Cannabis use is increasing among college students and commonly co-occurs with anxiety symptoms in this age group. Interventions that reduce anxiety may also reduce cannabis use. Behavioral economic theory suggests that substance use reductions are most likely when there is an increase in substance-free reinforcement. This randomized pilot trial evaluated the efficacy of a brief motivational intervention (BMI) for cannabis supplemented by either a substance-free activity session (SFAS) or a relaxation training (RT) session for reducing cannabis use, problems, craving, and anxiety symptoms. One hundred thirty-two college students (Mage = 19.9; 54% female; 67% White, 31% Black) who reported five or more past-month cannabis use days were randomized to: (a) assessment-only (AO); (b) BMI plus SFAS; or (c) BMI plus RT. Participants in the BMI conditions received two individual counselor-administered sessions plus a brief phone booster session. Outcomes were evaluated 1- and 6-months postintervention. Relative to assessment, both BMI + SFAS and BMI + RT were associated with significant reductions in cannabis problems and craving at 1-month follow-up, and significant reductions in anxiety at 6-month follow-up. Relative to AO, BMI + RT was associated with significant reductions in cannabis use at 1-month follow-up. There were no differences between BMI conditions. This pilot trial was not adequately powered to conclusively evaluate relative efficacy but provides preliminary support for the short-term efficacy of both two-session interventions for reducing anxiety and cannabis-related risk among nontreatment seeking emerging adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Stereotactic radiosurgery (SRS) has been established as a safe and alternative treatment for dural arteriovenous fistulas (dAVFs). While embolization alone is the most commonly used modality for the treatment of dAVFs, the adjunctive use of embolization with SRS, with the growing use of SRS, has gained increasing interest in the past few years. However, the relative efficacy and safety of SRS combined with embolization versus SRS alone for dAVFs remains uncertain. Hence, this systematic review aimed to evaluate the efficacy of SRS with adjunctive embolization for intracranial dAVFs. A systematic review and meta-analysis was conducted by searching electronic databases, including PubMed, Embase, and the Cochrane Library, up to August 2023. All studies evaluating the utilization of adjunctive embolization and SRS for dAVFs were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was conducted on the suitable outcomes. Eighteen studies involving 715 patients were included. The mean age of the participants in the study was 64.30 years in the adjunctive embolization group and 60.51 years in the SRS-alone group. In the adjunctive embolization group 41.3% of patients were female, compared with 47.1% in the SRS-only group. The dAVF obliteration rates were 64.7% and 65.7% in the adjunctive embolization and SRS-alone groups, respectively. These obliteration rates were comparable between the two groups (p = 0.96), as were the symptom improvement rates (p = 0.35). Adverse events were rare, and were more commonly associated with the adjunctive embolization procedure, although further causal analysis was not possible. This study provides evidence that adjunctive embolization plus SRS provides similar obliteration and symptom improvement rates compared with SRS alone, with both having very limited SRS-related adverse events. Considering the added burden and adverse events of additional endovascular treatment, the authors recommend embolization be reserved for more complex dAVFs or when embolization can potentially be curative alone or provide more rapid symptomatic relief or protection during the radiosurgical latency period.

Background: Awareness during anesthesia is a major anesthetic concern. Depth of anesthesia is commonly assessed in clinical practice by the patient’s clinical signs and symptoms such as blood pressure, heart rate variability, and body movement. At present, many studies have focused on qCON monitoring for sedative depth, but only a few studies have focused on qNOX monitoring for analgesic depth. Aims and Objectives: The aim of the present study was to evaluate the relative efficacy of qCON and qNOX versus commonly used vital signs such as blood pressure and heart rate in monitoring the anesthetic depth and analgesia. Materials and Methods: A total of 100 patients of either sex and of ASA Physical status I & II, scheduled for urogenital surgeries, were selected and randomly placed into two groups. Group A was monitored by conventional clinical technique and Group B was monitored by qCON and qNOX indices. The primary outcome was the total dose of propofol and fentanyl required to maintain the depth of anesthesia and analgesia. The secondary outcomes were propofol and fentanyl adjustment frequency, infusion duration, and quality of recovery from anesthesia. Results: Results showed statistically significant differences between the two groups in mean dose of both propofol (P=0.000) and fentanyl (P=0.006), adjustment frequency of both propofol (P=0.000) and fentanyl (P=0.010), time required to voluntary eye-opening (P=0.000) and extubation time (P=0.000) and visual analog scale score (P=0.000). There was no statistically significant difference found in infusion duration (P=0.317) and Ramsay Sedation Score (P=0.709) between the groups. Conclusion: Using the qCON and qNOX indices, an anesthesiologist can monitor the depth of anesthesia and analgesia more effectively and can adjust the anesthetic or analgesic drug dosing in a better possible way with lesser requirement of drugs than with conventional clinical monitoring.

