Short-term Safety Research Articles

Short-term Outcomes of a Dedicated Pelvic Exenteration Unit in a Tertiary Hospital in Malaysia

Background : Pelvic exenteration offers potentially curative resection for locally advanced pelvic malignancy. A dedicated unit performing this complex surgery is recommended to achieve optimal outcomes. Objectives : The aim of this paper is to show that pelvic exenterations can be performed with acceptable oncological and safe perioperative results in an appropriately resourced specialist centre. Methods : Patients undergoing pelvic exenteration in the Colorectal Unit, Hospital Kuala Lumpur between January 2017 and January 2024 were included. Patients operated in the initial setup period of the unit (January 2017 – July 2020) were compared to the second half (August 2020 – January 2024) with univariate analysis. Results : A total of 30 patients were included, with a significant increase in the unit caseload over the study period (n = 11 versus n = 19). There was an increased use of neoadjuvant therapy and an increase in stage of disease at presentation (p = 0.014) in the second half of the study period. More complex procedures were performed in the latter period, involving both bony and pelvic side wall resections. There was no difference in complication severity (Clavien Dindo) (p = 0.257) and R0 resection was achieved in 76.7% of operated cases. Conclusion : The development of a dedicated pelvic exenteration unit, leads to an increase in patient volume and an increase in the complexity of the procedures performed, without compromising short term outcomes and safety.

Endoscopic cardiac mucosal ligation: a novel minimally invasive procedure for gastroesophageal reflux disease

Background Our objective in this study was to evaluate the short-term clinical efficacy and safety of endoscopic cardiac mucosal ligation, a novel endoscopic procedure, in the treatment of gastroesophageal reflux disease (GERD). Methods Patients diagnosed with refractory GERD or recurrent patients due to drug withdrawal admitted to our hospital were recruited in this clinical trial. All GERD patients were treated with endoscopic cardiac mucosal ligation. Postoperatively, all patients received subsequent follow-ups for approximately four months to evaluate the efficacy and safety of this endoscopic procedure. Results A total of 13 GERD patients were enrolled. Endoscopic cardiac mucosal ligation was successfully performed in all cases. Postoperatively, relevant symptoms were significantly alleviated in 10 patients (76.9%). The average Gastroesophageal Reflux Disease Questionnaire (GERD-Q) score in all participants significantly decreased from preoperative 10.0 ± 3.5 to postoperative 7.8 ± 2.9 (p = .022). The average GERD symptom questionnaire score was 27.0 ± 12.0 prior to surgery, which significantly decreased to 18.3 ± 7.5 postoperatively (p = .032). No severe postoperative complications were observed during subsequent follow-ups. Conclusions Endoscopic cardiac mucosal ligation might be a novel effective and safe endoscopic procedure for GERD.

Short-term efficacy and safety of endoscopic injection of low dose of sclerotherapy and cyanoacrylate injection for type GOV1 gastric varices combined with endoscopic variceal ligation for esophageal varices.

To explore the short-term efficacy and safety of endoscopic low dose injection of sclerotherapy and cyanoacrylate for gastric varices (GVs) combined with endoscopic variceal ligation (EVL) for esophageal varices (EVs) in cirrhosis with type GOV1 varices. A total of 521 patients with cirrhosis and GOV1 varices, who were divided into emergence endoscopy treatment layer and secondary prophylaxis for rebleeding layer, were selected. All patients underwent combined therapy or EVL alone (ligation therapy) for the treatment of type GOV1 varices. The baseline between the two groups with significant differences were used as covariates for 1:1 propensity score matching. The early rebleeding rate was compared and the risk factors for rebleeding were identified in each layer. After propensity score matching, a total of 122 patients were included in the emergence endoscopy treatment layer, and 234 patients were included in the secondary prophylaxis layer. The early rebleeding rates in the combined therapy group vs. ligation therapy group was 4.92% vs. 16.39% (P = 0.04) and 2.56% vs. 1.71% (P = 0.65) in the emergency endoscopy layer and in the secondary prophylaxis layer, respectively. The median length of hospital stay after endoscopy was 8days vs. 9days (P = 0.004) and 7days vs. 6days (P = 0.47), in each layer respectively. There was no significant difference in the adverse reactions of endoscopic treatment. EVL treatment (OR: 3.84; 95% CI: 1.05-13.96; P = 0.04) and discontinuation of NSBB (non-selective beta-blocker) use after discharge (OR: 3.58; 95% CI: 1.20-10.67; P = 0.02) were independent risk factors for early rebleeding after endoscopy in the emergency endoscopy layer. Combined therapy is comparable with ligation therapy in the short-term efficacy and safety of in cirrhosis patients with secondary prophylaxis for rebleeding while it is superior to EVL alone in cirrhosis in the emergency endoscopy treatment as it could reduce the early rebleeding rate and shorten the length of hospital stay.

