Search Results for: Short Acting Opioid

Objectives
To assess the beneficial and harmful effects of duloxetine versus ‘active placebo’, placebo or no intervention for adults with major depressive disorder.

Design
Systematic review with meta-analysis and trial sequential analysis of randomised trials.

Data sources
Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO and other relevant databases up until January 2023. We requested clinical study reports from 36 competent authorities.

Eligibility criteria for selecting studies
All randomised clinical trials comparing duloxetine versus placebo, ‘active placebo’ or no intervention, irrespective of publication type, publication status, publication year and language for treatment of major depressive disorder in adults.

Data extraction and synthesis
Five authors in pairs extracted data using a standardised data extraction sheet. A third review author was consulted for disagreements. Intervention effects were assessed by both random-effects and fixed-effect model meta-analyses, risk of bias assessments were performed by two independent review authors using Cochrane’s risk of bias tool V.2 and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation.

Results
We included 28 trials randomising a total of 7872 participants. All results were at high risk of bias. The trials’ assessment time points were between 6 and 16 weeks after randomisation. Meta-analyses showed evidence of a beneficial effect of duloxetine on depressive symptoms (mean difference –1.81, Hamilton Depression Rating Scale (HDRS-17) points; 95% CI –2.34 to –1.28; heterogeneity I2=0.0%; 12 trials) and quality of life (mean difference –3.79 points, 95% CI –5.11 to –2.46; I2=0.0%; three trials), but the effect sizes were below our predefined minimal clinically important differences. Trial sequential analysis showed that we did not have enough information to assess the effects of duloxetine on serious adverse events (SAEs) (OR 0.67, 95% CI 0.44 to 1.02; I2=0.0%; 19 trials) or suicide or suicide attempts (OR 1.08, 95% CI 0.37 to 3.16; six trials). Duloxetine increased the risk of non-SAEs (risk ratio 1.27, 95% CI 1.22 to 1.32; I2=73.0%; 24 trials). The adverse events with the lowest number needed to harm (NNH) were nausea (NNH 6), dry mouth (NNH 13), somnolence (NNH 17), withdrawal syndrome (NNH 19), sweating (NNH 20), dizziness (NNH 21) and constipation (NNH 21).

Conclusions
Duloxetine appears to reduce depressive symptom scores and improve quality of life scores in the short term, but the effect sizes are minimal and of questionable patient importance. The short- and long-term effects of duloxetine on risks of SAEs and suicidality are uncertain. Duloxetine increases the risks of several short-term adverse events. Systematic assessments of benefits and harms over longer periods are required.

Trial registration number
PROSPERO 2016 CRD42016053931.

The remarkable success of direct-acting antivirals in curing hepatitis C led to concerted efforts in developing a cure for hepatitis B. Unlike hepatitis C, it is accepted that a sterilising cure is not feasible in the foreseeable future. Instead, functional cure defined as hepatitis B surface antigen (HBsAg) loss (below detection) and HBV DNA suppression (below quantification) sustained for at least 24 weeks after completion of treatment has been embraced.1 Nucleos(t)ide analogues (NA) currently in use, entecavir and tenofovir, are highly effective in maintaining suppression of HBV DNA replication and yields substantial clinical benefits including reduced rates of cirrhosis and hepatocellular carcinoma, but HBsAg loss remains elusive. Yet, if a functional cure is achieved, the benefits are multiple, with further reductions in the risk for liver-related outcomes,2 elimination of the need for long-term monitoring and NA treatment and addressing the stigma associated with HBsAg-positivity. Strategies…

Background and aims
RNA interference has been extensively explored in patients with chronic hepatitis B (CHB) infection. We aimed to characterise the long-term efficacy of small interfering RNA (siRNA) on hepatitis B surface antigen (HBsAg) suppression.

Methods
We prospectively followed up participants with CHB who received siRNA, either ARC-520 or JNJ-73763989 (JNJ-3989), in combination with nucleoside analogue (NUC) in our centre. Participants enrolled included 15 receiving 4 monthly injections of ARC-520, 38 receiving 3 injections of JNJ-3989 at 1, 2 or 4 weekly intervals and 5 receiving placebo in previous clinical trials. Serial blood sampling was performed according to the original protocols and on completion every 24 weeks until last follow-up (LFU) with mean duration of 52.5 months.