ABSTRACT Continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enhanced transmissibility, significant immune escape, and waning immunity call for booster vaccination. We evaluated the safety, immunogenicity, and efficacy of heterologous booster with a SARS-CoV-2 mRNA vaccine SYS6006 versus an active control vaccine in a randomized, open-label, active-controlled phase 3 trial in healthy adults aged 18 years or more who had received two or three doses of SARS-CoV-2 inactivated vaccine in China. The trial started in December 2022 and lasted for 6 months. The participants were randomized (overall ratio: 3:1) to receive one dose of SYS6006 (N = 2999) or an ancestral receptor binding region-based, alum-adjuvanted recombinant protein SARS-CoV-2 vaccine (N = 1000), including 520 participants in an immunogenicity subgroup. SYS6006 boosting showed good safety profiles with most AEs being grade 1 or 2, and induced robust wild-type and Omicron BA.5 neutralizing antibody response on Days 14 and 28, demonstrating immunogenicity superiority versus the control vaccine and meeting the primary objective. The relative vaccine efficacy against COVID-19 of any severity was 51.6% (95% CI, 35.5–63.7) for any variant, 66.8% (48.6–78.5) for BA.5, and 37.7% (2.4–60.3) for XBB, from Day 7 through Month 6. In the vaccinated and infected hybrid immune participants, the relative vaccine efficacy was 68.4% (31.1–85.5) against COVID-19 of any severity caused by a second infection. All COVID-19 cases were mild. SYS6006 heterologous boosting demonstrated good safety, superior immunogenicity and high efficacy against BA.5-associated COVID-19, and protected against XBB-associated COVID-19, particularly in the hybrid immune population. Trial registration: Chinese Clinical Trial Registry: ChiCTR2200066941

Abstract Aim: To determine the relative efficacy of platelet rich plasma therapy versus topical 0.1% tretinoin gel in the management of striae gravidarum. Objectives: To determine the degree of response to platelet rich plasma therapy in comparison with topical 0.1% tretinoin gel in striae gravidarum and to determine the treatment of choice amongst platelet rich plasma and topical 0.1% tretinoin gel. Material and Methods: Study design - A randomised control cross sectional comparative study among the female patients with striae gravidarum was carried out at department of Dermatology, Venereology & Leprosy, Base Hospital, Delhi Cantt, New Delhi. Results: There was early and fast clinical improvement in PRP group with continuous clinical improvement noticed in successive sittings although degree of improvement was lower in 5th and 6th sittings. There was also an earlier plateau of response, in tretinion group after 04 sittings with mild or little improvement in the last 02 sittings in comparison to the PRP group. Conclusion: Platelet Rich Plasma therapy was effective as compared to topical 0.1% Tretinoin gel in the management of Striae gravidarum. PRP had better treatment outcome as well as patient satisfaction.

The inhibitory effects of veralipride, a benzamide-class antipsychotic acting as dopamine D2 receptors antagonist incorporates a primary sulfonamide moiety and was investigated for its interactions with carbonic anhydrase (CA) isoforms. In vitro profiling using the stopped-flow technique revealed that veralipride exhibited potent inhibitory activity across all tested hCA isoforms, with exception of hCA III. Comparative analysis with standard inhibitors, acetazolamide (AAZ), and sulpiride, provided insights for understanding the relative efficacy of veralipride as CA inhibitor. The study reports the X-ray crystal structure analysis of the veralipride adduct with three human (h) isoforms, hCA I, II, and CA XII mimic, allowing the understanding of the molecular interactions rationalizing its inhibitory effects against each isoform. These findings contribute to our understanding of veralipride pharmacological properties and for the design of structural analogs endowed with polypharmacological properties.

