Long-term Prescription Research Articles

Social support and the association between post-traumatic stress disorder and risk for long-term prescription opioid use.

Post-traumatic stress disorder (PTSD) is common in patients with chronic pain, adversely affects chronic pain outcomes, and is associated with opioid use and adverse opioid outcomes. Social support is a robust predictor of PTSD incidence and course as well as chronic pain outcome. We determined whether the association between PTSD and persistent opioid use was modified by emotional support in a cohort of patients receiving opioids for noncancer pain. Eligible participants were ≥18 years and had completed a new period of prescription opioid use lasting 30 to 90 days. Bivariate associations between cohort characteristics and each key variable was assessed using χ 2 tests for categorical variables and t -tests for continuous variables. Interaction between PTSD and emotional support was assessed by a priori stratification on low vs high emotional support. Participants (n = 808) were 53.6 (SD ± 11.6) years of age, 69.8% female, 69.6% White, and 26.4% African American. Overall, 17.2% had probable PTSD. High emotional support was significantly ( P < 0.0001) more common among those without probable PTSD. Prescription opioid use at 6-month follow-up was significantly ( P = 0.0368) more common among patients with vs without probable PTSD. In fully adjusted models, PTSD was no longer associated with opioid use at 6-month follow-up among participants with high emotional support. Among those with lower emotional support, PTSD was significantly associated with opioid use at 6-month follow-up in unadjusted (odds ratio = 2.40; 95% confidence interval: 1.24-4.64) and adjusted models (odds ratio = 2.39; 95% confidence interval: 1.14-4.99). Results point to the hypothesis that improvement of emotional support in vulnerable patients with chronic pain and PTSD may help reduce sustained opioid use.

Opioid and dependence-forming medications co-prescription reduction and oversight: the OPIO-CHECK Quality Improvement Project (QIP) protocol and interim analysis.

Long-term opioid prescription to manage chronic non-cancer pain (CNCP) is rapidly rising, despite the lacking evidence supporting their safety and efficacy. Co-prescribing opioids with other dependence-forming medications (DFMs) causes fatal side effects. Clinicians are advised to avoid combinations of DFMs and, where suitable, deprescribe to improve patient safety. To review the number of patients registered to the Grange Medical Centre (Nuneaton, Warwickshire) who are co-prescribed an opioid and either benzodiazepine/gabapentinoid for CNCP and to reduce usage of these DFMs. The 'Model for Improvement' is used as a QIP framework. A database search was conducted on 5 October 2023 to identify the cohort of interest. The introduced changes included devising a resource pack outlining the up-to-date non-pharmacological pain management, support channels, and a medication review invitation sent to the identified patients. A pain management template has also been developed to be used by GPs and clinical pharmacists to support the medication review. Guided by the Plan-Do-Study-Act cycle, data will be re-measured to detect incremental changes in practice. In total, 123 patients were receiving co-prescriptions of opioids along with either benzodiazepine/gabapentinoid for CNCP out of the enlisted 12 360 patients. The majority were in the 70-79 years age range. It was also noted that around 66% of patients were females. The QIP's first cycle is currently being implemented. This QIP addresses a pressing need to reduce the usage of DFMs. The interim results will guide the change model in the Grange Medical Centre GP surgery and inform scoping of relevant clinical questions to improve patient safety.

