Risultati per: Short Acting Opioid

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 AWP282-AWP282, February 1, 2024. Background:While blood pressure variability (BPV) is associated with poor cardiovascular outcomes, the relationship between BPV obtained in a very short interval and stroke is unknown. We aim to examine the association between very short interval BPV and a history of stroke.Hypothesis:Higher BPV is associated with the likelihood of having a stroke.Methods:A cross-sectional study using 2017-2020 NHANES included 3 consecutive BP measurements taken 60 seconds apart. The average real variability (ARV) of systolic and diastolic BP (AVR-SBP and AVR-DBP) was assessed as an average of absolute difference in consecutive BP. The association of AVR-SBP and AVR-DBP and the history of stroke was examined by multiple logistic regression.Results:Of 9,693 adult participants, mean±SD age was 50±19 years and 51% were female. Up to 5% (487 patients) had a history of stroke. Mean of the three average SBP and DBP were 120±20 and 72±12 mmHg, respectively. Median (IQR) of ARV-SBP was 3.5 (2, 6) mmHg and of ARV-DBP was 2.4 (1.5, 4) mmHg. Patients with stroke had significantly higher SBP and ARV-SBP, but not DBP and ARV-DBP compared to non-stroke patients (mean difference (95%CI) of SBP 11 (9, 13); ARV-SBP 0.7, (0.4, 1.1); DBP 0.7 (-0.5, 1.9); ARV-DBP 0.1 (-0.2, 0.4)). For every one mmHg increase in ARV-SBP, there was a 4.6% significantly greater odds of stroke (OR (95%CI) 1.05 (1.02, 1.07)), while there were 1.6% greater odds of stroke for every one mmHg increase in ARV-DBP but no statistical significance (OR 1.02 (0.98, 1.05)). After adjusting for age, gender, race, ethnicity, and BMI, the odds of stroke were 2.8% significantly higher for every one mmHg increase in ARV-SBP (OR 1.03 (1.00, 1.05)) and the ARV – stroke association remained non-significant. ARV-SBP was only associated with stroke in patients who were diagnosed with a stroke at an age < 50 years old, while ARV-DBP was not associated with stroke regardless of the age when the stroke was diagnosed.Conclusions:ARV-SBP in a very short interval is associated with prior history of stroke in younger than 50 years old. Impaired cerebral vasculatures may affect autoregulation in younger patients with stroke, which possibly manifests as BPV. Longitudinal cohort studies to determine the association between BPV and stroke are required.

Stroke, Volume 55, Issue Suppl_1, Page AWP169-AWP169, February 1, 2024. Prothrombin complex concentrates (PCCs) are used to emergently reverse direct-acting oral anticoagulant (DOAC) activity. PCCs are recommended as an alternative to recombinant coagulation factor-Xa to reverse anticoagulation activity of apixaban or rivaroxaban. Measuring the degree of anticoagulation reversal in this population is limited. Thromboelastography (TEG) has been used to detect the presence of DOAC plasma levels in patients chronically taking a DOAC but has not been utilized to measure the effect on anticoagulant activity after PCC administration. We aimed to determine whether TEG R-time is useful in detecting the impact of PCC administration on anticoagulation activity in patients with anti-factor Xa-associated intracranial hemorrhage (ICH). We prospectively evaluated the utility of TEG to assess anticoagulation activity after factor Xa inhibitor reversal with 4-factor PCC. Adults with ICH taking apixaban or rivaroxaban were included. Patients were excluded if their last known dose of anticoagulation was >48 hours prior to arrival, had known apixaban or rivaroxaban blood levels

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:

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 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

Small bowel microbiome and associated postbiotics understanding is still in its infancy.

Chronic, or long-term, opioid use is associated with higher risk of addiction and death as well as poor inflammatory bowel disease (IBD) outcomes. Recent data estimate that up to 20% of adolescents and young adults (AYA) with IBD may be chronic opioid users. Models to predict chronic opioid use among AYA with IBD may support identification, clinical management, and follow-up of patients at high risk of opioid dependence. We aimed to develop a clinical predictive model based on administrative data for chronic opioid use among AYA with IBD.

As part of the Crohn’s & Colitis Foundation’s IBD Plexus, a novel prospective, longitudinal multicenter surgical inception cohort was implemented. In this first report from the first 100 patients enrolled, we aimed to assess patient reported outcomes before and after IBD surgery. We hypothesized surgery is associated with improved patient reported outcomes.

Numerous pathogenic processes are mediated by short noncoding RNAs (ncRNA). Twenty percent of inflammatory bowel disease (IBD) patients are labelled as IBD unclassified (IBDU) at disease onset. Most IBDU patients are reclassified as Crohn’s disease (CD) or ulcerative colitis (UC) within few years. Since the therapeutic methods for CD and UC differ, biomarkers that can forecast the categorization of IBDU into CD or UC are highly desired. Here, we investigated whether short ncRNAs can predict CD or UC among IBDU patients.

New England Journal of Medicine, Volume 390, Issue 4, January 2024.

Introduction
Radical cystectomy remains the standard treatment for intravesical Bacille Calmette-Guerin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) because potential bladder-preserving therapies are not well established. Combination of radiotherapy with programmed death-1 (PD-1) antibody may offer an optional bladder preservation treatment for high-risk/extremely high risk NMIBC. Hence, the current study aims to investigate the safety and efficacy of short-course radiotherapy (5×5 Gy) and toripalimab (PD-1 antibody) as a novel bladder sparing treatment in this population.

Methods and analysis
HOPE-04 is an open-label, single-arm, phase II study, designed to evaluate the safety and efficacy of short-course radiotherapy and toripalimab in patients with high-risk/extremely high risk NMIBC. Fifty-five patients with pathological and imaging diagnosed NMIBC with or without BCG treatment will be recruited. Radiotherapy of 5×5 Gy will be given to the whole bladder followed by a focal tumour bed boost and concomitant administration of toripalimab of 240 mg intravenous infusion every 21 days for 12 cycles (about 1 year). The primary endpoints are disease-free survival and safety. The secondary endpoint is overall survival. Additional indicators include implementation rate of salvage surgery and quality of life.

Ethics and dissemination
This trial has been approved by the Ethics Committee of West China Hospital, Sichuan University. Trial findings will be disseminated via peer reviewed journals and conference presentations.

Trial registration number
Chinese Ethics Committee of Registering Clinical Trials (ChiCTR2200059970).