High-dose opioid utilization and mortality among individuals initiating hemodialysis.
Ontology highlight
ABSTRACT: Background
Individuals undergoing hemodialysis in the United States frequently report pain and receive three-fold more opioid prescriptions than the general population. While opioid use is appropriate for select patients, high-dose utilization may contribute to an increased risk of death due to possible accumulation of opioid metabolites.Methods
We studied high-dose opioid utilization (≥120 morphine milligram equivalents [MME] per day) among adults initiating hemodialysis in the United States between 2007 and 2014 using national registry data. We calculated the cumulative incidence (%) of high-dose utilization and depicted trends in the average percentage of days individuals were exposed to opioids. We used adjusted Cox proportional hazards models to identify which opioid doses were associated with mortality.Results
Among 327,344 adults undergoing hemodialysis, the cumulative incidence of high-dose utilization was 14.9% at 2 years after initiating hemodialysis. Among patients with ≥1 opioid prescription during follow-up, the average percentage of days exposed to high-dose utilization increased from 13.9% in 2007 to 26.1% in 2014. Compared to 0MME per day, doses < 60MME were not associated with an increased risk of mortality, but high-dose utilization was associated with a 1.63-fold (95% CI, 1.57, 1.69) increased risk of mortality. The risk of mortality associated with opioid dose was highest in the first year after hemodialysis initiation.Conclusions
The risk of mortality associated with opioid utilization among individuals on hemodialysis increases as doses exceed 60MME per day and is greatest during periods of high-dose utilization. Patients and clinicians should carefully weigh the risks and benefits of opioid doses exceeding 60MME per day.
SUBMITTER: Daubresse M
PROVIDER: S-EPMC7901089 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundIt is uncertain whether consolidation in health care markets affects the quality of care provided and health outcomes.ObjectivesTo examine whether changes in market competition resulting from acquisitions by two large national for-profit dialysis chains were associated with patient mortality.MethodsWe identified patients initiating in-center hemodialysis between 2001 and 2009 from a registry of patients with end-stage renal disease in the United States. We considered two scenarios when evaluating consolidation from dialysis facility acquisitions: one in which we considered only those patients receiving dialysis in markets that became substantially more concentrated to have been affected by consolidation, and the other in which all patients living in hospital service areas where a facility was acquired were potentially affected. We used a difference-in-differences study design to examine the associations between market consolidation and changes in mortality rates.ResultsWhen we considered the 12,065 patients living in areas that became substantially more consolidated to have been affected by consolidation, we found a nominally significant (8%; 95% confidence interval 0%-17%) increase in likelihood of death after consolidation. Nevertheless, when we considered all 186,158 patients living in areas where an acquisition occurred to have been affected by consolidation, there was no observable effect of market consolidation on mortality.ConclusionsDecreased market competition may have led to increased mortality among a relatively small subset of patients initiating in-center hemodialysis in areas that became substantially more concentrated after two large dialysis acquisitions, but not for most of the patients living in affected areas.
| S-EPMC6740331 | biostudies-literature
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:ImportanceGabapentin prescriptions have drastically increased in the US due to off-label prescribing in settings such as opioid use disorder (OUD) treatment to manage a range of comorbid conditions and withdrawal symptoms, despite a lack of evidence.ObjectiveTo assess the purpose and associated risks of off-label gabapentin use in OUD treatment.Design, setting, and participantsThis retrospective recurrent-event case-control study with a crossover design used administrative claims data from MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Individuals aged 12 to 64 years with an OUD diagnosis and filling buprenorphine prescriptions were included in the primary analysis conducted from July 1, 2022, through June 1, 2023. Unit of observation was the person-day.ExposuresDays covered by filled gabapentin prescriptions.Main outcomes and measuresPrimary outcomes were receipt of gabapentin in the 90 days after initiation of buprenorphine treatment and drug-related poisoning. Drug-related poisonings were defined using codes from International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.ResultsA total of 109 407 patients were included in the analysis (mean [SD] age, 34.0 [11.2] years; 60 112 [54.9%] male). Among the 29 967 patients with Medicaid coverage, 299 (1.0%) were Hispanic, 1330 (4.4%) were non-Hispanic Black, 23 112 (77.1%) were non-Hispanic White, and 3399 (11.3%) were other. Gabapentin was significantly less likely to be prescribed to Black or Hispanic patients, and more likely to be prescribed to female patients, those with co-occurring substance use or mood disorders, and those with comorbid physical conditions such as neuropathic pain. Nearly one-third of persons who received gabapentin (4336 [31.1%]) had at least 1 drug-related poisoning after initiating buprenorphine treatment, compared with 13 856 (14.5%) among persons who did not receive gabapentin. Adjusted analyses showed that days of gabapentin use were not associated with hospitalization for drug-related poisoning (odds ratio, 0.98 [95% CI, 0.85-1.13]). Drug-related poisoning risks did not vary based on dosage.Conclusions and relevanceGabapentin is prescribed in the context of a myriad of comorbid conditions. Even though persons receiving gabapentin are more likely to have admissions for drug-related poisoning, these data suggest that gabapentin is not associated with an increased risk of drug-related poisoning alongside buprenorphine in adjusted analyses. More data on the safety profile of gabapentin in OUD settings are needed.
