Real-world genomic testing and treatment patterns of newly diagnosed adult acute myeloid leukemia patients within a comprehensive health system.

Background: We evaluated the frequency of genomic testing and treatment patterns by age category in patients with newly diagnosed (ND) acute myeloid leukemia (AML) treated in both academic- and community-based health systems within a single Midwestern State.

Methods: Retrospective analysis of data from the Indiana University Health System Enterprise Data Warehouse and two local cancer registries, of 629 patients aged ≥18 years with ND AML during 2011-2018. Primary outcome variables were, proportion of patients with genomic analysis and frequency of mutations.

Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial.

Background: Patients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population.

Methods: This was a multicenter, open-label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.

Streamlined Operational Approaches and Use of e-Technologies in Clinical Trials: Beat Acute Myeloid Leukemia Master Trial.

Advances in genomic technologies and an increased understanding of the molecular pathogenesis of cancer have resulted in development of new effective, mutation-targeted therapies. In turn, these informed the development of Master Trial designs to test these therapies. The Beat Acute Myeloid Leukemia (BAML) Master Trial (Sponsor: The Leukemia & Lymphoma Society) tests several targeted therapies in patients aged ≥ 60 years with AML based on genomic profiling obtained within 7 days of study enrollment.

A review of surgical and peri-operative factors to consider in emergency laparotomy care.

Patients undergoing emergency laparotomy are a heterogeneous group with regard to comorbidity, pre-operative physiological state and surgical pathology. There are many factors to consider in the peri-operative period for these patients. Surgical duration should be as short as possible for adequate completion of the procedure.

Readmissions after laparoscopic cholecystectomy in a UK District General Hospital.

Introduction: Laparoscopic cholecystectomy is the gold standard for the treatment of symptomatic gallstones and its practice as day case where possible is considered the standard over the last decade. However, readmission after surgery is recognised as a new problem.

Aim: The aim of this cohort observational study was to investigate the readmission rate in a district general hospital and identify the causes of readmission in order to explore ways by which this can be reduced or managed more cost effectively.

Streptococcus milleri and Recurrent Intra-Abdominal Abscesses: A Case Report and Literature Review.

We report a case of recurrent intra-abdominal abscesses as a postoperative complication following diverticular perforation in which Streptococcus milleri (SM) was isolated. SM is evaluated here as a potent pyogenic organism commonly associated with intra-abdominal abscess especially in the postoperative setting. With the commonly adopted conservative management, the challenges of recurrence and prolonged hospital stay experienced in the indexed case as well as many other previous reports are highlighted.

UHRF1 regulation of the Keap1-Nrf2 pathway in pancreatic cancer contributes to oncogenesis.

The cellular defence protein Nrf2 is a mediator of oncogenesis in pancreatic ductal adenocarcinoma (PDAC) and other cancers. However, the control of Nrf2 expression and activity in cancer is not fully understood. We previously reported the absence of Keap1, a pivotal regulator of Nrf2, in ∼70% of PDAC cases.

Design, synthesis and in vitro cell-based evaluation of the anti-cancer activities of hispolon analogs.

Phytochemicals play an important role in cancer therapy. Hispolon and 26 of its analogs (9 known and 17 new) were synthesized and evaluated for their antiproliferative activities in a panel of six independent human cancer cell lines using the in vitro cell-based MTT assay. Among the hispolon analogs tested, compound VA-2, the most potent overall, produced its most significant effect in the colon cancer cell lines HCT-116 (IC₅₀ 1.

A single-blind, placebo-controlled, dose-ranging trial of oral hepatic-directed vesicle insulin add-on to oral antidiabetic treatment in patients with type 2 diabetes mellitus.

The dose response of postprandial plasma glucose (PPG) to add-on, premeal oral hepatic-directed vesicle-insulin (HDV-I), an investigational lipid bio-nanoparticle hepatocyte-targeted insulin delivery system, was evaluated in a 3-test-meal/day model in type 2 diabetes patients. The single-blind, placebo-controlled, dose-escalating trial enrolled 6 patients with HbA(1c) 8.6 ± 2.

Tramadol hydrochloride extended-release once-daily in the treatment of osteoarthritis of the knee and/or hip: a double-blind, randomized, dose-ranging trial.

