IMPORTANCE Prolonged opioid use after surgery may be associated with opioid dependency and increased health care use. However, published studies have reported varying estimates of the magnitude of prolonged opioid use and risk factors associated with the transition of patients to longterm opioid use. OBJECTIVES To evaluate the rate and characteristics of patient-level risk factors associated with increased risk of prolonged use of opioids after surgery. DATA SOURCES For this systematic review and meta-analysis, a search of MEDLINE, Embase, and Google Scholar from inception to August 30, 2017, was performed, with an updated search performed on June 30, 2019. Key words may include opioid analgesics, general surgery, surgical procedures, persistent opioid use, and postoperative pain.STUDY SELECTION Of 7534 articles reviewed, 33 studies were included. Studies were included if they involved participants 18 years or older, evaluated opioid use 3 or more months after surgery, and reported the rate and adjusted risk factors associated with prolonged opioid use after surgery. DATA EXTRACTION AND SYNTHESISThe Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Two reviewers independently assessed and extracted the relevant data. MAIN OUTCOMES AND MEASURESThe weighted pooled rate and odds ratios (ORs) of risk factors were calculated using the random-effects model. RESULTSThe 33 studies included 1 922 743 individuals, with 1 854 006 (96.4%) from the US. In studies with available sex and age information, participants were mostly female (1 031 399; 82.7%) and had a mean (SD) age of 59.3 (12.8) years. The pooled rate of prolonged opioid use after surgery was 6.7% (95% CI, 4.5%-9.8%) but decreased to 1.2% (95% CI, 0.4%-3.9%) in restricted analyses involving only opioid-naive participants at baseline. The risk factors with the strongest associations with prolonged opioid use included preoperative use of opioids (OR, 5.32; 95% CI, 2.94-9.64) or illicit cocaine (OR, 4.34; 95% CI,) and a preoperative diagnosis of back pain (OR, 2.05; 95% CI, 1.63-2.58). No significant differences were observed with various study-level factors, including a comparison of major vs minor surgical procedures (pooled rate: 7.0%; 95% CI, 4.9%-9.9% vs 11.1%; 95% CI, 6.0%-19.4%; P = .20). Across all of our analyses, there was substantial variability because of heterogeneity instead of sampling error. (continued) Key Points Question What are the rate and risk factors associated with prolonged use of opioid medications after surgery? Findings In this systematic review and meta-analysis of 33 observational studies including more than 1.9 million patients, 7% of patients continued to fill opioid prescriptions more than 3 months after surgery. Preoperative use of opioids, illicit cocaine use, and pain conditions before surgery had the strongest associations with prolonged opioid use after surgery. Meaning The findings suggest that an eval...

IntroductionOpioids have been used for millennia for the treatment of pain. However, the long-term efficacy of opioids to treat chronic non-cancer pain continues to be debated. To evaluate opioids’ efficacy in chronic non-cancer pain, we performed a meta-analysis of published clinical trials for μ-opioid receptor agonists performed for US Food and Drug Administration approval.MethodsMEDLINE and Cochrane trial register were searched for enriched enrollment randomized withdrawal studies (before June 2016). Selection criteria included: adults, ≥10 subjects per arm, any chronic pain condition, double-blind treatment period lasting ≥12 weeks, and all μ-agonist opioids approved in the USA.ResultsFifteen studies met criteria. Opioid efficacy was statistically significant (p<0.001) versus placebo for pain intensity (standardized mean difference: −0.416), ≥30% and ≥50% improvement in pain (risk difference: 0.166 and 0.137), patient global impression of change (0.163), and patient global assessment of study medication (0.194). There were minor benefits on physical function and no effect on mental function.ConclusionOpioids are efficacious in the treatment of chronic non-cancer pain for up to 3 months in randomized controlled trials. This should be considered, alongside data on opioid safety, in the use of opioids for the treatment of chronic pain.

Analgesic trials frequently fail to demonstrate efficacy of drugs known to be efficacious. Poor pain reporting accuracy is a possible source for this low essay-sensitivity. We report the effects of Accurate-Pain-Reporting-Training (APRT) on the placebo response in a trial of Pregabalin for painful-diabetic-neuropathy. The study was a two-stage randomized, double-blind trial: In Stage-1 (Training) subjects were randomized to APRT or No-Training. The APRT participants received feedback on the accuracy of their pain reports in response to mechanical stimuli, measured by R-square score. In Stage-2 (Evaluation) all subjects entered a placebo-controlled, cross-over trial. Primary (24-h average pain intensity) and secondary (current, 24-h worst, and 24-h walking pain intensity) outcome measures were reported. Fifty-one participants completed the study. APRT patients (n = 28) demonstrated significant (p = 0.036) increases in R-square scores. The APRT group demonstrated significantly (p = 0.018) lower placebo response (0.29 ± 1.21 vs. 1.48 ± 2.21, mean difference ± SD = -1.19±1.73). No relationships were found between the R-square scores and changes in pain intensity in the treatment arm. In summary, our training successfully increased pain reporting accuracy and resulted in a diminished placebo response. Theoretical and practical implications are discussed.

