), spontaneous bacterial peritonitis ($12 664 AUD), hepatic encephalopathy ($9973 AUD) and ascites ($9001 AUD). There was no significant difference in the admissions or 30-day readmission rate from 2012 to 2018 financial year (FY). The total adjusted cost of cirrhotic admissions per year increased by 78% from FY2012 to FY2018. CONCLUSION: Hospital admission and readmission for decompensated CLD is common and associated with 40.8% 1-year mortality and high costs. Clearer delineation of goals of care and alternative ambulatory care models for decompensated CLD are urgently required to reduce the high costs and burden on health services.

Many Medicare Beneficiaries Do Not Fill High-Price Specialty Drug Prescriptions.

For high-price drugs, Medicare Part D beneficiaries who do not receive a low-income subsidy must pay a percentage of the drug's price for each medication fill. Without that subsidy, which lowers out-of-pocket spending, beneficiaries typically pay hundreds or thousands of dollars for a single fill. We estimated the proportion of Part D beneficiaries in fee-for-service Medicare, with and without a subsidy, who do not initiate treatment (that is, do not fill a new prescription) with high-price Part D drugs newly prescribed for four conditions. Examining 17,076 new prescriptions issued between 2012 and 2018 for Part D beneficiaries from eleven geographically diverse health systems, we found that beneficiaries receiving subsidies were nearly twice as likely to obtain the prescribed drug within ninety days as those without subsidies. Among beneficiaries without subsidies, we observed noninitiation for 30 percent of prescriptions written for anticancer drugs, 22 percent for hepatitis C treatments, and more than 50 percent for disease-modifying therapies for either immune system disorders or hypercholesterolemia. Our findings support current legislative efforts to increase the accessibility of high-price medications by reducing out-of-pocket expenses under Medicare Part D, particularly for beneficiaries without low-income subsidies.

Geographic differences in community oncology provider and practice location characteristics in the central United States.

PURPOSE: How care delivery influences urban-rural disparities in cancer outcomes is unclear. We sought to understand community oncologists' practice settings to inform cancer care delivery interventions. METHODS: We conducted secondary analysis of a national dataset of providers billing Medicare from June 1, 2019 to May 31, 2020 in 13 states in the central United States. We used Kruskal-Wallis rank and Fisher's exact tests to compare physician characteristics and practice settings among rural and urban community oncologists. FINDINGS: We identified 1,963 oncologists practicing in 1,492 community locations; 67.5% practiced in exclusively urban locations, 11.3% in exclusively rural locations, and 21.1% in both rural and urban locations. Rural-only, urban-only, and urban-rural spanning oncologists practice in an average of 1.6, 2.4, and 5.1 different locations, respectively. A higher proportion of rural community sites were solo practices (11.7% vs 4.0%, P<.001) or single specialty practices (16.4% vs 9.4%, P<.001); and had less diversity in training environments (86.5% vs 67.8% with <2 medical schools represented, P<.001) than urban community sites. Rural multispecialty group sites were less likely to include other cancer specialists. CONCLUSIONS: We identified 2 potentially distinct styles of care delivery in rural communities, which may require distinct interventions: (1) innovation-isolated rural oncologists, who are more likely to be solo providers, provide care at few locations, and practice with doctors with similar training experiences; and (2) urban-rural spanning oncologists who provide care at a high number of locations and have potential to spread innovation, but may face high complexity and limited opportunity for care standardization.

Impacts of a Medicaid "lock-in" program on opioid use disorder treatment and services and naloxone dispensing.