Government Direct-to-Consumer Education to Reduce Prescription Opioid Use

Direct-to-consumer education reduces chronic sedative use. The effectiveness of this approach for prescription opioids among patients with chronic noncancer pain remains untested. To evaluate the effectiveness of a government-led educational information brochure mailed to community-dwelling, long-term opioid consumers to reduce prescription opioid use compared with usual care. This cluster randomized clinical trial was conducted from July 2018 to January 2019 in Manitoba, Canada. All adults with long-term opioid prescriptions were enrolled (n = 4225). Participants were identified via the Manitoba Drug Program Information Network. Individuals receiving palliative care or with a diagnosis of cancer or dementia were excluded. Data were analyzed from July 2019 to March 2020. Participants were clustered according to their primary care clinic and randomized to the intervention (a codesigned direct-to-consumer educational brochure sent by mail) or usual care (comparator group). The main outcome was discontinuation of opioid prescriptions at the participant level after 6 months, ascertained by pharmacy drug claims. Secondary outcomes included dose reduction (in morphine milligram equivalents [MME]) and/or therapeutic switch. Reduction in opioid use was assessed using generalized estimating equations to account for clustering, with prespecified subgroup analyses by age and sex. Analysis was intention to treat. Of 4206 participants, 2409 (57.3%) were male; mean (SD) age was 60.0 (14.4) years. Mean (SD) baseline opioid use was comparable between groups (intervention, 157.7 [179.7] MME/d; control, 153.4 [181.8] MME/d). After 6 months, 235 of 2136 participants (11.0%) in 127 clusters in the intervention group no longer filled opioid prescriptions compared with 228 of 2070 (11.0%) in 124 clusters in the comparator group (difference, 0.0%; 95% CI, -1.9% to 1.9%). More participants in the intervention group than in the control group reduced their dose (1410 [66.0%] vs 1307 [63.1%]; difference, 2.8% [95% CI, 0.0%-5.7%]). Receipt of the brochure led to greater dose reductions for participants who were male (difference, 3.9%; 95% CI, 0.1%-7.7%), aged 18 to 64 years (difference, 3.7%; 95% CI, 0.2%-7.2%), or living in urban areas (difference, 5.9%; 95% CI, 1.9%-9.9%) compared with usual care. In this cluster randomized clinical trial, no significant difference in the prevalence of opioid cessation was observed after 6 months between the intervention and usual care groups; however, the intervention resulted in more adults reducing their opioid dose compared with usual care. ClinicalTrials.gov Identifier: NCT03400384.

The Legal Landscape for Opioid Treatment Agreements.

Opioid treatment agreements (OTAs) are documents that clinicians present to patients when prescribing opioids that describe the risks of opioids and specify requirements that patients must meet to receive their medication. Notwithstanding a lack of evidence that OTAs effectively mitigate opioids' risks, professional organizations recommend that they be implemented, and jurisdictions increasingly require them. We sought to identify the jurisdictions that require OTAs, how OTAs might affect the outcomes of lawsuits that arise when things go wrong, and instances in which the law permits flexibility for clinicians and health care institutions to adopt best practices. We surveyed the laws and regulations of all 50 states and the District of Columbia to identify which jurisdictions require the use of OTAs, the circumstances in which OTA use is mandatory, and the terms OTAs must include (if any). We also surveyed criminal and civil judicial decisions in which OTAs were discussed as evidence on which a court relied to make its decision to determine how OTA use influences litigation outcomes. Results show that a slight majority (27) of jurisdictions now require OTAs. With one exception, the jurisdictions' requirements for OTA use are triggered at least in part by long-term prescribing. There is otherwise substantial variation and flexibility within OTA requirements. Results also show that even in jurisdictions where OTA use is not required by statute or regulation, OTA use can inform courts' reasoning in lawsuits involving patients or clinicians. Sometimes, but not always, OTA use legally protects clinicians from liability. Our results show that OTA use is entwined with legal obligations in various ways. Clinicians and health care institutions should identify ways for OTAs to enhance clinician-patient relationships and patient care within the bounds of relevant legal requirements and risks.

Long-term benzodiazepine prescriptions in community psychiatry clinics.

Anecdotal evidence indicates that the prevalence of long-term benzodiazepine prescription is high and not in accordance with accepted prescribing guidelines. To determine the prevalence of long-term prescriptions of benzodiazepines and associations thereof in community psychiatry clinics. Of the 27 community psychiatry clinics, 5 were randomly selected. A descriptive, retrospective, and cross-sectional record review of files of 126 adult patients was conducted, to obtain sociodemographic and clinical characteristics. Descriptive statistics were presented as proportions and percentages. Fisher's exact test was used to determine any associations between long-term benzodiazepines use and demographic and clinical variables. Regression analyses were performed to determine the significance of any such associations. Approximately one out of every four patients were prescribed benzodiazepines. Most of the patients were males aged between 18 and 50 years, single and unemployed. The most common psychiatric diagnoses were bipolar disorders and psychotic disorders, and the majority had no comorbid medical illnesses or substance use. Ninety-three per cent of the patients were prescribed long-term (more than 180 days) benzodiazepines. There were no statistically significant associations between prescribing patterns and any sociodemographic and clinical characteristics (p > 0.05). This study found that nearly all the benzodiazepine prescriptions were long-term (over 180 days) and no statistically significant associations between this practice and any sociodemographic and clinical characteristics could be established. There is high prevalence rate of long-term benzodiazepine prescription in community psychiatry clinics, and as such clinical monitoring systems need to be established and enforced.

Electronic Real-Time Monitoring Reveals Limited Adherence to Long-Term Opioid Prescriptions in Pain Patients.

