Pudexacianinium (ASP5354) chloride for ureter visualization in participants undergoing laparoscopic, minimally invasive colorectal surgery.

Background: Intraoperative ureteral injury, a serious complication of abdominopelvic surgeries, can be avoided through ureter visualization. Near-infrared fluorescence imaging offers real-time anatomical visualization of ureters during surgery. Pudexacianinium (ASP5354) chloride is an indocyanine green derivative under investigation for intraoperative ureter visualization during colorectal or gynecologic surgery in adult and pediatric patients.

Evaluation and performance of a newly developed patient-reported outcome instrument for diarrhea-predominant irritable bowel syndrome in a clinical study population.

Background: To evaluate the psychometric properties of the newly developed seven-item Irritable Bowel Syndrome - Diarrhea predominant (IBS-D) Daily Symptom Diary and four-item Event Log using phase II clinical trial safety and efficacy data in patients with IBS-D. This instrument measures diarrhea (stool frequency and stool consistency), abdominal pain related to IBS-D (stomach pain, abdominal pain, abdominal cramps), immediate need to have a bowel movement (immediate need and accident occurrence), bloating, pressure, gas, and incomplete evacuation.

Methods: Psychometric properties and responsiveness of the instrument were evaluated in a clinical trial population [ClinicalTrials.

Diarrhea-predominant irritable bowel syndrome: creation of an electronic version of a patient-reported outcome instrument by conversion from a pen-and-paper version and evaluation of their equivalence.

Background: Subjects with diarrhea-predominant irritable bowel syndrome (IBS-D) experience abdominal cramping, bloating, pressure, and pain. Due to an absence of clinical biomarkers for IBS-D severity, evaluation of clinical therapy benefits depends on valid and reliable symptom assessments. A patient-reported outcome (PRO) instrument has been developed, comprising of two questionnaires - the IBS-D Daily Symptom Diary and IBS-D Symptom Event Log - suitable for clinical trials and real-world settings.

Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of ASP2408, a Potent Selective T-Cell Costimulation Modulator After Single and Multiple Ascending Doses in Healthy Volunteers and RA Patients.

ASP2408 is a next-generation anti-cytotoxic T lymphocyte antigen-4 fusion protein engineered for improved CD86 binding affinity as a treatment for rheumatoid arthritis (RA). In 72 healthy subjects (n = 6/treatment), ASP2408 was administered as single ascending doses intravenously at 0.003 to 10.

Cultural adaptation: translatability assessment and linguistic validation of the patient-reported outcome instrument for irritable bowel syndrome with diarrhea.

Background And Objective: Following a 2009 US Food and Drug Administration guidance, a new patient-reported outcome (PRO) instrument was developed to support end points in multinational clinical trials assessing irritable bowel syndrome with diarrhea (IBS-D) symptom severity. Our objective was to assess the translatability of the IBS-D PRO instrument into ten languages, and subsequently perform a cultural adaptation/linguistic validation of the questionnaire into Japanese and US Spanish.

Materials And Methods: Translatability assessments of the US English version of the IBS-D PRO were performed by experienced PRO translators who were native speakers of each target language and currently residing in target-language countries.

Psychometric assessment of the IBS-D Daily Symptom Diary and Symptom Event Log.

Purpose: Diarrhea-predominant irritable bowel syndrome (IBS-D) can considerably impact patients' lives. Patient-reported symptoms are crucial in understanding the diagnosis and progression of IBS-D. This study psychometrically evaluates the newly developed IBS-D Daily Symptom Diary and Symptom Event Log (hereafter, "Event Log") according to US regulatory recommendations.

A Phase 1 Dose-Escalation Study of ASP2409, a Selective T-Cell Costimulation Inhibitor, in Stable Rheumatoid Arthritis Patients on Methotrexate Therapy.

ASP2409 represents a new class of CTLA4-Ig molecules with higher binding avidity and selectivity to CD86. This first-in-human study was to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of ASP2409 in stable rheumatoid arthritis patients on methotrexate therapy with a randomized, double-blind, placebo-controlled dose-escalation study design. Patients were enrolled and randomized in each of 8 dose-escalation cohorts ranging from 0.

The effect of mirabegron on patient-related outcomes in patients with overactive bladder: the results of post hoc correlation and responder analyses using pooled data from three randomized Phase III trials.

Purpose: To understand how improvements in the symptoms of overactive bladder (OAB) seen with the β3-adrenoceptor agonist mirabegron 50 mg, correlate with patient experience as measured by validated and standard patient-reported outcomes (PROs), and to identify whether there is overall directional consistency in the responsiveness of PROs to treatment effect.

Methods: In a post hoc analysis of pooled data from three randomized, double-blind, placebo-controlled, 12-week Phase III trials of mirabegron 50 mg once daily, responder rates for incontinence frequency (≥50 % reduction in incontinence episodes/24 h from baseline to final visit), micturition frequency (≤8 micturitions/24 h at final visit), and PROs [minimally important differences in patient perception of bladder condition (PPBC) and subsets of the overactive bladder questionnaire (OAB-q) measuring total health-related quality of life (HRQoL), and symptom bother] were evaluated individually and in combination.