This 12-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial evaluated tramadol ER (extended-release tramadol) in the management of osteoarthritis pain. Adults with knee and/or hip osteoarthritis and baseline pain intensity of ≥40 on a 100-mm visual analog scale (0 = no pain, 100 = extreme pain) received once-daily tramadol ER 100 mg (n = 201), 200 mg (n = 199), or 300 mg (n = 199), celecoxib 200 mg (n = 202; to test model sensitivity), or placebo (n = 200). Coprimary efficacy variables were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, WOMAC physical function subscale, and patient global assessment of disease activity.

Hepatic-directed vesicle insulin: a review of formulation development and preclinical evaluation.

Hepatic-directed vesicle insulin (HDV-I), a novel investigational vesicle (<150 nm diameter) insulin delivery system that carries insulin and a specific hepatocyte-targeting molecule (HTM) in its phospholipid bilayer and has the ability to mimic a portal vein insulin infusion remotely [subcutaneous (SC) HDV-I] and noninvasively (oral HDV-I), has been developed. This review summarizes formulation development, subsequent refinements, and results of preclinical evaluation studies, including biodistribution, mechanistic, and toxicology studies of predominantly SC HDV-I, in various animal models. Studies conducted to date have confirmed the hepatocyte specificity of HDV and HDV-I and revealed that HDV-I can stimulate the conversion of hepatic glucose output to uptake at a dose that is <1% of the dose of regular insulin (RI) required for liver stimulation; suggest that the enhanced antihyperglycemic effect of HDV-I is due to hepatic glucose uptake; and in pancreatectomized dogs during an oral glucose tolerance test, HDV-I normalized blood glucose curves when compared to control curves in intact dogs and prevented secondary hypoglycemia in contrast to the same dose of RI.

Extended-release tramadol (tramadol ER) in the treatment of chronic low back pain.

Background: This study evaluated the safety and efficacy of tramadol ER 300 mg and 200 mg versus placebo once daily in the treatment of chronic low back pain, using an open-label run-in followed by, without washout, a randomized controlled study design.

Methods: Adults with scores > or = 40 on a pain intensity visual analog scale (VAS; 0 = no pain; 100 = extreme pain) received open-label tramadol ER, initiated at 100 mg once daily and titrated to 300 mg once daily during a three-week open-label run-in. Patients completing run-in were randomized to receive tramadol ER 300 mg, 200 mg, or placebo once daily for 12 weeks.

Open-label study of the safety and effectiveness of long-term therapy with extended-release tramadol in the management of chronic nonmalignant pain.

Background: Tramadol ER* is a once-daily oral analgesic for management of moderate-to-moderately severe chronic pain in adults who require around-the-clock treatment of pain. This study evaluated long-term safety of tramadol ER and effectiveness outcomes in the management of chronic, nonmalignant pain.

Methods: Patients enrolled directly for approximately 1 year of open-label tramadol ER treatment if they had chronic, nonmalignant pain (n = 919), or 'rolled over' for 38 weeks of open-label tramadol ER treatment if they completed either of two 12-week, placebo-controlled studies of tramadol ER for low back pain (n = 72) or osteoarthritis (n = 61).

Extended-release tramadol in the treatment of osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled clinical trial.

Objective: This study evaluated the efficacy and safety of tramadol extended-release (tramadol ER) tablets once daily in subjects with osteoarthritis pain.

Methods: This 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial included 1020 adults with osteoarthritis of the knee or hip and baseline pain intensity >or= 40 on a 100-mm pain visual analog scale (0 = no pain, 100 = extreme pain). Subjects took placebo or were titrated to a target dose of tramadol ER 100, 200, 300, or 400 mg once daily.

Efficacy and safety of a once-daily graded-release diltiazem formulation dosed at bedtime compared to placebo and to morning dosing in chronic stable angina pectoris.

Background: The efficacy and safety of a once-daily graded-release diltiazem hydrochloride (GRD) formulation dosed at 10 PM in doses of 180, 360, and 420 mg were compared with placebo and with GRD 360 mg dosed once daily at 8 AM in patients (n = 311) with chronic stable angina pectoris.

Methods: This was a 3-week multicenter, randomized, double-blind, double-dummy, parallel-group, placebo-controlled trial. Standard Bruce protocol treadmill stress test was performed at baseline and end point between 6 and 8 PM (trough for evening doses) and between 7 and 11 AM (trough for morning doses).

