Impact of opioid dose escalation on pain intensity: a retrospective cohort study.
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ABSTRACT:
SUBMITTER: Hayes CJ
PROVIDER: S-EPMC7510136 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimTo understand the potential harmful effects of dose escalation among patients with chronic, non-cancer pain (CNCP) on chronic opioid therapy.DesignRetrospective cohort study.SettingUnited States Veterans Healthcare Administration.ParticipantsVeterans with CNCP and on chronic opioid therapy were identified using data from fiscal years 2008-15. The Veteran sample was approximately 90% male and 70% white.MeasurementsDose escalators [increase of > 20% average morphine milligram equivalent (MME) daily dose] were compared with dose maintainers (change of ±20% average MME daily dose). A composite measure of subsequent substance use disorders (SUDs: opioid, non-opioid and alcohol use disorders) and opioid-related adverse outcomes (AOs: accidents resulting in wounds/injuries, opioid-related and alcohol and non-opioid medication-related accidents and overdoses, self-inflicted injuries) as well as the individual SUDs and AOs was examined. The primary analyses were conducted among a 1 : 1 matched sample of escalators and maintainers matched on propensity score and index date. Propensity scores were generated using demographic characteristics, medical comorbidities, medication and health-care utilization characteristics. Subgroup analyses were conducted by quartile of the propensity score. Sensitivity analyses were conducted using adjusted logistic regression, logistic regression using stabilized inverse probability of treatment weighting (SIPTW) and instrumental variable (IV) models using geographic variation in opioid dose escalation as the IV.FindingsThere were 32 420 maintainers and 20 767 escalators resulting in 19 358 (93.2%) matched pairs. Composite AOs [odds ratio (OR) = 1.31, 95% confidence interval (CI) = 1.23, 1.40], composite SUDs (OR = 1.31, 95% CI = 1.22, 1.41) and individual SUD and AO subtypes were higher among dose escalators, except for opioid-related accidents and overdoses and violence-related injuries. Subgroup analyses within the propensity score quartiles found similar results. Sensitivity analyses with the adjusted and SIPTW logistic regressions found similar results to the primary analyses for all outcomes except for opioid-related accidents and overdoses, which were found to be significantly higher among escalators. Sensitivity analyses with IV models provided mixed results with SUDs and the individual types of AOs.ConclusionEscalating the opioid dose for those with chronic, non-cancer pain is associated with increased risks of substance use disorder and opioid-related adverse outcomes.
| S-EPMC7263736 | biostudies-literature
Project description:To identify patient factors and health care utilization patterns associated with dose escalation during the first year of long-term opioid therapy for chronic pain.Retrospective cohort study using electronic health record data.University health system.Opioid naïve adults with musculoskeletal pain who received a new outpatient opioid prescription between July 1, 2011 and June 30, 2012 and stayed on opioids for 1 year.Mixed-effects regression was used to estimate patients' rate of opioid dose escalation. Demographics, clinical characteristics, and health care utilization for patients with and without dose escalation were compared.Twenty-three (9%) of 246 patients in the final cohort experienced dose escalation (defined as an increase in mean daily opioid dose of ?30-mg morphine equivalents over 1 year). Compared with patients without dose escalation, patients with escalation had higher rates of substance use diagnoses (17% vs 1%, P?=?0.01) and more total outpatient encounters (51 vs 35, P?=?0.002) over 1 year. Differences in outpatient encounters were largely due to more non face-to-face encounters (e.g., telephone calls, emails) among patients with dose escalation. Differences in age, race, concurrent benzodiazepine use, and mental health diagnoses between patients with and without dose escalation were not statistically significant. Primary care clinicians prescribed 89% of opioid prescriptions.Dose escalation during the first year of long-term opioid therapy is associated with higher rates of substance use disorders and more frequent outpatient encounters, especially non face-to-face encounters.
| S-EPMC4390410 | biostudies-literature
Project description:ObjectiveTo evaluate the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) for the treatment of unresectable liver metastases.MethodsTwenty-five patients with unresectable liver metastases treated with IMRT were enrolled from January 2003 to September 2016. The median longest diameter of the lesions was 3.3 cm (range, 1.6-16.7 cm). The fraction dose ranged from 2 to 5.2 Gy, with a median total dose of 50 Gy (range, 30-60 Gy).ResultsThe median follow-up was 9.2 months (range, 2.1-48.8 months). The overall survival rates at 1 and 2 years were 46.4% and 27.4%, respectively. The 1-year local control rate was 69.8%. The 1-year progression-free survival rate was 26.3%. One patient had grade 4 liver dysfunction. One case of grade 4 leukopenia and one case of grade 3 leukopenia occurred, and one case of grade 3 leukopenia and thrombocytopenia was observed.ConclusionIMRT may be a promising and safe treatment for unresectable liver metastases and can be used as a treatment option.
