Risultati per: Short Acting Opioid

In this issue of JAMA Internal Medicine, Suarez et al studied a population-based cohort of publicly insured pregnant individuals receiving methadone or buprenorphine for opioid use disorder (OUD) in the US. Their study adds considerably to the sparse literature on rates of congenital malformations among newborns with in utero exposure to buprenorphine and methadone. The authors found a 1% absolute risk reduction of congenital malformations from buprenorphine exposure compared with methadone. First-trimester exposure to methadone was associated with higher odds of cardiac malformations, oral clefts, and clubfoot than buprenorphine. In secondary analyses, they found that buprenorphine exposure was associated with higher odds of gastrointestinal-specific malformation, mostly pyloric stenosis.

National practice groups and decades of research strongly support treating opioid use disorder (OUD) as a chronic illness and specifically call for the use of evidence-based medications to treat OUD throughout pregnancy and beyond. The criterion-standard medications for OUD (MOUD), including during pregnancy, are buprenorphine (approved by the US Food and Drug Administration in 2002) and methadone (approved by the US Food and Drug Administration to treat OUD in 1972). While evidence suggests that pregnancy may represent a specific window of opportunity to engage individuals in MOUD and that MOUD leads to better outcomes for the maternal-infant dyad, fewer than 1 in 4 individuals with OUD receive treatment in any given month of pregnancy.

Introduction
In opioid therapy for cancer pain, opioid-induced nausea and vomiting (OINV) occur in 20%–40% of patients during initial opioid treatment or increasing opioid doses. OINV result in failure to achieve pain relief due to poor opioid adherence. Therefore, antiemetics are used to prevent OINV, but their efficacy and safety in this context have not yet been fully elucidated. Olanzapine is a promising antiemetic for the prophylaxis of chemotherapy-induced nausea and vomiting.

Methods and analysis
This single-arm, single-centre exploratory study will evaluate the prophylactic antiemetic efficacy and safety of 5 mg olanzapine in patients with cancer pain who are withholding initial regular opioid therapy. Thirty-five patients will be enrolled. The primary endpoint is the proportion of patients achieving complete control (CC) of OINV during 5 days of opioid treatment. CC was defined as the absence of emetic episodes, no need for rescue medication to treat nausea, and minimal or no nausea (3 or less on an 11-point categorical scale). Secondary endpoints include the complete response, defined as no emetic episodes and no use of rescue medication during the overall assessment period, the time from opioid initiation to first emetic episode, the time from opioid initiation to first rescue antiemetic administration, and adverse events graded by Patient-Reported Outcome (PRO) Common Terminology Criteria for Adverse Events (CTCAE) version 1.0 and CTCAE version 5.0.

Ethics and dissemination
This study protocol was approved by National Cancer Center Hospital Certified Review Board. The results will be used as preliminary data to conduct a validation study.

Trial registration number
Japan Registry of Clinical Trials (jRCT) jRCTs031220008.

Opioid exposure is associated with risk for serious falls in all age groups, but the oldest patients have the most risk.

Purpose
The Canadian Addiction Treatment Centre (CATC) cohort was established during a period of increased provision of opioid agonist treatment (OAT), to study patient outcomes and trends related to the treatment of opioid use disorder (OUD) in Canada. The CATC cohort’s strengths lie in its unique physician network, shared care model and event-level data, making it valuable for validation and integration studies. The CATC cohort is a valuable resource for examining OAT outcomes, providing insights into substance use trends and the impact of service-level factors.

Participants
The CATC cohort comprises 32 246 people who received OAT prescriptions between April 2014 and February 2021, with ongoing tri-annual updates planned until 2027. The cohort includes data from all CATC clinics’ electronic medical records and includes demographic information and OAT clinical indicators.

Findings to date
This cohort profile describes the demographic and clinical characteristics of patients being treated in a large OAT physician network. As well, we report the longitudinal OAT retention by treatment type during a time of increasing exposure to a contaminated dangerous drug supply. Notable findings also include retention differences between methadone (32% of patients at 1 year) and buprenorphine (20% at 1 year). Previously published research from this cohort indicated that patient-level factors associated with retention include geographic location, concurrent substance use and prior treatment attempts. Service-level factors such as telemedicine delivery and frequency of urine drug screenings also influence retention. Additionally, the cohort identified rising OAT participation and a substantial increase in fentanyl use during the COVID-19 pandemic.

Future plans
Future research objectives are the longitudinal evaluation of retention and flexible modelling techniques that account for the changes as patients are treated with OAT. Furthermore, future research aims are the use of conditional models, and linkage with provincial-level administrative datasets.

