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Introduction: The use of medical cannabis (MC) to treat a host of conditions has expanded considerably in the United States; however, precise quantitative assessments of purchasing characteristics are unknown. This study sought to characterize the trends in MC purchases, US dollars spent, and type and amount purchased by demographic and clinical characteristics. Materials and Methods: This descriptive exploratory association study examined statewide MC registry data in Arkansas linked at the person level with statewide transaction data documenting each MC purchase. MC transaction data (May 11, 2019-August 31, 2022) were assessed to identify persons who could be linked to the registry data and made at least one purchase. Individual demographic characteristics and MC qualifying conditions (QCs) were ascertained. Product types were classified into plant cannabis, cannabis extract for inhalation (vape), edibles, and others. The average daily total delta-9-tetrahydrocannabinol (THC) purchased was calculated based on the concentration and quantity purchased. Purchasing characteristics are described and demographic and clinical factors associated with THC purchased per day and dollars spent per year were estimated by ordinary least square regression and general linear models with a gamma distribution. Results: On average, 89,057 MC purchasers spent $3343 (interquartile range [IQR], $907-$4802), had 33.34 (IQR, 8.32-46.03) transaction days per year, and purchased 162.32 mg (IQR, 30.51-237.69) of THC per day. Most persons predominantly purchased plant cannabis (68.27%), followed by edibles (14.92%) and vape (11.96%). Individuals younger than 18 years of age (β=-78.23; 95% confidence interval [CI], -116.599 to -39.863), persons 70 and older (β = -122.30; 95% CI, -128.18 to -116.422), and women (β=-33.70; 95% CI, -35.95 to -31.446) purchased less THC per day than their counterparts after multivariate adjustment. The most common QCs were pain and post-traumatic stress disorder (PTSD), and compared to those with cancer, persons with pain (β = 26.30; 95% CI, 18.636-33.96) and PTSD (β = 38.34; 95% CI, 30.467-46.222) purchased more THC per day. Conclusion: The average THC purchased per person per day exceeds typically recommended daily doses for therapeutic uses, and further research is warranted to assess the safety and benefits of MC across these conditions.

Annona emarginata is a native Brazilian species capable of producing at least ten alkaloids of ecological, agronomic, and pharmacological importance. Some studies have explored the effect of external phytoregulators on the production of alkaloids, including the effect of auxins, which, like alkaloids, derive from the shikimic acid pathway. Thus, this study aimed to evaluate how indole acetic acid (IAA) and its inhibitor 2,3,5-triiodobenzoic acid (TIBA) impact the production of alkaloids and the primary metabolism of A. emarginata , which brings advances in the understanding of the mechanisms of alkaloid synthesis and can aid in the bioprospection of molecules of interest in Annonaceae. The design was completely randomized, with three treatments (control, IAA [10 -6 M] and TIBA [10 -6 M]) and five collection times (12, 36, 84, 156, and 324 h). The following variables were analyzed: total alkaloids, alkaloid profile, nitrate reductase activity, gas exchange in photosynthesis, chlorophyll a fluorescence, sugars, starch, and antioxidant activity. Of the twelve alkaloids analyzed, discretine and xylopine were not detected in the control plants; however, both were detected when IAA was applied (in roots and leaves) and xylopine (in roots) when the inhibitor was applied. The alkaloid asimilobine was not detected with the use of TIBA. Variations in alkaloid concentrations occurred in a punctual manner, without significant variations in photosynthesis and nitrate reductase activity, but with variations in the antioxidant system and sugar concentrations, mainly at 156 h, when the highest alkaloid concentrations were observed with the use of TIBA. It could be concluded that IAA is capable of selectively modulating the production of alkaloids in A. emarginata , either due to an external source or by the application of its inhibitor (TIBA).

Background: Immune checkpoint inhibitors (ICIs) have become the mainstay treatment for non-small cell lung cancer (NSCLC). However, there is a lack of studies assessing ICIs as subsequent treatment in older adults with NSCLC and brain metastasis (BM). This retrospective cohort study compared the real-world survival of older patients with NSCLC and BM at diagnosis [synchronous BM (SBM)] previously treated with chemotherapy receiving ICI versus chemotherapy as subsequent treatment., Methods: Patients with NSCLC and SBM ≥65 years previously treated with chemotherapy were identified using the SEER-Medicare database (2010-2019). Patients receiving new chemotherapy and/or Food and Drug Administration (FDA)-approved ICIs as second/third-line treatment were included, excluding those ever-receiving targeted therapies. Each ICI patient was matched to one chemotherapy patient by time to subsequent treatment (within ±30 days) from diagnosis. Overall survival (OS) time was measured from the start of subsequent treatment to death, censored at disenrollment from Medicare Part A/B, enrollment in Part C, or end of study (December 31, 2019), whichever came first. OS curves were estimated and compared using the Kaplan-Meier (KM) method and log-rank test. Hazard ratio (HR) was estimated using a multivariable-adjusted Cox proportional hazards model., Results: Matched cohorts included 546 patients [273 in each group; median age 71 (range, 65-87) years]. ICI patients were older, more likely non-Hispanic, with squamous cell carcinoma, and liver metastasis compared to chemotherapy. KM estimated better survival in ICI than chemotherapy {median survival: 209 days [95% confidence interval (CI): 160-275] vs. 155 days (95% CI: 135-187); log-rank P<0.001}. ICI was associated with a lower adjusted hazard of death [HR =0.63; 95% CI: 0.52-0.75; P<0.001] compared to subsequent chemotherapy treatment., Conclusions: In this population-based study of older patients with NSCLC and SBM previously treated with chemotherapy, subsequent treatment with ICI was associated with improved survival compared to chemotherapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-205/coif). B.C.M. receives royalties from Trestle Tree LLC for the commercialization of an opioid risk prediction tool that is unrelated to this investigation and receives honoraria for his service on the Midwest CEPAC which assesses the clinical and economic value of new health technologies. A.R. has obtained grant funding from Bristol Myers Squibb, Nico Corporation and the NIH which are not related to this work. She serves on multiple advisory boards (Nico Corporation, Medexus, and UCSC) which are not in conflict with this work. C.L. is supported by the American Cancer Society under award number RSGI‐23‐1039245‐01‐HOPS, and was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1 TR003107-02S2. Support of data acquisition was provided by the Arkansas Biosciences Institute, the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000. C.L. received research support (payment to the university) for unrelated projects sponsored by University of Utah/AstraZeneca, and received honoraria from PCORI for grant review. The other authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Aims: To assess the cost-effectiveness of a two-layer compression bandage versus a standard wool and crepe bandage following total knee arthroplasty, using patient-level data from the Knee Replacement Bandage Study (KReBS)., Methods: A cost-utility analysis was undertaken alongside KReBS, a pragmatic, two-arm, open label, parallel-group, randomized controlled trial, in terms of the cost per quality-adjusted life year (QALY). Overall, 2,330 participants scheduled for total knee arthroplasty (TKA) were randomized to either a two-layer compression bandage or a standard wool and crepe bandage. Costs were estimated over a 12-month period from the UK NHS perspective, and health outcomes were reported as QALYs based on participants' EuroQol five-dimesion five-level questionnaire responses. Multiple imputation was used to deal with missing data and sensitivity analyses included a complete case analysis and testing of costing assumptions, with a secondary analysis exploring the inclusion of productivity losses., Results: The base case analysis found participants in the compression bandage group accrued marginally fewer QALYs, on average, compared with those in the standard bandage group (reduction of 0.0050 QALYs (95% confidence interval (CI) -0.0051 to -0.0049)), and accumulated additional mean costs (incremental cost of £52.68 per participant (95% CI 50.56 to 54.80)). Findings remained robust to assumptions tested in sensitivity analyses, although considerable uncertainty surrounded the outcome estimates., Conclusion: Use of a two-layer compression bandage is marginally less effective in terms of health-related quality of life, and more expensive when compared with a standard bandage following TKA, so therefore is unlikely to provide a cost-effective option., Competing Interests: All authors report no competing interests., (© 2024 Ronaldson et al.)