BACKGROUND: "Lock-in" programs are used by health insurers to reduce the risk of adverse outcomes that can result from overutilization of opioids and other controlled substances. We estimated the association between North Carolina's Medicaid lock-in program and use of opioid use disorder treatment-related services and naloxone dispensing. METHODS: A cohort study of individuals who became eligible for a Medicaid lock-in program between December 2016 and December 2019 (n = 21,220). We compared those enrolled in the program to those eligible but not enrolled. Outcomes included rate of medication for opioid use disorder (MOUD); rate of other substance use disorder treatment (e.g., detoxification); and naloxone dispensing. RESULTS: The majority of beneficiaries enrolled in the program had recently received MOUD or other treatment prior to enrollment (59%). After controlling for several potential confounders, the program was associated with slight increases in MOUD use, compared to those eligible but not enrolled (adjusted rate ratio: 1.09, 95% CI: 1.04,1.14). Those enrolled in the program received, on average, 5.4 more days of MOUD per person per year than those eligible but not enrolled (adjusted risk difference: 5.43, 95% CI: 2.49,8.36). Naloxone dispensing was similar and low among those enrolled and not enrolled in the program (7-8%). CONCLUSIONS: Enrollment in a Medicaid lock-in program was associated with a small increase in the number of days with substance use disorder treatment. However, given the high prevalence of opioid use disorder among beneficiaries in the program, findings highlighted considerable opportunity for improvement in treatment utilization and retention and a need for increased naloxone dispensing.

Understanding health inequalities in Wales using the Blinder-Oaxaca decomposition method.

Background: Throughout Wales and the world, health inequality remains a problem that is interconnected with a wider and complex social, economic and environmental dynamic. Subsequently, action to tackle inequality in health needs to take place at a structural level, acknowledging the constraints affecting an individual's (or community's) capability and opportunity to enable change. While the 'social determinants of health' is an established concept, fully understanding the composition of the health gap is dependent on capturing the relative contributions of a myriad of social, economic and environmental factors within a quantitative analysis. Method: The decomposition analysis sought to explain the differences in the prevalence of these outcomes in groups stratified by their ability to save at least £10 a month, whether they were in material deprivation, and the presence of a limiting long-standing illness, disability of infirmity. Responses to over 4,200 questions within the National Survey for Wales (n = 46,189; 2016-17 to 2019-20) were considered for analysis. Variables were included based on (1) their alignment to a World Health Organization (WHO) health equity framework ("Health Equity Status Report initiative") and (2) their ability to allow for stratification of the survey sample into distinct groups where considerable gaps in health outcomes existed. A pooled Blinder-Oaxaca model was used to analyse inequalities in self-reported health (fair/poor health, low mental well-being and low life satisfaction) and were stratified by the variables relating to financial security, material deprivation and disability status. Results: The prevalence of fair/poor health was 75% higher in those who were financially insecure and 95% higher in those who are materially deprived. Decomposition of the outcome revealed that just under half of the health gap was "explained" i.e., 45.5% when stratifying by the respondent's ability to save and 46% when stratifying by material deprivation status. Further analysis of the explained component showed that "Social/Human Capital" and "Income Security/Social Protection" determinants accounted the most for disparities observed; it also showed that "Health Services" determinants accounted the least. These findings were consistent across the majority of scenarios modeled. Conclusion: The analysis not only quantified the significant health gaps that existed in the years leading up to the COVID-19 pandemic but it has also shown what determinants of health were most influential. Understanding the factors most closely associated with disparities in health is key in identifying policy levers to reduce health inequalities and improve the health and well-being across populations.

Intravital assessment of precapillary pulmonary arterioles of type 1 diabetic mice shows oxidative damage and increased tone in response to NOS inhibition.