Pain management physicians are increasingly focused on limiting prescription opioid abuse, yet existing tools for monitoring adherence have limited accuracy. Medication event monitoring system (MEMS) is an emerging technology for tracking medication usage in real-time but has not been tested in chronic pain patients on long-term opioid regimens. We conducted a pilot clinical trial to investigate the utility of MEMS for monitoring opioid adherence and compared to traditional methods including self-report diaries, urine drug screen (UDS), and physicians' opinions. Opioid-maintained chronic pain patients were recruited from a pain management clinic. Participants (n=28) were randomly assigned to either receive MEMS bottles containing their opioid medication for a 90-day period or to continue using standard medication bottles. MEMS bottles were configured to record and timestamp all bottle openings and the number of pills that were removed from the bottle (via measurement of weight change). Participants who received MEMS demonstrated highly heterogenous dosing patterns, with a substantial number of patients rapidly removing excessive amounts of medication and/or "stockpiling" medication. By comparison, physicians rated all participants as either "totally compliant" or "mostly compliant". UDS results did not reveal any illicit drug use, but 25% of participants (n=7) tested negative for their prescribed opioid metabolite. MEMS data did not correlate with physician-rated adherence (P=0.24) and UDS results (P=0.77). MEMS data consistently revealed greater non-adherence than self-report data (P<0.001). These results highlight the limits in our understanding of naturalistic patterns of daily opioid use in chronic pain patients as well as support the use of MEMS for detecting potential misuse as compared to routine adherence monitoring methods. Future research directions include the need to determine how MEMS could be used to improve patient outcomes, minimize harm, and aid in clinical decision-making. This study was preregistered on ClinicalTrials.gov (NCT03752411).

Hospital initiation of opioids and long-term prescribing among older adults in primary care - a cohort study

Abstract Introduction The upwards trend in opioid prescribing poses concern for older adults given risks associated with prolonged opioid use.[1] With patients 65 years or older being predominantly prescribed stronger opioids, minimising duration of therapy is important to reduce falls, fracture and hospitalisation risk.[2] Studies assessing the associations between initial prescription attributes and duration of opioid use have yet to be conducted in an Irish setting. Aim This study aims to assess long-term opioid prescribing in opioid-naive patients initiated on opioid therapy in hospital, and patient and discharge prescription factors associated with long-term opioid prescribing. Methods This retrospective cohort study included approximately 40,000 patients aged ≥65 years from 44 GP practices during 2012-2018 in Ireland. Using GP record and hospital discharge data, individuals initiating an opioid at hospital discharge who were opioid naive (no opioid prescription in the previous 365 days) were identified. The primary analysis excluded cancer-related hospitalisations based on ICD-10 classification. Among non-cancer-related hospitalisations, Cox regression analysis assessed associations between patient and discharge prescription factors (opioid drug, duration, tapering instructions, as needed use specified) with the duration of opioid continuation post-discharge. Results Overall, 975 non-cancer-related opioid-naive patients were initiated on opioids at discharge (48.4% male, mean age 77.9 years). Of the 975 patients, 141 (14.5%) were prescribed 2 opioids and 10 (1.0%) were prescribed 3 opioids. Forty-one percent (n=403) continued opioid therapy following discharge, and 8.2% (n=80) were continually prescribed for &amp;gt;365 days. Of those who discontinued therapy within 365 days, the mean time to discontinuation was 106 days. Initial prescription factors including morphine (HR 0.43, 95%CI 0.23-0.80); duration ≥14 days (HR 0.58, 95%CI 0.39-0.86); and no duration stated (HR 0.46, 95%CI 0.32-0.66) (Figure 1) had statistically significant associations with long-term opioid therapy among those with non-cancer hospitalisations, adjusting for other factors. Conclusion Opioid type and initial prescription characteristics such as duration were associated with longer duration of use. Although limited by lack of information on the specific indication for opioid use, this study is the first in the Irish setting to evaluate the prescribing factors which may be modified to reduce their contribution to prolonged opioid therapy post-discharge.