The mechanisms of AF development and progression are still not completely understood. Despite the relative efficacy of ablation, the risk of AF recurrence is substantial, particularly in patients with persistent AF (perAF). At present we do not have any reliable intra-procedural electrophysiologic predictors of long-term success of AF ablation other than pulmonary vein isolation. We evaluated selected intraprocedural pulmonary vein characteristics that may be helpful in future guidance of persistent AF ablation. 390 consecutive procedures using cryoballoon for initial AF ablation were divided by clinical presentation (paroxysmal or persistent AF), and by pulmonary vein (PV) response to pacing after completion of ablation (discrete electrogram elicited with pacing-"PV capture" or not-"Control"). Patients were followed (median 20 months) for recurrent atrial arrhythmias as the primary end point of the study. PV capture was identified in 20.3% and 17.1% and patients with paroxysmal and persistent AF respectively (ns). In patients with persistent AF presence of PV capture was associated with significantly better outcomes compared to patients without PV capture (p < 0.001). In the group "persistent AF and PV capture", an initial strategy of PV isolation and reisolation of the PVs (without additional lesions) for patients with recurrent atrial arrhythmias resulted in 20/23 (87%) patients in sinus rhythm off antiarrhythmic medications at study completion. In patients with paroxysmal AF, PV capture was not associated with outcome benefits. Specific electrophysiologic characteristics of PV (PV capture cycle length: PVCCL) did not have an impact on AF recurrence, although 25% shortening of PVCCL was observed after 60 s periods of pacing at short cycle lengths. No background demographic patient characteristic differences were identified between patients with vs. without PV capture. The presence of PV capture was associated with better outcomes in patients with persistent AF. PV capture may identify those patients with persistent AF in whom cryoballoon PV isolation alone is sufficient as an initial ablation procedure and as the primary ablation strategy for recurrent AF.

Abstract Introduction/Background Biologic treatments such as tralokinumab and dupilumab are therapeutic options for adult patients with moderate-to-­severe atopic dermatitis (AD) who do not achieve adequate control with topical treatments or phototherapy. To date, no trials have been conducted to directly evaluate the relative efficacy of these biologic treatments. Objectives Applying indirect comparison of efficacy, we examined the cost-per-responder of tralokinumab compared to dupilumab in combination with topical corticosteroids (TCS) for the treatment of moderate-to-serve AD in the United States (US) and Canada. Methods A cost-per-responder analysis was undertaken considering the Eczema Area and Severity Index 75 (EASI-75) and Investigator’s Global Assessment (IGA-0/1) response criteria over a 32-week period. For each treatment, the cost-per-­responder was computed by multiplying the treatment cost by the number needed to treat (NNT). Efficacy data were derived from an unanchored matching-adjusted indirect comparison (MAIC) utilizing patient-level data from ECZTRA-3 (tralokinumab) and aggregate data from LIBERTY AD CHRONOS (dupilumab). Treatment cost was defined as the drug cost of the biologic treatment with a duration corresponding to 32 weeks. TCS cost was not considered. Treatments were assumed to be administered every 2 weeks (Q2W). The costs were estimated based on Wholesale Acquisition Costs (WAC) from the US and ex-factory prices via the McKesson price list for Canada. All prices were converted to US dollars ($). Sensitivity analyses (SA) were conducted with every 4 week (Q4W) dosing beginning at week 16 for 10% and 20% of patients treated with tralokinumab. Results For the US, the average cost-per-responder was $62,714 (Q4W SA: 10%: $61,239; 20%: $59,763) for tralokinumab versus $63,993 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $82,419 (Q4W SA: 10%: $80,480; 20%: $78,450) for tralokinumab versus $118,835 for dupilumab considering the IGA 0/1 response criteria. For Canada, the average cost-per-responder was $22,846 (Q4W SA: 10%: $22,308; 20%: $21,771) for tralokinumab versus $26,475 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $30,024 (Q4W SA: 10%: $29,317; 20%: $28,611) for tralokinumab versus $49,165 for dupilumab considering the IGA 0/1 response criteria. Conclusions Assessing EASI-75 and IGA-0/1 response criteria at 32 weeks, this analysis indicates that tralokinumab in combination with TCS is associated with lower costs-per-responder compared with dupilumab in combination with TCS in the treatment of moderate-to-severe AD in the US and Canada.