| S-EPMC7607147 | biostudies-literature
Project description:PurposePostpartum opioid use remains common among women with uncomplicated vaginal delivery and may increase the risk of serious opioid-related events. Therefore, we examined the association between the dose of the first filled opioid prescription after vaginal delivery and the subsequent risk of serious opioid-related events.MethodsWe conducted a retrospective cohort study among women enrolled in Tennessee Medicaid with a vaginal delivery (2007-2015). We used Cox proportional hazards regression to model adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for serious opioid-related events after delivery according to the dose (morphine milligram equivalents [MME]) of the first postpartum opioid prescription, accounting for comorbidities, medication use, parity, and delivery complications. Serious opioid-related events were defined as the occurrence of persistent opioid use, a methadone or buprenorphine fill, opioid use disorder diagnosis, opioid overdose, or opioid-related death. We used filled pharmacy data to characterize the dose of the first postpartum opioid prescription filled within 4 days after delivery.ResultsMore than one-half of women (53.2%; n = 147,598) filled an opioid prescription within 4 days of a vaginal delivery. After accounting for baseline risk factors, filling a postpartum opioid prescription was associated with an increased risk of serious opioid-related events across all dose categories, compared with women filling none (aHR 1-99 MME, 1.52; 95% CI, 1.33-1.74; aHR 100-149 MME, 1.41; 95% CI, 1.26-1.58; aHR 150-199 MME, 1.40; 95% CI, 1.26-1.57: and aHR ≥200 MME, 1.60; 95% CI, 1.43-1.78).ConclusionsFilling a postpartum opioid prescription after a vaginal delivery was associated with an increased risk of serious opioid-related events, regardless of dose. Prescribing guidelines should discourage the routine prescribing of opioids after vaginal delivery.
| S-EPMC8260443 | biostudies-literature
Project description:ObjectivesOpioids are commonly administered in the emergency department (ED) and prescribed for the treatment of back pain. It is important to understand the unintended consequences of this approach to inform treatment decisions and the consideration of alternative treatments. Recent evidence has shown that ED opioid prescriptions are associated with future opioid use. The objective of this study was to measure the association of opioid administration in the ED to patients treated for back pain with future opioid use.MethodsThis is a retrospective study of opioid-naïve adults discharged from the ED with a diagnosis of back pain. Patients were stratified by opioid therapy (none, ED administration only, prescription only, or ED administration + prescription). Relative risks of ongoing opioid use (filling >90-day supply in 180 days following ED visit as documented in the prescription drug monitoring program) were calculated for each opioid-therapy group and compared to the no-opioid group.ResultsWe identified 24,487 opioid naïve back pain patients. The median age was 38 years, 55% were female, and 56% were non-Hispanic white. A total of 41% received no opioid, 10% were only administered an opioid in the ED, 18% only received a prescription, and 31% received an opioid in the ED + prescription. The adjusted relative risks of ongoing use compared to the no opioid group were as follows: ED only 1.9, prescription only 2.1, and ED + prescription 2.3. The increased risk persisted for other definitions of ongoing use and after adjustment for baseline pain scores.ConclusionsFor opioid-naïve patients with back pain, both administration of an opioid in the ED and opioid prescriptions are associated with a doubling of the risk of ongoing opioid use compared to patients not treated with opioids. This supports the consideration of minimizing exposure to opioids while treating back pain in the ED.