| S-EPMC10483381 | biostudies-literature
Project description:Background and objectivesMortality from benzodiazepine/opioid interactions is a growing concern in light of the opioid epidemic. Patients on hemodialysis suffer from a high burden of physical/psychiatric conditions, which are treated with benzodiazepines, and they are three times more likely to be prescribed opioids than the general population. Therefore, we studied mortality risk associated with short- and long-acting benzodiazepines and their interaction with opioids among adults initiating hemodialysis.Design, setting, participants, & measurementsThe cohort of 69,368 adults initiating hemodialysis (January 2013 to December 2014) was assembled by linking US Renal Data System records to Medicare claims. Medicare claims were used to identify dispensed benzodiazepines and opioids. Using adjusted Cox proportional hazards models, we estimated the mortality risk associated with benzodiazepines (time varying) and tested whether the benzodiazepine-related mortality risk differed by opioid codispensing.ResultsWithin 1 year of hemodialysis initiation, 10,854 (16%) patients were dispensed a short-acting benzodiazepine, and 3262 (5%) patients were dispensed a long-acting benzodiazepine. Among those who were dispensed a benzodiazepine during follow-up, codispensing of opioids and short-acting benzodiazepines occurred among 3819 (26%) patients, and codispensing of opioids and long-acting benzodiazepines occurred among 1238 (8%) patients. Patients with an opioid prescription were more likely to be subsequently dispensed a short-acting benzodiazepine (adjusted hazard ratio, 1.66; 95% confidence interval, 1.59 to 1.74) or a long-acting benzodiazepine (adjusted hazard ratio, 1.11; 95% confidence interval, 1.03 to 1.20). Patients dispensed a short-acting benzodiazepine were at a 1.45-fold (95% confidence interval, 1.35 to 1.56) higher mortality risk compared with those without a short-acting benzodiazepine; among those with opioid codispensing, this risk was 1.90-fold (95% confidence interval, 1.65 to 2.18; P interaction<0.001). In contrast, long-acting benzodiazepine dispensing was inversely associated with mortality (adjusted hazard ratio, 0.84; 95% confidence interval, 0.72 to 0.99) compared with no dispensing of long-acting benzodiazepine; there was no differential risk by opioid dispensing (P interaction=0.72).ConclusionsCodispensing of opioids and short-acting benzodiazepines is common among patients on dialysis, and it is associated with higher risk of death.
| S-EPMC7274292 | biostudies-literature
Project description:Background and objectiveOlder adults initiating dialysis have a high risk of mortality and that risk may be related to potentially inappropriate medications (PIMs). Our objective was to identify and validate mortality risk associated with American Geriatrics Society Beers Criteria PIM classes and concomitant PIM use.MethodsWe used US Renal Data System data to establish a cohort of adults aged ≥ 65 years initiating dialysis (2013-2014) and had no PIM prescriptions in the 6 months prior to dialysis initiation. In a development cohort (40% sample), adjusted Cox proportional hazards models were performed to determine which of 30 PIM classes were associated with mortality (or "high-risk" PIMs). Adjusted Cox models were performed to assess the association of the number of "high-risk" PIM fills/month with mortality. All models were repeated in the validation cohort (60% sample).ResultsIn the development cohort (n = 15,570), only 13 of 30 PIM classes were associated with a higher mortality risk. Compared with those with no "high-risk" PIM fills/month, patients having one "high-risk" PIM fill/month had a 1.29-fold (95% confidence interval 1.21-1.38) increased risk of death; those with two or more "high-risk" PIM fills/month had a 1.40-fold (95% confidence interval 1.24-1.58) increased risk. These findings were similar in the validation cohort (n = 23,569).ConclusionsOnly a minority of Beers Criteria PIM classes may be associated with mortality in the older dialysis population; however, mortality risk increases with concomitant use of "high-risk" PIMs. Additional studies are needed to confirm these associations and their underlying mechanisms.
