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The relationships of characteristics of the initial opioid prescription 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 U.S. We identified 1,353,902 persons aged ≥14 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 one 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 above 90 morphine milligram equivalents (HR=0.91, CI: 0.91–0.92); initiated on tramadol (HR=0.90, CI: 0.89–0.91) or long-acting opioids (HR=0.78, CI: 0.75–0.80); 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 = 0.70, 0.70–0.71; 5–7 days’ supply = 0.48, 0.47–0.48; 8–10 days’ supply = 0.37, 0.37–0.38; 11–14 days’ supply = 0.32, 0.31–0.33; 15–21 days’ supply = 0.29, 0.28– 0.29; ≥22 days supplied = 0.20, 0.19–0.20). 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.

Background and Purpose— The objective of the study is to compare the cost-effectiveness of oral anticoagulants among atrial fibrillation patients at an increased stroke risk. Methods— A Markov model was constructed to project the lifetime costs and quality-adjusted survival (QALYs) of oral anticoagulants using a private payer’s perspective. The distribution of stroke risk (CHADS 2 score: congestive heart failure, hypertension, advanced age, diabetes mellitus, stroke) and age of the modeled population was derived from a cohort of commercially insured patients with new-onset atrial fibrillation. Probabilities of treatment specific events were derived from published clinical trials. Event and downstream costs were determined from the cost of illness studies. Drug costs were obtained from 2015 National Average Drug Acquisition Cost data. Results— In the base case analysis, warfarin was the least costly ($46 241; 95% CI, 44 499–47 874) and apixaban had the highest QALYs (9.38; 95% CI, 9.24–9.48 QALYs). Apixaban was found to be a cost-effective strategy over warfarin (incremental cost-effectiveness ratio=$25 816) and dominated other anticoagulants. Probabilistic sensitivity analysis showed that apixaban had at least a 61% chance of being the most cost-effective strategy at willingness to pay value of $100 000 per QALY. Among patients with CHADS 2 ≥3, dabigatran was the dominant strategy. The model was sensitive to efficacy estimates of apixaban, dabigatran, and edoxaban and the cost of these drugs. Conclusions— All the newer oral anticoagulants compared were more effective than adjusted dosed warfarin. Our model showed that apixaban was the most effective anticoagulant in a general atrial fibrillation population and has an incremental cost-effectiveness ratio <$50 000/QALY. For those with higher stroke risk (CHADS 2 ≥3), dabigatran was the most cost-effective treatment option.

Oxidative stress is a major mechanism of a variety of renal diseases. Tocopherols and tocotrienols are well known antioxidants. This study aimed to determine whether ␥-tocotrienol (GT3) protects against mitochondrial dysfunction and renal proximal tubular cell (RPTC) injury caused by oxidants. Primary cultures of RPTCs were injured by using tert-butyl hydroperoxide (TBHP) in the absence and presence of GT3 or ␣-tocopherol (AT). Reactive oxygen species (ROS) production increased 300% in TBHP-injured RPTCs. State 3 respiration, oligomycinsensitive respiration, and respiratory control ratio (RCR) decreased 50, 63, and 47%, respectively. The number of RPTCs with polarized mitochondria decreased 54%. F 0 F 1 -ATPase activity and ATP content decreased 31 and 65%, respectively. Cell lysis increased from 3% in controls to 26 and 52% at 4 and 24 h, respectively, after TBHP exposure. GT3 blocked ROS production, ameliorated decreases in state 3 and oligomycinsensitive respirations and F 0 F 1 -ATPase activity, and maintained RCR and mitochondrial membrane potential (⌬⌿ m ) in injured RPTCs. GT3 maintained ATP content, blocked RPTC lysis at 4 h, and reduced it to 13% at 24 h after injury. Treatment with equivalent concentrations of AT did not block ROS production and cell lysis and moderately improved mitochondrial respiration and coupling. This is the first report demonstrating the protective effects of GT3 against RPTC injury by: 1) decreasing production of ROS, 2) improving mitochondrial respiration, coupling, ⌬⌿ m , and F 0 F 1 -ATPase function, 3) maintaining ATP levels, and 4) preventing RPTC lysis. Our data suggest that GT3 is superior to AT in protecting RPTCs against oxidant injury and may prove therapeutically valuable for preventing renal injury associated with oxidative stress.

Limited evidence exists on how non-cancer pain (NCP) affects an individual’s health-related quality of life (HRQoL). This study aimed to validate the Medical Outcomes Study Short Form-12 Version 2 (SF-12v2), a generic measure of HRQoL, in a NCP cohort using the Medical Expenditure Panel Survey Longitudinal Files. The SF Mental Component Summary (MCS12) and SF Physical Component Summary (PCS12) were tested for reliability (internal consistency and test-retest reliability) and validity (construct: convergent and discriminant; criterion: concurrent and predictive). A total of 15,716 patients with NCP were included in the final analysis. The MCS12 and PCS12 demonstrated high internal consistency (Cronbach’s alpha and Mosier’s alpha > 0.8), and moderate and high test-retest reliability, respectively (MCS12 intraclass correlation coefficient (ICC): 0.64; PCS12 ICC: 0.73). Both scales were significantly associated with a number of chronic conditions (p < 0.05). The PCS12 was strongly correlated with perceived health (r = 0.52) but weakly correlated with perceived mental health (r = 0.25). The MCS12 was moderately correlated with perceived mental health (r = 0.42) and perceived health (r = 0.33). Increasing PCS12 and MCS12 scores were significantly associated with lower odds of reporting future physical and cognitive limitations (PCS12: OR = 0.90 95%CI: 0.89–0.90, MCS12: OR = 0.94 95%CI: 0.93–0.94). In summary, the SF-12v2 is a reliable and valid measure of HRQoL for patients with NCP.

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. Highrisk 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.

Pressure retarded osmosis (PRO) is a technology that can be utilized to recover energy from the mixing of freshwater with seawater. This source of renewable energy is sizeable and in the past decade several investigations analyzed its potential. The vast majority of studies focused on mass transfer problems across the membrane in order to improve membrane productivity and just recently studies started to look at membrane module efficiencies and parasitic loads within the PRO facility. In this article, the net specific energy production from a facility-scale PRO system was determined and optimized by using a novel simulation method that integrates parasitic loads and efficiencies of the PRO facility components and combines the model with an optimization software in a linked system optimization scheme. It was found that the overall net specific energy that may be recovered by a river-to-sea PRO facility is approximately 0.12 kWh per m 3 of permeate. Furthermore, a sensitivity analysis was performed to elucidate the relationship between net specific energy and power density as functions of membrane area, flow rates, and operating pressures. In general, in order to maximize resource recovery, a low power density, thus a low membrane productivity, must be accepted.

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. Subgroup 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 subgroup 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.