Background: Studies examining racial and ethnic disparities in-hospital mortality for patients hospitalized with COVID-19 had mixed results. Findings from patients within academic medical centers (AMCs) are lacking, but important given the role of AMCs in improving health equity., Objective: The purpose of this study is to assess whether minority patients hospitalized with COVID-19 in National COVID Cohort Collaborative (N3C) institutions, which consist predominantly of AMCs, have higher mortality rates relative to White patients., Design: A retrospective analysis of patients hospitalized with COVID-19 was performed. Logistic regression analysis was used to test the primary hypothesis. A separate analysis tested whether there were differences by race and ethnicity during the delta variant phase of the pandemic., Patients: All hospitalized patients with COVID-19 who were above 17 years old were categorized by race and ethnicity as Black, Hispanic, Asian, White, Other, and Unknown., Main Measures: In-hospital mortality for patients with a known hospital outcome formed the primary outcome measure. Race and ethnicity were the primary independent variables., Key Results: There were 103,702 in-hospital Covid-19 admissions with 14,207 (13.7%) hospital deaths. Unadjusted in-hospital mortality for White patients was approximately 26% higher than for Black patients. After multivariable adjustment, none of the racial and ethnic groups had significantly different odds of in-hospital mortality compared to White patients. Only Hispanic patients had an odds ratio greater than one that was insignificant (OR = 1.06; 95% CI = 0.92-1.20). Findings for the delta variant phase were similar with the exception of the unknown category (OR = 1.90; 95% CI = 1.05-3.46)., Conclusions: Disparities in-hospital mortality outcomes by race or ethnicity were not found in COVID-19 patients hospitalized in AMCs. AMCs are expected to lead health delivery systems in eliminating disparities associated with structural racism. The null findings are consistent with the hypothesis of no difference in hospital outcomes by race or ethnicity in academic medical centers., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Martin and Dr. Tilford receive royalties from Trestle Tree LLC for an opioid risk prediction tool that is unrelated to the current manuscript. Dr. Tilford also receives consulting fees from Merck for work unrelated to the current manuscript. No other author has any conflict of interest to disclose., (© 2024 The Authors.)

Climate change and extreme climatic events, such as marine heatwaves (MHWs), are threatening seagrass ecosystems. Metabolomics can be used to gain insight into early stress responses in seagrasses and help to develop targeted management and conservation measures. We used metabolomics to understand the temporal and mechanistic response of leaf metabolism in seagrasses to climate change. Two species, temperate Posidonia australis and tropical Halodule uninervis, were exposed to a combination of future warming, simulated MHW with subsequent recovery period, and light deprivation in a mesocosm experiment. The leaf metabolome of P. australis was altered under MHW exposure at ambient light while H. uninervis was unaffected. Light deprivation impacted both seagrasses, with combined effects of heat and low light causing greater alterations in leaf metabolism. There was no MHW recovery in P. australis. Conversely, the heat-resistant leaf metabolome of H. uninervis showed recovery of sugars and intermediates of the tricarboxylic acid cycle under combined heat and low light exposure, suggesting adaptive strategies to long-term light deprivation. Overall, this research highlights how metabolomics can be used to study the metabolic pathways of seagrasses, identifies early indicators of environmental stress and analyses the effects of environmental factors on plant metabolism and health., (© 2023 The Authors. New Phytologist © 2023 New Phytologist Foundation.)

Objective: To assess the concordance between and benefit of adding prescription drug monitoring program (PDMP) data to all-payer claims database (APCD) data for identifying and classifying opioid exposure among insured individuals., Data Sources and Study Setting: Arkansas APCD and PDMP., Study Design: Enrollees in APCD were classified as (1) true positives: if they received opioids in both databases, (2) false positives: if they only received opioids in APCD, (3) true negatives: if they had no opioid exposure in both databases, (4) false negatives: if they only received opioids in the PDMP database. Specificity, sensitivity, negative, and positive predictive values were calculated using PDMP as the "gold standard" database source. Subjects were also categorized as those who received any opioid, chronic opioid, high-dose opioid, or high-risk opioid therapies., Data Collection/extraction Methods: Arkansas residents continuously enrolled with pharmacy coverage in 2016 were included. APCD and PDMP were linked using an encrypted enrollee identifier, gender, and year of birth., Principal Findings: The degree of concordance in opioid exposure between the two databases among 1,411,565 enrollees was high (sensitivity = 92.67%, specificity = 96.13%, positive predictive value = 91.60%, negative predictive value = 96.65%). Enrollees classified as having any opioid (APCD: 31.64% vs. PDMP: 31.26% vs. APCD+PDMP: 33.93%), chronic opioid (APCD: 7.81% vs. PDMP: 7.54% vs. APCD+PDMP: 8.24%), high-dose opioid (APCD: 10.60% vs. PDMP: 9.62% vs. APCD+PDMP: 11.33%), or high-risk opioid (APCD: 5.28% vs. PDMP: 5.33% vs. APCD+PDMP: 6.20%) therapies, were similar using only APCD versus PDMP versus the combined APCD and PDMP data sources., Conclusions: Claims data sources, such as APCDs, are fairly accurate in identifying opioid exposure and the level of opioid exposure among persons with continuous pharmacy coverage., (© 2022 Health Research and Educational Trust.)