This study assesses the proportion of US substance use and mental health care facilities that offered any medications for opioid use disorder and, specifically, long-acting injectable buprenorphine in 2021.

Congenital malformations were slightly less common with buprenorphine than with methadone.

Introduction
People who are dependent on opioids experience acute pain similar to other individuals. However, treating acute pain in these patients renders unique challenges such as opioid-induced hyperalgesia, opioid tolerance, withdrawal and stigma from healthcare providers. Thus, it is crucial to identify effective strategies for treating acute pain in this population and to highlight gaps in knowledge to create a high standard of care. The main objective of the proposed scoping review is to identify current strategies for treating the acute pain in individuals with opioid dependence or use disorder.

Methods and analysis
MEDLINE via the PubMed interface, Embase and Cochrane Central, Web of Science: Conference Proceedings Citation Index and Google Scholar will be searched. Forward and backward citation searching of the final included studies will also be conducted. Two independent reviewers will screen the titles and abstracts of sources, review and assess relevant full-text studies and extract data. Data will be presented in a diagram and will contribute to a qualitative thematic analysis.

Ethics and dissemination
Data will be gathered from publicly accessible sources, so ethics approval is not necessary. The results will be disseminated through a peer-reviewed journal and reported at conferences related to addiction medicine.

Trial registration number
10.17605/OSF.IO/BG6SJ.

Objective
Management of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) improves lung function and health status and reduces COPD exacerbation risk versus monotherapy. This study described treatment use, healthcare resource utilisation (HCRU), healthcare costs and outcomes following initiation of single-device ICS/LABA as initial maintenance therapy (IMT).

Design
Retrospective cohort study.

Setting
Primary care, England.

Data sources
Linked data from the Clinical Practice Research Datalink Aurum and Hospital Episode Statistics datasets.

Participants
Patients with COPD and ≥1 single-device ICS/LABA prescription between July 2015 and December 2018 were included.

Primary and secondary outcome measures
Treatment pathways, COPD-related HCRU and healthcare costs, COPD exacerbations, time to triple therapy, medication adherence (proportion of days covered ≥80%) and indexed treatment time to discontinuation. Data for patients without prior maintenance therapy history (IMT users) and non-triple users were assessed over a 12-month follow-up period.

Results
Of 13 451 new ICS/LABA users, 5162 were IMT users (budesonide/formoterol, n=1056; beclomethasone dipropionate/formoterol, n=2427; other ICS/LABA, n=1679), for whom at 3 and 12 months post-index, 45.6% and 39.4% were still receiving any ICS/LABA. At >6 to ≤12 months, the proportion of IMT users with ≥1 outpatient visit (10.1%) and proportion with ≥1 inpatient stay (12.6%) had increased from those at 3 months (9.0% and 7.4%, respectively). Inpatient stays contributed most to total COPD-related healthcare costs. For non-triple IMT users, at 3 and 12 months post-index, 4.5% and 13.7% had ≥1 moderate-to-severe COPD exacerbation. Time to triple therapy initiation and time to discontinuation of index medication ranged from 45.9 to 50.2 months and 2.3 to 2.8 months between treatments. Adherence was low across all time points (21.5–27.6%). Results were similar across indexed therapies.

Conclusions
In the year following treatment initiation, ICS/LABA adherence was poor and many patients discontinued or switched therapies, suggesting that more consideration and optimisation of treatment is required in England for patients initiating single-device ICS/LABA therapy.

Introduction
The preliminary result of the TORCH trial has shown a promising complete response (CR) for managing locally advanced rectal cancer with neoadjuvant short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor. For locally advanced colon cancer (LACC) with bulky nodal disease and/or clinically T4, neoadjuvant chemotherapy followed by colectomy with en bloc removal of regional lymph nodes is the suggested treatment. However, the CR rate is less than 5%. TORCH-C will aim to investigate neoadjuvant SCRT combined with chemotherapy and PD-1 inhibitor in LACC.

Methods and analysis
TORCH-C is a randomised, prospective, multicentre, double-arm, open, phase II trial of SCRT combined with chemotherapy and immunotherapy in LACC with microsatellite stable (MSS) patients and cT4 or bulky nodes. Eligible patients will be identified by the multidisciplinary team. 120 patients will be randomised 1:1 to the intervention or control arm. The patients in the control arm will receive four cycles of capecitabine plus oxaliplatin (CAPOX). The patients in the intervention arm will receive SCRT, followed by four cycles of CAPOX and PD-1 inhibitor (serplulimab). Both arms will receive curative surgery, followed by four cycles of CAPOX. The primary endpoint is pathological complete regression.
TORCH-C (TORCH-colon) trial aims to investigate whether the combination of immunotherapy and chemoradiotherapy improves the treatment effect in LACC with MSS. TORCH-C will establish the TORCH platform, a key part of our long-term strategy to develop neoadjuvant treatment for colorectal cancer.