Changes in analgesic prescribing among older adults hospitalised for osteoarthritis or joint replacements

Abstract Introduction Osteoarthritis is a chronic, progressive joint disease, associated with frequent pain, and functional decline. The primary risk factor for developing osteoarthritis is advanced age. Older patients are more susceptible to the adverse effects of commonly prescribed analgesics such as opioids and non-steroidal anti-inflammatory drugs (NSAIDs), owing to a greater prevalence of comorbidities and age-related changes in this cohort. The analgesic burden and prescribing trends in this cohort are largely unknown in the Irish context despite their increased susceptibility to adverse effects. Aim This study aims to evaluate analgesic prescribing patterns before and after an osteoarthritis or joint arthroplasty related hospital admission in patients aged ≥65 years and to identify factors associated with long-term prescribing of opioids and oral NSAIDs post-discharge. Methods This was an observational study of older adults with an osteoarthritis or joint arthroplasty hospitalisation. Data were collected for a larger study from 44 general practices in Ireland from 2012-2018 and included general practice records (12 months pre/post-index hospitalisation) and hospital discharge summaries, which was extracted as anonymous data from the practice software system. The analysis described prevalence of use of analgesics in the 12 months pre and post their hospitalisation. To assess long-term prescribing, multivariable analysis assessed discharge prescription and patient characteristics associated with opioid and oral NSAID use 3-12 months post-discharge. Results Overall, 738 individuals were included (52.9% female, mean age 78.1 years). Compared to 12 months pre-hospitalisation, patients were less likely to be prescribed a weak opioid or oral NSAID from discharge to 3 months post-discharge, or in the 3-12 months post-discharge. For strong opioids, prescribing was significantly less likely in the 3-12 months post-discharge compared to pre-discharge (odds ratio (OR) 0.54, 95%CI 0.40-0.74). Female sex (OR 1.61, 95%CI 1.10-2.36), strong opioid prescribing at discharge (OR 2.47, 95%CI 1.56-3.90) and pregabalin discharge prescribing (OR 2.21, 95%CI 1.12-4.33) were significantly associated with long-term strong opioid prescribing 3-12 months post-discharge. For oral NSAID prescribing, lower age (OR 0.97, 95%CI 0.95-1.00), female sex (OR 1.56, 95%CI 1.08-2.25), and discharge prescribing of strong opioids (OR 1.94, 95%CI 1.23-3.04) were significantly associated. Conclusion The use of opioids and oral NSAIDs is typically reduced for patients post-discharge from an osteoarthritis or joint arthroplasty hospitalisation. Female sex and strong opioids at discharge are associated with the prescribing of strong opioids and oral NSAIDs. Although our study was limited by use of prescription records which may not accurately represent what was dispensed or utilised by patients, it is the first to examine changing patterns of analgesic prescribing among osteoarthritis/joint arthroplasty patients. This contributes knowledge on modifiable characteristics which could reduce long-term use of these medications where appropriate.

Implementation of Opioid Safety Efforts: Influence of Academic Detailing on Adverse Outcomes Among Patients in the Veterans Health Administration.

The Veterans Health Administration (VA) implemented academic detailing (AD) to support safer opioid prescribing and overdose prevention initiatives. Patient-level data were extracted monthly from VA's electronic health record to evaluate whether AD implementation was associated with changes in all-cause mortality, opioid poisoning inpatient admissions, and opioid poisoning emergency department (ED) visits in an observational cohort of patients with long-term opioid prescriptions (≥45-day supply of opioids 6 months prior to a given month with ≤15 days between prescriptions). A single-group interrupted time series analysis using segmented logistic regression for mortality and Poisson regression for counts of inpatient admissions and ED visits was used to identify whether the level and slope of these outcomes changed in response to AD implementation. Among 955 376 unique patients (19 431 241 person-months), there were 53 369 deaths (29 025 pre-AD; 24 344 post-AD), 1927 opioid poisoning inpatient admissions (610 pre-AD; 1317 post-AD), and 408 opioid poisoning ED visits (207 pre-AD; 201 post-AD). Immediately after AD implementation, there was a 5.8% reduction in the odds of all-cause mortality (95% confidence interval [CI]: 0.897, 0.990). However, patients had a significantly increased incidence rate of inpatient admissions for opioid poisoning immediately after AD implementation (incidence rate ratio = 1.523; 95% CI: 1.118, 2.077). No significant differences in ED visits for opioid poisoning were observed. AD was associated with decreased all-cause mortality but increased inpatient hospitalization for opioid poisoning among patients prescribed long-term opioids. Mechanisms via which AD's efforts influenced opioid-related outcomes should be explored.