Results
Among the 53 NUC+siRNA-treated participants (mean age 46.8, baseline HBsAg 3.08 log, 83% previously on NUC, 34% hepatitis B e antigen+), the proportion of patients achieving HBsAg seroclearance or

An estimated 9% of people in the US aged 2 years or older had anemia from August 2021 to August 2023, according to data from the National Center for Health Statistics (NCHS). Overall, 13% of females had anemia compared with about 6% of males, and prevalence was highest among females during adolescence through midlife. Like most nations charged with reducing anemia prevalence, the US fell short of the World Health Assembly’s goals to curb the condition in women of reproductive age by half by 2025.

Objective
The primary study aims were to evaluate the implementation, mechanisms and context of a timely short-term specialised palliative care intervention for older people with frailty (Frailty+ intervention) as well as to assess the feasibility of a randomised controlled trial to evaluate Frailty+. Our secondary aim was to describe any preliminary effects of Frailty+.

Design
Pilot randomised controlled trial with process evaluation.

Setting/Participants
We aimed to recruit 50 adults (≥70 years) with Clinical Frailty Scale score 5–7, and complex care needs and their main family carer, if available, from two Belgian hospitals on discharge.

Interventions
Patients were randomised to the Frailty+ intervention alongside standard care or standard care alone.

Outcome measures
Implementation and trial feasibility were assessed through interviews, focus groups and quantitative data. The primary outcome to be used in a potential full-scale trial if the study is feasible and implementable was mean change in five palliative care symptoms over 8 weeks.

Results
We enrolled 37 patients (19 intervention, 18 control) and 26 family carers (15 intervention, 11 control). Patients and family carers valued the home visits from palliative care nurses, and nurses saw value in Frailty+. But most patients received only one visit over 8 weeks, and nurses did not organise foreseen multidisciplinary meetings, referring to absence of urgent needs. Many aspects of the trial methods were feasible, but recruitment was challenging. The baseline mean score on the five palliative care symptoms was 6.0 and 5.6 in intervention and control group, respectively; and 4.5 and 4.1 at 8 weeks (adjusted ratio 1.0, ie, no effects on symptoms).

Conclusions
While Frailty+ was generally welcomed by older people with frailty, families and palliative care nurses, our process evaluation uncovered multiple barriers, mostly rooted in the current organisation of specialised palliative care that is tailored to advanced stages of illness. Ensuring timely access requires efforts beyond timely referral alone, and implies profound organisational and cultural change.

Trial registration number
ISRCTN39282347.

This cross-sectional study assesses acquisitions of US opioid treatment programs by private equity firms overall and at the zip-code level.

This randomized clinical trial compares the effectiveness of an integrated pain team vs pharmacist collaborative management on pain and opioid dosage.

This study describes patterns of reduction in illicit opioid use of patients both labeled as a success and nonsuccess based on an abstinent-based treatment outcome rule.

Introduction
Postsurgical hypoparathyroidism (PoSH) is an iatrogenic condition that occurs as a complication of several different procedures with thyroid surgery being the most common. PoSH has significant short- and long-term morbidities. The volume of thyroid surgery is increasing, and PoSH is therefore likely to increase. Some studies have shown promising results using near-infrared fluorescence (NIRF) imaging in reducing the risk of PoSH which has the potential to significantly reduce morbidity and costs associated with monitoring and treatment.

Methods and analysis
NIFTy is an unblinded, parallel group, multicentre, seamless phase II/III randomised controlled trial in patients undergoing total or completion thyroidectomy. The trial incorporates a process evaluation (IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up framework) 2a) to inform the trial protocol, a phase II (IDEAL 2b) analysis using a surrogate primary outcome of 1 day transient hypocalcaemia to determine early futility and phase III (IDEAL 3) assessment of the primary outcome of PoSH at 6 months after surgery. 454 participants will be randomised on a 1:1 basis to evaluate thyroid surgery with NIRF and indocyanine green against standard thyroid surgery in reducing PoSH at 6 months after surgery, with the phase II analysis occurring once data are available for 200 participants. Analysis in both phases will be using multilevel logistic regression incorporating random effects with respect to surgeon and adjusting for minimisation factors. Phase III secondary outcomes include protracted hypoparathyroidism, hypercalcaemia, complications, length of stay, readmissions and patient reported quality of life using the Short Form 36 Health Survey Questionnaire and Hypoparathyroid Patient Questionnaire instruments.

Ethics and dissemination
NIFTy is funded by National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme (Grant Ref: 17/11/27) and approved by a Research Ethics Committee (reference: 21/WA/0375) and Health Research Authority (HRA). Trial results will be disseminated through conference presentations, peer-reviewed publication and through relevant patient groups.

