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Opiate Exposure and Predictors of Increased Opiate Use After Ureteroscopy.
Kang C, Shu X, Herrell SD, Miller NL, Hsi RS
(2019) J Endourol 33: 480-485
MeSH Terms: Adult, Aged, Analgesics, Opioid, Body Mass Index, Female, Humans, Kidney Calculi, Male, Middle Aged, Multivariate Analysis, Opioid-Related Disorders, Postoperative Period, Retrospective Studies, Risk, Tennessee, Ureteroscopy
Show Abstract · Added February 26, 2019
Kidney stone formers are at risk for opioid dependence. The aim of this study is to describe opiate exposure and determine predictors of prolonged opiate use among kidney stone formers after surgery. A retrospective review was performed among patients who underwent ureteroscopy for upper tract stone disease. Prescription data were ascertained from a statewide prescribing database. Demographic data and surgical factors were collected from the electronic medical record. Predictors of additional postsurgery prescriptions filled within 30 days and persistent opiate use 60 days after ureteroscopy were determined. Among 208 patients, 127 (61%) had received preoperative opiate prescriptions within 30 days before surgery. Overall, 12% ( = 25) of patients required an additional opiate prescription within 30 days after ureteroscopy, and 7% ( = 14) of patients continued to use opiate medications more than 60 days postoperatively. Patients continuing to use opiates long-term were not chronic opiate users. For both outcomes, preoperative opiate exposure, including number of prescriptions, days prescribed, and unique providers had significant associations (all  < 0.05). Additionally, younger age ( = 0.049) was associated with obtaining an additional opiate prescription within 30 days. Lower BMI ( = 0.02) and higher ASA score ( = 0.03) were predictors of continued opiate use more than 60 days after ureteroscopy. The majority of stone formers have had opiate exposure before surgery, often from multiple providers. Approximately 1 in 8 stone formers who undergo ureteroscopy require additional opiate prescriptions within 30 days. A small but significant population receive opiates beyond the immediate postoperative period.
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16 MeSH Terms
The association between endogenous opioid function and morphine responsiveness: a moderating role for endocannabinoids.
Bruehl S, Burns JW, Morgan A, Koltyn K, Gupta R, Buvanendran A, Edwards D, Chont M, Kingsley PJ, Marnett L, Stone A, Patel S
(2019) Pain 160: 676-687
MeSH Terms: Adult, Analgesics, Opioid, Chronic Pain, Double-Blind Method, Endocannabinoids, Exercise, Female, Humans, Low Back Pain, Male, Middle Aged, Morphine, Naloxone, Opioid Peptides, Pain Measurement, Regression Analysis, Surveys and Questionnaires, Treatment Outcome
Show Abstract · Added April 12, 2019
We sought to replicate previous findings that low endogenous opioid (EO) function predicts greater morphine analgesia and extended these findings by examining whether circulating endocannabinoids and related lipids moderate EO-related predictive effects. Individuals with chronic low-back pain (n = 46) provided blood samples for endocannabinoid analyses, then underwent separate identical laboratory sessions under 3 drug conditions: saline placebo, intravenous (i.v.) naloxone (opioid antagonist; 12-mg total), and i.v. morphine (0.09-mg/kg total). During each session, participants rated low-back pain intensity, evoked heat pain intensity, and nonpain subjective effects 4 times in sequence after incremental drug dosing. Mean morphine effects (morphine-placebo difference) and opioid blockade effects (naloxone-placebo difference; to index EO function) for each primary outcome (low-back pain intensity, evoked heat pain intensity, and nonpain subjective effects) were derived by averaging across the 4 incremental doses. The association between EO function and morphine-induced back pain relief was significantly moderated by endocannabinoids [2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)]. Lower EO function predicted greater morphine analgesia only for those with relatively lower endocannabinoids. Endocannabinoids also significantly moderated EO effects on morphine-related changes in visual analog scale-evoked pain intensity (2-AG), drug liking (AEA and 2-AG), and desire to take again (AEA and 2-AG). In the absence of significant interactions, lower EO function predicted significantly greater morphine analgesia (as in past work) and euphoria. Results indicate that EO effects on analgesic and subjective responses to opioid medications are greatest when endocannabinoid levels are low. These findings may help guide development of mechanism-based predictors for personalized pain medicine algorithms.
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18 MeSH Terms
Postoperative Opiate Use in Urological Patients: A Quality Improvement Study Aimed at Improving Opiate Disposal Practices.
Cabo J, Hsi RS, Scarpato KR
(2019) J Urol 201: 371-376
MeSH Terms: Analgesics, Opioid, Humans, Pain Management, Pain, Postoperative, Patient Education as Topic, Postoperative Period, Prescription Drug Misuse, Quality Improvement, Retrospective Studies, Tennessee, Urologic Surgical Procedures
Show Abstract · Added February 26, 2019
PURPOSE - We aimed to determine trends in postoperative opiate management among urological patients, identify associations with opiate keeping and foster appropriate opiate disposal after surgery via introduction of an educational handout.
MATERIALS AND METHODS - We retrospectively analyzed opiate practices in 68 patients who had undergone urological surgery. In a separate consecutive cohort of 59 patients we distributed a handout detailing FDA (Food and Drug Administration) approved disposal methods. Patient opiate obtainment, use and disposal were assessed via telephone interviews with prescription filling data verified using the Tennessee CSMD (Controlled Substances Monitoring Database). Opiate keeping was defined as possessing any opiates more than 3 weeks after surgery or more than 4 times the duration of the postoperative prescription, whichever was longer.
RESULTS - Opiate keeping was observed in 41 patients (72%) in our initial cohort. Of these patients 68% left the medication unsecured at home. Major barriers to opiate disposal included concern for return of disease specific pain in 44% of patients and unrelated pain in 29%. As assessed on a short test, opiate keepers were less knowledgeable about safe disposal practices compared to nonkeepers (72% vs 85%, p = 0.005). Among opiate keepers there was an improvement in knowledge scores after the intervention (66% to 77%, p = 0.03). When comparing pre-education to post-education, there was no detectable improvement in the rate of opiate keeping (72% vs 68%, p = 0.66) or proper disposal (9% vs 8%, p = 1.0).
CONCLUSIONS - Opiate keeping is common following urological surgery and a major barrier to disposal is concern for the return of disease specific pain. Future interventions aimed at limiting opiate keeping should combine evidence-based prescription practices and targeted patient education.
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11 MeSH Terms
The use of prescribed opioid analgesics & the risk of serious infections.
Wiese AD, Grijalva CG
(2018) Future Microbiol 13: 849-852
MeSH Terms: Analgesics, Opioid, Humans, Infections, Opioid-Related Disorders, Substance-Related Disorders, United States
Added July 27, 2018
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Opioid Analgesic Use and Risk for Invasive Pneumococcal Diseases: A Nested Case-Control Study.
Wiese AD, Griffin MR, Schaffner W, Stein CM, Greevy RA, Mitchel EF, Grijalva CG
(2018) Ann Intern Med 168: 396-404
MeSH Terms: Adolescent, Adult, Aged, Analgesics, Opioid, Case-Control Studies, Child, Child, Preschool, Female, Humans, Male, Middle Aged, Pneumococcal Infections, Population Surveillance, Retrospective Studies, Risk Factors, Tennessee
Show Abstract · Added July 27, 2018
Background - Although certain opioid analgesics have immunosuppressive properties and increase the risk for infections in animals, the clinical effects of prescription opioid use on infection risk among humans are unknown.
Objective - To test the hypothesis that prescription opioid use is an independent risk factor for invasive pneumococcal disease (IPD).
Design - Nested case-control study.
Setting - Tennessee Medicaid database linked to Medicare and Active Bacterial Core surveillance system databases (1995 to 2014).
Patients - 1233 case patients with IPD aged 5 years and older matched to 24 399 control participants by diagnosis date, age, and county of residence.
Measurements - Opioid use was measured on the basis of pharmacy prescription fills. Invasive pneumococcal disease was defined by the isolation of Streptococcus pneumoniae from a normally sterile site. The odds of current opioid use were compared between the case and control groups, accounting for known IPD risk factors. Secondary analyses categorized opioid use by opioid characteristics, applied an IPD risk score to assure comparability between exposure groups, and analyzed pneumonia and nonpneumonia IPD cases separately.
Results - Persons in the case group had greater odds than control participants of being current opioid users (adjusted odds ratio [aOR], 1.62 [95% CI, 1.36 to 1.92]). Associations were strongest for opioids that were long acting (aOR, 1.87 [CI, 1.24 to 2.82]), of high potency (aOR, 1.72 [CI, 1.32 to 2.25]), or were used at high dosages (50 to 90 morphine milligram equivalents [MME]/d: aOR, 1.71 [CI, 1.22 to 2.39]; ≥90 MME/d: aOR, 1.75 [CI, 1.33 to 2.29]). Results were consistent when the IPD risk score was taken into account and pneumonia and nonpneumonia IPD were analyzed separately.
Limitations - Unmeasured confounding and measurement error, although sensitivity analyses suggested that neither was likely to affect results. Actual opioid use and other nonprescription use (such as illicit opioid use) were not measured.
Conclusion - Opioid use is associated with an increased risk for IPD and represents a novel risk factor for these diseases.
Primary Funding Source - National Institutes of Health.
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16 MeSH Terms
Preoperative Belladonna and Opium Suppository for Ureteral Stent Pain: A Randomized, Double-blinded, Placebo-controlled Study.
Lee FC, Holt SK, Hsi RS, Haynes BM, Harper JD
(2017) Urology 100: 27-32
MeSH Terms: Adjuvants, Anesthesia, Adult, Aged, Analgesics, Opioid, Atropa belladonna, Atropine, Double-Blind Method, Female, Humans, Male, Middle Aged, Opium, Pain, Postoperative, Parasympatholytics, Phytotherapy, Plant Extracts, Preoperative Care, Prospective Studies, Quality of Life, Scopolamine, Stents, Suppositories, Ureteroscopy, Urinary Calculi
Show Abstract · Added January 16, 2018
OBJECTIVE - To investigate whether the use of a belladonna and opium (B&O) rectal suppository administered immediately before ureteroscopy (URS) and stent placement could reduce stent-related discomfort.
METHODS - A randomized, double-blinded, placebo-controlled study was performed from August 2013 to December 2014. Seventy-one subjects were enrolled and randomized to receive a B&O (15 mg/30 mg) or a placebo suppository after induction of general anesthesia immediately before URS and stent placement. Baseline urinary symptoms were assessed using the American Urological Association Symptom Score (AUASS). The Ureteral Stent Symptom Questionnaire and AUASS were completed on postoperative days (POD) 1, 3, and after stent removal. Analgesic use intraoperatively, in the recovery unit, and at home was recorded.
RESULTS - Of the 71 subjects, 65 had treatment for ureteral (41%) and renal (61%) calculi, 4 for renal urothelial carcinoma, and 2 were excluded for no stent placed. By POD3, the B&O group reported a higher mean global quality of life (QOL) score (P = .04), a better mean quality of work score (P = .05), and less pain with urination (P = .03). The B&O group reported an improved AUASS QOL when comparing POD1 with post-stent removal (P = .04). There was no difference in analgesic use among groups (P = .67). There were no episodes of urinary retention. Age was associated with unplanned emergency visits (P <.00) and "high-pain" measure (P = .02) CONCLUSION: B&O suppository administered preoperatively improved QOL measures and reduced urinary-related pain after URS with stent. Younger age was associated with severe stent pain and unplanned hospital visits.
Copyright © 2016 Elsevier Inc. All rights reserved.
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24 MeSH Terms
Strategies for Flipping the Script on Opioid Overprescribing.
Wright AP, Becker WC, Schiff GD
(2016) JAMA Intern Med 176: 7-8
MeSH Terms: Analgesics, Opioid, Chronic Pain, Electronic Health Records, Humans, Inappropriate Prescribing, Medical Order Entry Systems
Added November 7, 2019
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Opioid Analgesics and the Risk of Serious Infections Among Patients With Rheumatoid Arthritis: A Self-Controlled Case Series Study.
Wiese AD, Griffin MR, Stein CM, Mitchel EF, Grijalva CG
(2016) Arthritis Rheumatol 68: 323-31
MeSH Terms: Adult, Age Factors, Analgesics, Opioid, Antirheumatic Agents, Arthritis, Rheumatoid, Codeine, Cohort Studies, Delayed-Action Preparations, Dextropropoxyphene, Hospitalization, Humans, Hydrocodone, Immunosuppressive Agents, Incidence, Infections, Medicaid, Middle Aged, Morphine, Oxycodone, Retrospective Studies, Risk Factors, Tennessee, United States
Show Abstract · Added July 27, 2018
OBJECTIVE - Animal studies and in vitro human studies suggest that certain opioid analgesics impair crucial immune functions. This study was undertaken to determine whether opioid use is associated with increased risk of serious infection in patients with rheumatoid arthritis (RA).
METHODS - We conducted a self-controlled case series analysis on a retrospective cohort of 13,796 patients with RA enrolled in Tennessee Medicaid in 1995-2009. Within-person comparisons of the risk of hospitalization for serious infection during periods of opioid use versus non-use were performed using conditional Poisson regression. Fixed confounders were accounted for by design; time-varying confounders included age and use of disease-modifying antirheumatic drugs, glucocorticoids, and proton-pump inhibitors. In additional analyses, risks associated with new opioid use, use of opioids known to have immunosuppressive properties, use of long-acting opioids, and different opioid dosages were assessed. Sensitivity analyses were performed to account for potential protopathic bias and confounding by indication.
RESULTS - Among 1,790 patients with RA who had at least 1 hospitalization for serious infection, the adjusted incidence rate of serious infection was higher during periods of current opioid use compared to non-use, with an incidence rate ratio (IRR) of 1.39 (95% confidence interval [95% CI] 1.19-1.62). The incidence rate was also higher during periods of long-acting opioid use, immunosuppressive opioid use, and new opioid use compared to non-use (IRR 2.01 [95% CI 1.52-2.66], IRR 1.72 [95% CI 1.33-2.23], and IRR 2.38 [95% CI 1.65-3.42], respectively). Results of sensitivity analyses were consistent with the main findings.
CONCLUSION - In within-person comparisons of patients with RA, opioid use was associated with an increased risk of hospitalization for serious infection.
© 2016, American College of Rheumatology.
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23 MeSH Terms
Development of an algorithm to identify serious opioid toxicity in children.
Chung CP, Callahan ST, Cooper WO, Murray KT, Hall K, Dudley JA, Stein CM, Ray WA
(2015) BMC Res Notes 8: 293
MeSH Terms: Adolescent, Algorithms, Analgesics, Opioid, Child, Child, Preschool, Clinical Coding, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Male, Medicaid, Predictive Value of Tests, Reproducibility of Results, Severity of Illness Index, Tennessee, United States
Show Abstract · Added February 4, 2016
BACKGROUND - The use of opioids is increasing in children; therefore, opioid toxicity could be a public health problem in this vulnerable population. However, we are not aware of a published algorithm to identify cases of opioid toxicity in children using administrative databases. We sought to develop an algorithm to identify them. After review of literature and de-identified computer profiles, a broad set of ICD-9 CM codes consistent with serious opioid toxicity was selected. Based on these codes, we identified 195 potential cases of opioid toxicity in children enrolled in Tennessee Medicaid. Medical records were independently reviewed by two physicians; episodes considered equivocal were reviewed by an adjudication committee. Cases were adjudicated as Group 1 (definite/probable), Group 2 (possible), or Group 3 (excluded).
RESULTS - Of the 195 potential cases, 168 (86.2%) had complete records for review and 85 were confirmed cases. The overall positive predictive value (PPV) for all codes was 50.6%. The PPV for codes indicating: unintentional opioid overdose (25/31) was 80.7%; intentional opioid overdose (15/30) was 50.0%, adverse events (33/58) was 56.9%, the presence of signs or symptoms compatible with opioid toxicity (12/47) was 25.5%, and no cases were confirmed in records from the two deaths. Of the confirmed cases, 65.8% were related to therapeutic opioid use.
CONCLUSION - For studies utilizing administrative claims to quantify incidence of opioid toxicity in children, our findings suggest that use of a broad set of screening codes coupled with medical record review is important to increase the completeness of case ascertainment.
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Prescription opioid epidemic and infant outcomes.
Patrick SW, Dudley J, Martin PR, Harrell FE, Warren MD, Hartmann KE, Ely EW, Grijalva CG, Cooper WO
(2015) Pediatrics 135: 842-50
MeSH Terms: Analgesics, Opioid, Cohort Studies, Female, Humans, Infant, Newborn, Longitudinal Studies, Male, Neonatal Abstinence Syndrome, Pain, Pregnancy, Pregnancy Complications, Prescription Drugs, Retrospective Studies
Show Abstract · Added July 27, 2018
BACKGROUND AND OBJECTIVES - Although opioid pain relievers are commonly prescribed in pregnancy, their association with neonatal outcomes is poorly described. Our objectives were to identify neonatal complications associated with antenatal opioid pain reliever exposure and to establish predictors of neonatal abstinence syndrome (NAS).
METHODS - We used prescription and administrative data linked to vital statistics for mothers and infants enrolled in the Tennessee Medicaid program between 2009 and 2011. A random sample of NAS cases was validated by medical record review. The association of antenatal exposures with NAS was evaluated by using multivariable logistic regression, controlling for maternal and infant characteristics.
RESULTS - Of 112,029 pregnant women, 31,354 (28%) filled ≥ 1 opioid prescription. Women prescribed opioid pain relievers were more likely than those not prescribed opioids (P < .001) to have depression (5.3% vs 2.7%), anxiety disorder (4.3% vs 1.6%) and to smoke tobacco (41.8% vs 25.8%). Infants with NAS and opioid-exposed infants were more likely than unexposed infants to be born at a low birth weight (21.2% vs 11.8% vs 9.9%; P < .001). In a multivariable model, higher cumulative opioid exposure for short-acting preparations (P < .001), opioid type (P < .001), number of daily cigarettes smoked (P < .001), and selective serotonin reuptake inhibitor use (odds ratio: 2.08 [95% confidence interval: 1.67-2.60]) were associated with greater risk of developing NAS.
CONCLUSIONS - Prescription opioid use in pregnancy is common and strongly associated with neonatal complications. Antenatal cumulative prescription opioid exposure, opioid type, tobacco use, and selective serotonin reuptake inhibitor use increase the risk of NAS.
Copyright © 2015 by the American Academy of Pediatrics.
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