Treatment Failure and Long-Term Prescription Risk for Guideline-Recommended Hypnotics in Japan

Although insomnia guidelines recommend the use of several individual hypnotics, the most useful hypnotic for treating insomnia in a clinical setting remains unclear. To determine which guideline-recommended hypnotics have lower risks of monotherapy failure and which hypnotics have a higher risk of long-term prescription for insomnia treatment. This retrospective observational cohort study used data from the Japan Medical Data Center Claims Database from April 1, 2005, to March 31, 2021. Participants included adults whose first prescribed pharmaceutical treatment for insomnia was guideline-recommended hypnotic monotherapy. Data were analyzed from December 24, 2022, to September 26, 2023. Suvorexant, ramelteon, eszopiclone, zolpidem, and triazolam monotherapy. The primary outcome was monotherapy failure, defined as a change in hypnotic or having an additional hypnotic prescribed for insomnia within 6 months of the first prescription of a guideline-recommended hypnotic monotherapy. The secondary outcome was monotherapy discontinuation, defined as no prescription of any hypnotic for 2 consecutive months within 6 months after prescribing a guideline-recommended hypnotic in patients for whom monotherapy did not fail. Monotherapy failure and discontinuation were compared using Cox proportional hazards and logistic regression models, respectively. The study included 239 568 adults (median age, 45 [IQR, 34-55] years; 50.2% women) whose first prescription for insomnia was guideline-recommended hypnotic monotherapy. During the 6-month follow-up period, 24 778 patients (10.3%) experienced failure of monotherapy with a guideline-recommended hypnotic. In comparison with eszopiclone, there were more cases of monotherapy failure for ramelteon (adjusted hazard ratio [AHR], 1.23 [95% CI], 1.17-1.30; P < .001), fewer cases for zolpidem (AHR, 0.84 [95% CI, 0.81-0.87]; P < .001) and triazolam (AHR, 0.82 [95% CI, 0.78-0.87]; P < .001), and no significant difference between suvorexant and eszopiclone. Among those without monotherapy failure, monotherapy was discontinued in 84.6% of patients, with more discontinuations for ramelteon (adjusted odds ratio [AOR], 1.31 [95% CI, 1.24-1.40]; P < .001) and suvorexant (AOR, 1.20 [95% CI, 1.15-1.26]; P < .001) than for eszopiclone and no significant difference between zolpidem or triazolam and eszopiclone. Due to uncontrolled confounding factors in this cohort study, no conclusions regarding the pharmacologic properties of guideline-recommended hypnotics can be drawn based on these results. Further studies accounting for confounding factors, including diagnoses of chronic vs acute insomnia disorder, insomnia and psychiatric symptom severity, and physician attitudes toward hypnotic prescription, are needed.

Barriers and Facilitators Affecting Long-Term Antibiotic Prescriptions for Acne Treatment

Dermatologists prescribe more oral antibiotics per clinician than clinicians in any other specialty. Despite clinical guidelines that recommend limitation of long-term oral antibiotic treatments for acne to less than 3 months, there is little evidence to guide the design and implementation of an antibiotic stewardship program in clinical practice. To identify salient barriers and facilitators to long-term antibiotic prescriptions for acne treatment. This qualitative study assessed data collected from stakeholders (including dermatologists, infectious disease physicians, dermatology resident physicians, and nonphysician clinicians) via an online survey and semistructured video interviews between March and August 2021. Data analyses were performed from August 12, 2021, to January 20, 2024. Online survey and qualitative video interviews developed with the Theoretical Domains Framework. Thematic analyses were used to identify salient themes on barriers and facilitators to long-term antibiotic prescriptions for acne treatment. Among 30 participants (14 [47%] males and 16 [53%] females) who completed the study requirements and were included in the analysis, knowledge of antibiotic guideline recommendations was high and antibiotic stewardship was believed to be a professional responsibility. Five salient themes were to be affecting long-term antibiotic prescriptions: perceived lack of evidence to justify change in dermatologic practice, difficulty navigating patient demands and satisfaction, discomfort with discussing contraception, iPLEDGE-related barriers, and the absence of an effective system to measure progress on antibiotic stewardship. The findings of this qualitative study indicate that multiple salient factors affect long-term antibiotic prescribing practices for acne treatment. These factors should be considered in the design and implementation of any future outpatient antibiotic stewardship program for clinical dermatology.

Influence of the long-term postbiotics prescription on cardiometabolic risk factors in patients with coronary