Ethics and dissemination
This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (approval number: 2211265-12).

Trial registration number
NCT05732493

Stroke, Volume 55, Issue Suppl_1, Page ATP230-ATP230, February 1, 2024. Introduction:Atrial fibrillation (AF) and cancer are both independently associated with worse outcomes in patients with acute ischemic stroke. Few studies have evaluated the impact of AF on outcomes of cancer-related stroke. We aimed to determine if AF is associated with worse short-term outcomes in patients with stroke and comorbid cancer.Methods:Using the 2016-2019 National Inpatient Sample, we identified all hospitalizations with diagnosis codes for cancer and ischemic stroke. The primary exposure was a diagnosis of AF. The primary outcome was in-hospital mortality. The secondary outcomes were length-of-stay and discharge other than to home. We used multivariable logistic and linear regression models, as appropriate, adjusted for age, gender, race-ethnicity, and the Charlson Comorbidity Index, to examine the association between AF and study outcomes.Results:Among 150,200 hospitalizations with diagnoses of cancer and ischemic stroke (mean age 72 years, 53% male), 40,084 (26.7%) included comorbid AF. Compared to hospitalizations without AF, hospitalizations with AF had higher rates of in-hospital mortality (14.8% vs 12.1%, p

Stroke, Volume 55, Issue Suppl_1, Page ATMP35-ATMP35, February 1, 2024. Objective:Stroke disrupts inhibitory and excitatory networks in the brain. To develop better therapies, we need to understand the role of inhibitory and excitatory systems. Paired-pulse transcranial magnetic stimulation (ppTMS) allows for evaluation of these inhibitory and excitatory systems. Our objective was to explore the relationship between Short Interval Intracortical Inhibition (SICI) and Intracortical Facilitation (ICF) ppTMS measures for tibialis anterior (TA) and measures of lower limb motor function in chronic stroke.Methods:Lower limb motor function was evaluated with Fugl-Meyer for Lower Limb (FM), gait speed (max and preferred), Timed-up-and-go (TUG), Functional Gait Assessment (FGA) and Gait Assessment and Intervention Tool (GAIT). SICI was collected with interstimulus interval of 2ms and ICF with 10ms. The conditioning stimulus was 90% and test stimulus was 120% of active motor threshold. Motor evoked potentials (MEPs) were collected for both paretic or non-paretic TAs while volitionally activated to 20% of maximum effort. SICI and ICF were calculated as percent of test stimulus (TS) amplitude. Analysis included descriptive statistics and linear models controlling for age, months post-stroke, and gender. TUG test time was log-transformed.Results:Study participants (n=34) were 66±8 years old, 4.9±4 years after stroke and 76% male. Mean±SD FM was 25.1±3.7 and preferred gait speed was 0.52±0.30 m/s. Relative to TS amplitude, SICI was 107±27% and ICF was 175±71% for paretic leg and, for non-paretic leg, SICI was 108±42% and ICF was 159±66%. For paretic leg after controlling for ICF, a 10% lower SICI was associated with the following: 0.89 point better FM (95% CI: 0.37-1.42), 14% better TUG (95% CI: 3-23%), 0.08 m/s faster max speed (95% CI: 0.02-0.14), and 0.05 m/s faster preferred walking speed (95% CI: 0.01-0.10). For non-paretic limb, a 10% lower SICI was associated with a 0.43 point better FGA (95% CI: 0.11-0.76) while a 10% lower ICF was associated with a 0.73 point better GAIT (95% CI: 0.37-1.10).Conclusion:Greater inhibition with paired pulse of both paretic and non-paretic limbs was predictive better motor abilities. These findings are related to previous work and warrant future investigations.

Stroke, Volume 55, Issue Suppl_1, Page ATP185-ATP185, February 1, 2024. Introduction:The Resolute Onyx stent has shown promise as an effective treatment for symptomatic intracranial atherosclerotic disease (sICAD), with positive clinical outcomes and low procedural complication rates. However, previous studies were limited by small sample sizes and lacked long-term follow-up.Methods:In this retrospective analysis, we examined patients who underwent Resolute Onyx stent placement for sICAD. Primary outcomes included stroke, intracerebral hemorrhage (ICH), and mortality rates at 1-, 6-, 12-, and 18-month follow-ups, and in-stent restenosis. Multivariable logistic regression identified predictors of stroke and mortality. Subgroup analyses assessed patients who underwent stenting at least 8 days after the qualifying event to ensure comparability with WEAVE registry data.Results:Our study included 77 patients with 84 procedures. The mean age was 61.9±13.0, with 35% being female. The median time from qualifying event to procedure was 5 days (IQR: 2-11). Among adherent patients, no disease-related deaths occurred after the first month. However, one ICH and two strokes occurred within 6 and 12 months, respectively. Comparison of WEAVE-matched and non-matched patients revealed no significant difference in complications during short- and long-term follow-up. Postprocedural complications within 72 hours were