Microvascular dilation, important for peripheral tissue glucose distribution, also modulates alveolar perfusion and is inhibited by loss of bioavailable nitric oxide (NO) in diabetes mellitus (DM). We hypothesized that DM-induced oxidative stress decreases bioavailable NO and pulmonary precapillary arteriolar diameter, causing endothelial injury. We examined subpleural pulmonary arterioles after acute NO synthase (NOS) inhibition with NG-nitro-l-arginine methyl ester (l-NAME) in streptozotocin (STZ)- and saline (CTRL)-treated C57BL/6J mice. Microvascular changes were assessed by intravital microscopy in the right lung of anesthetized mice with open chest and ventilated lungs. Arteriolar tone in pulmonary arterioles (27.2-48.7 µm diameter) increased in CTRL mice (18.0 ± 11% constriction, P = 0.034, n = 5) but decreased in STZ mice (13.6 ± 7.5% dilation, P = 0.009, n = 5) after l-NAME. Lung tissue dihydroethidium (DHE) fluorescence (superoxide), inducible NOS expression, and protein nitrosylation (3-nitrotyrosine) increased in STZ mice and correlated with increased glucose levels (103.8 ± 8.8 mg/dL). Fluorescently labeled fibrinogen administration and fibrinogen immunostaining showed fibrinogen adhesion, indicating endothelial injury in STZ mice. In CTRL mice, vasoconstriction to l-NAME was likely due to the loss of bioavailable NO. Vasodilation in STZ mice may be due to decreased formation of a vasoconstrictor or emergence of a vasodilator. These findings provide novel evidence that DM targets the pulmonary microcirculation and that decreased NO bioavailability and increased precapillary arteriolar tone could potentially lead to ventilation-perfusion abnormalities, exacerbating systemic DM complications.NEW & NOTEWORTHY Diabetes pulmonary and microvascular consequences are well recognized but have not been characterized. We assessed lung microvascular changes in a live anesthetized mouse model of type 1 diabetes, using a novel intravital microscopy technique. Our results show new evidence that a diabetes-induced decrease in lung nitric oxide bioavailability underlies oxidative damage, enhanced platelet activation, and endothelial injury causing pulmonary microvascular dysfunction and altered vasoreactivity. These findings could provide novel strategies to prevent or reverse diabetes systemic consequences.

Health costs of women with chronic overlapping pain conditions by opioid and complementary and integrative health use.

OBJECTIVE: To estimate differences in average annual health care expenditures of adult women with chronic overlapping pain conditions (COPCs) by pain treatment modality as follows: (1) no long-term opioid or complementary and integrative health (CIH) use; (2) CIH only use; (3) long-term opioid only use; and (4) long-term opioid and CIH use. DATA SOURCE: Cross-sectional Medical Expenditure Panel Survey data (2012-2016). STUDY DESIGN: We estimated differences between average annual expenditures of adult women with COPCs by their use of long-term opioids and CIH modalities. Generalized linear regression with a log link function was used to estimate adjusted marginal effects in annual expenditures. The distribution family was chosen based on Modified Park Tests. We controlled for pain severity, patient demographic characteristics, physical limitations, comorbidities, mental health, insurance status, physical therapy use, and census region. We also employed propensity-score based marginal mean weighting through stratification to balance our treatment groups on observed covariates. DATA COLLECTION/EXTRACTION METHODS: We identified adult women (>17 years) with one or more self-reported COPC using 3-digit International Classification of Diseases (ICD)-9/10-Clinical Modification (CM) codes (N = 9169) and categorized their use of CIH and long-term opioids. PRINCIPAL FINDINGS: Compared to women without long-term opioid or CIH use, CIH only use was significantly associated with lower inpatient expenditures (-$947 [-$1699, -$196]; p-value < 0.01), higher office-based expenditures ($1345 [$944, $1746]; p-value < 0.001), and higher patient out-of-pocket expenditures ($628 [$409, $848]; p-value < 0.001). Long-term opioid use, alone or in combination with CIH, was significantly associated with higher expenditures (p-value < 0.05) in total and across all utilization categories compared to women without any long-term opioid or CIH use. CONCLUSIONS: Our results indicate that CIH treatment approaches for chronic pain have the potential to be utilized without increasing overall costs. Future research should further examine the role of CIH modalities in achieving cost-effective pain management that reduces avoidable opioid use.

Metal stents are safe and cost-effective for preoperative biliary drainage in resectable pancreaticobiliary tumours.