Objective: The objective of this study was to estimate the association between early use of physical therapy (PT) or chiropractic care and incident opioid use and long-term opioid use in individuals with a low back pain (LBP) diagnosis., Methods: A retrospective cohort study was conducted using data from Arkansas All Payers' Claims Database. Adults with incident LBP diagnosed in primary care or emergency departments between July 1, 2013, and June 30, 2017, were identified. Participants were required to be opioid naïve in the 6-month baseline period and without cancer, cauda equina syndrome, osteomyelitis, lumbar fracture, and paraplegia/quadriplegia in the entire study period. PT and chiropractic treatment were documented over the ensuing 30 days starting on the date of LBP. Any opioid use and long-term opioid use (LTOU) in 1-year follow-up were assessed. Multivariable logistic regressions controlling for covariates were estimated., Results: A total of 40 929 individuals were included in the final sample, with an average age of 41 years and 65% being women. Only 5% and 6% received PT and chiropractic service, respectively, within the first 30 days. Sixty-four percent had incident opioid use, and 4% had LTOU in the follow-up period. PT was not associated with incident opioid use (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.98-1.18) or LTOU (OR, 1.19; 95% CI, 0.97-1.45). Chiropractic care decreased the odds of opioid use (OR, 0.88; 95% CI, 0.80-0.97) and LTOU (OR, 0.56; 95% CI, 0.40-0.77)., Conclusion: In this study we found that receipt of chiropractic care, though not PT, may have disrupted the need for opioids and, in particular, LTOU in newly diagnosed LBP., (© 2022 by National University of Health Sciences.)

Background: Early identification of hereditary cancer risk would save lives, but genetic testing (GT) has been inadequate. We assessed i) trends for hereditary breast and ovarian cancer (HBOC), Lynch syndrome, and other GT and ii) factors associated with receipt of GT., Methods: We used data from the Arkansas All-Payer Claims Database from January 2013 through June 2018 (commercial, Medicaid), December 2017 (state employee), or December 2016 (Medicare) and identified enrollees with ≥1 month of enrollment. Using Current Procedural Terminology (CPT-4) codes, rates for GT were calculated per 100,000 person-quarters and time series regressions estimated. Second, GT and covariate information for enrollees with 24 months of continuous enrollment were used to estimate separate logistic regression models for each GT category., Results: Among 2,520,575 unique enrollees, HBOC testing rates were 2.2 (Medicaid), 22.0 (commercial), 40.4 (state employee), and 13.1(Medicare) per 100,000 person-quarters and increased linearly across all plans. Older age (OR=1.24; 95%CI 1.20 - 1.28), female sex (OR=18.91; 95%CI 13.01 - 28.86), higher comorbidity burden (OR=1.08; 95%CI 1.05 - 1.12), mental disorders (OR=1.53; 95%CI 1.15 - 2.00), and state employee coverage (OR=1.65; 95%CI 1.37 - 1.97) were positively associated with HBOC testing. Less than 1 of 10,000 enrollees received Lynch syndrome testing, while < 5 of 10,000 received HBOC testing., Conclusion: GT rates for hereditary cancer syndromes have increased in Arkansas but remain low. Receipt of GT was explained with high discrimination by sex and plan type., Impact: Expansion of GT for hereditary cancer risk in Arkansas is needed to identify high-risk individuals who could benefit from risk-reduction strategies., (© 2022. The Author(s).)

Background: Individuals aged ≥75 years are the fastest-growing population starting dialysis for end-stage kidney disease (ESKD) due to living longer with coronary artery disease. ESKD alone can increase bleeding risk, but P2Y 12 inhibitor (P2Y12-I) antiplatelet medications prescribed for cardiovascular treatment can exacerbate this risk in patients with ESKD. The age-specific rates of bleeding complications in dialysis patients with ESKD on P2Y12-I remain unclear, as does how age modifies the bleeding risk from P2Y12-I use in these patients., Methods: In a retrospective cohort study, we collected data on 40,972 patients receiving maintenance hemo- or peritoneal dialysis who were newly prescribed P2Y12-I therapy between 2011 and 2015 from the USRDS registry. We analyzed the effect of age on the time to first bleed and the interactions between age and P2Y12-I type on modifying the effects of a bleed., Results: Twenty percent of the cohort were aged ≥75 years. There were 3096 (8%) gastrointestinal (GI) and 1298 (3%) intracranial (IC) bleeding events during a median follow-up of 1 year. Annual incidence rates for IC bleeds were 2% in those aged <55 years and 3% in those aged ≥75 years. Rates for GI bleeds were 4% in those aged <55 years and 9% in those aged ≥75 years. On clopidogrel, prasugrel, and ticagrelor, for every decade increase in age of the cohort members, the risk of IC bleed increased by 9%, 55%, and 59%, and the risk of GI bleed increased by 21%, 28%, and 39%, respectively. At age ≥75 years, prasugrel was associated with a greater risk of IC bleed than clopidogrel. At age ≥60 years, ticagrelor was associated with a greater risk of GI bleed than clopidogrel., Conclusions: More potent P2Y12-Is (prasugrel and ticagrelor) were associated with a disproportionately higher risk of IC bleed with increasing age compared with that of clopidogrel-prasugrel was much worse than clopidogrel at age ≥75 years. All three drugs were associated with only modest increase in the risk of GI bleed with every decade increase in age-ticagrelor was much worse than clopidogrel at ≥60 years of age. These results highlight the need for head-to-head clinical trials for the use of P2Y12-Is in patients with ESKD to determine age cutoffs where the risk of bleeding outweighs the benefits of thrombosis prevention., Competing Interests: S.S. Hedayati reports honoraria from the American College of Physicians for participation in Nephrology MKSAP and the American Society of Nephrology Post-Graduate Education Program; and an advisory or leadership role for the American Heart Association (study sections), ACP, and the MKSAP Nephrology Committee. B. Martin reports consultancy for eMaxHealth LLC; honoraria from the Institute of Clinical and Economic Review (ICER) as a member of the Midwest Comparative Effectiveness Public Advisory Council; and patents or royalties for Trestle Tree LLC. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

The purpose of this study was to evaluate changes in pain intensity among Veterans transitioning from long-term opioid therapy (LTOT) to either intermittent therapy or discontinuation compared to continued LTOT. Pain intensity was assessed using the Numeric Rating Scale in 90-day increments starting in the 90-day period prior to potential opioid transitions and the two ensuing 90-day periods after transition. Primary analyses used a 1:1 greedy propensity matched sample. A total of 29,293 Veterans switching to intermittent opioids and 5,972 discontinuing opioids were matched to Veterans continuing LTOT. Covariates were well balanced after matching except minor differences in baseline mean pain scores. Pain scores were lower in the follow up periods for those switching to intermittent opioids and discontinuing opioids compared to those continuing LTOT (0-90 days: Intermittent: 3.79, 95%CI: 3.76, 3.82; LTOT: 4.09, 95%CI: 4.06, 4.12, P < .0001; Discontinuation: 3.06, 95%CI: 2.99, 3.13; LTOT: 3.86, 95%CI: 3.79, 3.94, P = <.0001; 91-180 days: Intermittent: 3.76, 95%CI: 3.73, 3.79; LTOT: 3.99, 95%CI: 3.96, 4.02, P < .0001; Discontinuation: 3.01, 95%CI: 2.94, 3.09; LTOT: 3.80, 95%CI: 3.73, 3.87, P = <.0001). Sensitivity analyses found similar results. Discontinuing opioid therapy or switching to intermittent opioid therapy was not associated with increased pain intensity. PERSPECTIVE: This article evaluates the association of switching to intermittent opioid therapy or discontinuing opioids with pain intensity after using opioids long-term. Pain intensity decreased after switching to intermittent therapy or discontinuing opioids, but remained relatively stable for those continuing long-term opioid therapy. Switching to intermittent opioids or discontinuing opioids was not associated with increased pain intensity., (Copyright © 2021. Published by Elsevier Inc.)