Results: Mirabegron 50 mg demonstrated greater improvement from baseline to final visit than placebo for each of the responder analyses, whether for individual objective and subjective outcomes or combinations thereof.

Qualitative development of a patient-reported outcome symptom measure in diarrhea-predominant irritable bowel syndrome.

Objectives: Despite a documented clinical need, no patient reported outcome (PRO) symptom measure meeting current regulatory requirements for clinically relevant end points is available for the evaluation of treatment benefit in diarrhea-predominant IBS (IBS-D).

Methods: Patients (N=113) with IBS-D participated in five study phases: (1) eight concept elicitation focus groups (N=34), from which a 17-item IBS-D Daily Symptom Diary and four-item IBS-D Symptom Event Log (Diary and Event Log) were developed; (2) one-on-one cognitive interviews (N=11) to assess the instrument's comprehensiveness, understandability, appropriateness, and readability; (3) four data triangulation focus groups (N=32) to confirm the concepts elicited; (4) two hybrid (concept elicitation and cognitive interview) focus groups (N=16); and (5) two iterative sets of one-on-one cognitive interviews (N=20) to further clarify the symptoms of IBS-D and debrief a revised seven-item Diary and four-item Event Log.

Results: Of thirty-six concepts initially identified, 22 were excluded because they were not saturated, not clinically relevant, not critical symptoms of IBS-D, considered upper GI symptoms, or too broad or vaguely defined.

Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure.

Background: This study evaluated the efficacy and safety of levosimendan, a positive inotropic drug with vasodilator effects, given intravenously to patients with acutely decompensated heart failure (ADHF).

Methods: We performed 2 sequential trials, the first to develop a new measure of efficacy in 100 patients, and the second to use this measure to evaluate levosimendan in an additional 600 patients. Patients admitted with ADHF received placebo or intravenous levosimendan for 24 h in addition to standard treatment.

Effects of intravenous ABT-870 (iron (III)-hydroxide oligosaccharide) on mean arterial pressure and heart rate in the anaesthetized beagle: comparison with other iron-containing haematinic agents.

Iron-deficiency anaemia, a complication of end-stage renal disease (ESRD), is often treated with parenteral iron therapies that have been shown to produce dose-limiting hypotension in patients. ABT-870 (iron-(III)-hydroxide-oligosaccharide) is comprised of elemental iron complexed with oligosaccharide, a composition that we hypothesised would allow the hypotensive effects of parenteral iron therapy to be overcome, thus allowing a rapid rate of infusion to be well tolerated. Mean arterial pressure (MAP) and heart rate (HR) were monitored in anaesthetized dogs following the infusion of ABT-870 and iron sucrose administered at doses of 7.

A model for the interim analysis process: a case study.

To evaluate data from a clinical trial before its completion, researchers routinely perform interim analyses. However, if not performed carefully, interim analyses can compromise the integrity of a clinical trial. In the last 10-15 years, regulatory authorities and the pharmaceutical industry have developed procedures and guidelines to allow trial sponsors access to unblinded data in an ongoing clinical trial without affecting the outcome.

Sevoflurance: approaching the ideal inhalational anesthetic. a pharmacologic, pharmacoeconomic, and clinical review.

Sevoflurane is a safe and versatile inhalational anesthetic compared with currently available agents. Sevoflurane is useful in adults and children for both induction and maintenance of anesthesia in inpatient and outpatient surgery. Of all currently used anesthetics, the physical, pharmacodynamic, and pharmacokinetic properties of sevoflurane come closest to that of the ideal anesthetic (200).

The effects of sevoflurane on serum creatinine and blood urea nitrogen concentrations: a retrospective, twenty-two-center, comparative evaluation of renal function in adult surgical patients.

Unlabelled: Despite mounting clinical evidence that supports its safety, the question of the potential adverse effects of sevoflurane on renal function continues to generate some controversy. This study retrospectively evaluated pooled renal laboratory data from 22 different clinical trials that compared sevoflurane with three widely used anesthetics. The trials examined postoperative changes in serum creatinine and blood urea nitrogen levels from a total of 3, 436 ASA physical status I-IV adult surgical patients administered either sevoflurane (n = 1941) or a control drug (isoflurane, enflurane, or propofol; n = 1495) as the maintenance anesthetic.

Inhalation toxicity study of a haloalkene degradant of sevoflurane, Compound A (PIFE), in Sprague-Dawley rats.

Background: Under certain circumstances in the clinical setting, contact of the anesthetic sevoflurane with a CO2 absorbent (e.g., soda lime, Baralyme) leads to the formation of a degradant designated as pentafluoroisopropenyl fluoromethyl ether (PIFE; Compound A).