| S-EPMC10441684 | biostudies-literature
Project description:ImportanceMergers and acquisitions among health care institutions are increasingly common, and dialysis markets have undergone several decades of mergers and acquisitions.ObjectiveTo examine the outcomes of hemodialysis facility acquisitions independent of associated changes in market competition resulting from acquisitions.Design, setting, and participantsCohort study using difference-in-differences (DID) analyses to compare changes in health outcomes over time among in-center US dialysis facilities that were acquired by a hemodialysis chain with facilities located nearby but not acquired. Multivariable Cox proportional hazards regression models and negative binomial models with predicted marginal effects were developed to examine health outcomes, controlling for patient, facility, and geographic characteristics. All facility ownership types were examined together and stratified analyses were conducted of facilities that were independently owned and chain owned prior to acquisitions. The study was conducted from January 2001 to September 2015; 174 905 patients starting in-center dialysis in the 3 years before and following dialysis facility acquisitions were included. Data were analyzed from March 2017 to December 2018.ExposuresAcquisition by a hemodialysis chain.Main outcomes and measuresTwelve-month hazard of death and hospital days per patient-year were the primary outcomes.ResultsOf the 174 905 patients included in the study, 79 705 were women (45.6%), 24 409 (14.0%) were of Hispanic ethnicity, 61 815 (35.3%) were black, 105 272 (60.2%) were white, and 1247 (0.7%) were Native American. Mean (SD) age was 65 (15) years. Before acquisitions, adjusted mortality and hospitalization rates were 10% (95% CI, -16% to -5%) and 2.9 days per patient-year (95% CI, -3.8 to -2.0) lower, respectively, at independently owned facilities that were acquired compared with those that were not acquired, while hospitalization rates were 0.7 days (95% CI, -1.2 to -2.0) lower at chain-owned facilities that were acquired compared with those that were not acquired. In stratified analyses of independently owned facilities, mortality decreases were smaller at acquired (-8.4%; 95% CI, -14% to -25%) vs nonacquired (-20.3%; 95% CI, -25.8% to -14.3%) facilities (DID P < .001). Similarly, hospitalization rates did not change at acquired facilities and decreased by 2.6 days per patient-year (95% CI, -3.6 to -1.7 days) at nonacquired facilities (DID P < .001). Acquisitions were not associated with changes in health outcomes at chain-owned facilities. Slower reductions in mortality and hospitalization rates at independently owned facilities contributed to significant differences in hospitalizations (-2.0 days; 95% CI, -2.5 to -1.6, at nonacquired vs 0.9 days; 95% CI, -1.3 to -0.5, at acquired facilities; DID, P < .001) across all ownership types but not mortality (DID, P = .28) with regard to acquisitions.Conclusions and relevanceAcquisition of independently owned dialysis facilities by larger dialysis organizations was associated with slower decreases in mortality and hospitalization rates, as nonacquired facilities appeared to experience more rapid improvements in outcomes over time.
| S-EPMC6537810 | biostudies-literature
Project description:AimsTo examine the impact of national clinical practice guidelines and provincial drug policy interventions on prevalence of high-dose opioid prescribing and rates of hospitalization for opioid toxicity.DesignInterventional time-series analysis.SettingOntario, Canada, from 2003 to 2014.ParticipantsOntario Drug Benefit (ODB) beneficiaries aged 15 to 64 years from 2003 to 2014.InterventionsPublication of Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain (May 2010) and implementation of Ontario's Narcotics Safety and Awareness Act (NSAA; November 2011).MeasurementsThree outcomes were explored: the rate of opioid use among ODB beneficiaries, the prevalence of opioid prescriptions exceeding 200 mg and 400 mg morphine equivalents per day, and rates of opioid-related emergency department visits and hospital admissions.FindingsOver the 12 year study period, the rate of opioid use declined 15.2%, from 2764 to 2342 users per 10,000 ODB eligible persons. The rate of opioid use was significantly impacted by the Canadian clinical practice guidelines (p-value = .03) which led to a decline in use, but no impact was observed by the enactment of the NSAA (p-value = .43). Among opioid users, the prevalence of high-dose prescribing doubled (from 4.2% to 8.7%) over the study period. By 2014, 40.9% of recipients of long-acting opioids exceeded daily doses of 200 mg morphine or equivalent, including 55.8% of long-acting oxycodone users and 76.3% of transdermal fentanyl users. Moreover, in the last period, 18.7% of long-acting opioid users exceeded daily doses of 400 mg morphine or equivalent. Rates of opioid-related emergency department visits and hospital admissions increased 55.0% over the study period from 9.0 to 14.0 per 10,000 ODB beneficiaries from 2003 to 2013. This rate was not significantly impacted by the Canadian clinical practice guidelines (p-value = .68) or enactment of the NSAA (p-value = .59).ConclusionsAlthough the Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain led to a decline in opioid prescribing rates among ODB beneficiaries these guidelines and subsequent Ontario legislation did not result in a significant change in rates of opioid-related hospitalizations. Given the prevalence of high dose opioid prescribing in this population, this suggests that improved strategies and programs for the safe prescribing of long-acting opioids are needed.