Co-designing Culturally Safe Indigenous Birth in High-Risk Obstetrics: Implementing Joyce's Principle with Inuit and Cree Families and Their Medical Providers.

Introduction. Maternal evacuation-the transfer of women from remote communities to urban hospitals for childbirth-negatively affects many Indigenous Peoples in Canada. A working group of perinatal service providers in Montreal sought to enhance cultural safety in a high-risk obstetrical unit serving evacuee Indigenous families. This article describes co-design, implementation, and evaluation of short-term cultural safety interventions with Indigenous stakeholders. Methods. Indigenous families and their non-Indigenous service providers displayed their recommendations for culturally safe birth using fuzzy cognitive mapping (FCMs). Joyce's Principle-a framework for securing culturally safe healthcare for Indigenous Peoples-guided their implementation. Results. Four high-priority FCM recommendations included an Indigenous-led cultural safety training for hospital staff. Third party evaluation showed a positive influence on cultural safety knowledge and actions. Discussion. Health services designed with Indigenous stakeholders in accordance with Joyce's Principle have the potential to enhance cultural safety of maternal evacuation.

Treatment of atopic dermatitis with abrocitinib in real practice in Spain: efficacy and safety results from a 24-week multicenter study.

Abrocitinib, a selective JAK 1 inhibitor, was recently approved in Europe. Despite its approval, real-world data on its efficacy and safety in treating moderate-to-severe atopic dermatitis (AD) remains limited. This study aimed to evaluate the short-term effectiveness and safety of abrocitinib in a real-life setting for patients with moderate-to-severe AD. We conducted a retrospective multicenter study involving adult patients with moderate-to-severe AD who started abrocitinib treatment between May 1, 2023, and September 30, 2023, in 15 Spanish hospitals. Treatment doses were 100 or 200 mg daily, based on clinical assessment. Data collection included patient demographics, AD history, comorbidities, previous treatments, and disease severity indicators such as SCORing atopic dermatitis (SCORAD), Eczema Area and Severity Index (EASI), body surface area, and Peak Pruritus NRS scores at baseline, 4, 12, and 24 weeks. Quality of life was measured using the Dermatology Life Quality Index (DLQI), and safety was assessed by monitoring adverse reactions and various biochemical parameters. The cohort comprised 76 patients with an average age of 33.93 years; 57.89% were male. Before abrocitinib, 36.84% were naïve to advanced therapies. The baseline mean scores were SCORAD 47.04, EASI 21.79, and DLQI 15.01. At Week 24, there were significant improvements: EASI was reduced to 2.81, and 70.58% of the patients achieved EASI 75. However, 18.42% discontinued treatment mainly due to inefficacy or adverse effects. The safety profile was favorable, with 22.37% reporting mild adverse events (AEs) and one serious case of cutaneous lymphoma. This first Spanish series assessing abrocitinib in real-world conditions reveals a significant improvement in AD symptoms and quality of life in a range of severity and prior treatment failures. Abrocitinib was well-tolerated, with few serious AEs, highlighting its potential as an effective treatment option for AD.

Real-World safety and effectiveness of evolocumab in primary hypercholesterolemia and mixed dyslipidemia in Saudi Arabia