Trial registration number
ISRCTN59074092.

Introduction
Acute uncomplicated urinary tract infection (UTI) is a common condition with potentially serious sequelae that is mostly diagnosed and managed in primary care settings. Around half of all women have a UTI in their lifetime, and a quarter experience an infection caused by organisms resistant to more than one antibiotic. Reducing inappropriate prescribing of antibiotics is a core tenet of antimicrobial stewardship. However, current diagnostics for UTI are unfit for purpose in acute (highest prescribing) settings, being too slow to inform the required immediate decision-making and often confounded by sample contamination.
Rapid point-of-care diagnostic tests (POCTs) that facilitate timely decision-making are potential solutions to this problem. Several such tests have reached advanced stages of technology readiness, but their diagnostic performance has not been evaluated in primary care with clinical users. To progress novel tests towards implementation, a diagnostic field study is required, to allow for parallel and sequential evaluation of multiple tests in a primary care population.

Methods and analysis
We will recruit participants assigned female at birth from primary care clinics in England who contact their clinic with symptoms of acute uncomplicated UTI. Eligible participants will complete a short questionnaire to capture symptoms and symptom severity and will provide a urine sample. Samples will be split and initially tested using novel index tests (POCTs) and conventional urinalysis ‘dipstick’ at the primary care clinic. The second part of the sample will be processed at a National Health Service-based reference laboratory using a modified reference standard including microscopy, microbiological culture, pathogen speciation and antimicrobial susceptibility testing. The UTI reference standard culture, although based on the national methods, is modified to provide accurate bacterial counts, better to define a microbiological diagnosis of UTI. Susceptibility testing will be performed using ‘gold-standard’ methods, not usually performed in diagnostic laboratories. The primary outcome will be the diagnostic performance (sensitivity, specificity, positive and negative predictive values) of POCTs for detection of UTI and antimicrobial susceptibility for POCTs that include antimicrobial susceptibility testing. Secondary outcomes will include the symptom profile of patients presenting with uncomplicated UTI, a theoretical determination of how use of POCT results might change prescribing, an understanding of POCT failure rate and qualitative capture of the experiences of those using the POCT to deliver the study in primary care clinics.

Ethics and dissemination
Ethical approval was received from the London Central Research Ethics Committee (23/LO/0371) and the UK Health Research Authority. We will publish the findings of The plaTform fOr Urinary tract infection diagnostiC evAluatioN evaluations in peer-reviewed medical journals and more broadly following a dissemination plan formulated by a communications specialist in consultation with patients and the public.

Trial registration number
ISRCTN80937472.

Introduction
Long-acting insulin analogues are the standard of care for people with type 1 diabetes (T1D) in high-income countries but remain largely inaccessible and understudied in low-resource settings. In settings where glycaemic control is typically poor and food insecurity is common, long-acting insulin analogues may offer tangible clinical benefits for people with T1D. To determine whether insulin glargine, a long-acting insulin analogue, reduces the risk of serious hypoglycaemia and/or improves glycaemic time-in-range (TIR) versus human insulin regimens in this population, we are conducting the Human vs Analogue Insulin for Youth with Type 1 Diabetes in Low-Resource Settings randomised controlled trial.

Methods and analysis
This is a 1:1 randomised, parallel-group clinical trial comparing biosimilar insulin glargine with human insulin (Neutral Protamine Hagedorn (NPH) or premixed 70/30 insulin) in 400 youth with type 1 diabetes (T1D) recruiting in Dhaka, Bangladesh (n=250) and Mwanza, Tanzania (n=150). Blinded continuous glucose monitors will be used to assess glycaemic control in both study arms over 14-day periods at baseline and at 3, 6 and 12 months after randomisation. The co-primary outcomes are the per cent time in serious hypoglycaemia (

Objectives
Traditionally, patients have had passive roles in medical education; however, there have been increasing efforts to partner with communities to create authentic representation of laypeople in medical education. Communities’ perspectives of these initiatives have rarely been reported in the literature. This study explores the perspectives of members of community-based organisations (CBOs) who were partnered with a community engagement programme for intercalating medical students at Imperial College London.

Design
A qualitative study using semistructured interviews was conducted, employing reflexive thematic analysis.

Setting
London, UK.

Participants
A total of five participants (one member from five CBOs who agreed to participate) were interviewed for this study. The selection criterion was direct involvement in the community engagement programme.

