Peripheral inflammatory and metabolic markers as potential biomarkers in treatment-resistant schizophrenia: Insights from a Qatari Cohort.

Schizophrenia presents significant diagnostic and treatment challenges, particularly in distinguishing between treatment-resistant (TRS) and non-treatment-resistant schizophrenia (NTRS). This cross-sectional study analyzed routine laboratory parameters as potential biomarkers to differentiate TRS, NTRS, and healthy individuals within a Qatari cohort. The study included 31 TRS and 38 NTRS patients diagnosed with schizophrenia, alongside 30 control subjects from the Qatar Biobank.

Leucovorin and Fluorouracil With or Without Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer.

Purpose: In a previous study of treatment for advanced colorectal cancer, the LV5FU2 regimen, comprising leucovorin (LV) plus bolus and infusional fluorouracil (5FU) every 2 weeks, was superior to the standard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen. This phase III study investigated the effect of combining oxaliplatin with LV5FU2, with progression-free survival as the primary end point.

Patients And Methods: Four hundred twenty previously untreated patients with measurable disease were randomized to receive a 2-hour infusion of LV (200 mg/m/d) followed by a 5FU bolus (400 mg/m/d) and 22-hour infusion (600 mg/m/d) for 2 consecutive days every 2 weeks, either alone or together with oxaliplatin 85 mg/m as a 2-hour infusion on day 1.

Thick and diffuse cisternal clot independently predicts vasospasm-related morbidity and poor outcome after aneurysmal subarachnoid hemorrhage.

Objective: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant morbidity and mortality. The presence of thick, diffuse subarachnoid blood may portend a worse clinical course and outcome, independently of other known prognostic factors such as age, aneurysm size, and initial clinical grade.

Methods: In this post hoc analysis, patients with aSAH undergoing surgical clipping (n = 383) or endovascular coiling (n = 189) were pooled from the placebo arms of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS)-2 and CONSCIOUS-3 randomized, double-blind, placebo-controlled phase 3 studies, respectively.

Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction.

Background: Oral P2Y receptor antagonists exhibit delayed onset of platelet inhibition in patients with acute myocardial infarction (AMI). Selatogrel is a potent, highly selective, and reversible P2Y receptor antagonist with a rapid onset and short duration of action.

Objectives: This study sought to assess inhibition of platelet aggregation following subcutaneous administration of selatogrel in patients with AMI.

Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes.

Aims: To study the pharmacodynamics and pharmacokinetics of selatogrel, a novel P2Y12 receptor antagonist for subcutaneous administration, in patients with chronic coronary syndromes (CCS).

Methods And Results: In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcutaneous selatogrel (8 mg, n = 114; or 16 mg, n = 115) was compared with placebo (n = 116) (ClinicalTrials.gov: NCT03384966).

Thick and Diffuse Subarachnoid Blood as a Treatment Effect Modifier of Clazosentan After Subarachnoid Hemorrhage.

Background and Purpose- Clazosentan, an endothelin receptor antagonist, has been shown to reduce angiographic vasospasm and vasospasm-related morbidity after aneurysmal subarachnoid hemorrhage (SAH), although no effect on long-term functional outcome has been demonstrated. Thick clot on initial computed tomography is associated with an increased risk of vasospasm and delayed cerebral ischemia. In this post hoc analysis, we hypothesized that use of clazosentan in this subpopulation would provide stronger benefit.

Reversal of Vasospasm with Clazosentan After Aneurysmal Subarachnoid Hemorrhage: A Pilot Study.

Background: Clazosentan, an endothelin-1 receptor antagonist, has been shown to prevent the development of large vessel angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). It has been hypothesized that clazosentan can also reverse established angiographic vasospasm.

Methods: The REVERSE (resynchronization reverses remodeling in systolic left ventricular dysfunction) study was a prospective, multicenter, open-label, 2-stage pilot study of adult patients with aSAH who had received intravenous clazosentan (15 mg/hour) after developing moderate-to-severe angiographic vasospasm.

Efficacy and safety of almorexant in adult chronic insomnia: a randomized placebo-controlled trial with an active reference.

Background And Objectives: The orally active dual OXR and OXR antagonist, almorexant, targets the orexin system for the treatment of primary insomnia. This clinical trial assessed the effect of almorexant on sleep maintenance and other sleep endpoints, and its safety and tolerability in adults.

Patients And Methods: Prospective, randomized, double-blind, placebo-controlled, active referenced trial in male and female adults aged 18-64 years with chronic, primary insomnia.

Efficacy and safety of setipiprant in seasonal allergic rhinitis: results from Phase 2 and Phase 3 randomized, double-blind, placebo- and active-referenced studies.

Background: Antagonism of chemoattractant receptor-homologous molecule on T-helper type-2 cells (CRTH2), a G-protein coupled receptor for prostaglandin D2, could be beneficial for treating allergic disorders. We present findings on the efficacy and safety/tolerability of a CRTH2 antagonist (setipiprant) in participants with seasonal allergic rhinitis (AR) in a real-life setting over 2 weeks.