Stroke, Volume 55, Issue Suppl_1, Page ATP208-ATP208, February 1, 2024. Background:The aging of the population is associated with an increasing number of stroke patients with pre-existing dementia. However, the association between pre-stroke dementia and functional outcome after acute ischemic stroke (AIS) has not been fully investigated. We aimed to investigate the association between PED and functional outcome in patients with AIS.Methods:We conducted a sub-analysis of the PASTA registry, an observational, multicenter registry of 1,043 patients with stroke receiving oral anticoagulants in Japan, by including patients with AIS with atrial fibrillation (AF). PED was defined as any type of dementia that was present prior to the index stroke. Poor outcome was defined as a modified Rankin Scale (mRS) score of 3-5 or death (mRS score 6). We compared the clinical characteristics and the rate of recanalization therapy between PED and non-PED and determined the effect of PED on stroke outcome.Results:Of all 493 participants (median age, 80 years; 212, 43.0% women), 86 (17.4%) had PED. PED were older (P

Stroke, Volume 55, Issue Suppl_1, Page A98-A98, February 1, 2024. Rationale:Direct-acting oral anticoagulants (DOACs) are commonly prescribed with antiseizure medications (ASMs) due to concurrency and causal links between atrial fibrillation (AF) and epilepsy. However, enzyme-inducing-ASMs (EI-ASMs) may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk.Methods:We leveraged large-scale healthcare data to conduct an emulated target trial among a nationally representative cohort with AF and epilepsy. Thromboembolic and bleeding event rates were contrasted between adults on DOACs + EI-ASMs versus active comparators on DOACs + non-enzyme inducing ASMs. Data-adaptive high-dimensional propensity score matching was employed to control for observed confounders and proxies for unobserved confounders. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.Results:Among incident ASM + DOAC users, we identified 14,078 and 14,158 episodes that met eligibility criteria for assessment of thromboembolic and bleeding outcomes, respectively. Incidence per 1,000 person-years was 88.5 for thromboembolic events and 68.3 for major bleeding events. Compared with use of non-enzyme inducing ASMs, use of EI-ASMs with DOACs was not associated with a difference in thromboembolic events (aHR=1.10, 95% CI: 0.82-1.46), but was associated with a reduction in major bleeding events (aHR=0.63, 95% CI: 0.44-0.89).Conclusions:EI-ASMs were not associated with alteration in DOAC efficacy. These real-world data are reassuring for the care of adults with epilepsy who require anticoagulation, particularly across a larger global community where EI-ASMs remain mainstays. Further research is needed on the reduction in bleeding risk with EI-ASMs, as this may be suggestive of pharmacokinetic interactions lowering DOAC levels without negating therapeutic effects.

Stroke, Volume 55, Issue Suppl_1, Page AWMP52-AWMP52, February 1, 2024. Background:The estimated range for the prevalence of Opioid Use Disorder (OUD) among adolescents and adults in the United States in 2019 was between 6.7 million and 7.6 million individuals. The overall mortality rate is increasing over the last 20 years.Objective:This study aimed to assess the trends in stroke-related mortality in chronic opioid users in different demographics in the United States.Methods:We analyzed Center for Disease Control and Prevention Wide-Ranging On-Line Data for the Epidemiologic Research database examined from 1999 to 2020 for multiple causes of death MCD-ICD 10 Codes. Stroke-related mortality rates, with and without opioid use, were stratified by age, sex, and race/ethnicity and expressed as age-adjusted mortality rates (AAMRs) per 100,000 persons. Annual percent change (APC) from 1999-2020 was calculated and graphically plotted.Results:Between 1999 and 2020, The were 307,615 stroke-related deaths and 358,322 opioid-related deaths occurred among adults (15-55), and 1615 deaths were related to stroke and opioid use. The age-adjusted mortality rate (AAMR) steadily increased from 0.1 in 1999 to 0.8 in 2020, with an annual percent change (APC):9.6 % (CI: 8.0-12.14). Men and women had unreliable differences from 1999 till 2011. Men had consistently higher AAMR than women from 2011 (AAMR men: 0.4 vs. women: 0.2; p: