The Association Between Receipt of Guideline-Concordant Long-Term Opioid Therapy and All-Cause Mortality.
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ABSTRACT: Purpose
For patients receiving long-term opioid therapy (LtOT), the impact of guideline-concordant care on important clinical outcomes--notably mortality--is largely unknown, even among patients with a high comorbidity and mortality burden (e.g., HIV-infected patients). Our objective was to determine the association between receipt of guideline-concordant LtOT and 1-year all-cause mortality.Methods
Among HIV-infected and uninfected patients initiating LtOT between 2000 and 2010 through the Department of Veterans Affairs, we used Cox regression with time-updated covariates and propensity-score matched analyses to examine the association between receipt of guideline-concordant care and 1-year all-cause mortality.Results
Of 17,044 patients initiating LtOT between 2000 and 2010, 1048 patients (6%) died during 1 year of follow-up. Patients receiving psychotherapeutic co-interventions (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.51-0.75; P?ConclusionsProviders should use caution in initiating LtOT in conjunction with benzodiazepines and untreated SUDs. Patients receiving LtOT may benefit from multi-modal treatment that addresses chronic pain and its associated comorbidities across multiple disciplines.
SUBMITTER: Gaither JR
PROVIDER: S-EPMC4835362 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
Publications
The Association Between Receipt of Guideline-Concordant Long-Term Opioid Therapy and All-Cause Mortality.
Gaither Julie R JR Goulet Joseph L JL Becker William C WC Crystal Stephen S Edelman E Jennifer EJ Gordon Kirsha K Kerns Robert D RD Rimland David D Skanderson Melissa M Justice Amy C AC Fiellin David A DA
Journal of general internal medicine 20160501 5
<h4>Purpose</h4>For patients receiving long-term opioid therapy (LtOT), the impact of guideline-concordant care on important clinical outcomes--notably mortality--is largely unknown, even among patients with a high comorbidity and mortality burden (e.g., HIV-infected patients). Our objective was to determine the association between receipt of guideline-concordant LtOT and 1-year all-cause mortality.<h4>Methods</h4>Among HIV-infected and uninfected patients initiating LtOT between 2000 and 2010 t ...[more]
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Project description:BackgroundWhile the relationship between long-term opioid therapy (LTOT) dose and overdose is well-established, LTOT's association with all-cause mortality is less understood, especially among people living with HIV (PLWH). There is also limited information regarding the association of LTOT cessation or interruption with mortality.MethodsAmong PLWH and matched uninfected male veterans in care, we identified those who initiated LTOT. Using time-updated cox regression, we examined the association between all-cause mortality, unnatural death, and overdose, and opioid use categorized as 1-20 (reference group), 21-50, 51-90, and ≥ 91 mg morphine equivalent daily dose (MEDD).ResultsThere were 22,996 patients on LTOT, 6,578 (29 %) PLWH and 16,418 (71 %) uninfected. Among 5,222 (23 %) deaths, 12 % were unnatural deaths and 6 % overdoses. MEDD was associated with risk of all 3 outcomes; compared to patients on 1-20 mg MEDD, adjusted risk for all-cause mortality monotonically increased (Hazard Ratios (HR) [95 % CI] for 21-50 mg MEDD = 1.36 [1.21, 1.52], 51-90 mg MEDD = 2.06 [1.82, 2.35], and ≥ 91 mg MEDD = 3.03 [2.71, 3.39]). Similar results were seen in models stratified by HIV. LTOT interruption was also associated with all-cause, unnatural, and overdose mortality (HR [95 % CI] 2.30 [2.09, 2.53], 1.47 [1.13, 1.91] and 1.52 [1.04, 2.23], respectively).ConclusionsAmong PLWH and uninfected patients on LTOT we observed a strong dose-response relationship with all 3 mortality outcomes. Opioid risk mitigation approaches should be expanded to address the potential effects of higher dose on all-cause mortality in addition to unnatural and overdose fatalities.