Cable bacteria are sulfide-oxidising, filamentous bacteria that reduce toxic sulfide levels, suppress methane emissions and drive nutrient and carbon cycling in sediments. Recently, cable bacteria have been found associated with roots of aquatic plants and rice (Oryza sativa). However, the extent to which cable bacteria are associated with aquatic plants in nature remains unexplored. Using newly generated and public 16S rRNA gene sequence datasets combined with fluorescence in situ hybridisation, we investigated the distribution of cable bacteria around the roots of aquatic plants, encompassing seagrass (including seagrass seedlings), rice, freshwater and saltmarsh plants. Diverse cable bacteria were found associated with roots of 16 out of 28 plant species and at 36 out of 55 investigated sites, across four continents. Plant-associated cable bacteria were confirmed across a variety of ecosystems, including marine coastal environments, estuaries, freshwater streams, isolated pristine lakes and intensive agricultural systems. This pattern indicates that this plant-microbe relationship is globally widespread and neither obligate nor species specific. The occurrence of cable bacteria in plant rhizospheres may be of general importance to vegetation vitality, primary productivity, coastal restoration practices and greenhouse gas balance of rice fields and wetlands., (© 2021 The Authors. New Phytologist © 2021 New Phytologist Foundation.)

Increasing emphasis on guidelines and prescription drug monitoring programs highlight the role of healthcare providers in pain treatment. Objectives of this study were to identify characteristics of key players and influence of opioid prescribers through construction of a referral network of patients with chronic pain. A retrospective cohort study was performed and patients with commercial or Medicaid coverage with chronic back, neck, or joint pain were identified using the Arkansas All-Payer Claims-Database. A social network comprised of providers connected by patient referrals based on 12-months of healthcare utilization following chronic pain was constructed. Network measures evaluated were indegree and eigen (referrals obtained), betweenness (involvement), and closeness centrality (reach). Outcomes included influence of providers, opioid prescribers, and brokerage status. Exposures included provider demographics, specialties and network characteristics. There were 51,941 chronic pain patients who visited 8,110 healthcare providers. Primary care providers showed higher betweenness and closeness whereas specialists had higher indegree. Opioid providers showed higher centrality compared to non-opioid providers, which decreased with increasing volume of opioid prescribing. Non-pharmacologic providers showed significant brokerage scores. Findings from this study such as primary care providers having better reach, non-central positions of high-volume prescribers and non-pharmacologic providers having higher brokerage can aid interventional physician detailing. PERSPECTIVE: Opioid providers held central positions in the network aiding provider-directed interventions. However, high-volume opioid providers were at the borders making them difficult targets for interventions. Primary care providers had the highest reach, specialists received the most referrals and non-pharmacological providers and specialists acted as brokers between non-opioid and opioid prescribers., (Copyright © 2021 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The majority of surgical wounds are closed (for example with sutures or staples) and so heal by primary intention. Where closure is not possible, or the wound subsequently breaks down, wounds may be left to heal from the bottom up (healing by secondary intention). Surgical wound healing by secondary intention (SWHSI) frequently presents a significant management challenge. Additional treatments are often required during the course of healing, and thus a significant financial burden is associated with treating these wounds. Increasingly, negative pressure wound therapy (NPWT) is used in the management of SWHSI. This wound dressing system provides a negative pressure (vacuum) to the wound, removing fluid into a canister, which is believed to be conducive to wound healing. Despite the increasing use of NPWT, there is limited robust evidence for the effectiveness of this device. A well-designed and conducted randomised controlled trial is now required to ascertain if NPWT is a clinically and cost-effective treatment for SWHSI., Methods: SWHSI-2 is a pragmatic, multi-centre, cross surgical specialty, two arm, parallel group, randomised controlled superiority trial. Adult patients with a SWHSI will be randomised to receive either NPWT or usual care (no NPWT) and will be followed up for 12 months. The primary outcome will be time to healing (defined as full epithelial cover in absence of a scab) in number of days since randomisation. Secondary outcomes will include key clinical events (hospital admission or discharge, treatment status, reoperation, amputation, antibiotic use and death), wound infection, wound pain, health-related quality of life, health utility and resource use., Discussion: Given the increasing use of NPWT, despite limited high-quality supporting evidence, the SWHSI-2 Trial will provide robust evidence on the clinical and cost-effectiveness of NPWT in the management of SWHSI. The SWHSI-2 Trial opened to recruitment in May 2019 and is currently recruiting across 20 participating centres., Trial Registration: ISRCTN 26277546 . Prospectively registered on 25 March 2019., (© 2021. The Author(s).)

Background: Although the clinical significance and treatment management of opioid use disorder (OUD) is sufficiently discussed, utilization of healthcare services associated with OUD has not been adequately studied in the United States., Objective: To provide a descriptive assessment of the utilization of health care services for adults with OUD in the United States., Study Design: A retrospective cross-sectional study design based on the National Inpatient Sample (NIS) developed by the Healthcare Cost and Utilization Project., Setting: All OUD cases included in the 2016 NIS database. Adults aged 18 years or older were included in the study., Methods: We analyzed a stratified probability sampling of 7.1 million hospital discharges weighted to 35.7 million national discharges. We used ICD-10-CM codes to identify OUD cases. Groups were compared using the Student's t-test for continuous variables and the chi-square test for categorical variables. Total cost per hospital discharge was determined by converting the total per case hospital charge to a hospital cost estimate (estimate = total charges X hospital cost-to-charge ratio)., Results: In 2016, an estimated 741,275 Americans were associated with OUD. Among patients with OUD, 73% were White, 12% were African-American, 8% were Hispanic, 0.6% Asian-American/Pacific Islander, 0.9% were Native Americans, and 2% were other race; 49% of patients with OUD were women. A large proportion (43%) of the OUD hospitalizations were billed to Medicaid. The average hospital length of stay for all OUD patients was 5.6 days, and the average cost per discharge was $11,233. A higher average LOS was observed for patients who died during hospitalization (8.4 days), Asian-American/Pacific Islander patients (6.8 days), patients covered by self-pay (6.8 days), patients with median household income of 71,000 or more (5.8 days), patients discharged from hospitals in the Northeast ($10,540) and patients discharged from hospitals in large hospitals ($12,570). The most frequently observed diagnosis associated with patients with OUD were alcohol/drug abuse or dependence, psychosis, and septicemia., Limitations: These data sources are comprised of hospital discharge records, originally collected for billing purposes, and may be subject to provider biases and variations in coding practices., Conclusions: In the United States, very few health issues have garnered the attention of such diverse sectors as the opioid crisis. Our analysis of 2016 NIS data found that patients with OUD accounted for approximately 740,000 discharges that year. This represents about a 55% increase over 2015. We also demonstrate that inpatient settings provide a unique opportunity for targeting evidence-based, comprehensive interventions at patients with OUD. Key words: Opioid use disorder, discharge diagnosis, hospital resource utilization, cost-to-charge ratio, HCUP, NIS, AHRQ.