BACKGROUNDS: To compare the complication rates and overall costs of self-expandable metal stents (SEMS) and plastic stents (PS) in clinically indicated preoperative biliary drainage (PBD) prior to a pancreatoduodenectomy (PD). METHODS: We conducted an Australian multicentre retrospective cohort study using the databases of four tertiary hospitals. Adult patients who underwent clinically indicated endoscopic PBD prior to PD from 2010 to 2019 were included. Rates of complications attributable to PBD, surgical complications and pre-operative endoscopic re-intervention were calculated. Costing data were retrieved from our Financial department. RESULTS: Among the 157 included patients (mean age 66.6 ± 9.8 years, 45.2% male), 49 (31.2%) received SEMS and 108 received PS (68.8%). Baseline bilirubin was 187.5 ± 122.6 µmol/L. Resection histopathology showed mainly adenocarcinoma (93.0%). Overall SEMS was associated less complications (12.2% vs. 28.7%, p = 0.02) and a lower pre-operative endoscopic re-intervention rate (4.3 vs. 20.8%, p = 0.03) compared with PS. There was no difference in post-PD complication rates. On multivariate logistic regression analysis, stent type was an independent risk factor of PBD complication (OR of SEMS compared to PS 0.24, 95% CI 0.07-0.79, p = 0.02) but not for any secondary outcome measures. Upfront material costs were $56USD for PS and $1991USD for SEMS. Accounting for rates of complications, average costs were similar ($3110USD for PS and $3026USD for SEMS). CONCLUSION: In resectable pancreaticobiliary tumours, SEMS for PBD was associated with reduced risk of overall PBD-related complications and pre-surgical endoscopic reintervention rates and was comparable to PS in terms of overall cost.

Trends in Medicare Part D coverage of generics with equivalent brand-name drugs.

OBJECTIVES: To evaluate whether increased placement of generic drugs on higher cost-sharing tiers in Medicare Part D is associated with coverage of multisource brand-name drugs, plan type, or product characteristics. STUDY DESIGN: Descriptive study of Medicare Prescription Drug Formulary Files. METHODS: We analyzed plan coverage and tiering of brand-name drugs and matched generics from 2013-2019. We compared tiering changes and estimated out-of-pocket spending by tier for all Part D plans and by plan type (Medicare Advantage prescription drug [MA-PD] vs stand-alone prescription drug plan [PDP]) for covered generic drugs. Finally, we identified the generic products commonly placed on higher tiers in 2019 and categorized them based on clinical characteristics. RESULTS: Across 5,220,488 plan-product combinations in 2019, 76.4% of generic drug observations reflected coverage on Part D plan formularies, compared with only 12.1% of brand-name drugs. Between 2013 and 2019, the share of observations reflecting covered generics on lower tiers decreased from 76.8% to 53.9%, whereas the share on higher tiers increased from 7.5% to 28.0%. MA-PD plans were more likely than PDPs to place generic drugs on lower tiers, even among plan sponsors offering both plan types. Despite these trends, higher tier placement does not appear to be related to more generous coverage of brand-name products. Instead, in 2019, 70% of high-tier generics had multiple formulations, required heightened clinical monitoring, or had head-to-head treatment options available. CONCLUSIONS: Although Part D plans have increasingly placed covered generic drugs on higher formulary tiers over time, this may be partly explained by a drug's clinical profile and availability of substitutes rather than preferred brand-name drug coverage.

Opioid Use Disorder and Overdose in Older Adults With Breast, Colorectal, or Prostate Cancer.