Meta-analyses on the relative efficacy of psychodynamic psychotherapy (PDT) and cognitive behavioral therapy (CBT) for depressive disorders are limited by heterogeneity in diagnostic samples and comparators and a lack of equivalence testing. We addressed this through a meta-analytic test of the equivalence of manualized PDT and CBT in treating adults with depressive disorders as determined by diagnostic interviews. Sensitivity analyses evaluated the impact of pretreatment differences, mixed diagnostic samples, author allegiance, study quality, year of publication and outliers on findings. A comprehensive literature search across multiple databases using reliable screening methods identified nine randomized controlled trials directly comparing manualized PDT and CBT for diagnosed depressive disorders in adults. Following pre-registration, we employed random effect models for our meta-analyses and two one-sided test procedures for equivalence testing. Independent raters determined that all studies were of adequate quality. Immediately posttreatment, depressive symptoms were statistically equivalent across PDT and CBT (k = 9; g = -0.11, 90% confidence interval [90% CI]: -0.24 to 0.02, pequivalence = .048, pNHST = .212, I2 = 32.7). At follow-up, the longest time point within a year, depressive symptoms were neither statistically equivalent nor statistically different (k = 6; g = -0.16, 90% CI: -0.31 to -0.02, pequivalence = .184, pNHST = .126, I2 = 0.00). The efficacy of manualized PDT is equal to manualized CBT immediately at posttreatment for depressive disorders in the adult general population. Nevertheless, insufficient data exists to reach a conclusion regarding equivalence at follow-up.

Objective: This randomized controlled trial investigated the efficacy of dynamic relational group therapy (DRT) relative to group psychodynamic supportive therapy (PST) in improving perfectionism-related attitudes and components of the perfectionistic self-relationship. Method: Based on a comprehensive conceptualization of perfectionism, 80 community-recruited, highly perfectionistic individuals were randomly allocated to 12 sessions of group DRT (n = 41; 5 groups) or group PST (n = 39; 5 groups). Patients completed measures of dysfunctional attitudes, self-criticism, self-esteem, and self-reassurance at pre-, mid-, and post-treatment, and six months post-treatment. Results: Multigroup latent growth curve modeling revealed significant (p < .05) decreases in dysfunctional attitudes, concern over mistakes, two types of self-criticism, and self-esteem problems, along with a significant increase in self-reassurance, from pre-treatment to six-month follow-up in both DRT and PST. Moderate-to-large between-group differences favoring DRT over PST were found for dysfunctional attitudes and self-reassurance. A majority of patients in both conditions maintained reliable improvement at six-month follow-up in dysfunctional attitudes, concern over mistakes, and self-criticism focused on inadequacy. Conclusion: Findings provide evidence for the use of psychodynamic group therapy approaches in treating perfectionism-related attitudes and self-relational elements of perfectionism, and support the relative efficacy of DRT for dysfunctional attitudes and self-reassurance.

Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1-12. There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1-12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: -1.65 [-2.49, -0.81]; p < 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.

A myriad of factors influence young people’s vulnerability and the likelihood of becoming NEET. Moreover, the share of young NEETs in European countries is very high. Institutional and governmental initiatives aiming to promote the inclusion of young people in the labour market are of paramount importance. However, the socio-economic conditions and the level of vulnerability alongside other socio-demographic characteristics are likely to influence the extent to which young people ultimately engage with such programmes. The current study ascertains whether previous experience of informal work increases young people’s propensity to participate in programmes offered by public employment services, such as the Youth Guarantee Programme. Indeed, we hypothesise that the experience of working without a contract makes young people more aware and concerned about the risk of remaining trapped in a spiral of vulnerable jobs. To test this, we used data from a survey of 4,273 NEETs and focused on Italy, Portugal, and Spain. The study’s findings contribute to a better understanding of the relationship between past experience in the informal economy and engagement with the Youth Guarantee. Besides contributing to the literature, the study can also contribute to policy making and practitioners’ assessment of the relative efficacy of Youth Guarantee initiatives among different subgroups of young NEET and tailor the interventions accordingly. In other words, the outcomes of this study should signal to governments that greater efforts should be made to implement initiatives reaching out to young people, as well as acting to reduce the precariousness in job contracts, which negatively impacts their quality of life.