Effects of graded-release diltiazem versus ramipril, dosed at bedtime, on early morning blood pressure, heart rate, and the rate-pressure product.

Background: Therapeutic agents for the treatment of hypertension may differ in their efficacy during the early morning period, a time when both morbid and mortal cardiovascular events are increased compared to other times of the day.

Methods: We studied the effects of a graded-release delivery system of diltiazem (diltiazem HCL extended release tablets) versus ramipril, both dosed at bedtime, on blood pressure (BP), heart rate, and the heart rate-systolic BP product during the first 4 hours after awakening in a double-blind, titration-to-effect trial. There were 261 men and women enrolled in the trial with an untreated sitting diastolic BP of 90 to 109 mm Hg and ambulatory daytime diastolic BP of 85 to 109 mm Hg.

Antihypertensive efficacy of night-time graded-release diltiazem versus morning amlodipine in African Americans.

Background: The effect of a once daily night-time (10 pm) graded-release diltiazem (GRD) on early morning blood pressure (BP), heart rate (HR), and rate-pressure product (RPP) were compared with the effect of morning (8 am) amlodipine in 262 African American individuals with hypertension.

Methods: The multicenter, randomized, double-blind, parallel-group, dose-to-effect trial evaluated changes from baseline in BP, HR, and RPP (HR x systolic BP) by ambulatory BP monitoring during the first 4 h after awakening (diastolic BP = primary), between 6 am and 12 noon, and over a 24-h period. Patients were randomized to night-time GRD 360 mg (n = 132) or morning amlodipine 5 mg (n = 130) for 6 weeks, and were titrated to GRD 540 mg or amlodipine 10 mg after 6 weeks if clinic systolic BP/diastolic BP (SBP/DBP) was > or = 130/85 mm Hg.

Efficacy and safety of extended-release, once-daily tramadol in chronic pain: a randomized 12-week clinical trial in osteoarthritis of the knee.

The efficacy and safety of a once-daily extended-release formulation of tramadol hydrochloride (tramadol ER) was evaluated in patients with moderate to severe chronic pain of osteoarthritis (OA). This was a randomized, double-blind, placebo-controlled, parallel-group, 12-week study. Eligible patients with radiographically confirmed OA of the knee meeting the American College of Rheumatology diagnostic criteria, defined by knee pain and presence of osteophytes, plus at least age >50 years, morning stiffness <30 minutes in duration, and/or crepitus, entered a 2-7 day washout period during which all analgesics were discontinued.

Efficacy and safety of a once daily graded-release diltiazem formulation in essential hypertension.

Background: The efficacy and safety of a chronotherapeutic, graded-release diltiazem HCl extended-release (GRD) 120-, 240-, 360- and 540-mg dose administered once-daily at bedtime (10 PM) were evaluated in a 7-week randomized, double-blind comparison to placebo and to GRD 360 mg administered once-daily at 8 AM in 478 patients with moderate-to-severe essential hypertension.

Methods: We assessed the change from baseline to end point in trough diastolic blood pressure (DBP) at 6 PM to 10 PM and in mean DBP from 6 AM to 12 noon between GRD 360 mg PM and GRD 360 mg AM, measured by ambulatory BP monitoring (ABPM).

Results: Bedtime doses of GRD showed dose-related mean reductions in trough DBP that were significant for GRD doses of 240 mg and higher.

Asian sildenafil efficacy and safety study (ASSESS-1): a double-blind, placebo-controlled, flexible-dose study of oral sildenafil in Malaysian, Singaporean, and Filipino men with erectile dysfunction. The Assess-1 Study Group.

Objectives: To evaluate the efficacy, safety, and tolerability of oral sildenafil in Asian men with erectile dysfunction of various causes (organic, psychogenic, or mixed) and of more than 6 months' duration.

Methods: In this double-blind, parallel-group trial conducted at eight centers in Malaysia, the Philippines, and Singapore, 254 men, 26 to 78 years old, were randomized to 12 weeks of sildenafil or placebo taken as needed 1 hour before anticipated sexual activity. Initially, the sildenafil (n = 127) or matching placebo (n = 127) dose was 50 mg but could be increased to 100 mg or decreased to 25 mg because of a lack of efficacy or intolerance, respectively.