| S-EPMC8079173 | biostudies-literature
Project description:BACKGROUND:Despite known risks of using chronic opioid therapy (COT) for pain, the risks of discontinuation of COT are largely uncharacterized. OBJECTIVE:To evaluate mortality, prescription opioid use, and primary care utilization of patients discontinued from COT, compared with patients maintained on opioids. DESIGN:Retrospective cohort study of patients with chronic pain enrolled in an opioid registry as of May 2010. PARTICIPANTS:Patients with chronic pain enrolled in the opioid registry of a primary care clinic at an urban safety-net hospital in Seattle, WA. MAIN OUTCOMES AND MEASURES:Discontinuation from the opioid registry was the exposure of interest. Pre-specified main outcomes included mortality, prescription and primary care utilization data, and reasons for discontinuation. Data was collected through March 2015. KEY RESULTS:The study cohort comprised 572 patients with a mean age of 54.9?±?10.1 years. COT was discontinued in 344 patients (60.1%); 254 (73.8%) discontinued patients subsequently filled at least one opioid prescription in Washington State, and 187 (54.4%) continued to visit the clinic. During the study period, 119 (20.8%) registry patients died, and 21 (3.7%) died of definite or possible overdose: 17 (4.9%) discontinued patients died of overdose, whereas 4 (1.75%) retained patients died of overdose. Most patients had at least one provider-initiated reason for COT discontinuation. Discontinuation of COT was associated with a hazard ratio for death of 1.35 (95% CI, 0.92 to 1.98, p?=?0.122) and for overdose death of 2.94 (1.01-8.61, p?=?0.049), after adjusting for age and race. CONCLUSIONS:In this cohort of patients prescribed COT for chronic pain, mortality was high. Discontinuation of COT did not reduce risk of death and was associated with increased risk of overdose death. Improved clinical strategies, including multimodal pain management and treatment of opioid use disorder, may be needed for this high-risk group.
| S-EPMC6854174 | biostudies-literature
Project description:ObjectiveTo assess the association between long term prescription opioid treatment medically dispensed for non-cancer pain and the initiation of injection drug use (IDU) among individuals without a history of substance use.DesignRetrospective cohort study.SettingLarge administrative data source (containing information for about 1.7 million individuals tested for hepatitis C virus or HIV in British Columbia, Canada) with linkage to administrative health databases, including dispensations from community pharmacies.ParticipantsIndividuals age 11-65 years and without a history of substance use (except alcohol) at baseline.Main outcome measuresEpisodes of prescription opioid use for non-cancer pain were identified based on drugs dispensed between 2000 and 2015. Episodes were classified by the increasing length and intensity of opioid use (acute (lasting <90 episode days), episodic (lasting ≥90 episode days; with <90 days' drug supply and/or <50% episode intensity), and chronic (lasting ≥90 episode days; with ≥90 days' drug supply and ≥50% episode intensity)). People with a chronic episode were matched 1:1:1:1 on socioeconomic variables to those with episodic or acute episodes and to those who were opioid naive. IDU initiation was identified by a validated administrative algorithm with high specificity. Cox models weighted by inverse probability of treatment weights assessed the association between opioid use category (chronic, episodic, acute, opioid naive) and IDU initiation.Results59 804 participants (14 951 people from each opioid use category) were included in the matched cohort, and followed for a median of 5.8 years. 1149 participants initiated IDU. Cumulative probability of IDU initiation at five years was highest for participants with chronic opioid use (4.0%), followed by those with episodic use (1.3%) and acute use (0.7%), and those who were opioid naive (0.4%). In the inverse probability of treatment weighted Cox model, risk of IDU initiation was 8.4 times higher for those with chronic opioid use versus those who were opioid naive (95% confidence interval 6.4 to 10.9). In a sensitivity analysis limited to individuals with a history of chronic pain, cumulative risk for those with chronic use (3.4% within five years) was lower than the primary results, but the relative risk was not (hazard ratio 9.7 (95% confidence interval 6.5 to 14.5)). IDU initiation was more frequent at higher opioid doses and younger ages.ConclusionsThe rate of IDU initiation among individuals who received chronic prescription opioid treatment for non-cancer pain was infrequent overall (3-4% within five years) but about eight times higher than among opioid naive individuals. These findings could have implications for strategies to prevent IDU initiation, but should not be used as a reason to support involuntary tapering or discontinuation of long term prescription opioid treatment.
| S-EPMC8600402 | biostudies-literature
Project description:BackgroundSurgeons often see patients with pain to exclude organic pathology and consider surgical treatment. We examined factors associated with long-term opioid therapy among patients with foot/ankle, anorectal, and temporomandibular joint pain to aid clinical decision making.MethodsUsing the IBM MarketScan® Research Database, we conducted a retrospective cohort analysis of patients aged 18-64 with a clinical encounter for foot/ankle, anorectal, or temporomandibular joint pain (January 2007-September 2015). Multivariable logistic regression was used to estimate adjusted odds ratios for factors associated with long-term opioid therapy, including age, sex, geographic region, pain condition, psychiatric diagnoses, and surgical procedures in the previous year.ResultsThe majority of the cohort of 1,500,392 patients were women (61%). Within the year prior to the first clinical encounter for a pain diagnosis, 14% had an encounter for a psychiatric diagnosis, and 11% had undergone a surgical procedure. Long-term opioid therapy was received by 2.7%. After multivariable adjustment, older age (age 50-64 vs. 18-29: aOR 4.47, 95% CI 4.24-4.72, p < 0.001), region (South vs. Northeast, aOR 1.76, 95% CI 1.70-1.81, p < 0.001), recent surgical procedure (aOR 1.83, 95% CI 1.78-1.87, p < 0.001), male sex (aOR 1.14, 95% CI 1.12-1.16, p < 0.001) and recent psychiatric diagnosis (aOR 2.49, 95% CI 2.43-2.54, p < 0.001) were independently associated with long-term opioid therapy.ConclusionAmong patients with foot/ankle, anorectal, or temporomandibular joint pain, the risk of long-term opioid therapy significantly increased with older age, recent psychiatric diagnoses and surgical history. Surgeons should be aware of these risk factors in order to make high quality clinical decisions in consultations with these patients.