Purpose: The objective of this study was to identify the trajectories that patients take after initiating long-term opioid therapy (LTOT)., Materials and Methods: Using a retrospective cohort design, veterans with chronic non-cancer pain (CNCP) initiating LTOT were identified. Group-based trajectory models were used to identify opioid therapy trajectories based on days of opioid supply (primary outcome) and average daily morphine milligram equivalent dose (AMME; secondary outcome) in each 180-day period following initiation of LTOT., Results: A total of 438,398 veterans with CNCP initiated LTOT. Nine trajectories were identified: 33.7% with persistent, high days covered, 17.7% with persistent, moderate days covered, 16.6% with slow, persistent days-covered reduction, 2.4% with days-covered reduction followed by increase, 4.6% with delayed days-covered reduction, 4.1% with rapid days-covered reduction, 10.9% with moderate-paced discontinuation, 3.4% with delayed discontinuation, and 6.5% with rapid discontinuation. Patients following discontinuation trajectories were more likely to be younger, persons of color, use more supportive services (eg, physical therapy), and received less opioid days' supply and lower doses prior to initiating LTOT as compared to patients following persistent opioid days-covered trajectories. AMME trajectories were similar to days-covered trajectories., Conclusion: Among persons initiating LTOT, nine opioid trajectories emerged which can be broadly characterized into three main trajectory groups: persistent opioid therapy (2 trajectories), reductions in opioid therapy (4 trajectories), and discontinuation (3 trajectories). A majority of patients (51.4%) maintained persistent opioid therapy. Further research is needed to assess the risks of opioid-related adverse outcomes among the identified trajectories., Competing Interests: Dr. Martin receives royalties from TrestleTree LLC for the commercialization of an opioid risk prediction tool, which is unrelated to the current study. Dr. Martin is a paid consultant for eMaxHealth Systems for unrelated projects; also serves as a member of the Midwest CEPAC of ICER and receives compensation for reviews for work unrelated to this study. The remaining authors have no conflicts of interest to declare., (© 2021 Hayes et al.)

Introduction: Fatal overdoses from opioids increased four-fold from 1999 to 2009, and they are now the leading cause of death among Americans under 50. Legislation has been passed by every state to increase access to naloxone but dispensing by community pharmacies remains low., Objectives: The objective of this study was to pilot test a proactive opioid overdose counseling intervention and a passive naloxone intervention, and the implementation strategies developed to support their delivery, in rural community pharmacies on relevant implementation outcomes., Methods: The interventions, implementation strategies, and the overall pilot study approach were developed in a collaborative partnership with a regional supermarket pharmacy chain. They selected 2 rural pharmacies to participate in the pilot study and 2 non-intervention pharmacies to serve as comparison sites. Two interventions were pilot tested in the 2 intervention pharmacies: 1)a proactive opioid overdose counseling intervention and 2) a passive naloxone intervention. An explanatory sequential mixed-methods design was utilized to evaluate adoption, feasibility, acceptability, and appropriateness outcomes after the 3-month observation period., Results: Between the 2 intervention pharmacies, 130 patients received the opioid overdose counseling intervention. 44 (33.8%) were prescribed and dispensed naloxone. Zero naloxone prescriptions were written or dispensed at the comparison pharmacies. Interviews with pharmacy staff found the interventions to be feasible, acceptable, and appropriate in their settings., Conclusion: This small scale pilot study in partnership with a regional supermarket pharmacy chain had positive results with a third of patients who received the opioid overdose counseling intervention being dispensed naloxone. However, the majority of patients did not receive naloxone indicating additional revisions to the intervention components and/or implementation strategies are needed to improve the overall impact of the interventions.

Background: Human Papillomavirus (HPV) is the most common sexually transmitted disease in the United States (US), with 12 cancer causing strains. Vaccination rates in the southern US fall below the national average. Pharmacists provide an opportunity to improve vaccination rates., Objectives: The objectives of this study were to 1) identify barriers and facilitators to providing the HPV vaccine and Vaccines for Children (VFC) program participation in pharmacies and clinics, and 2) assess pharmacy staff, clinic staff, and parent perceptions of 3 collaboration models to improve HPV vaccination., Methods: A developmental formative evaluation was conducted with pharmacy staff, primary care clinic staff, and parents of adolescent children. Interview guides were informed by the Consolidated Framework for Implementation Research (CFIR). Barriers and facilitators to HPV vaccination and VFC participation were explored. Additionally, acceptability of 3 collaboration models were explored: 1) a shared-responsibility model in which a physician provides the first dose of HPV vaccine with the second provided in the pharmacy, 2) a pharmacy-based model in which a clinic refers patients to the pharmacy to receive both doses, and 3) an insourced model in which pharmacists schedule days to provide the vaccine in the collaborating clinic., Results: Twenty-nine interviews were conducted between August 2019 and June 2020. Both pharmacy and clinic staff had positive views toward the HPV vaccine and vaccinations in general. Pharmacists and physicians reported parental awareness and education as a barrier to HPV vaccination. Counseling about HPV vaccine was reported as being more time-consuming because of the stigma associated with the vaccine. Parents were willing to have their children vaccinated for HPV in the pharmacy but desired their child's physician be involved in the immunization process. The shared-responsibility model was the most favored of the 3 collaboration models., Conclusion: Perceptions of the HPV vaccine and vaccination in pharmacies were positive. Collaboration between clinics and pharmacies to improve HPV vaccination rates is viewed positively by pharmacy staff, clinic staff, and parents. This study will guide implementation of pharmacist-physician collaborative models to improve vaccination through pharmacy participation in the VFC program and HPV vaccination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Seagrasses and lucinid bivalves inhabit highly reduced sediments with elevated sulphide concentrations. Lucinids house symbiotic bacteria (Ca. Thiodiazotropha) capable of oxidising sediment sulphide, and their presence in sediments has been proposed to promote seagrass growth by decreasing otherwise phytotoxic sulphide levels. However, vast and productive seagrass meadows are present in ecosystems where lucinids do not occur. Hence, we hypothesised that seagrasses themselves host these sulphur-oxidising Ca. Thiodiazotropha that could aid their survival when lucinids are absent. We analysed newly generated and publicly available 16S rRNA gene sequences from seagrass roots and sediments across 14 seagrass species and 10 countries and found that persistent and colonising seagrasses across the world harbour sulphur-oxidising Ca. Thiodiazotropha, regardless of the presence of lucinids. We used fluorescence in situ hybridisation to visually confirm the presence of Ca. Thiodiazotropha on roots of Halophila ovalis, a colonising seagrass species with wide geographical, water depth range, and sedimentary sulphide concentrations. We provide the first evidence that Ca. Thiodiazotropha are commonly present on seagrass roots, providing another mechanism for seagrasses to alleviate sulphide stress globally.