IntroductionEvolocumab’s short-term efficacy and safety were proven in phase-3 clinical trial, but its long-term safety and effectiveness in the Saudi population are yet to be studied. The aim of this study was to assess the long-term safety and effectiveness of evolocumab in Saudi patients with primary hypercholesterolemia or mixed dyslipidemia. MethodA retrospective cohort study evaluated adult patients who had newly been prescribed evolocumab for hypercholesterolemia or mixed dyslipidemia. Safety events included myocardial infarction, unstable angina, stroke, transient ischemic attack, heart failure, rhabdomyolysis, renal dysfunction, and myalgia. Effectiveness outcomes included changes in lipid profiles from baseline, assessed at 6-, 12-, 18-, and 24-month. ResultsThe study sample were 469 who newly prescribed evolocumab, from which 69.1 % being male, were included. The most prevalent comorbidities were coronary artery disease, diabetes, and hypertension. Statin was the most commonly used therapy. The most common adverse events at 6-month follow-up, based on the incidence rate per 1000 person-years, were coronary revascularization (63.20), myalgia (44.96), myocardial infarction (31.53), unstable angina (31.49), heart failure (26.94), rhabdomyolysis without renal dysfunction (8.93), transient ischemic attack (4.46), and rhabdomyolysis with renal dysfunction (4.46). Stroke incidence increased with follow-up length, from 8.87 per 1000 person-years at 6 months to 12.84 per 1000 person-years at 24 months. Evolocumab use significantly reduced LDL and total cholesterol levels at 6, 12, 18, and 24 months follow-up, while having no significant effect on HDL or triglycerides levels. ConclusionEvolocumab appeared to be safe and effective therapeutic option for patients with primary hypercholesterolemia or mixed dyslipidemia to potentially reduce LDL levels to therapeutic levels when statins are insufficient.

Understanding the impact of COVID-19 on yoga instruction: Examining teaching methodology, class components, and injury patterns in the Northeastern US

ObjectivesThis study aimed to examine the impact of COVID-19 on the perspectives of yoga instructors (YIs) regarding teaching methodology, class components, and yoga-related injuries among their clients DesignA cross-sectional design in this study. SettingA total of 407 YIs from Northeastern United States completed a customized, web-based survey. Main outcome measuresChi-square tests were carried out to determine changes in yoga teaching format before and during the pandemic, as well as the counts of yoga related injuries between face-to-face (FtoF) and online teaching format. Independent t tests were used to compare the characteristics of yoga teaching elements. ResultsDuring the pandemic, 47 % of YIs adopted online teaching, followed by a mixed (45.9 %) format and FtoF (7.1 %) instruction. Both online and FtoF classes showed similar trends, with most reporting class sizes of 4–6, followed by 7–9 and then 1–3 students. Regardless of the teaching format, most YIs performed sun salutations and practiced mixed yoga styles. Among the YIs teaching yoga online, 84.6 % expressed their willingness to continue offering online classes post-pandemic and perceived the quality of online yoga teaching as high. Importantly, the number of injuries was low, and there were no significant differences in injury counts between FtoF (3.6 %) and online (4.2 %) teaching formats (p > 0.05). The most common injury in all forms of teaching yoga was a sprain/strain (42.9 %). ConclusionsThese findings could inform the development of research studies to examine the long-term feasibility and effectiveness of delivering online yoga since short-term benefits, safety, and YI acceptance appear favorable.

Biodiversity-safeguarding threshold for urea-fertilizer application on paddy fields: Protozoa-based toxicity tests

Urea is a widely applied fertilizer to enhance crop yields. Ecological risks associated with the excessive application of urea fertilizer threaten the paddy fields' sustainable agriculture and biodiversity preservation. There are no practical thresholds based on proven data on microbial communities. Protozoa are nitrogen-sensitive organisms. For the first time, this study conducted acute and chronic urea toxicity tests on eight species of organisms. The results indicate that Blepharisma sp. is the most sensitive species to urea exposure and is a suitable indicator for determining the safe threshold of urea. This study estimated the predicted no-effect concentration using species sensitivity distribution curves. Subsequently, it established the threshold for urea application in rice fields based on the fields' area and the surface water's height. The short-term safety threshold for urea in the studied paddy field with black soil is 87.7mg/L, equivalent to 43.85kg of urea per hectare for a single nitrogen fertilizer application. The long-term safety threshold is 5.02mg/L, representing the concentration for re-applicating urea. The biodiversity-safeguarding application threshold provides the basis for developing a urea fertilizer reduction protocol to safeguard the paddy fields' biodiversity.