| S-EPMC7644145 | biostudies-literature
Project description:Importance:Adults with mental health conditions are more likely than those without to receive long-term opioid therapy. Less is known about opioid therapy among adolescents, especially those with mental health conditions. Objective:To examine associations between preexisting mental health conditions and treatments and initiation of any opioid and long-term opioid therapy among adolescents. Design, Setting, and Participants:A cohort of 1 224 520 incident opioid recipients without cancer diagnoses aged 14 to 18 years at first receipt was extracted from nationwide commercial health care claims data from January 1, 2003, to December 31, 2014. Analysis was conducted from August 19, 2016, to November 16, 2017. Associations between preexisting mental health conditions and treatments and any opioid receipt were examined by comparing recipients with nonrecipients matched on sex, calendar year and years of age of first enrollment, and months of enrollment (prior to the index month for recipients, ever for nonrecipients). Associations between preexisting mental health conditions and treatments and subsequent long-term opioid therapy were examined among recipients with at least 6 months' follow-up using Cox proportional hazards regressions adjusted for demographics. Exposures:Mental health condition diagnoses and treatments recorded in inpatient, outpatient, and filled-prescription claims prior to opioid receipt. Main Outcomes and Measures:Opioid receipt, defined as any opioid analgesic prescription claim, and long-term opioid therapy, defined as more than 90 days' supply within a 6-month window having no gaps in supply of more than 32 days. Results:Of the 1 224 520 new opioid recipients included, the median age at first receipt was 17 years (interquartile range, 16-18 years), and 51.1% were female. Median follow-up after first receipt was 625 days (interquartile range, 255-1268 days). Adolescents with anxiety, mood, neurodevelopmental, sleep, and nonopioid substance use disorders and most mental health treatments were significantly more likely to receive any opioid (odds ratios from 1.13 [95% CI, 1.10-1.16] for nonopioid substance use disorders to 1.69 [95% CI, 1.58-1.81] for nonbenzodiazepine hypnotics). Among the 1 000 453 opioid recipients (81.7%) who had at least 6 months' follow-up, the cumulative incidence of long-term opioid therapy was 3.0 (95% CI, 2.8-3.1) per 1000 recipients within 3 years after first opioid receipt. All preexisting mental health conditions and treatments were strongly associated with higher rates of long-term opioid therapy (adjusted hazard ratios from 1.73 [95% CI 1.54-1.95] for attention-deficit/hyperactivity disorder to 8.90 [95% CI, 5.85-13.54] for opioid use disorder). Conclusions and Relevance:Commercially insured adolescents with many types of preexisting mental health conditions and treatments were modestly more likely to receive any opioid and were substantially more likely to subsequently transition to long-term opioid therapy relative to those without, although overall rates of long-term opioid therapy were low.
| S-EPMC5875328 | biostudies-literature
Project description:BACKGROUND:Hitherto only studies with selected populations have found an increased all-cause mortality of some selected opioids compared to selected non-opioids for chronic non-cancer pain (CNCP). We have examined the all-cause mortality for CNCP associated with all established opioids compared to non-opioid analgesic therapy (anticonvulsants, antidepressants, dipyrone, non-steroidal agents). METHODS:The study used the InGef (Institute for Applied Health Research Berlin) database which is an anonymized healthcare claims database including 4,711,668 insured persons who were covered by 61 German statutory health insurances between 2013 and 2017.The health insurance companies are the owners of the database. All-cause mortality was determined from death certificates. Adjusted hazard ratios (HRs) including age, gender, comorbidity index, and propensity score as covariates and risk differences (RD) in incidence of death between patients with long-term opioid therapy (LTOT) and control-drug therapy were calculated. RESULTS:The mean age of participants was 66?years; 55% were women. There were 554 deaths during 10,435 person-years for the LTOT patients, whereas there were 340 deaths during 11,342 person-years in the control group. The HR for all-cause mortality was 1.59 (95% CI, 1.38-1.82) with a risk difference of 148 excess deaths (95% CI 99-198) per 10,000 person-years. The elevated risk of death for LTOT was confined to the out-of-hospital deaths: LTOT patients had 288 out-of-hospital deaths during 10,435 person-years (276 per 10,000 person-years) whereas there were 110 deaths during 11,342 person-years (97 per 10,000 person-years) in the control group. HR was 2.29 (95% CI 1.86, 2.83). Although our propensity score matching model indicated a good classification, residual confounding cannot be fully excluded. The opioid group had a higher prevalence of heart failure and a higher use of anti-thrombotic and antiplatelet agents and of psycholeptics. CONCLUSIONS:LTOT for CNCP compared to non-opioid analgesics was associated with an increased risk for all-cause mortality. When considering treatment options for patients with CNCP, the relevant risk of increased all-cause mortality with opioids should be discussed. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03778450, Registered on 7 December 2018.