Objectives: To determine the cost-effectiveness of pharmacy-based intranasal naloxone distribution to high-risk prescription opioid (RxO) users., Methods: We developed a Markov model with an attached tree for pharmacy-based naloxone distribution to high-risk RxO users using 2 approaches: one-time and biannual follow-up distribution. The Markov structure had 6 health states: high-risk RxO use, low-risk RxO use, no RxO use, illicit opioid use, no illicit opioid use, and death. The tree modeled the probability of an overdose happening, the overdose being witnessed, naloxone being available, and the overdose resulting in death. High-risk RxO users were defined as individuals with prescription opioid doses greater than or equal to 90 morphine milligram equivalents (MME) per day. We used a monthly cycle length, lifetime horizon, and US healthcare perspective. Costs (2018) and quality-adjusted life-years (QALYs) were discounted 3% annually. Microsimulation was performed with 100 000 individual trials. Deterministic and probabilistic sensitivity analyses were conducted., Results: One-time distribution of naloxone prevented 14 additional overdose deaths per 100 000 persons, with an incremental cost-effectiveness ratio (ICER) of $56 699 per QALY. Biannual follow-up distribution led to 107 additional lives being saved with an ICER of $84 799 per QALY compared with one-time distribution. Probabilistic sensitivity analyses showed that a biannual follow-up approach would be cost-effective 50% of the time at a willingness-to-pay (WTP) threshold of $100 000 per QALY. Naloxone effectiveness and proportion of overdoses witnessed were the 2 most influential parameters for biannual distribution., Conclusion: Both one-time and biannual follow-up naloxone distribution in community pharmacies would modestly reduce opioid overdose deaths and be cost-effective at a WTP of $100 000 per QALY., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

The development of early warning indicators that identify ecosystem stress is a priority for improving ecosystem management. As microbial communities respond rapidly to environmental disturbance, monitoring their composition could prove one such early indicator of environmental stress. We combined 16S rRNA gene sequencing of the seagrass root microbiome of Halophila ovalis with seagrass health metrics (biomass, productivity and Fsulphide) to develop microbial indicators for seagrass condition across the Swan-Canning Estuary and the Leschenault Estuary (south-west Western Australia); the former had experienced an unseasonal rainfall event leading to declines in seagrass health. Microbial indicators detected sites of potential stress that other seagrass health metrics failed to detect. Genera that were more abundant in 'healthy' seagrasses included putative methylotrophic bacteria (e.g. Methylotenera and Methylophaga), iron cycling bacteria (e.g. Deferrisoma and Geothermobacter) and N2 fixing bacteria (e.g. Rhizobium). Conversely, genera that were more abundant in 'stressed' seagrasses were dominated by putative sulphur-cycling bacteria, both sulphide-oxidising (e.g. Candidatus Thiodiazotropha and Candidatus Electrothrix) and sulphate-reducing (e.g. SEEP-SRB1, Desulfomonile and Desulfonema). The sensitivity of the microbial indicators developed here highlights their potential to be further developed for use in adaptive seagrass management, and emphasises their capacity to be effective early warning indicators of stress., (© FEMS 2019.)

Objective: To determine the association of medical marijuana legalization with prescription opioid utilization., Methods: A 10% sample of a nationally representative database of commercially insured population was used to gather information on opioid use, chronic opioid use, and high-risk opioid use for the years 2006-2014. Adults with pharmacy and medical benefits for the entire calendar year were included in the population for that year. Multilevel logistic regression analysis, controlling for patient, person-year, and state-level factors, were used to determine the impact of medical marijuana legalization on the three opioid use measures. Sub-group analysis among cancer-free adults and cancer-free adults with at least one chronic non-cancer pain condition in the particular year were conducted. Alternate regression models were used to test the robustness of our results including a fixed effects model, an alternate definition for start date for medical marijuana legalization, a person-level analysis, and a falsification test., Results: The final sample included a total of 4,840,562 persons translating into 15,705,562 person years. Medical marijuana legalization was found to be associated with a lower odds of any opioid use: OR = 0.95 (0.94-0.96), chronic opioid use: OR = 0.93 (0.91-0.95), and high-risk opioid use: OR = 0.96 (0.94-0.98). The findings were similar in both the sub-group analyses and all the sensitivity analyses. The falsification tests showed no association between medical marijuana legalization and prescriptions for antihyperlipidemics (OR = 1.00; CI 0.99-1.01) or antihypertensives (OR = 1.00; CI 0.99-1.01)., Conclusions: In states where marijuana is available through medical channels, a modestly lower rate of opioid and high-risk opioid prescribing was observed. Policy makers could consider medical marijuana legalization as a tool that may modestly reduce chronic and high-risk opioid use. However, further research assessing risk versus benefits of medical marijuana legalization and head to head comparisons of marijuana versus opioids for pain management is required.

Seagrasses thrive in anoxic sediments where sulphide can accumulate to phytotoxic levels. So how do seagrasses persist in this environment? Here, we propose that radial oxygen loss (ROL) from actively growing root tips protects seagrasses from sulphide intrusion not only by abiotically oxidising sulphides in the rhizosphere of young roots, but also by influencing the abundance and spatial distribution of sulphate-reducing and sulphide-oxidising bacteria. We used a novel multifaceted approach combining imaging techniques (confocal fluorescence in situ hybridisation, oxygen planar optodes, and sulphide diffusive gradients in thin films) with microbial community profiling to build a complete picture of the microenvironment of growing roots of the seagrasses Halophila ovalis and Zostera muelleri. ROL was restricted to young root tips, indicating that seagrasses will have limited ability to influence sulphide oxidation in bulk sediments. On the microscale, however, ROL corresponded with decreased abundance of potential sulphate-reducing bacteria and decreased sulphide concentrations in the rhizosphere surrounding young roots. Furthermore, roots leaking oxygen had a higher abundance of sulphide-oxidising cable bacteria; which is the first direct observation of these bacteria on seagrass roots. Thus, ROL may enhance both abiotic and bacterial sulphide oxidation and restrict bacterial sulphide production around vulnerable roots, thereby helping seagrasses to colonise sulphide-rich anoxic sediments.