| S-EPMC5156349 | biostudies-literature
Project description:ImportanceRapid reduction or discontinuation of long-term opioid therapy may increase risk of opioid overdose or opioid use disorder (OUD). Current guidelines for chronic pain management caution against rapid dose reduction but are based on limited evidence.ObjectiveTo characterize the association between rapid reduction or abrupt discontinuation of opioid therapy (vs maintained or gradual reduction) and incidence of opioid overdose and OUD among patients prescribed high-dose, long-term opioid therapy (HDLTOT).Design, setting, and participantsThis retrospective cohort study was conducted among patients aged 18 to 64 years who were prescribed HDLTOT (≥90 daily morphine milligram equivalents for ≥90% of 90 days) from January 2006 to September 2018, with follow-up up to 4 years after cohort entry. Claims data were drawn from a large private health insurer in North Carolina and analyzed from March 1, 2006, to September 30, 2018.ExposuresTime-varying exposure of rapid dose reduction or discontinuation (>10% dose reduction/week) vs maintenance, increase, or gradual reduction or discontinuation.Main outcomes and measuresThe main outcome was incident opioid overdose (fatal or nonfatal) or diagnosed OUD. Inverse probability-weighted cumulative incidence of outcomes were estimated using the cumulative incidence function and hazard ratios (HRs) using marginal structural Fine-Gray models as a function of rapid dose tapering or discontinuation (vs gradual reduction or discontinuation or maintained or increased), accounting for competing risks.ResultsA total of 19 443 patients (median [IQR] age, 49 [41-55] years; 10 073 [51.8%] men) who received HDLTOT were identified. Rapid reduction or discontinuation was associated with higher risk of fatal and nonfatal overdoses compared with gradual reduction after the first year (year 1: HR, 1.43; 95% CI, 0.94-2.18; years 2-4: HR, 1.95; 95% CI, 1.31-2.90). There was no association between rapid reduction or discontinuation and diagnosed OUD through 2 years of follow-up; however, the hazard of incident OUD among patients exposed to rapid tapering or discontinuation was greater 25 to 48 months after the start of follow-up (HR, 1.28; 95% CI, 1.01-1.63).Conclusions and relevanceIn this cohort study, rapid dose reduction or discontinuation was associated with increased risk of opioid overdose and OUD during long-term follow-up. These findings reinforce prior concerns about safety of rapid dose reductions for patients receiving HDLTOT and highlight the need for caution when reducing opioid doses.
| S-EPMC9047650 | biostudies-literature
Project description:Few data are available regarding the association of dialyzer type with prognosis. In Japan, dialyzers are classified as types I, II, III, IV, and V based on β2-microglobulin clearance rates of < 10, < 30, < 50, < 70, and ≥ 70 mL/min, respectively. We investigated the relationship of the 5 dialyzer types with 1-year mortality. This nationwide cohort study used data collected at the end of 2008 and 2009 by the Japanese Society for Dialysis Therapy Renal Data Registry. We enrolled 203,008 patients on maintenance hemodialysis who underwent hemodialysis for at least 1 year and were managed with any of the 5 dialyzer types. To evaluate the association of dialyzer type with 1-year all-cause mortality, Cox proportional hazards models and propensity score-matched analyses were performed. After adjustment of the data with clinicodemographic factors, the type I, II, and III groups showed significantly higher hazard ratios (HRs) than the type IV dialyzers (reference). After adjustment for Kt/V and β2-microglobulin levels, the HRs were significantly higher in the type I and II groups. After further adjustment for nutrition- and inflammation-related factors, the HRs were not significantly different between the type IV and type I and II groups. However, type V dialyzers consistently showed a significantly lower HR. With propensity score matching, the HR for the type V dialyzer group was significantly lower than that for the type IV dialyzer group. Additional long-term trials are required to determine whether type V dialyzers, which are high-performance dialyzers, can improve prognosis.
| S-EPMC8192518 | biostudies-literature
Project description:[This corrects the article DOI: 10.1371/journal.pone.0167479.].
| S-EPMC5249127 | biostudies-literature