Tolerability

Background: Bowel anastomoses are common procedures in both elective and emergency general surgery Therefore, the aim of this study was to assess the safety, tolerability and outcome of early oral feeding after small bowel anastomosis.

Methodology: This is a Quasi experimental study conducted at Surgical unit (ward 26) Jinnah postgraduate medical center, Karachi, Pakistan, during the period from March 2014 to November 2016. In the present study we investigated 59 cases, their ages ranging from 17-45 years.
Results: Out of 35 elective cases, 51.4% were operated for ileoleal and 20% were operated for ileocolic anastomosis. Out of the 24 emergency cases, 75%, 20.8%, and 4.2% were presenting with, Penetrating abdominal trauma, Blunt trauma, and Intestinal obstruction section to internal hernia.
Conclusion: Early oral feeding is safe and if associated with careful selection and 3
multimodal postoperative care promotes faster convalescence following small bowel surgery.

Keywords: Bowel anastomosis; Abdominal trauma; Intestinal obstruction; Nasogastric tubes; Anastomosis; Blunt trauma, Restoration; Internal hernia; Bowel surgery; Mobilization; Protocols; Restoration; Tolerability; Diverticulitis; Prevention, Abdominus  plane.

OBJECTIVE Data related to the safety and tolerability of treatments for pediatric type 2 diabetes are limited. The TODAY clinical trial assessed severe adverse events (SAEs) and targeted nonsevere adverse events (AEs) before and after treatment failure, which was the primary outcome (PO). RESEARCH DESIGN AND METHODS Obese 10- to 17-year-olds (N = 699) with type 2 diabetes for <2 years and hemoglobin A1c (A1C) ≤8% on metformin monotherapy were randomized to one of three treatments: metformin, metformin plus rosiglitazone (M + R), or metformin plus lifestyle program (M + L). Participants were followed for 2–6.5 years. RESULTS Gastrointestinal (GI) disturbance was the most common AE (41%) and was lower in the M + R group (P = 0.018). Other common AEs included anemia (20% before PO, 14% after PO), abnormal liver transaminases (16, 15%), excessive weight gain (7, 9%), and psychological events (10, 18%); the AEs were similar across treatments. Permanent medication reductions/discontinu...

AdADOSE was a 12-week, international, observational study conducted in the Middle East and Russia where patients received nifedipine gastrointestinal therapeutic system (GITS) at a daily dose of 30, 60, or 90 mg as part of an antihypertensive combination therapy. This subgroup analysis of the AdADOSE study assesses the efficacy and tolerability of nifedipine GITS combination therapy when used specifically at the 60-mg strength. Patients with hypertension who received a daily nifedipine GITS dose of 60 mg, either at constant dose (n = 686) or up-titrated from 30 mg (n = 392), were analyzed. Target blood pressure (BP) was <140/90 mmHg (or <130/80 mmHg for those at high/very high cardiovascular risk). Following nifedipine GITS combination therapy, target BP was achieved by 33.7% patients in the 60 mg group (previously untreated, 42.5%; previously treated, 32.0%) and 32.4% patients in the 30-60 mg group (previously untreated, 45.2%; previously treated, 30.7%). Mean systolic BP/dia...

OBJECTIVE Data related to the safety and tolerability of treatments for pediatric type 2 diabetes are limited. The TODAY clinical trial assessed severe adverse events (SAEs) and targeted nonsevere adverse events (AEs) before and after treatment failure, which was the primary outcome (PO). RESEARCH DESIGN AND METHODS Obese 10- to 17-year-olds (N = 699) with type 2 diabetes for <2 years and hemoglobin A1c (A1C) ≤8% on metformin monotherapy were randomized to one of three treatments: metformin, metformin plus rosiglitazone (M + R), or metformin plus lifestyle program (M + L). Participants were followed for 2–6.5 years. RESULTS Gastrointestinal (GI) disturbance was the most common AE (41%) and was lower in the M + R group (P = 0.018). Other common AEs included anemia (20% before PO, 14% after PO), abnormal liver transaminases (16, 15%), excessive weight gain (7, 9%), and psychological events (10, 18%); the AEs were similar across treatments. Permanent medication reductions/discontinu...

OBJECTIVE Data related to the safety and tolerability of treatments for pediatric type 2 diabetes are limited. The TODAY clinical trial assessed severe adverse events (SAEs) and targeted nonsevere adverse events (AEs) before and after treatment failure, which was the primary outcome (PO). RESEARCH DESIGN AND METHODS Obese 10- to 17-year-olds (N = 699) with type 2 diabetes for <2 years and hemoglobin A1c (A1C) ≤8% on metformin monotherapy were randomized to one of three treatments: metformin, metformin plus rosiglitazone (M + R), or metformin plus lifestyle program (M + L). Participants were followed for 2–6.5 years. RESULTS Gastrointestinal (GI) disturbance was the most common AE (41%) and was lower in the M + R group (P = 0.018). Other common AEs included anemia (20% before PO, 14% after PO), abnormal liver transaminases (16, 15%), excessive weight gain (7, 9%), and psychological events (10, 18%); the AEs were similar across treatments. Permanent medication reductions/discontinu...