Methods: A Phase 2 trial and a Phase 3 trial were conducted at seven centers in Texas, USA during the Mountain Cedar pollen season.

A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis.

Ruxolitinib, a potent Janus kinase 1/2 inhibitor, resulted in rapid and durable improvements in splenomegaly and disease-related symptoms in the 2 phase III COMFORT studies. In addition, ruxolitinib was associated with prolonged survival compared with placebo (COMFORT-I) and best available therapy (COMFORT-II). We present a pooled analysis of overall survival in the COMFORT studies using an intent-to-treat analysis and an analysis correcting for crossover in the control arms.

Safety, tolerability and pharmacokinetics of single escalating doses of indacaterol, a once-daily beta2-agonist bronchodilator, in subjects with COPD.

Objectives: To assess the safety and tolerability of 4 doses of indacaterol, a once-daily beta2-agonist, in subjects with chronic obstructive pulmonary disease (COPD). The 24-h bronchodilator effect and pharmacokinetics of indacaterol were also investigated.

Methods: 16 subjects aged 43 - 72 years with mild/moderate COPD were each given single doses of indacaterol of 400, 1,000, 2,000 and 3,000 µg, via a single-dose dry powder inhaler.

Bronchodilator effects of indacaterol and formoterol in patients with COPD.

Background: Resting inspiratory capacity (IC) reflects static hyperinflation in chronic obstructive pulmonary disease (COPD). This study compared the effects of formoterol and indacaterol, a novel once-daily ultra-long-acting beta(2)-agonist (or ultra-LABA), on resting IC and forced expiratory volume in 1 s (FEV(1)).

Methods: Thirty patients with COPD (mean FEV(1)/FVC 0.

Reduction in labile plasma iron during treatment with deferasirox, a once-daily oral iron chelator, in heavily iron-overloaded patients with beta-thalassaemia.

This subgroup analysis evaluated the effect of once-daily oral deferasirox on labile plasma iron (LPI) levels in patients from the prospective, 1-yr, multicentre ESCALATOR study. Mean baseline liver iron concentration and median serum ferritin levels were 28.6 +/- 10.

Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with beta-thalassaemia: the ESCALATOR study.

Objective: Many patients with transfusional iron overload are at risk for progressive organ dysfunction and early death and poor compliance with older chelation therapies is believed to be a major contributing factor. Phase II/III studies have shown that oral deferasirox 20-30 mg/kg/d reduces iron burden, depending on transfusional iron intake.

Methods: The prospective, open-label, 1-yr ESCALATOR study in the Middle East was designed to evaluate once-daily deferasirox in patients > or =2 yr with beta-thalassaemia major and iron overload who were previously chelated with deferoxamine and/or deferiprone.

Octreotide LAR vs. surgery in newly diagnosed patients with acromegaly: a randomized, open-label, multicentre study.

Objective: This prospective randomized study evaluated the efficacy and safety of octreotide LAR vs. surgery in newly diagnosed acromegalic patients.

Methods: Totally 104 male and female patients were enrolled in a 50-week, exploratory, open-label and randomized study.

FTY720 versus mycophenolate mofetil in de novo renal transplantation: six-month results of a double-blind study.

Background: FTY720 is a novel immunomodulator that was developed to produce optimal graft protection with improved safety and tolerability. Phase II studies have demonstrated the efficacy of FTY720 up to the doses of 2.5 mg with full-dose cyclosporine (FDC).

FTY720 versus MMF with cyclosporine in de novo renal transplantation: a 1-year, randomized controlled trial in Europe and Australasia.

FTY720 is a novel immunomodulator investigated in de novo renal transplantation and other therapeutic areas including multiple sclerosis. This 1-year multicenter, randomized, phase III study in 668 de novo renal transplant patients compared FTY720 2.5 mg plus full-dose cyclosporine (FDC) or FTY720 5.

Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial.

Everolimus is a proliferation signal inhibitor with immunosuppressive activity that may reduce the rate of progression of chronic rejection, bronchiolitis obliterans syndrome (BOS), after lung transplantation. In a randomized, double-blind clinical trial, 213 BOS-free maintenance patients received everolimus (3 mg/day) or azathioprine (AZA, 1-3 mg/kg/day) in combination with cyclosporine and corticosteroids. The prospectively defined primary endpoint was the incidence of efficacy failure (decline in FEV1 >15%[deltaFEV1 >15%], graft loss, death or loss to follow-up) at 12 months.

Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer.

Purpose: In a previous study of treatment for advanced colorectal cancer, the LV5FU2 regimen, comprising leucovorin (LV) plus bolus and infusional fluorouracil (5FU) every 2 weeks, was superior to the standard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen. This phase III study investigated the effect of combining oxaliplatin with LV5FU2, with progression-free survival as the primary end point.

Patients And Methods: Four hundred twenty previously untreated patients with measurable disease were randomized to receive a 2-hour infusion of LV (200 mg/m(2)/d) followed by a 5FU bolus (400 mg/m(2)/d) and 22-hour infusion (600 mg/m(2)/d) for 2 consecutive days every 2 weeks, either alone or together with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1.