Subtotal vaginal hysterectomy with cervical ring preservation and cervical stump suspension to the sacrospinous ligament in women with pelvic organ prolapse: An exposed cohort study

To evaluate the short-term safety and efficacy of vaginal hysterectomy with cervical preservation in patients with genital prolapse stages II to IV. This is a descriptive case series study. It included women with genital prolapse stages II to IV, indicated for vaginal hysterectomy, with negative cervicovaginal cytology for malignancy, who underwent subtotal vaginal hysterectomy with suspension of the cervical stump to the sacrospinous ligament between June 1 and December 31, 2023, at a high-complexity general clinic. Sociodemographic variables and complications six months postoperatively were analyzed. The surgical technique is presented, and descriptive analysis, along with a detailed surgical technique exposition of cervical stump suspension to the sacrospinous ligament, was conducted. During the described period, 10 patients consulted, of whom eight met the inclusion criteria. The mean duration of the surgical procedure was 133 minutes. Average blood loss was 200 cc. One patient required analgesic use of pregabalin for peripheral neuropathic pain, achieving adequate postoperative pain control. No other intraoperative or postoperative complications were reported. No prolapse recurrence was observed six months postevaluation. Subtotal vaginal hysterectomy with cervical stump suspension to the sacrospinous ligament is a surgical repair technique that could be considered for the management of uterine prolapse. Randomized studies comparing this technique with other management alternatives are needed to evaluate its long-term efficacy and safety.

Safety of left atrial appendage amputation during cardiothoracic surgery

Abstract Background Patients with atrial fibrillation (AF) are at risk for ischemic strokes, often originating from the left atrial appendage (LAA). Preventive LAA amputation (LAAA) during cardiac surgery has been shown to reduce ischemic stroke risk, both in patients with and without AF. However, the short-term safety and functional implication of LAAA in non-AF patients remain poorly understood. Besides possible surgical complications, there are suggestions that LAAA could lead to postoperative AF or influence neurohumoral changes resulting in fluid overload. Purpose To evaluate the safety of LAAA in patients without a history of AF undergoing routine cardiac surgery. Methods Patients underwent elective cardiac surgery between May 5 2015 and April 18 2018 in two high volume centers. Main inclusion criteria were a CHA2DS2-VASc≥ 2 and no history of AF. Patients without a history of AF, that participated in the PREDICT-AF study underwent concomitant LAAA and were compared with patients undergoing cardiothoracic surgery who were approached for participation in PREDICT-AF, but declined and subsequently did not undergo LAAA. Informed consent for the retrospective use of data was obtained through an opt-out procedure in these patients. The primary outcome of this analysis was the number of patients with any serious adverse event within 30 days postoperatively. Secondary outcomes were AF within 30 days postoperatively, death, rethoracotomy, time on extra corporal circulation(ECC) and heart failure related symptoms assessed through congestion on x-chest and weight trends. Adverse events were independently adjudicated by a cardiothoracic surgeon using pre-specified definitions. Results 150 patients in PREDICT-AF underwent LAAA. 284 Eligible patients declined participation and formed the control group. Patients in the LAAA group were more frequently male (87.3% vs 72.5%; p=0.001), were taller (176.0cm ± 8.2 vs 172.6cm ± 9.9; p<0.001) and weighed more (86.1kg CI[80.0, 92.2] vs 81.6kg CI[71.9, 91.1]; p=0.001) compared to controls. There were no significant differences in occurrences of serious adverse events (8% vs 12%; p=0.265), deaths (1.3% vs 1.8%; p=1) or rethoracotomies (3.3% vs 1.8%; p=0.483) between the LAAA and control group. Also, there was no difference in the incidence of postoperative AF (57, 38% vs 90, 31.7%; p=0.225), ECC time (104.5 minutes CI[81.0, 129.0] vs 98.0 CI[80.0, 124.5] p=0.371) or the presence of chest x-ray congestion (26.0% vs 27.8%; p=0.771) between the groups (Figure 1A). The spline plot of perioperative weight change from baseline, reveals no notable differences between the two groups (Figure 1B). Conclusion LAAA during routine cardiothoracic surgery is not associated with more surgical complications, postoperative atrial fibrillation or heart failure related symptoms. Given the generally high AF risk in patients undergoing cardiothoracic surgery, a strategy to preemptively resect the LAA may be feasible and safe.Figure 1 A & B

A systematic review and meta-analysis of the efficacy and safety of combined mechanical circulatory support in cardiogenic shock complicating acute myocardial infarction