Results
Three key themes were identified aligning with the core principles of co-production: building partnership, reciprocity in partnership and maintenance of relationship. Partnership development was influenced by the CBOs’ perception of students which caused power differentials in the development of learning plans. Reciprocity refers to a multidirectional benefit pathway resulting from the community involvement programme, which had short-term and anticipated long-term effects. Relationships built were maintained via a service evaluation report, and participants discussed how attitudes of academic institutions towards collaboration influence communities’ ability to participate in medical education.

Conclusions
The perspectives of CBOs reported in this study demonstrate that factors important to partnership development in community-engaged medical education are consistent with the key principles of co-production. Supported by literature, the findings emphasise that community involvement can be linked to social accountability and sustainable health practice. Provided that the possible risks/challenges are appropriately identified and mitigated to facilitate co-productive partnerships between stakeholders, the involvement of CBOs in medical education has the potential to provide benefits for communities, students and educational institutions.

Stroke, Volume 56, Issue Suppl_1, Page ATMP30-ATMP30, February 1, 2025. Background:The prehospital scales have been developed to identify stroke patients with large vessel occlusion (LVO) to facilitate rapid transport to appropriate stroke centres. In practice, these stroke scales have moderate accuracy. There is a pressing need for adjunct easy-to-use and interpret diagnostic devices to improve prehospital stroke diagnosis and LVO detection. We aim to determine whether a machine learning algorithm using adjunct electroencephalography (EEG) Spectra can improve the accuracy of LVO detectionMethods:Adult patients with suspected acute stroke were prospectively enrolled as soon as possible on arrival at the emergency department. A wearable MuseTMheadband (InteraXon Inc, Canada) with an embedded 4-channel EEG was used for a resting 3-minute recording. EEG Spectra including relative alpha, beta, theta and delta spectral powers, delta-alpha ratio (DAR) and pairwise-derived brain symmetry indices (pdBSI) were calculated. These indices were compared between patients with LVO and non-LVO groups. The accuracy of LVO detection was tested with the aid of supervised machine learning(ML) algorithms including EEG Spectra, Los Angeles Motor Stroke Scale (LAMS), sex and side of stroke.Results:A total of 142 patients were included in the analysis with a mean age of 69.6±13.7 years, 60(42.2%) females, (Stroke Subtype:113[79.6%] were ischemic stroke, 22[15.5%] stroke mimics, 7[4.9%] intracerebral hemorrhage) and median NIHSS 5(2-11). Thirty-seven(26.1%) patients had LVO and EEG was acquired at a median of 6h 45m (3h 29m – 14h 15m) after symptom onset. Relative alpha spectral power was lower in both affected (p

Stroke, Volume 56, Issue Suppl_1, Page ATP313-ATP313, February 1, 2025. Background:Lipoprotein(a) (lp(a)) concentrations is an independent risk factor of atherosclerotic cardiovascular disease (ASCVD). The association between lp(a) and prognosis of ischemic stroke patients is uncertain.Hypothesis:The study is aimed to investigate the shape and the association of the risk of short-term and long-term stroke recurrence across the distribution of lp(a) concentrations, and explore whether combining ASCVD risk has an influence on the association.Method:Patients with acute ischemic stroke within 7 days in the Third China National Stroke Registry (CNSR-III) having lp(a) measurements were included in the study. The outcomes were stroke recurrence within one year and two years. ASCVD risk included diabetes mellitus, stroke history and early onset. Based on ASCVD risk and lp(a) concentrations, there were four groups: lp(a)70 mg/dL without ASCVD risk. To display the shape of the relationship between lp(a) and stroke recurrence within two years, lp(a) concentrations were modeled using natural cubic splines with median concentration serving as the reference adjusted by confounders. And the association was assessed using Cox proportional hazards models and Kaplan-Meier curves.Result:Among 9952 included patients with the mean age of 63 years and 69% of male, the median lp(a) concentrations was 18.06 (inter-quartile range, 8.85-35.66) mg/dL. The relationship between lipoprotein(a) and stroke recurrence appeared linear across the distribution. Compared to patients with lp(a)=50 mg/dL was associated with a higher risk of stroke recurrence (adjusted HR for one-year outcome:1.19, 95%CI: 1.01-1.41, p =0.04; adjusted HR for two-year outcome:1.21, 95%CI: 1.04-1.40, p =0.01). Compared to patients with lp(a)70 mg/dL without ASCVD risk (HR:0.90, 95%CI: 0.65-1.26, p =0.55).Conclusion:Lipoprotein(a) concentrations was associated with short-term and long-term prognosis of ischemic stroke, with a linear risk gradient across the distribution. Baseline ASCVD risk may influence the association between lp(a) and stroke recurrence.