Abstract Background Despite effective anti-TNF agents in treating Crohn’s disease (CD), some recipients experience primary or secondary non-responses, requiring alternative options. Ustekinumab and vedolizumab have not been compared in randomized controlled trials (RCTs) among CD population. Thus, we used real-world data to compare ustekinumab and vedolizumab at 12 weeks after failure of TNF inhibitors. Methods A retrospective study was conducted at a tertiary hospital in Dammam, Saudi Arabia. Patients with CD who had not responded to anti-TNF agents and had never been exposed to vedolizumab and/or ustekinumab were included. Children ≤ 18 years of age, naïve CD patients, CD patients using only anti-TNF agents, and patients who lost follow up were excluded. Primary endpoints were clinical improvements, which were measured by Harvey-Bradshaw Index scores at 12 weeks, and clinical remission, which was measured as an ordinal outcome. Remission clinically, biochemically, and endoscopically; clinical response; cumulative steroid dose; and corticosteroid-free days were secondary endpoints. Using probabilistic Bayesian models and proportional odds models, we analyzed outcomes, and the posterior distribution was used to calculate the probability of treatment effectiveness. A national institutional review board approved the study. Results Five hundred forty-six patients received biological agents for inflammatory bowel disease, of whom 101 received biological agents for CD; 71 patients received ustekinumab, and 30 patients received vedolizumab. The baseline characteristics were similar except for perianal disease, which was frequently reported in ustekinumab arm (P = 0.006). Most of the patients were male (54.5%), with a median age of 32 (IQR: 26.0-38.0). Most patients (51.5%) had stricturing disease in the Ileocolonic site (70.3%). For ustekinumab, the median HBI score was 5 (IQR: 3.0 -8.0) whereas for vedolizumab, it was 5 (IQR: 4.0 -7.0). In table 1, a Bayesian multivariable proportional odds model revealed a 40% reduction in median HBI scores at 12 weeks favoring ustekinumab, with an aOR of 0.60 (95% CI: 0.25 to 1.31) and a probability of effectiveness of 75% for ustekinumab. At 12 weeks, the ordinal outcome scale was 39% lower for ustekinumab arm, with an aOR of 0.61 (95% CI: 0.26 to 1.35) and a probability of effectiveness of 73% for ustekinumab arm. Secondary endpoints showed favorable results for ustekinumab reaching up to a 90% probability of effectiveness. Conclusion Among CD patients who failed anti-TNF therapies, ustekinumab was more effective than vedolizumab. To validate these results and determine these treatments’ relative efficacy in managing CD, further investigations, including prospective studies and RCTs, are essential.

Abstract Background Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). In the absence of head-to-head randomised controlled trials (RCTs), network meta-analyses (NMA) offer insight into the comparative effectiveness of treatment options. NMA were conducted to examine the relative efficacy of etrasimod vs other advanced therapies (AT) with licensed dosing (European Medicines Agency) for the treatment of UC in patients naïve to biologic agents and/or Janus kinase inhibitors. Methods A systematic literature review (SLR) was performed on 15 November 2022, and covered all available records without time limit, using NICE DSU and PRISMA guidelines. NMA were conducted under a Bayesian framework, and a multinomial fixed-effect approach was used to model outcomes, clinical response and clinical remission, in the induction phase and among induction phase responders in the maintenance phase, in patients naïve to AT. Reported outcomes from trials with a treat-through design, such as ELEVATE UC 52, were recalculated to mimic those of a responder re-randomisation design; only responders in the induction phase were analysed in the maintenance phase. Data are presented as median relative risk (RR) of the treatment vs its comparator, along with corresponding 95% credible intervals (CrI). Prespecified sensitivity analyses were performed. Results Of 81 studies identified from the SLR, 21 and 11 RCTs were included in the induction and maintenance networks, respectively. For induction and maintenance phases, all therapies demonstrated benefit over placebo, consistent with phase 3 clinical trial data. In the NMA for clinical remission in the induction phase, etrasimod 2 mg had a statistically significant benefit over adalimumab 80/40 mg and 160/80 mg (RR [95% CrI] for treatment vs etrasimod 0.49 [0.29–0.78] and 0.67 [0.50–0.92], respectively), filgotinib 100 mg (0.55 [0.37–0.84]) and placebo; conversely, upadacitinib 45 mg had statistically significant benefit vs etrasimod (1.47 [1.07–2.03]; Table). There were no statistically significant differences for etrasimod vs other comparators. Similar results were observed for clinical response. In the maintenance phase, there were no statistically significant differences between etrasimod 2 mg and other treatments for clinical remission and clinical response (Table). Conclusion With respect to clinical remission and clinical response during induction and maintenance phases, etrasimod efficacy was similar to most comparators as a first-line AT. Differences in trial design and risk-benefit profiles of AT should be considered when interpreting NMA results.

Abstract Background Treatment options for moderate to severe ulcerative colitis (UC) are increasing rapidly, but lack of comparative efficacy trials make treatment choices a clinical challenge. We aimed to compare the relative efficacy of biologics and small molecules in achieving endoscopic and histological remission in patients with moderate to severe UC. Methods The literature was searched between January 1990 and July 2023. Phase 3 placebo or active comparator randomized controlled trials (RCTs) were included to assess the efficacy of biologics or small molecule drugs as induction or maintenance therapies for patients with UC. The primary outcome was induction and maintenance of endoscopic improvement (Mayo endoscopic score ≤1), whereas secondary outcomes were the induction and maintenance of endoscopic (Mayo endoscopic score = 0) and histological remission. Sub-analysis was performed based on previous exposure to biologic therapy. We used a random effects model and reported data as odd ratio (OR) with 95% confidence intervals (CIs). Results We identified 34 studies that met our inclusion criteria, with a total of 12,227 patients with UC. Upadacitinib was superior to most biologics in inducing endoscopic improvement and remission as well as maintaining endoscopic improvement and histological remission. Etrasimod ranked second, after upadacitinib, in maintenance of endoscopic improvement in both biologic naive (80.4%) and experienced (78.9%) patients. Infliximab was superior to adalimumab (OR 1.88, 95% CI, 1.07; 3.29) and vedolizumab (OR1.85, 95% CI, 1.13; 3.03) in inducing endoscopic improvement in overall UC patients. Filgotinib 200 mg (OR 4.76, 95% CI, 1.89; 5.88) and vedolizumab (OR 4.16, 95% CI, 2.94; 6.25) were superior to adalimumab in maintaining histological remission. In biologic naive patients, infliximab was found to be superior to adalimumab (OR 1.80, 95% CI, 1.05;3.07), vedolizumab (OR 5.20, 95% CI, 2.04;7.69), and golimumab (OR 6.30, 95% CI, 3.39;9.71) in inducing endoscopic improvement Conclusion Upadacitinib appears to be superior to other therapies in achieving both endoscopic improvement and remission as well as maintaining histological remission. Furthermore, etrasimod, filgotinib and tofacitinib ranked high in achieving these outcomes. This study highlights the role of small molecules drugs as effective alternatives to biologics.

ObjectivesAlthough various multi-week mindfulness programs have been introduced for stress reduction over the past decades, there is still little evidence on the effectiveness of short, self-applied interventions. This study aims to compare the effectiveness of virtual reality mindfulness and audio mindfulness, as well as a simple colouring session.MethodSixty-seven participants were initially enrolled, with 64 remaining after exclusions. They were randomly allocated to one of three face-to-face stress management interventions: virtual reality (VR) mindfulness, audio mindfulness or colouring. Before and after the 10-min intervention, questionnaires were administered to assess differences in perceived stress, psychological well-being, and engagement. Heart rate was also measured to indicate physiological stress.ResultsVR mindfulness was the only intervention to significantly increase wellbeing. Both VR and colouring significantly reduced stress, with VR producing the largest reduction in heart rate, though this was not statistically significant when compared to baseline. The three conditions were perceived as highly engaging, with the highest scores corresponding to VR mindfulness and the lowest to audio mindfulness.ConclusionsThis study shows that a single brief session of VR mindfulness can produce short-term beneficial effects in people at high risk of stress, greater than those achieved through colouring and audio mindfulness. This suggests promising direct implications for university mental health services, although future research is needed to explore long-term benefits as well as the relative efficacy of longer interventions.PreregistrationThis study is not preregistered.