The aim of this research was to evaluate the influence of long-term postbiotics prescription on CardioMetabolic Risk Factors (CMRF) in patients with Coronary Artery Disease (CAD) and Atrial Fibrillation (AF). 124 patients with CAD and AF paroxysm patients were divided by stratified randomization 1:3 into two groups: I (31 patients) and II (93 patients). Stratification was done according to the patient's age, gender, body mass index, and Total Cholesterol (TC). All patients received Standard Therapy (ST), according to the latest European Society of Cardiology guidelines: β-blockers, HMG-CoA-inhibitors (statins), anticoagulants, and, if necessary, angiotensin-converting enzyme inhibitors or angiotensin-II receptor blockers, calcium antagonists, diuretics, and/or antiarrhythmics. The I group patients’ received ST and postbiotic prescription during 6 months: rebamipide (2-(4-chlorobenzolamino)-3-[2(1H))-quinolon-4-yl] propionic acid) (100 mg 3 times a day) and glycine (100 mg 3 times a day). The II group patients received only ST. All patients were examined two times: during the initial investigation and after 6 months of treatment. After treatment in I group patients’ a significant decrease in TC (by 10.00%), low density lipoproteins (by 19.50%), Apolipoprotein B (by 12.92%), Interleucin-6 (by 12.40%), C-reactive protein (by 15.89%), TriMethylAmine (TMA) (by 19.32%), TriMethylAmine-N-Oxide (TMAO) (by 27.24%) was found (p&lt;0.05) versus II group patients. After treatment all patients had significant improvement in CMRF (p&lt;0.05): TC (by 44.01%), low density lipoproteins (by 52.90%), Interleucin-6 (by 27.52%), C-reactive protein (by 20.13%), TMA (by 14.66%), TMAO (by 33.91%), and significant increase in TMA/TMAO (by 23.45%), but I group got better values. In conclusion, long-term (6 months) postbiotics (propionic acid and glycine) prescription has a marked positive influence on CMRF in patients with CAD and AF. Keywords: glycine, propionic acid, arrhythmia, cardiovascular disorders, dyslipidemia, inflammation.

Relationships of Self-reported Opioid Use and Misuse and Pain Severity With Probable Major Depression Among Participants With Spinal Cord Injury

ObjectivesTo examine the relations of pain intensity, opioid use, and opioid misuse with depressive symptom severity and probable major depression (PMD) among participants with spinal cord injuries (SCI), controlling for demographic, injury, and socioeconomic characteristics. Study DesignCohort study. SettingMedical University in the Southeastern United States (US). ParticipantsParticipants (N=918) were identified from 1 of 2 sources including a specialty hospital and a state-based surveillance system in the Southeastern US. Participants were a minimum of 18 years old at enrollment and had SCI with non-complete recovery. Participants were on average 57.5 years old at the time of the study and an average of 24.4 years post SCI onset. InterventionsNot applicable. Main Outcome MeasuresParticipants completed a self-report assessment that included frequency of prescription opioid use and misuse, based on the National Survey on Drug Use and Health (NSDUH), and the PHQ – 9 to measure depressive symptom severity and PMD. ResultsOpioid use, opioid misuse, and pain intensity were related to elevated depressive symptom severity and higher odds of PMD. Non-Hispanic Blacks had fewer depressive symptoms and lower odds of PMD, as did those with higher incomes. Veterans had lower risk of PMD, whereas ambulatory participants had a higher risk of PMD. Age at SCI onset had a mixed pattern of significance, whereas years of education and years since injury were not significant. ConclusionsThe relation between pain intensity with depressive symptom severity and PMD was profound, consistent with the biopsychosocial model of pain. The greater risk of PMD and higher depressive symptom severity among those using opioids and misusing opioids raises further concern about long-term prescription opioid use. Alternative treatments are needed.

Pharmacokinetics-Informed Neural Network for Predicting Opioid Administration Moments with Wearable Sensors.

Long-term and high-dose prescription opioid use places individuals at risk for opioid misuse, opioid use disorder (OUD), and overdose. Existing methods for monitoring opioid use and detecting misuse rely on self-reports, which are prone to reporting bias, and toxicology testing, which may be infeasible in outpatient settings. Although wearable technologies for monitoring day-to-day health metrics have gained significant traction in recent years due to their ease of use, flexibility, and advancements in sensor technology, their application within the opioid use space remains underexplored. In the current work, we demonstrate that oral opioid administrations can be detected using physiological signals collected from a wrist sensor. More importantly, we show that models informed by opioid pharmacokinetics increase reliability in predicting the timing of opioid administrations. Forty-two individuals who were prescribed opioids as a part of their medical treatment in-hospital and after discharge were enrolled. Participants wore a wrist sensor throughout the study, while opioid administrations were tracked using electronic medical records and self-reports. We collected 1,983 hours of sensor data containing 187 opioid administrations from the inpatient setting and 927 hours of sensor data containing 40 opioid administrations from the outpatient setting. We demonstrate that a self-supervised pre-trained model, capable of learning the canonical time series of plasma concentration of the drug derived from opioid pharmacokinetics, can reliably detect opioid administration in both settings. Our work suggests the potential of pharmacokinetic-informed, data-driven models to objectively detect opioid use in daily life.