Stroke, Volume 56, Issue Suppl_1, Page ATMP32-ATMP32, February 1, 2025. Introduction:Facilitating evidence-based uptake of new medication regimens for disease prevention is a well-recognized public health challenge. Using data from GWTG-Stroke, researchers previously reported that, after minor ischemic stroke (NIHSS 0-3), the use of aspirin-clopidogrel for stroke prevention is highly variable despite guideline recommendations. We sought to explore potential changes in dual antiplatelet therapy (DAPT) use in patients with moderate ischemic stroke (NIHSS 4-5) after the publication of the THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial in 2020.Methods:We used the GWTG-Stroke registry to describe patterns of DAPT use in the U.S. from 2019 to 2023. All patients with a final diagnosis of ischemic stroke, NIHSS 4-5, hospital arrival within 24 hours, who lacked an indication for anticoagulation (e.g., atrial fibrillation) and were not treated with thrombolysis/thrombectomy were included in our study. Patients with NIHSS 4-5 (moderate stroke) were not included in prior randomized controlled trials of aspirin-clopidogrel for short-term stroke prevention but were included in THALES. We reported basic demographic features of our cohort and used the Cochran-Armitage trend test to report changes in aspirin-ticagrelor use by year.Results:We identified a total of 40,624 acute ischemic stroke patients with NIHSS 4-5 during the study period. The mean age was 68 years and 47% of patients were women. We found that a total of 20,293 (50%) patients were discharged on aspirin-clopidogrel whereas 1,335 (3.5%) were discharged on aspirin-ticagrelor. The use of both DAPT regimens significantly increased over time (Figure 1, p

Stroke, Volume 56, Issue Suppl_1, Page ATMP40-ATMP40, February 1, 2025. Introduction:Stroke patients experience higher levels of social isolation (SI) compared to their age matched healthy cohorts which is associated with poor quality of life and increased morbidity and mortality. However, frequency and associates of SI among patients with intracerebral hemorrhage (ICH) have not been described.Methods:Data for adult ( >18 years) primary non-traumatic ICH patients with prospectively collected Patient-Reported Outcomes Measurement Information System (PROMIS) measures and modified Rankin scores (mRS) on 1-year follow up were extracted from a stroke outcomes registry for a 7-hospital stroke certified healthcare system. Socioeconomic deprivation was measured using the state-level Area Deprivation Index (ADI; high deprivation defined as ADI > 7). Comorbidity burden was graded by Charlson Comorbidity Index (CCI). The PROMIS short form v2.0 social isolation 4a score was used to assess SI, with SI considered positive at T-scores above 54.9 and further categorized into mild (55-60) and moderate-severe (≥60). Patients with mRS ≥ 3 were considered functionally dependent. Descriptive statistics are provided as proportions (%) and medians with interquartile ranges (IQR). Demographic and comorbidity differences were assessed using chi-squared and Mann-Whitney U tests.Results:The cohort included 110 ICH patients (age median [IQR]: 60 [47-71], 43.6% female), of whom 20% were Hispanic and had a racial distribution of 59.0% White, 27.2% Black, 8.2% Asian, 5.5% other (Table 1). Overall, 24 (21.8%) patients experienced some degree of social isolation (54.2% mild, and 45.8% moderate-severe). Among patients with 1-year SI, 33.3% were initially discharged home, 33.3% to rehab, 16.7% to long-term acute care (LTAC), 12.5% to skilled-nursing facility, and 4.2% other. SI patients had higher comorbidity burden (vs non-isolation group; 95.8% vs. 68.6%, p=0.025), higher rates of functional dependence (70.8% vs. 30.8%, p=0.001), and higher rates of diabetes (33.3% vs 12.8%, p=0.040). Finally, patients with moderate-severe SI showed a significantly greater proportion of high socioeconomic deprivation (vs mild; 54.5% vs 7.7%, p=0.039) (Table 2).Conclusion:More than 1 in 5 ICH patients may experience long-term SI particularly those with higher comorbidity burden. Furthermore, long-term dependency is associated with higher likelihood of SI among ICH patients. .SI risk stratification for ICH patients is a critical gap in improving post-ICH outcomes.