BACKGROUND: Despite high rates of opioid therapy, evidence about the risk of preventable opioid harms among cancer survivors is underdeveloped. Our objective was to estimate the odds of opioid use disorder (OUD) and overdose following breast, colorectal, or prostate cancer diagnosis among Medicare beneficiaries. METHODS: We conducted a retrospective cohort study using 2007-2014 Surveillance, Epidemiology, and End Results-Medicare data for cancer survivors with a first cancer diagnosis of stage 0-III breast, colorectal, or prostate cancer at age 66-89 years between 2008 and 2013. Cancer survivors were matched to up to 2 noncancer controls on age, sex, and Surveillance, Epidemiology, and End Results region. Using Firth logistic regression, we estimated adjusted 1-year odds of OUD or nonfatal opioid overdose associated with a cancer diagnosis. We also estimated adjusted odds of OUD and overdose separately and by cancer stage, prior opioid use, and follow-up time. RESULTS: Among 69 889 cancer survivors and 125 007 controls, the unadjusted rates of OUD or nonfatal overdose were 25.2, 27.1, 38.9, and 12.4 events per 10 000 patients in the noncancer, breast, colorectal, and prostate samples, respectively. There was no association between cancer and OUD. Colorectal survivors had 2.3 times higher odds of opioid overdose compared with matched controls (adjusted odds ratio = 2.33, 95% confidence interval = 1.49 to 3.67). Additionally, overdose risk was greater in those with more advanced disease, no prior opioid use, and preexisting mental health conditions. CONCLUSIONS: Opioid overdose was a rare, but statistically significant, outcome following stage II-III colorectal cancer diagnosis, particularly among previously opioid-naïve patients. These patients may require heightened screening and intervention to prevent inadvertent adverse opioid harms.

Medicaid prescription limits and their implications for naloxone accessibility.

BACKGROUND: Expanding access to and utilization of naloxone is a vitally important harm reduction strategy for preventing opioid overdose deaths, particularly in vulnerable populations like Medicaid beneficiaries. The objective of this study was to characterize the landscape of monthly prescription fill limit policies in Medicaid programs and their potential implications for expanding naloxone use for opioid overdose harm reduction. METHODS: A cross-sectional, multi-modal online and telephonic data collection strategy was used to identify and describe the presence and characteristics of monthly prescription fill limit policies across state Medicaid programs. Contextual characteristics were described regarding each state's Medicaid enrollment, opioid prescribing rates, and overdose death rates. Data collection and analysis occurred between February and May 2020. RESULTS: Medicaid-covered naloxone fills are currently subject to monthly prescription fill limit policies in 10 state Medicaid programs, which cover 20 % of the Medicaid population nationwide. Seven of these programs are located in states ranking in the top 10 highest per-capita opioid prescribing rates in the country. However, 8 of these programs are located in states with opioid overdose death rates below the national average. CONCLUSIONS: Medicaid beneficiaries at high risk of opioid overdose living in states with monthly prescription fill limits may experience significant barriers to obtaining naloxone. Exempting naloxone from Medicaid prescription limit restrictions may help spur broader adoption of naloxone for opioid overdose mortality prevention, especially in states with high opioid prescribing rates. Achieving unfettered naloxone coverage in Medicaid is critical as opioid overdoses and Medicaid enrollment increase amid the COVID-19 pandemic.

Association of Current Opioid Use With Serious Adverse Events Among Older Adult Survivors of Breast Cancer.

Importance: National efforts to improve safe opioid prescribing focus on preventing misuse, overdose, and opioid use disorder. This approach overlooks opportunities to better prevent other serious opioid-related harms in complex populations, such as older adult survivors of cancer. Little is known about the rates and risk factors for comprehensive opioid-related harms in this population. Objective: To determine rates of multiple opioid-related adverse drug events among older adults who survived breast cancer and estimate the risk of these events associated with opioid use in the year after completing cancer treatment. Design, Setting, and Participants: This retrospective cohort study used 2007 to 2016 Surveillance, Epidemiology and End Results-Medicare data from fee-for-service Medicare beneficiaries with first cancer diagnosis of stage 0 to III breast cancer at age 66 to 90 years from January 1, 2008, through December 31, 2015, who completed active breast cancer treatment. Data were analyzed from October 31, 2019, to June 10, 2020. Exposures: Repeated daily measure indicating possession of any prescription opioid supply in Medicare Part D prescription claims. Main Outcomes and Measures: Adjusted risk ratios (aRRs), estimated using modified Poisson generalized estimating equation models, for adverse drug events related to substance misuse (ie, diagnosed opioid abuse, dependence, or poisoning), other adverse drug events associated with opioid use (ie, gastrointestinal events, infections, falls and fractures, or cardiovascular events), and all-cause hospitalization associated with opioid supply the prior day, controlling for patient characteristics. Results: Among 38 310 women included in the study (mean [SD] age, 74.3 [6.3] years), there were 0.010 (95% CI, 0.008-0.011) adverse drug events related to substance misuse per 1000 person-days, 0.237 (95% CI, 0.229-0.245) other adverse drug events associated with opioid use per 1000 person-days, and 0.675 (95% CI, 0.662-0.689) all-cause hospitalizations per 1000 person-days. Opioid use was associated with increased risk of adverse drug events related to substance misuse (aRR, 14.62; 95% CI, 9.69-22.05; P < .001), other adverse drug events related to opioid use (aRR, 2.50; 95% CI, 2.11-2.96; P < .001), and all-cause hospitalization (aRR, 2.77; 95% CI, 2.55-3.02; P < .001). In a dose-response effect, individuals with high daily opioid doses had consistently higher risks of all study outcomes compared with individuals who had low opioid doses. Compared with days with no opioid exposure, the risk of any adverse drug event related to substance misuse was 3.4-fold higher for individuals with a current opioid supply ≥50 mg morphine equivalent dose per day (aRR, 3.40; 95% CI, 2.47-4.68; P < .001), while the risk was 2.3-fold higher for individuals with 1 to 49 mg morphine equivalent dose per day (aRR, 2.29; 95% CI, 1.89-2.77; P < .001). Conclusions and Relevance: These findings suggest that among older adults who survived breast cancer, continued prescription opioid use in the year after completing active cancer treatment was associated with an immediate increased risk of a broad range of serious adverse drug events related to substance misuse and other adverse drug events associated with opioid use. Clinicians should consider the comprehensive risks of managing cancer pain with long-term opioid therapy.

Changes in Opioid Prescribing Patterns Among Generalists and Oncologists for Medicare Part D Beneficiaries From 2013 to 2017.

Importance: In response to the opioid epidemic, policies aiming to reduce opioid prescribing, misuse, and abuse may have the unintended consequence of restricting access to necessary opioid therapy for cancer-related pain. It is unknown how opioid prescribing patterns have changed among generalists and oncologists during this era. Objective: To examine trends in opioid prescription rates for Medicare Part D beneficiaries from 2013 to 2017 among oncologists and generalists. Design, Setting, and Participants: This repeated cross-sectional study of generalist physicians (internal medicine, family medicine, geriatric medicine, general practice) and oncology specialists (medical oncology, hematology-oncology, and radiation oncology) analyzed the Medicare Provider Utilization and Payment Data: Part D prescriber files from 2013 to 2017. Exposures: Generalist vs oncology specialty. Main Outcomes and Measures: Outcomes included physician-level rates of both opioid and long-acting opioid prescriptions per 100 Medicare Part D beneficiaries. Poisson regression was used to estimate annual predicted outcome rates and incidence rate ratios, adjusting for prescriber characteristics and state fixed effects. Results: We analyzed the prescribing patterns of 251 820 generalists and 14 210 oncologists. From 2013 to 2017, the annual adjusted predicted mean rate of opioid prescriptions per 100 Medicare beneficiaries decreased from 68.2 to 49.7 among generalists (adjusted incidence rate ratio [aIRR] = 0.73; 95% CI, 0.73-0.73) and from 77.8 to 58.8 among oncologists (aIRR = 0.76; 95% CI, 0.74-0.77). The rate of long-acting opioid prescriptions per 100 Medicare beneficiaries also decreased from 8.0 to 5.4 for generalists (aIRR = 0.67; 95% CI, 0.66-0.68) and from 18.6 to 13.3 for oncologists (aIRR = 0.72; 95% CI, 0.69-0.74). Conclusions and Relevance: We found large declines in opioid prescription rates for Medicare beneficiaries by generalists and oncologists from 2013 to 2017. Opioid policy and advocacy appear to have been effective in reducing the extent of opioid prescribing in the Medicare population. Similar declines between generalists and oncologists raise concern that access to cancer pain management may have been inadvertently restricted. How much of the decrease in prescribing by oncologists is appropriate vs inappropriate deserves further investigation.