| S-EPMC7362543 | biostudies-literature
Project description:ImportanceAttempts to discontinue opioid therapy to reduce the risk of overdose and adhere to prescribing guidelines may lead patients to be exposed to variability in opioid dosing. Such dose variability may increase the risk of opioid overdose even if therapy discontinuation is associated with a reduction in risk.ObjectiveTo examine the association between opioid dose variability and opioid overdose.Design, setting, and participantsA nested case-control study was conducted in a large Colorado integrated health plan and delivery system from January 1, 2006, through June 30, 2018. Cohort members were individuals prescribed long-term opioid therapy.ExposuresDose variability was defined as the SD of the milligrams of morphine equivalents across each patient's follow-up and categorized based on the quintile distribution of the SD in the cohort (0-5.3, 5.4-9.1, 9.2-14.6, 14.7-27.2, and >27.2 mg of morphine equivalents).Main outcomes and measuresOpioid overdose cases were identified using International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Each case patient with overdose was matched to up to 20 control patients using risk set sampling. Conditional logistic regression models were used to generate matched odds ratios and 95% CIs, adjusted for age, sex, race/ethnicity, drug or alcohol use disorder, tobacco use, benzodiazepine dispensings, medical comorbidities, mental health disorder, opioid dose, and opioid formulation.ResultsIn a cohort of 14 898 patients (mean [SD] age, 56.3 [16.0] years; 8988 [60.3%] female) prescribed long-term opioid therapy, 228 case patients with incident opioid overdose were matched to 3547 control patients. The mean (SD) duration of opioid therapy was 36.7 (33.7) months in case patients and 33.0 (30.9) months in control patients. High-dose variability (SD >27.2 mg of morphine equivalents) was associated with a significantly increased risk of overdose compared with low-dose variability (matched odds ratio, 3.32; 95% CI, 1.63-6.77) independent of opioid dose.Conclusions and relevanceVariability in opioid dose may be a risk factor for opioid overdose, suggesting that practitioners should seek to minimize dose variability when managing long-term opioid therapy.
| S-EPMC6481879 | biostudies-literature
Project description:Importance:Polyneuropathy is one of the most common painful conditions managed within general and specialty clinics. Neuropathic pain frequently leads to decisions about using long-term opioid therapy. Understanding the association of long-term opioid use with functional status, adverse outcomes, and mortality among patients with polyneuropathy could influence disease-specific decisions about opioid treatment. Objectives:To quantify the prevalence of long-term opioid use among patients with polyneuropathy and to assess the association of long-term opioid use with functional status, adverse outcomes, and mortality. Design, Setting, and Participants:A retrospective population-based cohort study was conducted of prescriptions given to patients with polyneuropathy and to controls in ambulatory practice between January 1, 2006, and December 31, 2010, to determine exposure to long-term opioid use as well as other outcomes. The latest follow-up was conducted through November 25, 2016. Exposures:Long-term opioid therapy, defined by 1 or multiple consecutive opioid prescriptions resulting in 90 continuous days or more of opioid use. Main Outcomes and Measures:Prevalence of long-term opioid therapy among patients with polyneuropathy and controls. Patient-reported functional status, documented adverse outcomes, and mortality were compared between patients with polyneuropathy receiving long-term opioid therapy (≥90 days) and patients with polyneuropathy receiving shorter durations of opioid therapy. Results:Among the 2892 patients with polyneuropathy (1364 women and 1528 men; mean [SD] age, 67.5 [16.6] years) and the 14 435 controls (6827 women and 7608 men; mean [SD] age, 67.5 [16.5] years), patients with polyneuropathy received long-term opioids more often than did controls (545 [18.8%] vs 780 [5.4%]). Patients with polyneuropathy who were receiving long-term opioids had multiple functional status markers that were modestly poorer even after adjusting for medical comorbidity, including increased reliance on gait aids (adjusted odds ratio, 1.9; 95% CI, 1.4-2.6); no functional status markers were improved by long-term use of opioids. Adverse outcomes were more common among patients with polyneuropathy receiving long-term opioids, including depression (adjusted hazard ratio, 1.53; 95% CI, 1.29-1.82), opioid dependence (adjusted hazard ratio, 2.85; 95% CI, 1.54-5.47), and opioid overdose (adjusted hazard ratio, 5.12; 95% CI, 1.63-19.62). Conclusions and Relevance:Polyneuropathy increased the likelihood of long-term opioid therapy. Chronic pain itself cannot be ruled out as a source of worsened functional status among patients receiving long-term opioid therapy. However, long-term opioid therapy did not improve functional status but rather was associated with a higher risk of subsequent opioid dependency and overdose.