| S-EPMC8384768 | biostudies-literature
Project description:The recommended phase 2 doses of molecularly targeted agents, determined by using an ordinal dose-finding method that only uses toxicity data at first cycle, may not be optimal. Some researchers have proposed the use of relative dose intensity that can account for late-onset, cumulative, and low-grade toxicities to determine the recommended phase 2 dose (RP2D). In this study, we proposed two dose escalation methods based on the observed relative dose intensities (RDIs) between the pre-specified intervals (cycles) for toxicity evaluation used in combination with DLT evaluation in the first cycle. First, we propose the modified 3 + 3 design that incorporates longitudinal RDI assessment. Second, we propose the sequential assessment method for longitudinal RDI (SARDI) to achieve faster dose escalation compared to that of the modified 3 + 3 design. Simulation studies demonstrated that the SARDI was, in many cases, superior to the ordinal and modified 3 + 3 designs in respect to the selection rate of true RP2D and study period. The two proposed methods could also in some cases decrease the average number of patients enrolled in the trial compared to that of the ordinary 3 + 3 design. Incorporation of the RDI assessment into the 3 + 3 design is not difficult and does not require the use of complex statistical techniques. Therefore, we believe that investigators who routinely use the 3 + 3 design in practice can easily use our proposed methods.
| S-EPMC6883296 | biostudies-literature
Project description:BackgroundA subset of patients with severe COVID-19 develop a hyperinflammatory syndrome, which might contribute to morbidity and mortality. This study explores a specific phenotype of COVID-19-associated hyperinflammation (COV-HI), and its associations with escalation of respiratory support and survival.MethodsIn this retrospective cohort study, we enrolled consecutive inpatients (aged ≥18 years) admitted to University College London Hospitals and Newcastle upon Tyne Hospitals in the UK with PCR-confirmed COVID-19 during the first wave of community-acquired infection. Demographic data, laboratory tests, and clinical status were recorded from the day of admission until death or discharge, with a minimum follow-up time of 28 days. We defined COV-HI as a C-reactive protein concentration greater than 150 mg/L or doubling within 24 h from greater than 50 mg/L, or a ferritin concentration greater than 1500 μg/L. Respiratory support was categorised as oxygen only, non-invasive ventilation, and intubation. Initial and repeated measures of hyperinflammation were evaluated in relation to the next-day risk of death or need for escalation of respiratory support (as a combined endpoint), using a multi-level logistic regression model.FindingsWe included 269 patients admitted to one of the study hospitals between March 1 and March 31, 2020, among whom 178 (66%) were eligible for escalation of respiratory support and 91 (34%) patients were not eligible. Of the whole cohort, 90 (33%) patients met the COV-HI criteria at admission. Despite having a younger median age and lower median Charlson Comorbidity Index scores, a higher proportion of patients with COV-HI on admission died during follow-up (36 [40%] of 90 patients) compared with the patients without COV-HI on admission (46 [26%] of 179). Among the 178 patients who were eligible for full respiratory support, 65 (37%) met the definition for COV-HI at admission, and 67 (74%) of the 90 patients whose respiratory care was escalated met the criteria by the day of escalation. Meeting the COV-HI criteria was significantly associated with the risk of next-day escalation of respiratory support or death (hazard ratio 2·24 [95% CI 1·62-2·87]) after adjustment for age, sex, and comorbidity.InterpretationAssociations between elevated inflammatory markers, escalation of respiratory support, and survival in people with COVID-19 indicate the existence of a high-risk inflammatory phenotype. COV-HI might be useful to stratify patient groups in trial design.FundingNone.
| S-EPMC7442426 | biostudies-literature