No abstract

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.