| S-EPMC5710534 | biostudies-literature
Project description:BACKGROUND:Partnered status is an independent predictor of clinical outcomes, including overall survival, among patients with cancer. However, the mechanisms by which partnered status impacts survival are not fully understood and to the authors' knowledge the associations between partnered status and the specific attributes of chemotherapy have not been studied to date. METHODS:The current study was an observational study of patients with resected American Joint Committee on Cancer (AJCC) stage III colon cancer diagnosed from 2008 through 2015 and recruited from an academic cancer center and 2 large community oncology practices. Outcome measures were specific attributes of adjuvant chemotherapy. Partnered status (partnered vs unpartnered) was the primary independent variable. Bivariate comparisons between independent variables and the primary outcomes were performed. Associations between partnered status and the outcomes also were analyzed using multivariable generalized estimating equations using a logit link. RESULTS:Data were collected from 436 patients. Of these patients, approximately 65% were from community oncology practices. Approximately 62% were partnered (married or living with a partner), and approximately 86% received adjuvant chemotherapy. Among these individuals, 87% received multiagent chemotherapy and 65% completed 6 months of therapy. Partnered patients were found to have a higher odds of completing chemotherapy (odds ratio, 1.98; 95% CI, 1.04-3.77). CONCLUSIONS:In this innovative investigation of the associations between partnered status and specific attributes of curative-intent chemotherapy, approximately 35% of patients terminated chemotherapy early. Having a partner increased the odds of completing therapy, which may be one mechanism through which having a partner improves disease-specific outcomes among patients with colon cancer. Identifying those aspects of partner support that can be reproduced with community or clinical personnel may help unpartnered patients to complete the recommended course of curative-intent chemotherapy.
| S-EPMC6856404 | biostudies-literature
Project description:IntroductionLittle is known about long-term prescription opioid utilization in the Military Health System. The objectives of this study were to examine predictors of any prescription opioid receipt, and predictors of long-term opioid utilization among active duty soldiers in the year following deployment.Materials and methodsThe analytic sample consisted of Army active duty soldiers returning from deployment to Operation Enduring Freedom, Operation Iraqi Freedom, or Operation New Dawn in fiscal years 2008-2014 (N = 540,738). The Heckman probit procedure was used to jointly examine predictors of any opioid prescription receipt and long-term opioid utilization (i.e., an episode of 90 days or longer where days-supply covered at least two-thirds of days) in the postdeployment year. Predictors were based on diagnoses and characteristics of opioid prescriptions.ResultsMore than one-third of soldiers (34.8%, n = 188,211) had opioid receipt, and among those soldiers, 3.3% had long-term opioid utilization (or 1.1% of the cohort, n = 6,188). The largest magnitude predictors of long-term opioid utilization were receiving a long-acting opioid within the first 30 days of the episode, diagnoses of chronic pain (no specified source), back/neck pain, or peripheral/central nervous system pain, and severe pain score in vital records.ConclusionsSoldiers returning from deployment were more likely to receive an opioid prescription than the overall active duty population, and 1.1% initiated a long-term opioid episode. We report a declining rate of opioid receipt and long-term opioid utilization among Army members from fiscal years 2008-2014. This study demonstrates that the most important predictors of opioid receipt were not demographic factors, but generally clinical indicators of acute pain or physical trauma.