Abstract Background Cardiogenic shock complicating acute myocardial infarction (CSAMI) is a severe complication associated with unacceptably high mortality rates. Since early revascularisation was introduced more than 20 years ago, no subsequent innovation has demonstrated conclusive efficacy in reducing mortality in CSAMI. While mechanical circulatory support (MCS) has emerged as a potential intervention, randomised controlled trials evaluating independent use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and intra-aortic balloon pump (IABP) have not shown benefit in CSAMI. In contrast, systematic reviews of observational studies have revealed significant mortality reduction when CSAMI was treated with combined use of MCS, specifically VA-ECMO in conjunction with a left ventricular (LV) unloading device (Impella or IABP). Combination MCS (VA-ECMO + LV unloading) may therefore present a promising approach to CSAMI, but an unresolved dilemma concerning the optimal selection between two LV unloading devices (VA-ECMO + Impella vs VA-ECMO + IABP) warrants further investigation and clarification. Purpose We perform the first systematic review and meta-analysis assessing the short-term efficacy and safety of VA-ECMO + Impella versus VA-ECMO + IABP in treatment of CSAMI. Methods A systematic search was performed on the EMBASE and MEDLINE databases. Studies reporting the short-term (30-day/inpatient) mortality and complications of adult patients with CSAMI treated with VA-ECMO + Impella and VA-ECMO + IABP were included. Fixed effect meta-analyses using Mantel-Haenszel model was used to analyse the pooled odds ratio for short-term mortality and major complications. Subgroup analysis was performed including studies with ACS predominant CS (Cause of CS 100% by AMI). Results Four observational studies with 14,247 patients were included. These studies showed high heterogeneity for the total CSAMI cohort and low heterogeneity for the ACS predominant cohort. There was no significant difference in mortality between VA-ECMO + Impella and VA-ECMO + IABP 56.5% vs 66.5%; OR, 0.90; 95% CI, 0.79–1.02; P=0.09. However, VA-ECMO + Impella was associated with significantly lower mortality in patients with ACS predominant CS 53.2% vs 67.7%; OR, 0.72; 95% CI, 0.62–0.85; P<0.0001. VA-ECMO + Impella was associated with significantly higher risk of major bleeding 15.1% vs 8.6%; OR, 1.87; 95% CI, 1.50–2.32; P<0.00001 and vascular complications 15.0% vs 6.7%; OR, 1.75; 95% CI, 1.41–2.18; P<0.00001. Conclusions When comparing LV unloading devices in patients with CSAMI requiring combination MCS, VA-ECMO + Impella was superior in mortality reduction only in the cohort where 100% of CS was caused by AMI. Concomitantly, VA-ECMO + Impella was associated with greater risk of major bleeding and vascular complications. Additional randomised studies are needed to validate and strengthen the findings presented in these observational data.Forrest plot on short-term mortalityForrest plot on major complications

Comparative Outcomes of Unilateral vs Bilateral Revascularization in Moyamoya Disease: A Multicenter Retrospective Study.

Moyamoya disease (MMD) is characterized by progressive steno-occlusion of the internal carotid arteries, leading to compensatory collateral vessel formation. The optimal surgical approach for MMD remains debated, with bilateral revascularization potentially offering more comprehensive protection but involving more extensive surgery compared to unilateral revascularization. This study aims to compare bilateral revascularization and unilateral revascularization short-term safety profile in the treatment of MMD. This multicenter retrospective study included patients with MMD who underwent surgical revascularization at 13 academic institutions. Patients were categorized into unilateral and bilateral revascularization groups. Data collected included demographics, clinical characteristics, and outcomes. Propensity score matching was used to balance baseline characteristics. Statistical analyses were conducted using Stata (V.17.0; StataCorp). A total of 497 patients were included, including 90 who had bilateral revascularization and 407 who had unilateral revascularization. Bilateral revascularization was associated with more perioperative asymptomatic strokes (10% vs 2.4%; odds ratio [OR] 4.41, 95% CI 1.73 to 11.19, P = .002) and higher rates of excellent functional outcomes (modified Rankin Scale 0-1) at discharge (92.2% vs 79.1%; OR 3.12, 95% CI 1.39 to 7, P = .006). After propensity score matching, 57 matched pairs were analyzed. There was a higher rate, though not statistically significant difference, of perioperative stroke in the bilateral revascularization group (15.7% vs 8.7%; OR 1.95, 95% CI 0.61 to 6.22, P = .26). No significant differences were noted in modified Rankin scale 0 to 1 and 0 to 2 scores at discharge, National Institute of Health Stroke Scale at discharge, intraoperative complications, or length of hospital stay. The follow-up stroke rates were also not significantly different (OR 0.40, 95% CI 0.11 to 1.39, P = .15). This study found no significant differences between bilateral and unilateral revascularization in MMD. Patients who had bilateral revascularization had higher tendency of perioperative stroke, though not statistically significant. Further prospective studies are needed to validate these results.

Efficacy and safety of thalidomide in patients with β-thalassemia intermedia and major.

To investigate the short-term and long-term efficacy and safety of thalidomide in the treatment of intermediate and severe β-thalassemia. We analyzed patients with intermediate and severe β-thalassemia treated at our hospital from February 2019 to February 2024. Patients who received treatment for more than 3 months were included. The efficacy of thalidomide was assessed by comparing changes in hemoglobin (Hb), ferritin, bilirubin, and Hb electrophoresis before and after treatment. Adverse drug reactions during treatment were also recorded. A total of 42 β-thalassemia patients were included, with thalidomide dosages ranging from 75 to 150 mg/d. The response rates at 1, 3, and 6 months of treatment were 73.8% (31/42), 75.0% (24/32), and 94.7% (18/19), respectively. The increase in Hb levels was primarily attributed to fetal hemoglobin (HbF). After 1 month of treatment, the HbF percentage increased from a baseline of 34.04 ± 27.58% to 56.25 ± 28.40% (P < .001). At 3 and 6 months, HbF further increased to 67.21 ± 27.12% (P < .001) and 73.93 ± 22.96% (P < .001), respectively. The average duration of thalidomide treatment was 25.3 ± 9.2 months (range: 4-60 months), with 6 patients treated for over 60 months and 18 patients for over 48 months. Two homozygous patients who failed thalidomide treatment achieved Hb levels above 100 g/L and discontinued transfusion therapy after 3 months of hydroxyurea treatment. The most common adverse reaction was somnolence, which was mild and tolerable. Thalidomide demonstrates significant and sustained therapeutic effects in β-thalassemia patients. The adverse reactions are mild and tolerable, allowing patients to continue treatment.

Comparative Validation of Scintillator Materials for X-Ray-Mediated Neuronal Control in the Deep Brain.

When exposed to X-rays, scintillators emit visible luminescence. X-ray-mediated optogenetics employs scintillators for remotely activating light-sensitive proteins in biological tissue through X-ray irradiation. This approach offers advantages over traditional optogenetics, allowing for deeper tissue penetration and wireless control. Here, we assessed the short-term safety and efficacy of candidate scintillator materials for neuronal control. Our analyses revealed that lead-free halide scintillators, such as Cs3Cu2I5, exhibited significant cytotoxicity within 24 h and induced neuroinflammatory effects when injected into the mouse brain. In contrast, cerium-doped gadolinium aluminum gallium garnet (Ce:GAGG) nanoparticles showed no detectable cytotoxicity within the same period, and injection into the mouse brain did not lead to observable neuroinflammation over four weeks. Electrophysiological recordings in the cerebral cortex of awake mice showed that X-ray-induced radioluminescence from Ce:GAGG nanoparticles reliably activated 45% of the neuronal population surrounding the implanted particles, a significantly higher activation rate than europium-doped GAGG (Eu:GAGG) microparticles, which activated only 10% of neurons. Furthermore, we established the cell-type specificity of this technique by using Ce:GAGG nanoparticles to selectively stimulate midbrain dopamine neurons. This technique was applied to freely behaving mice, allowing for wireless modulation of place preference behavior mediated by midbrain dopamine neurons. These findings highlight the unique suitability of Ce:GAGG nanoparticles for X-ray-mediated optogenetics. The deep tissue penetration, short-term safety, wireless neuronal control, and cell-type specificity of this system offer exciting possibilities for diverse neuroscience applications and therapeutic interventions.

Infliximab versus interferon-alpha in the treatment of Behçet's Syndrome: Clinical data from the BIO-BEH&Ccedil;ET'S randomised controlled trial.