325 Background: The phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies reported statistically significant improvement in PFS and OS with 1L zolbetuximab (anti-claudin-18 isoform 2 [CLDN18.2]) + mFOLFOX6 or CAPOX in pts with CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma. This network meta-analysis (NMA) indirectly compared the relative efficacy of 1L therapies. Methods: A systematic literature review of phase 2, 3, or unknown phase randomized, global trials of 1L therapies (capecitabine + cisplatin [CX]; capecitabine + oxaliplatin [CAPOX]; fluorouracil + cisplatin [CF]; oxaliplatin + folinic acid + fluorouracil [FOLFOX]; S-1 + cisplatin [SC]; nivolumab + CAPOX/FOLFOX; pembrolizumab + CF/CAPOX or CX; and zolbetuximab + CAPOX/FOLFOX) in adults with LA unresectable or mG/GEJ adenocarcinoma. To form a connected main network, FOLFOX and CAPOX were assumed equally efficacious and combined. In the latest publicly available data, hazard ratios (HRs) of PFS and OS for intent-to-treat (ITT) populations were extracted or reconstructed from Kaplan-Meier curves when not reported as inputs for Bayesian fixed-effects NMAs. Comparative effectiveness was reported using median HR and 95% credible intervals (CrIs). Results: Trials reporting ITT populations were included, resulting in 9 trials (6663 pts) for PFS analysis and 10 trials (6735 pts) for OS analysis representing 8 regimens. Pts were randomly assigned to an experimental arm vs FOLFOX/CAPOX. Pts on 1L zolbetuximab, nivolumab, or pembrolizumab in combination with CF/CAPOX or FOLFOX/CAPOX had significantly reduced risk of disease progression or death vs FOLFOX/CAPOX (Table). Zolbetuximab + FOLFOX/CAPOX had the highest probability of being ranked first in treatment efficacy for both PFS (probability =0.54) and OS (0.36); followed by pembrolizumab + CX (0.27) and pembrolizumab + CF/CAPOX (0.13) for PFS; and by pembrolizumab + CF/CAPOX (0.3) and nivolumab + FOLFOX/CAPOX (0.24) for OS. Conclusions: This NMA examined the relative benefit of different targeted therapies when combined with chemotherapy. Zolbetuximab + FOLFOX/CAPOX for CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma confers a significant PFS and OS benefit, similar to that achieved with PD-1/PD-L1 inhibitors + CF/CAPOX or FOLFOX/CAPOX. [Table: see text]

Interspinous devices (ISD) constitute a minimally invasive (MI) alternative to open surgery (i.e., laminectomy/decompression with/without fusion (i.e., posterior lumbar interbody fusion (PLIF)/posterolateral instrumented fusion (PLF)) for treating lumbar spinal stenosis (LSS). Biomechanically, static and/or dynamic ISD "offload" pressure on the disc space, increase intervertebral foraminal/disc space heights, reverse/preserve lordosis, limit range of motion (ROM)/stabilize the surgical level, and reduce adjacent segment disease (ASD). Other benefits reported in the literature included; reduced operative time (OR Time), length of hospital stay (LOS), estimated blood loss (EBL), and improved outcomes (i.e., ODI (Oswestry Disability Index), VAS (Visual Analog Scale), and/or SF-36 (Short-Form 36)). Various studies documented the relative efficacy and outcomes of original (i.e., Wallis), current (i.e., X-STOP, Wallis, DIAM, Aperius PercLID), and new generation (i.e., Coflex, Superion Helifix, In-Space) ISD used to treat LSS vs. open surgery. Although ISD overall resulted in comparable or improved outcomes vs. open surgery, the newer generation ISD provided the greatest reductions in critical cost-saving parameters (i.e., OR time, LOS, and lower reoperation rates of 3.7% for Coflex vs. 11.1% for original/current ISD) vs. original/current ISD and open surgery. Further, the 5-year postoperative study showed the average cost of new generation Coflex ISD/decompressions was $15,182, or $11,681 lower than the average $26,863 amount for PLF. Patients undergoing new generation ISD for LSS exhibited comparable or better outcomes, but greater reductions in OR times, EBL, LOS, ROM, and ASD vs. those receiving original/current ISD or undergoing open surgery.

Network meta-analysis (NMA) is an extension of pairwise meta-analysis (PMA) which combines evidence from trials on multiple treatments in connected networks. NMA delivers internally consistent estimates of relative treatment efficacy, needed for rational decision making. Over its first 20 years NMA's use has grown exponentially, with applications in both health technology assessment (HTA), primarily re-imbursement decisions and clinical guideline development, and clinical research publications. This has been a period of transition in meta-analysis, first from its roots in educational and social psychology, where large heterogeneous datasets could be explored to find effect modifiers, to smaller pairwise meta-analyses in clinical medicine on average with less than six studies. This has been followed by narrowly-focused estimation of the effects of specific treatments at specific doses in specific populations in sparse networks, where direct comparisons are unavailable or informed by only one or two studies. NMA is a powerful and well-established technique but, in spite of the exponential increase in applications, doubts about the reliability and validity of NMA persist. Here we outline the continuing controversies, and review some recent developments. We suggest that heterogeneity should be minimized, as it poses a threat to the reliability of NMA which has not been fully appreciated, perhaps because it has not been seen as a problem in PMA. More research is needed on the extent of heterogeneity and inconsistency in datasets used for decision making, on formal methods for making recommendations based on NMA, and on the further development of multi-level network meta-regression.

To review the efficacy and safety of two common postoperative regimens following Kahook Dual Blade goniotomy with phacoemulsification cataract extraction (KDB-CE). This is a retrospective review of eyes undergoing KDB-CE from May 2016 to 2018 by a single surgeon. Almost 12-month follow-up data were assessed for two common postop regimens-treatment with (1) topical prednisolone acetate 1% with pilocarpine 1% (pred-pilo) or (2) difluprednate 0.05% postoperatively. Postoperative results were compared to each respective baseline intraocular pressure (IOP) levels. There were 53 eyes in the difluprednate group and 25 eyes in the pred-pilo group. In the difluprednate group, the IOP decreased at postoperative day 1 (POD1) [16 ± 5 baseline vs 15 ± 5 POD1, mean ± standard deviation (SD) in mm Hg, and p = 0.321], but increased at postoperative week 1 (POW1) due to a 15% rate of IOP-spikes (19 ± 9, p = 0.099). The number of IOP-lowering drops decreased from baseline (2 ± 1 drops) to 1 ± 1 drops at POD1 (p < 0.0001), and remained at 1 ± 1 drops through postoperative month 12 (POM12) (p < 0.0001). In the pred-pilo group, there was a statistically significant decrease in mean IOP at POW1 (16 ± 4 POW1 vs 18 ± 6 baseline, p = 0.044), which persisted through POM6. The number of IOP-lowering drops was not statistically significantly lower from baseline at POM3 (2 ± 1 at POM3, p = 0.188). Spikes in IOP, corneal edema, and hyphema were the most common complications. Both postoperative regimens were effective following KDB-CE at reducing IOP at 12 months. The difluprednate group was likely to experience an IOP-spike at POW1 but used fewer IOP-lowering drops 12 months after KDB goniotomy. In the pred-pilo group, the number of IOP-lowering drops was equivalent to baseline levels at POM3. Aside from IOP spikes, there were similar complication rates observed between the two postoperative regimens. Due to demographic differences, it was not possible to compare relative IOP-lowering efficacy between the two postoperative regimens. It is efficacious and safe to use either postoperative regimen following KBD-CE. Postoperative trajectories may differ with respect to the postoperative regimen, but further randomized controlled trials are needed to compare various topical steroid medications for postoperative regimens following KDB-CE. Birnbaum F, Wakil S, Vu DM, et al. Postoperative Management of Kahook Dual Blade Goniotomy with Phacoemulsification Cataract Extraction. J Curr Glaucoma Pract 2023;17(4):169-174.