| S-EPMC6329665 | biostudies-literature
Project description:ImportanceGuidelines recommend against routine breast and prostate cancer screenings in older adults with less than 10 years' life expectancy. One study using a claims-based prognostic index showed that receipt of cancer screening itself was associated with lower mortality, suggesting that the index may misclassify individuals when used to inform cancer screening, but this finding was attributed to residual confounding because the index did not account for functional status.ObjectiveTo examine whether cancer screening remains significantly associated with all-cause mortality in older adults after accounting for both comorbidities and functional status.Design, setting, and participantsThis cohort study included individuals older than 65 years who were eligible for breast or prostate cancer screening and who participated in the 2004 Health and Retirement Study. Data were linked to Medicare claims from 2001 to 2015. Data analysis was conducted from January to November 2020.Main outcomes and measuresA Cox model was used to estimate the association between all-cause mortality over 10 years and receipt of screening mammogram or prostate-specific antigen (PSA) test, adjusting for variables in a prognostic index that included age, sex, comorbidities, and functional status. Potential confounders (ie, education, income, marital status, geographic region, cognition, self-reported health, self-care, and self-perceived mortality risk) of the association between cancer screening and mortality were also tested.ResultsThe breast cancer screening cohort included 3257 women (mean [SD] age, 77.8 [7.5] years); the prostate cancer screening cohort included 2085 men (mean [SD] age, 76.1 [6.8] years). Receipt of screening mammogram was associated with lower hazard of all-cause mortality after accounting for all index variables (adjusted hazard ratio [aHR], 0.67; 95% CI, 0.60-0.74). A weaker, but still statistically significant, association was found for screening PSA (aHR 0.88; 95% CI, 0.78-0.99). None of the potential confounders attenuated the association between screening and mortality except for cognition, which attenuated the aHR for mammogram from 0.67 (95% CI, 0.60-0.74) to 0.73 (95% CI, 0.64-0.82) and the aHR for PSA from 0.88 (95% CI, 0.78-0.99) to 0.92 (95% CI, 0.80-1.05), making PSA screening no longer statistically significant.Conclusions and relevanceIn this study, cognition attenuated the observed association between cancer screening and mortality among older adults. These findings suggest that existing mortality prediction algorithms may be missing important variables that are associated with receipt of cancer screening and long-term mortality. Relying solely on algorithms to determine cancer screening may misclassify individuals as having limited life expectancy and stop screening prematurely. Screening decisions need to be individualized and not solely dependent on life expectancy prediction.
| S-EPMC8170538 | biostudies-literature
Project description:Bariatric surgery is effective in reducing all-cause and cause-specific long-term mortality. Whether the long-term mortality benefit of surgery applies to all ages at which surgery is performed is not known.To examine whether gastric bypass surgery is equally effective in reducing mortality in groups undergoing surgery at different ages.All-cause and cause-specific mortality rates and hazard ratios (HRs) were estimated from a retrospective cohort within 4 categories defined by age at surgery: younger than 35 years, 35 through 44 years, 45 through 54 years, and 55 through 74 years. Mean follow-up was 7.2 years. Patients undergoing gastric bypass surgery seen at a private surgical practice from January 1, 1984, through December 31, 2002, were studied. Data analysis was performed from June 12, 2013, to September 6, 2015. A cohort of 7925 patients undergoing gastric bypass surgery and 7925 group-matched, severely obese individuals who did not undergo surgery were identified through driver license records. Matching criteria included year of surgery to year of driver license application, sex, 5-year age groups, and 3 body mass index categories.Roux-en-Y gastric bypass surgery.All-cause and cause-specific mortality compared between those undergoing and not undergoing gastric bypass surgery using HRs.Among the 7925 patients who underwent gastric bypass surgery, the mean (SD) age at surgery was 39.5?