Objective. To determine factors associated with advanced pharmacy practice experience (APPE) performance in the pre-pharmacy and Doctor of Pharmacy (PharmD) curriculum and establish whether performance on the multiple mini interview (MMI) independently predicts APPE evaluation scores. Methods. A multi-case MMI has been used in the admissions process since 2008. Students are scored anywhere from 1 to 7 (unsatisfactory to outstanding) on each interview. Traditional factors (GPA, PCAT, etc.) are also used in the admissions determination. Pearson product-moment correlation and ordinary least squares regression were used to explore the relationships between admissions data, pharmacy GPA, and APPE evaluation scores for the graduating classes of 2011-2014. These analyses identified which factors (pharmacy GPA, PCAT, MMI score, age, gender, rurality, resident status, degree, and underrepresented minority status) related to APPE performance. Results. Students (n=432) had a mean APPE score of 4.6; a mean MMI score of 5.5; mean pharmacy GPA, PCAT and age of 3.14, 73.2, 22.6 years, respectively. Pre-pharmacy GPA and pharmacy GPA positively correlated with mean APPE scores. MMI score demonstrated positive correlations with overall APPE score; including subcategories patient care, documentation, drug information/EBM, public health, and communication. MMI scores were positively related to overall APPE scores in the multivariable regression. Variables showing negative associations with APPE scores included a pre-pharmacy GPA of <3.0 (ref= GPA >3.5) and pharmacy school GPA of >3.0 - 3.5 and GPA 2.6 - 3.0 when compared to GPAs >3.5. Conclusion. GPA (pre-pharmacy and pharmacy) and MMI positively correlate with preceptor-rated performances in the APPE year.

Objective: These analyses examined opioid initiation and chronic use among Iraq (OIF) and Afghanistan (OEF/OND) veterans with a new diagnosis of traumatic brain injury (TBI) in the Veterans Health Administration (VHA)., Methods: Data were obtained from national VHA data repositories. Analyses included OEF/OIF/OND veterans with a new TBI diagnosis in 2010-2012 who used the VHA at least twice, had not received a VHA opioid prescription in the 365 days before diagnosis, and had at least 365 days of data available after TBI diagnosis., Results: Analyses included 35,621 veterans. Twenty-one percent initiated opioids; among new initiators, 23% used chronically. The mean dose was 24.0 mg morphine equivalent dose (MED) daily (SD = 24.26); mean days supplied was 60.52 (SD = 74.69). Initiation was significantly associated with age 36-45 years (odds ratio [OR] = 1.09, 95% CI = 1.01-1.17, P = 0.04), female gender (OR = 1.22, P < 0.001), having back pain (OR = 1.38, P < 0.0001), arthritis/joint pain (OR = 1.24, P < 0.0001), or neuropathic pain (OR = 1.415, P < 0.02). In veterans age 36-45 years, those living in small rural areas had higher odds of chronic opioid use (OR = 1.31, P < 0.0001, and OR = 1.33, P = 0.006, respectively) and back pain (OR = 1.36, P = 0.003). Headache/migraine pain was associated with decreased odds of chronic opioid use (OR = 0.639, P = 0.003)., Conclusions: Prevalence of opioid use is relatively low among OEF/OIF/OND veterans with newly diagnosed TBI who are using VHA. Among those who initiated opioids, about 25% use them chronically. Prescribing was mostly limited to moderate doses, with most veterans using opioids for approximately two months of the 12-month study period.

Seagrass roots host a diverse microbiome that is critical for plant growth and health. Composition of microbial communities can be regulated in part by root exudates, but the specifics of these interactions in seagrass rhizospheres are still largely unknown. As light availability controls primary productivity, reduced light may impact root exudation and consequently the composition of the root microbiome. Hence, we analyzed the influence of light availability on root exudation and community structure of the root microbiome of three co-occurring seagrass species, Halophila ovalis, Halodule uninervis and Cymodocea serrulata . Plants were grown under four light treatments in mesocosms for 2 weeks; control (100% surface irradiance (SI), medium (40% SI), low (20% SI) and fluctuating light (10 days 20% and 4 days 100%). 16S rDNA amplicon sequencing revealed that microbial diversity, composition and predicted function were strongly influenced by the presence of seagrass roots, such that root microbiomes were unique to each seagrass species. Reduced light availability altered seagrass root exudation, as characterized using fluorescence spectroscopy, and altered the composition of seagrass root microbiomes with a reduction in abundance of potentially beneficial microorganisms. Overall, this study highlights the potential for above-ground light reduction to invoke a cascade of changes from alterations in root exudation to a reduction in putative beneficial microorganisms and, ultimately, confirms the importance of the seagrass root environment - a critical, but often overlooked space.

The relationships between the initial opioid prescription characteristics and pain etiology with the probability of opioid discontinuation were explored in this retrospective cohort study using health insurance claims data from a nationally representative database of commercially insured patients in the United States. We identified 1,353,902 persons aged 14 years and older with no history of cancer or substance abuse, with new opioid use episodes and categorized them into 11 mutually exclusive pain etiologies. Cox proportional hazards models were estimated to identify factors associated with time to opioid discontinuation. After accounting for losses to follow-up, the probability of continued opioid use at 1 year was 5.3% across all subjects. Patients with chronic pain had the highest probability for continued opioid use followed by patients with inpatient admissions. Patients prescribed doses ≥90 morphine milligram equivalents (hazard ratio [HR] = .91; 95% confidence interval [CI], .91-.92), initiated with tramadol (HR = .89; 95% CI, .89-.90) or long-acting opioids (HR = .79; 95% CI, .77-.82) were less likely to discontinue opioids. Increasing days' supply of the first prescription was consistently associated with a lower likelihood of opioid discontinuation (HRs, CIs: 3-4 days' supply = .70, .70-.71; 5-7 days' supply = .48, .47-.48; 8-10 days' supply = .37, .37-.38; 11-14 days' supply = .32, .31-.33; 15-21 days' supply = .29, .28-.29; ≥22 days supplied = .20, .19-.20). The direction of this relationship was consistent across all pain etiologies. Clinicians should initiate patients with the lowest supply of opioids to mitigate unintentional long-term opioid use., Perspective: This study shows that characteristics of the first opioid prescription, particularly duration of the prescription, are significant predictors of continued opioid use irrespective of the indication for an opioid prescription. These data should encourage prescribers to initiate patients using the minimum effective opioid dose and duration to reduce unintended long-term use and could motivate policies that restrict the initial supply of opioids., (Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background: Nonadherence produces considerable health consequences and economic burden to patients and payers. One approach to improve medication nonadherence that has gained interest in recent years is the use of smartphone adherence apps. The development of smartphone adherence apps has increased rapidly since 2012; however, literature evaluating the clinical app and effectiveness of smartphone adherence apps to improve medication adherence is generally lacking., Objective: The aims of this study were to (1) provide an updated evaluation and comparison of medication adherence apps in the marketplace by assessing the features, functionality, and health literacy (HL) of the highest-ranking adherence apps and (2) indirectly measure the validity of our rating methodology by determining the relationship between our app evaluations and Web-based consumer ratings., Methods: Two independent reviewers assessed the features and functionality using a 4-domain rating tool of all adherence apps identified based on developer claims. The same reviewers downloaded and tested the 100 highest-ranking apps including an additional domain for assessment of HL. Pearson product correlations were estimated between the consumer ratings and our domain and total scores., Results: A total of 824 adherence apps were identified; of these, 645 unique apps were evaluated after applying exclusion criteria. The median initial score based on descriptions was 14 (max of 68; range 0-60). As a result, 100 of the highest-scoring unique apps underwent user testing. The median overall user-tested score was 31.5 (max of 73; range 0-60). The majority of the user tested the adherence apps that underwent user testing reported a consumer rating score in their respective online marketplace. The mean consumer rating was 3.93 (SD 0.84). The total user-tested score was positively correlated with consumer ratings (r=.1969, P=.04)., Conclusions: More adherence apps are available in the Web-based marketplace, and the quality of these apps varies considerably. Consumer ratings are positively but weakly correlated with user-testing scores suggesting that our rating tool has some validity but that consumers and clinicians may assess adherence app quality differently., (©Lindsey E Dayer, Rebecca Shilling, Madalyn Van Valkenburg, Bradley C Martin, Paul O Gubbins, Kristie Hadden, Seth Heldenbrand. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 19.04.2017.)