Whilst biologic therapy is used for Behçet's Syndrome of all subtypes refractory to first-line immunomodulation, there has been an absence of high-quality evidence-and no predictive biomarkers to optimally inform choice. BIO-BEH&Ccedil;ET'S was a randomised, controlled, head-to-head clinical trial comparing the two most frequently used biologics in active refractory Behçet's. Bayesian-designed, pragmatic, standard of care, two-arm, parallel head-to-head trial at four UK centres. Patients with active disease randomised to infliximab or interferon-α2a, and received follow-up with symptom-directed examination at Weeks 12 and 24. Primary outcome was Behçet's Disease Activity Index (BDAI) at 12 weeks. Secondary outcomes included BDAI at 24 weeks and significant improvement in individual organ systems, including ocular symptoms, oral and genital ulcers, arthritis pain, quality of life, disease activity, and steroid use. Biomarkers were also investigated but are reported elsewhere. 79 patients were recruited. Both treatments were equally effective, with a mean difference of 0.13 in BDAI (80% CI: -0.19, 0.46). No significant differences were observed for secondary outcomes, though there were clinically significant within-group reductions for each over time. A modest steroid-sparing effect was observed, with complete cessation of steroids in 20% and 44% of those randomised to infliximab and interferon-α2a, respectively. There was a trend for minor benefit in favour of infliximab in terms of tolerability and persistence. In this first reported, high-quality, head-to-head trial of two biologics in Behçet's, both infliximab and interferon-α2a showed comparable short-term clinical efficacy and safety in refractory active disease of all subtypes. EudraCT: 2014-005390-36; ISRCTN: ISRCTN49793874.

Model-Informed Drug Development-Based Approval of Intravenous Secukinumab for the Treatment of Adult Patients with Active Psoriatic Arthritis, Active Ankylosing Spondylitis, and Active Non-Radiographic Axial Spondyloarthritis.

On October 6, 2023, the US Food and Drug Administration (FDA) approved an intravenous (IV) formulation and dosage of Cosentyx® (secukinumab), for the treatment of adult patients with active psoriatic arthritis (PsA), active ankylosing spondylitis (AS), and active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation. Clinical pharmacokinetics (PK), efficacy, and short-term placebo-controlled safety data were available from clinical studies (NCT04156620 and NCT04209205) with the to-be-marketed IV formulation using a maintenance dosage 3 mg/kg every 4 weeks (q4w), which was different from the dose approved (1.75 mg/kg q4w). The IV dosage of 3 mg/kg utilized in these two trials resulted in exposures (Cmax,ss) significantly higher than those for the approved subcutaneous (SC) regimens. Further, there is limited long-term safety information available for this 3 mg/kg q4w IV dose. To address this important limitation, a model-informed drug development (MIDD) approach was employed to leverage available clinical PK, efficacy, and safety data from the secukinumab development program to identify a maintenance IV dosing regimen, 1.75 mg/kg IV q4w, that better approximated the relevant SC secukinumab exposures for which efficacy and safety have been established. The MIDD analyses were used to support approval of this IV dosing regimen not directly studied in the indications sought for licensure, PsA, AS, and nr-AxSpA.

Delayed onset Spontaneous Hyphema after OMNI® Surgical System

Minimally invasive glaucoma surgery (MIGS) offers options for glaucoma treatment that have generally improved safety profiles compared with filtering surgery. MIGS vary in design and procedure, but all angle-based MIGS function by bypassing or removing aqueous humor outflow resistance at the level of the trabecular meshwork. This can lower intraocular pressure but also remove the blood-aqueous barrier. Most studies of MIGS report on relatively short-term safety, but awareness of potential long-term complications is critical for optimal patient management. This case report describes a patient with recurrent and refractory delayed onset spontaneous hyphema after OMNI procedure. To the best of our knowledge, this is the first case report describing this complication of the OMNI surgical system.

Agomelatine in pediatric patients with moderate to severe major depressive disorder: an open-label extension study.

Major depressive disorder (MDD) in young people is a common psychiatric disorder, but treatment options are limited. Agomelatine has demonstrated short-term efficacy and safety in pediatric patients. We report here the results of a 92-week open-label extension (OLE). The international, multicenter, double-blind, study randomized 400 patients (80 children, 320 adolescents) with moderate-to-severe MDD to one of four treatment groups: agomelatine 10mg (n = 102), agomelatine 25mg (n = 95), placebo (n = 103), and fluoxetine 10-20mg (n = 100). After 12weeks, patients who could benefit from treatment continuation were offered entry into an optional OLE during which they received agomelatine 10 or 25mg for a further 92weeks. A total of 339 patients (271 adolescents) entered the OLE. Treatment groups considered for the OLE analysis reflected those received in the double-blind and OLE periods: agomelatine (10 or 25mg) in both (ago/ago, n = 170); placebo then agomelatine 10-25mg (pcb/ago, n = 85); or fluoxetine then agomelatine 10-25mg (fluox/ago, n = 84). Mean age (± SD) at entry into the double-blind phase (Week 0) was 13.6 ± 2.7years and 61.9% were female. Mean changes in Children's Depression Rating Scale revised (CDRS-R) raw total score from Week 12 to last post-Week 12 value in the three groups were - 16.3 ± 12.2 (ago/ago), - 18.9 ± 16.1 (pcb/ago), and - 16.1 ± 15.5 (fluox/ago), reflecting the difference in efficacy between treatments during the double-blind period, and heterogeneity at W12 between the treatment groups. Adverse events considered related to treatment occurred in 14.5% of patients: 15.3% ago/ago, 16.5% pcb/ago, and 10.7% fluox/ago. Three patients (all adolescents) experienced treatment-related severe adverse events: two treated with ago/ago and one treated with pcb/ago. Among the adolescents, one treatment-related severe adverse event in a patient in the pcb/ago group led to study withdrawal. Agomelatine was associated with continuous improvement in depressive symptoms without unexpected safety signals. These findings support the safe use of agomelatine in a pediatric population with moderate-to-severe MDD for up to 104weeks.Trial registration No: EUDRACT No. 2015-002181-23.