(10.5) years, and the mean (SD) presurgical body mass index was 45.3?(7.4). Compared with 7925 matched individuals not undergoing surgery, adjusted all-cause mortality after gastric bypass surgery was significantly lower for patients 35 through 44 years old (HR, 0.54; 95% CI, 0.38-0.77), 45 through 54 years old (HR, 0.43; 95% CI, 0.30-0.62), and 55 through 74 years old (HR, 0.50; 95% CI, 0.31-0.79; P?<?.003 for all) but was not lower for those younger than 35 years (HR, 1.22; 95% CI, 0.82-1.81; P = .34). The lack of mortality benefit in those undergoing gastric bypass surgery at ages younger than 35 years primarily derived from a significantly higher number of externally caused deaths (HR, 2.53; 95% CI, 1.27-5.07; P = .009), particularly among women (HR, 3.08; 95% CI, 1.4-6.7; P = .005). Patients undergoing gastric bypass surgery had a significantly lower age-related increase in mortality than severely obese individuals not undergoing surgery (P?=?.001).Gastric bypass surgery was associated with improved long-term survival for all patients undergoing surgery at ages older than 35 years, with externally caused deaths only elevated in younger women. Gastric bypass surgery is protective against mortality even for older patients and also reduces the age-related increase in mortality observed in severely obese individuals not undergoing surgery.
| S-EPMC5055061 | biostudies-literature
Project description:ImportanceNonpharmacologic methods of reducing the risk of new chronic opioid use among patients with musculoskeletal pain are important given the burden of the opioid epidemic in the United States.ObjectiveTo determine the association between early physical therapy and subsequent opioid use in patients with new musculoskeletal pain diagnosis.Design, setting, and participantsThis cross-sectional analysis of health care insurance claims data between January 1, 2007, and December 31, 2015, included privately insured patients who presented with musculoskeletal pain to an outpatient physician office or an emergency department at various US facilities from January 1, 2008, to December 31, 2014. The sample comprised 88 985 opioid-naive patients aged 18 to 64 years with a new diagnosis of musculoskeletal shoulder, neck, knee, or low back pain. The data set (obtained from the IBM MarketScan Commercial database) included person-level International Classification of Diseases, Ninth Revision or Tenth Revision diagnosis codes, Current Procedural Terminology codes, and date of service as well as pharmaceutical information (National Drug Code, generic name, dose, and number of days supplied). Early physical therapy was defined as at least 1 session received within 90 days of the index date, the earliest date a relevant diagnosis was provided. Data analysis was conducted from March 1, 2018, to May 18, 2018.Main outcomes and measuresOpioid use between 91 and 365 days after the index date.ResultsOf the 88 985 patients included, 51 351 (57.7%) were male and 37 634 (42.3%) were female with a mean (SD) age of 46 (11.0) years. Among these patients, 26 096 (29.3%) received early physical therapy. After adjusting for potential confounders, early physical therapy was associated with a statistically significant reduction in the incidence of any opioid use between 91 and 365 days after the index date for patients with shoulder pain (odds ratio [OR], 0.85; 95% CI, 0.77-0.95; P = .003), neck pain (OR, 0.92; 95% CI, 0.85-0.99; P = .03), knee pain (OR, 0.84; 95% CI, 0.77-0.91; P < .001), and low back pain (OR, 0.93; 95% CI, 0.88-0.98; P = .004). For patients who did use opioids, early physical therapy was associated with an approximately 10% statistically significant reduction in the amount of opioid use, measured in oral morphine milligram equivalents, for shoulder pain (-9.7%; 95% CI, -18.5% to -0.8%; P = .03), knee pain (-10.3%; 95% CI, -17.8% to -2.7%; P = .007), and low back pain (-5.1%; 95% CI, -10.2% to 0.0%; P = .046), but not for neck pain (-3.8%; 95% CI, -10.8% to 3.3%; P = .30).Conclusions and relevanceEarly physical therapy appears to be associated with subsequent reductions in longer-term opioid use and lower-intensity opioid use for all of the musculoskeletal pain regions examined.
| S-EPMC6324326 | biostudies-literature