To evaluate the long-term tolerability of telcagepant for acute treatment of intermittent migraine attacks. Background.- Telcagepant is a calcitonin gene-related peptide (CGRP) receptor antagonist being investigated for the acute treatment of migraine. Migraine patients were randomized 2:1 to double-blind treatment with telcagepant 280/300 mg or rizatriptan 10 mg for an acute mild, moderate, or severe migraine. Patients could administer a second dose within 2-24 hours for nonresponse or migraine recurrence. Patients could treat up to 8 attacks per month for up to 18 months. Safety assessments included spontaneous reports of adverse events and collection of vital signs, electrocardiograms, and laboratory assessments. The primary endpoint was the percentage of patients with ≥ 1 triptan-related adverse events in the 14-day period post dose. Of 1068 patients randomized, 641 (90%) patients treated ≥ 1 attack with telcagepant and 313 (88%) treated ≥ 1 attack with rizatriptan. A total of 19,820 attacks were treated with telcagepant (mean per patient = 31) and 10,981 with rizatriptan (mean per patient = 35). Fewer triptan-related adverse events (difference: -6.2%; 95% CI -10.4, -2.6; P < .001) and drug-related adverse events (difference: -15.6%; 95% CI -22.2, -9.0) were reported for telcagepant vs rizatriptan. The most common adverse events appeared to have generally similar incidence proportions between the treatment groups. Those with an incidence > 5% in the telcagepant group were dry mouth (9.7%, rizatriptan = 13.7%), somnolence (9.2%, rizatriptan = 16.6%), dizziness (8.9%, rizatriptan = 10.2%), and nausea (9.0%, rizatriptan = 6.4%). Telcagepant was generally well tolerated when administered for the acute intermittent treatment of migraine for up to 18 months. The incidences of triptan-related and drug-related adverse events favored telcagepant over rizatriptan.

The aim of this study was to characterize the pharmacokinetics and to evaluate the safety of risperidone ISM in patients with schizophrenia or schizoaffective disorder after a single gluteal intramuscular injection at three different dose strengths (50, 75, and 100 mg). A total of 36 patients were randomized and blood samples were collected to measure the plasma concentrations. The pharmacokinetic of the active moiety was biphasic for all three dose groups, and the mean plasma concentration was 21.45, 24.60, and 29.68 ng/ml in the 50, 75, and 100 mg group, respectively, 24 h after dose administration; 22.81, 24.57, and 31.41 ng/ml in the 50, 75, and 100 mg group, respectively, 48 h after dose administration, and 12.26, 17.31, and 20.01 ng/ml in the 50, 75, and 100 mg group, respectively, 30 days after dose administration. Overall, 34 patients experienced at least one treatment-emergent adverse event (TEAE). Two patients experienced a serious TEAE and no deaths occurred. There were n...

Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose (14.9 % vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL arm. Study-E: mild or moderate AEs Schramm et al. Malaria Journal 2013, 12:250

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington’s disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington’s Disease Rating Scale (UHDRS), and exploratory measures of prob...

Background For uncomplicated Plasmodium falciparum malaria, highly efficacious single-dose treatments are expected to increase compliance and improve treatment outcomes, and thereby may slow the development of resistance. The efficacy and safety of a single-dose combination of artefenomel (800 mg) plus ferroquine (400/600/900/1200 mg doses) for the treatment of uncomplicated P. falciparum malaria were evaluated in Africa (focusing on children ≤ 5 years) and Asia. Methods The study was a randomized, double-blind, single-dose, multi-arm clinical trial in patients aged > 6 months to  5 years and 20 Asian patients. None of the treatment arms met the target efficacy criterion for PCR-adjusted ACPR at Day 28 (lower limit of 95% confidence interval [CI] > 90%). PCR-adjusted ACPR at Day 28 [95% CI] in the PP Set ranged from 78.4% [64.7; 88.7%] to 91.7% [81.6; 97.2%] for the 400 mg to 1200 mg ferroquine dose. Efficacy rates were low in Vietnamese patients, ranging from 20 to 40%. A cle...

Angiotensin-(1-7) is an endogenous peptide of the renin-angiotensin system in humans. It has several properties, which make it of great interest for healthcare, such as in systemic/ pulmonary hypertension treatment, insulin resistance improvement, reduction of visceral obesity and cardiac remodeling and arrhythmias. In this randomized double-blinded controlled phase I study we aimed to determine safety, tolerability, and pharmacokinetic properties of the new drug, angiotensin-(1-7) included in Hydroxypropyl β-cyclodextrin [Ang(1-7)/HPβCD)] in healthy adult volunteers, who were recruited in accordance to inclusion and exclusion criteria. Thirty-two volunteers ( 18-40 years-old ) were admitted to a hospital clinical research ward and remained under observation for two days, during which they received a single oral dose of Ang(1-7)HPβCD (equivalent to 0.35, 1.75 or 7.0 mg of the peptide) or placebo (N=8/ group). Vital signs and side effects were recorded according to the study protocol...