Naldemedine and Magnesium Oxide as First-Line Medications for Opioid-Induced Constipation: A Comparative Database Study in Japanese Patients With Cancer Pain.

Introduction Naldemedine and magnesium oxide are common first-line early laxative medications used in the real-world scenario in Japan, for patients with cancer pain who receive opioid prescriptions, as per a nationwide hospital claims database study. However, the real-world prescription patterns and associated outcomes are unknown. Methods In this retrospective, cohort study using the Medical Data Vision (MDV) database (January 2018 to December 2020), data were collected from eligible patients (who had a long-term prescription of strong opioids, for >30 days) in Japan with naldemedine or magnesium oxide as the first-line laxative prescription, for a long-term opioid prescription for cancer pain with ≥6 months post-opioid observation period. A laxative prescription within three days after the opioid prescription date was termed an "early" prescription. The composite incidence of dose increase or addition/change of laxatives at three months after the start of the opioid prescription was the primary endpoint after adjusting baseline characteristics between the treatment arms by propensity score matching. Results After propensity score matching, 1717 and 544 patients who were prescribed naldemedine and magnesium oxide each were included in the early prescription and non-early prescription groups, respectively. Even after matching, the incidence of death was not adjusted enough and was significantly higher in the naldemedine arm than in the magnesium oxide arm in the non-early group but comparable in the early group. The incidence of addition, change, or dose increase was significantly higher in the naldemedine arm than in the magnesium oxide arm of the early prescription group (hazard ratio (95% confidence interval), 1.08 (1.00, 1.17); p=0.0402); the incidence was comparable between the arms of the non-early group. Conclusion These findings may provide valuable insights into real-world clinical treatment patterns and preliminary evidence for the selection of first-line medications to mitigate opioid-induced constipation in Japanese patients with cancer pain.

Identifying provider, patient and practice factors that shape long-term opioid prescribing for cancer pain: a qualitative study of American and Australian providers

IntroductionPrescribing long-term opioid therapy is a nuanced clinical decision requiring careful consideration of risks versus benefits. Our goal is to understand patient, provider and context factors that impact the decision...

The status of drug evaluation in older adults in the United Kingdom: Bridging the representation gap.

Older adults are persistently underrepresented in clinical drug trials worldwide, despite increasing multiple long-term conditions and significant prescribing in this demographic. We discuss systemic challenges such as the exclusion of people with comorbid conditions and the lack of assessment for comorbidities as modifiers of treatment effects and highlight the rising trend of polypharmacy, especially among the oldest age groups, which is linked to a significant percentage of unplanned hospitalizations and medication errors. The consequences of these trends prompted the United Kingdom National Overprescribing review, culminating in a set of recommendations for drug development tailored to older adults. Building on this, two critical reports released in April 2023 by the International Longevity Centre (ILC) and the Nuffield Council on Bioethics (NCOB) are discussed. These reports emphasize the importance of diversity and inclusion in clinical trials, advocating for ethical frameworks and methodologies that cater to the complex needs of older adults. The development of inclusive criteria, innovative statistical methodologies, and the integration of patient-reported outcomes are needed to address the persistent barriers to older adult participation in research, suggesting that pragmatic trials, exemplified by the UK's RECOVERY trial during the COVID-19 pandemic, could pave the way for more inclusive research practices.

Characteristics of patients with non-cancer pain and long-term prescription opioid use who have used medical versus recreational marijuana

ObjectiveMarijuana use is increasingly common among patients with chronic non-cancer pain (CNCP) and long-term opioid therapy (LTOT). We determined if lifetime recreational and medical marijuana use were associated with more frequent and higher dose prescription opioid use.DesignCross-sectionalSubjectsEligible patients (n=1,037), who had a new period of prescription opioid use lasting 30-90 days, were recruited from two midwestern health care systems to a study of long-term prescription opioid use and mental health outcomes. The present cross-sectional analyses uses baseline data from this on-going cohort study.MethodsPrimary exposures were participant reported lifetime recreational and medical marijuana use versus no lifetime marijuana use. Prescription opioid characteristics included daily versus non-daily opioid use and ≥50 morphine milligram equivalent (MME) dose per day vs. <50 MME. Multivariate, logistic regression models estimated the association between lifetime recreational and medical marijuana use vs. no use and odds of daily and higher dose prescription opioid use, before and after adjusting for confounding.ResultsThe sample was an average of 54.9 (SD±11.3) years of age, 57.3% identified as female gender, 75.2% identified as White, and 22.5% identified as Black race. Among all participants, 44.4% were never marijuana users, 21.3% were recreational only, 7.7% medical only and 26.6% were both recreational and medical marijuana users. After controlling for all confounders, lifetime recreational marijuana use, as compared to no use, was significantly associated with increased odds of daily prescription opioid use (OR=1.61; 95%CI:1.02-2.54). There was no association between lifetime recreational or medical marijuana use and daily opioid dose.ConclusionLifetime medical marijuana use is not linked to current opioid dose, but lifetime recreational use is associated with more than a 60% odds of being a daily prescription opioid user. Screening for lifetime recreational marijuana use may identify patients with chronic pain who are vulnerable to daily opioid use which increases risk for adverse opioid outcomes. Prospective data is needed to determine how marijuana use influences the course of LTOT and vice versa.