Previous studies have shown a robust correlation between variability of clinical pain scores and responsiveness to placebo (but not active drug) in pain studies, but explanations for these relationships are lacking. We investigated this further by assessing relationship between the Focused Analgesia Selection Test (FAST), a psychophysical method that quantifies pain reporting variability in response to experimental stimuli, variability of daily clinical pain scores as captured using diary, and response to treatment in the context of a randomized controlled crossover trial of naproxen vs placebo in knee osteoarthritis. Evoked pain using the Staircase-Evoked Pain Procedure served as the primary efficacy endpoint. Variability of daily pain scores and the FAST were assessed at baseline. Fifty-five subjects completed the study and were included in the analyses. Our results indicated a statistically significant, moderate linear relationship between variability of clinical and experimental pain reports (r = −0.416, P = 0.004). Both correlated with the placebo response (r = 0.393, P = 0.004; r =−0.371, P = 0.009; respectively), but only the FAST predicted the treatment difference between naproxen and placebo, as demonstrated both in a regression model (P = 0.002, Beta = 0.456, t = 3.342) and in a receiver operating characteristic curve (0.721) analysis. Our results extend previous findings to include a correlation between experimental pain variability and the placebo response and suggest that experimental pain variability is a better predictor of patients who respond preferentially to drug over placebo. A theoretical model unifying these observations is proposed, and practical implications are discussed.

Patients on IV-PCA continue to experience serious complications as a result of preventable errors. Multi-modal interventions including educational training and the development and adoption of PCA devices with improved safety features are needed to improve safety.

Background:The aim of this study was to determine the current magnitude and characteristics of intravenous patient-controlled analgesia (IV-PCA) errors, and to identify opportunities for improving the PCA modality.Methods:We conducted a descriptive analysis of IV-PCA medication errors submitted to the MEDMARX database. Events were restricted to those occurring in inpatient hospital settings between 1 January 2005 and 31 December 2015. IV-PCA errors were classified by error category, cause of error, error type, level of care rendered, and actions taken.Results:A total of 1948 IV-PCA errors were identified as potential errors (3.9%), nonharmful errors (89.5%), or harmful errors (6.7%) based on the National Coordinating Council for Medication Error Reporting and Prevention taxonomy for categorizing medication errors. Of these, 19.1% required a clinical intervention to address the deleterious effects of the error, indicating an underestimation of the risks associated with IV-PCA errors. The most frequent types of errors were improper dose/quantity (43.2%) and omission errors (19.9%). While human performance deficit was the leading cause of error (50.2%), other common causes included failure to follow procedure and protocol (42.2%) and improper use of the pump (22.7%). Although remedial actions were often taken to prevent error recurrence, actions were taken to rectify the systemic deficits that led to errors in only a minority of cases (11.8%).Conclusion:Preventable errors continue to pose unnecessary risks to patients receiving IV-PCA. Multimodal analgesic regimens and novel PCA systems that reduce human error are needed to prevent errors while preserving the advantages of PCA for the management of acute pain.

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BACKGROUND: The benefit-risk profile of direct oral anticoagulants (DOACs) compared with warfarin, and between DOACs in patients with atrial fibrillation (AF) and chronic liver disease is unclear. METHODS: We conducted a new-user, retrospective cohort study of patients with AF and chronic liver disease who were enrolled in a large, US-based administrative database between January 1, 2011, and December 31, 2017. We assessed the effectiveness and safety of DOACs (as a class and individually) compared with warfarin, and between DOACs in patients with AF and chronic liver disease. The primary outcomes were hospitalization for ischemic stroke/systemic embolism and hospitalization for major bleeding. Inverse probability treatment weights were used to balance the treatment groups on measured confounders. RESULTS: Overall, 10 209 participants were included, with 4421 (43.2%) on warfarin, 2721 (26.7%) apixaban, 2211 (21.7%) rivaroxaban, and 851 (8.3%) dabigatran. The incidence rates per 100 person-years for ischemic stroke/systemic embolism were 2.2, 1.4, 2.6, and 4.4 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. The incidence rates per 100 person-years for major bleeding were 7.9, 6.5, 9.1, and 15.0 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. After inverse probability treatment weights, the risk of hospitalization for ischemic stroke/systemic embolism was significantly lower between DOACs as a class (hazard ratio [HR], 0.64 [95% CI, 0.46–0.90]) or apixaban (HR, 0.40 [95% CI, 0.19–0.82]) compared with warfarin, but not significantly different between rivaroxaban versus warfarin (HR, 0.76 [95% CI, 0.47–1.21]) or rivaroxaban versus apixaban (HR, 1.73 [95% CI, 0.91–3.29]). Compared with warfarin, the risk of hospitalization for major bleeding was lower with DOACs as a class (HR, 0.69 [95% CI, 0.58–0.82]), apixaban (HR, 0.60 [95% CI, 0.46–0.78]), and rivaroxaban (HR, 0.79 [95% CI, 0.62–1.0]). However, the risk of hospitalization for major bleeding was higher for rivaroxaban versus apixaban (HR, 1.59 [95% CI, 1.18–2.14]). CONCLUSION: Among patients with AF and chronic liver disease, DOACs as a class were associated with lower risks of hospitalization for ischemic stroke/systemic embolism and major bleeding versus warfarin. However, the incidence of clinical outcomes among patients with AF and chronic liver disease varied between individual DOACs and warfarin, and in head-to-head DOAC comparisons.