Infection risk with JAK inhibitors in dermatoses: a meta-analysis.

Evolving evidence suggests that Janus Kinase Inhibitors (JAKi) may predispose to certain infections, including tuberculosis and human herpes viruses. This review aimed to compare the infection risk in patients on a systemic JAKi for a dermatologic indication to a placebo. A systematic review was carried out from inception to June 2023, using the EMBASE, Medline, SCOPUS, and Cochrane Library of Registered Trials databases. Eligible studies included placebo-controlled randomized trials that investigated the incidence of infection in patients with a dermatologic indication. Primary outcomes included the most commonly reported infections pertaining to serious and opportunistic infections, upper respiratory tract infections, nasopharyngitis, herpes simplex, varicella zoster, tuberculosis, neutropenia, and lymphopenia. A meta-analysis of incidence ratios was conducted to determine odds ratios (OR), with a 95% confidence interval (CI) analysis. The meta-analysis found no increased risk of serious (OR: 0.92, 95% CI: 0.61-1.43, P = 0.74) or opportunistic infections (OR: 0.65, 95% CI: 0.32-1.31, P = 0.23). The incidence of varicella-zoster infections was significantly higher in the JAKi cohort (OR: 1.72, 95% CI: 1.08-2.72, P = 0.022). From 25 studies, there was no overall increased risk of herpes simplex infections (OR: 1.43, 95% CI: 0.93-2.23, P = 0.102) to placebo; however, a significantly higher risk in those with atopic dermatitis to alopecia areata was demonstrated (OR: 1.73, 95% CI: 1.13-2.69, P = 0.013). The results of this analysis do not suggest an increased risk of serious and opportunistic infections in those on JAKi compared to placebo. However, they support an increased risk of varicella-zoster infections and a higher risk of herpes simplex infections in those with atopic dermatitis to alopecia areata. The results of this report support these agents' short-term safety but signal that vigilance should be practiced in patients at risk for serious or recurrent herpes virus infections.

Efficacy and Safety of Suxiao Jiuxin Pills in the Treatment of Chronic Coronary Syndrome with Intolerance to Adverse Effects of Long-acting Nitrates: A Multicenter, Randomized, Double-blind, Placebo-controlled Study

BackgroundThis study aims to investigate the short-term effects and safety of adjunct Suxiao Jiuxin Pills (SJPs) on conventional therapy in chronic coronary syndrome (CCS) patients who are intolerant to the adverse effects of long-acting nitrates.MethodsThis was a multicenter, randomized, double-blind, placebo-controlled trial. A total of 174 CCS participants from eight clinical study centers in China were included in the modified intention-to-treat analyses. Participants with CCS and intolerance to the adverse effects of long-acting nitrates were recruited and randomized to either the SJPs or the placebo group for a duration of 4 weeks.ResultsCompared to the placebo group, the SJPs group showed a significant improvement in the efficacy rate after 4 weeks (OR = 2.43, 95% CI = 1.32 to 4.47, P = 0.004). Besides, individuals without a history of alcohol consumption showed a greater improvement in the SAQ summary score compared to those with a history of alcohol consumption.ConclusionAdjunctive SJPs enhance the effectiveness of short-term conventional anti-angina treatment for patients with CCS who experience intolerance to long-acting nitrates, without significant adverse effects during application.Trial registrationChinese Clinical Trials Registry Platform, ChiCTR2100050066. Registered 16 August 2021, https://www.chictr.org.cn/showproj.html?proj=131470.