Primary and Specialty Care Trainees' Perceptions About Proton Pump Inhibitor Use.

Proton pump inhibitors (PPIs) are widely prescribed with proven efficacy in many indications, yet longstanding controversy about potential adverse events persists. We aimed to acquire knowledge about perceptions of outpatient PPI long-term prescribing (≥8 wk) among primary and specialty care trainees at 2 Canadian Universities. Family medicine, internal medicine, and gastroenterology trainees completed a web-based survey that included 20 clinical scenarios assessing trainee knowledge about PPI efficacy. Contextual PPI prescribing decisions were also elicited, balancing possible PPI indications versus side effects. Management strategies were compared between junior and senior trainees, as well as across training programs. Over a 4-month period,163 trainees (age <26 y: 12%; age 26 to 45: 88%; 59% females) participated in the survey (family medicine: 51%, internal medicine: 44%, and gastroenterology: 5%); 83% were considered junior residents. Only 42% had received formal education on prescribing PPI long-term. Overall, 93% believed they would benefit from such teaching, with 98% stating they would follow related guidelines. No between-group differences were noted in knowledge of appropriate PPI indications nor possible side effects when comparing juniors to seniors, or among different specialties. Across different management scenarios, inappropriate PPI discontinuation was chosen by 14.3% to 67.2%, whereas inappropriate PPI continuation was reported in up to 57%. Trainee seniority and specialty did not differ in appropriate deprescribing rates. Training level and primary versus specialty care settings are associated with frequent inappropriate PPI prescribing and deprescribing. These findings highlight the need for and may inform future educational programs on PPI usage.

A patient activation intervention in primary care for patients with chronic pain on long term opioid therapy: results from a randomized control trial

BackgroundGiven significant risks associated with long-term prescription opioid use, there is a need for non-pharmacological interventions for treating chronic pain. Activating patients to manage chronic pain has the potential to improve health outcomes. The ACTIVATE study was designed to evaluate the effectiveness of a 4-session patient activation intervention in primary care for patients on long-term opioid therapy.MethodsThe two-arm, pragmatic, randomized trial was conducted in two primary care clinics in an integrated health system from June 2015—August 2018. Consenting participants were randomized to the intervention (n = 189) or usual care (n = 187). Participants completed online and interviewer-administered surveys at baseline, 6- and 12- months follow-up. Prescription opioid use was extracted from the EHR. The primary outcome was patient activation assessed by the Patient Activation Measure (PAM). Secondary outcomes included mood, function, overall health, non-pharmacologic pain management strategies, and patient portal use. We conducted a repeated measure analysis and reported between-group differences at 12 months.ResultsAt 12 months, the intervention and usual care arms had similar PAM scores. However, compared to usual care at 12 months, the intervention arm demonstrated: less moderate/severe depression (odds ratio [OR] = 0.40, 95%CI 0.18–0.87); higher overall health (OR = 3.14, 95%CI 1.64–6.01); greater use of the patient portal’s health/wellness resources (OR = 2.50, 95%CI 1.42–4.40) and lab/immunization history (OR = 2.70, 95%CI 1.29–5.65); and greater use of meditation (OR = 2.72; 95%CI 1.61–4.58) and exercise/physical therapy (OR = 2.24, 95%CI 1.29–3.88). At 12 months, the intervention arm had a higher physical health measure (mean difference 1.63; 95%CI: 0.27–2.98).ConclusionThis trial evaluated the effectiveness of a primary care intervention in improving patient activation and patient-reported outcomes among adults with chronic pain on long-term opioid therapy. Despite a lack of improvement in patient activation, a brief intervention in primary care can improve outcomes such as depression, overall health, non-pharmacologic pain management, and engagement with the health system.Trial RegistrationThe study was registered on 10/27/14 on ClinicalTrials.gov (NCT02290223).