Because long-term opioid use often begins with treatment of acute pain (1), in March 2016, the CDC Guideline for Prescribing Opioids for Chronic Pain included recommendations for the duration of opioid therapy for acute pain and the type of opioid to select when therapy is initiated (2). However, data quantifying the transition from acute to chronic opioid use are lacking. Patient records from the IMS Lifelink+ database were analyzed to characterize the first episode of opioid use among commercially insured, opioid-naïve, cancer-free adults and quantify the increase in probability of long-term use of opioids with each additional day supplied, day of therapy, or incremental increase in cumulative dose. The largest increments in probability of continued use were observed after the fifth and thirty-first days on therapy; the second prescription; 700 morphine milligram equivalents cumulative dose; and first prescriptions with 10- and 30-day supplies. By providing quantitative evidence on risk for long-term use based on initial prescribing characteristics, these findings might inform opioid prescribing practices.

Psoriatic arthritis (PsA) is a chronic inflammatoryarthropathy that affects joints and entheses andis associated with psoriasis (PsO). There are fiveclinical patterns of PsA: symmetrical polyarthritis,distal interphalangeal arthropathy, asymmetricaloligoarthritis, arthritis mutilans, and spondylitis, withor without sacroiliitis. Concerning PsA, the goals oftherapy are to control inflammation, prevent articulardamage, and reduce discomfort in the affected joints.Although there are many therapeutic options forthe treatment of PsAs, physicians most often beginwith nonsteroidal anti-inflammatory drugs (NSAIDs)for mild disease. Disease-modifying anti-rheumaticdrugs (DMARDS) are reserved for moderate to severedisease. Apremilast may be a useful option for somepatients.

Background: Recently published asthma guidelines by the European Respiratory Society and the American Thoracic Society (ERS-ATS) define severe disease based on medication use and control level. These guidelines also emphasize that asthma severity involves certain biomarker phenotypes, one of them being eosinophilic phenotype. The quantification of the influence of eosinophil level toward predicting disease severity can help decision makers manage therapy better earlier., Objective: To develop a risk-scoring algorithm to identify patients at greater risk of developing uncontrolled severe asthma as defined by ERS-ATS guidelines., Methods: Data on asthma patients were extracted from the EMRClaims + database from January 2004 to July 2011. Patients with continuous enrollment 12 months before and after the date of the first encounter with a diagnosis of asthma (index date) with at least 1 blood eosinophil test result in the 12 months after the index date, but before the development of uncontrolled severe asthma or the study end date, were included. Uncontrolled severe asthma was defined as the first date on which all criteria of the ERS-ATS definition were first satisfied in the 12 months after the index date. Age (≥ 50 years vs. < 50 years), race, and sex were measured at index, and the Charlson Comorbidity Index (CCI) score (> 0 vs. 0) was measured in the pre-index period. Elevated eosinophil level was defined as a test result with ≥ 400 cells/µL. The study cohort was randomly split 50-50 into derivation and validation samples. Cox proportional hazards regression was used to develop the risk score for uncontrolled severe asthma using the derivation cohort with independent variables of eosinophil level, age, sex, race, and CCI. A bootstrapping procedure was used to generate 1,000 samples from the derivation cohort. Variables significant in ≥ 50% of the samples were retained in the final regression model. A risk score was then calculated based on the coefficient estimates of the final model. C-statistic was used to test the model's discrimination power., Results: The study included 2,405 patients, 147 (6%) of whom developed uncontrolled severe asthma. Higher eosinophil level and CCI score > 0 were significantly and independently associated with an increased risk of uncontrolled severe asthma in the derivation cohort (HR = 1.90, 95% CI = 1.17-3.08 and HR = 2.00, 95% CI = 1.28-3.13, respectively); findings were similar in the validation cohort. Total risk score was categorized as 0, 2, and 4. All models showed good C-statistics (0.79-0.80), indicating favorable model discrimination. There was a significantly greater number of patients with uncontrolled severe asthma in the risk score segments of 2 and 4 compared with 0 (each P < 0.0001)., Conclusions: A risk stratification tool using peripheral eosinophil counts and CCI can be used to predict the development of uncontrolled severe asthma., Disclosures: This study was funded by Teva Pharmaceuticals. eMAX Health Systems was a consultant to Teva Pharmaceuticals for this study and received payment from Teva Pharmaceuticals for work on this study. Casciano and Dotiwala are employed by eMAX Health Systems. Krishnan, Li, and Martin received payment from eMAX Health Systems for work on this study. Small was employed by Teva Pharmaceuticals at the time of this study. Study concept and design were contributed primarily by Casciano, Krishnan, Small, and Martin, along with Li and Dotiwala. Dotiwala, Casciano, Small, and Li collected the data, along with Martin and Li and Krishnan. Data interpretation was provided by Martin, Casciano, and Li, with assistance from the other authors. The manuscript was written by Li, Casciano, Dotiwala, and Small, with assistance from the other authors, and revised by Dotiwala, Small, Li, and Martin, with assistance from Krishnan and Casciano.