Quality Assurance of Depression Ratings in Psychiatric Clinical Trials.

Background: Extensive experience with antidepressant clinical trials indicates that interrater reliability (IRR) must be maintained to achieve reliable clinical trial results. Contract research organizations have generally accepted 6 points of rating disparity between study site raters and central "master raters" as concordant, in part because of the personnel turnover and variability within many contract research organizations. We developed and tested an "insourced" model using a small, dedicated team of rater program managers (RPMs), to determine whether 3 points of disparity could successfully be demonstrated as a feasible standard for rating concordance.

NRX-101 (D-Cycloserine + Lurasidone) Is Active against Drug-Resistant Urinary Pathogens In Vitro.

D-Cycloserine (DCS) is a broad-spectrum antibiotic that is currently FDA-approved to treat tuberculosis (TB) disease and urinary tract infection (UTI). Despite numerous reports showing good clinical efficacy, DCS fell out of favor as a UTI treatment because of its propensity to cause side effects. NRX-101, a fixed-dose combination of DCS and lurasidone, has been awarded Qualified Infectious Disease Product and Fast Track Designation by the FDA.

D-cycloserine is not susceptible to self-administration using an intravenous self-administration model in male ketamine-habituated Sprague-Dawley rats.

Objective: N-methyl-d-aspartate receptor (NMDAR) antagonist antidepressants have known potential for abuse liability. The aim of this study was to evaluate the abuse liability of D-cycloserine (DCS), using a self-administration paradigm in which DCS was tested for its efficacy in substituting for ketamine in ketamine-dependent rats.

Methods: A standard intravenous self-administration study was conducted in male adult Sprague-Dawley rats to study abuse liability.

NRX-101, a Rapid-Acting Anti-Depressant, Does Not Cause Neurotoxicity Following Ketamine Administration in Preclinical Models.

Agents that act at the N-methyl-D-aspartate receptor (NMDAR), such as ketamine, have gained increasing attention as rapid-acting antidepressants; however, their use has been limited by potential neurotoxicity. Recent FDA guidance requires a demonstration of safety on histologic parameters prior to the initiation of human studies. D-cycloserine (DCS) is a partial NMDA agonist that, along with lurasidone, is being investigated as a treatment for depression.

The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial.

Objectives: Respiratory failure is a lethal complication of COVID-19 that has remained resistant to drug therapy. Vasoactive intestinal peptide (VIP) is shown in nonclinical studies to upregulate surfactant production, inhibit cytokine synthesis, prevent cytopathy, and block replication of the severe acute respiratory syndrome coronavirus 2 virus in pulmonary cells. The study aims to determine whether Aviptadil (synthetic VIP) can improve survival and recovery in patients with COVID-19 respiratory failure compared with placebo and demonstrate biological effects in such patients.

Brief Report: Rapid Clinical Recovery From Critical Coronavirus Disease 2019 With Respiratory Failure in a Pregnant Patient Treated With IV Vasoactive Intestinal Peptide.

Background: Aviptadil, a synthetic form of human vasoactive intestinal peptide, has entered clinical trials to treat critical coronavirus disease 2019 pneumonia with respiratory failure. Vasoactive intestinal peptide protects the lung against a broad array of injuries by binding to the vasoactive intestinal peptide receptor 1 receptor of alveolar type II cells, the cells that severe acute respiratory syndrome coronavirus 2 binds to. As the role of Aviptadil in treating pregnant patients with critical coronavirus disease 2019 pneumonia is unknown, the authors report successful treatment in such a patient who is ineligible for phase 3 trials of Aviptadil.

Association Between Eliminating Water From Surgical Hand Antisepsis at a Large Ophthalmic Surgical Hospital and Cost.

Importance: Alcohol-based surgical scrub is recommended for presurgical antisepsis by leading health organizations. Despite this recommendation, water-based scrub techniques remain common practice at many institutions.

Objective: To calculate the potential financial savings that a large, subspecialty ophthalmic surgical center can achieve with a conversion to waterless surgical hand preparation.

Objectives of teaching direct ophthalmoscopy to medical students.

Purpose: To propose the objectives of undergraduate training in direct ophthalmoscopy (DO).

Method: Narrative review of the literature on (i) opinions about the expected proficiency from students in DO, and (ii) estimates of its diagnostic value.

Results: (i) Authorities disagree on the proficiency in DO that they expect from students.

Improvements in patient-reported outcomes and visual acuity after bilateral implantation of multifocal intraocular lenses with +3.0 diopter addition: multicenter clinical trial.

Purpose: To assess changes in patient-reported outcomes, satisfaction, vision quality, and visual acuity after bilateral implantation of multifocal intraocular lenses (IOLs) with a 3.00 D addition (add) in cataract patients.

Setting: Twelve study centers, United States.

The retinal oxysterol pathway: a unifying hypothesis for the cause of age-related macular degeneration.

Purpose Of Review: To summarize recent findings implicating toxic agents resulting in photooxidation of cholesterol in the etiology of age-related macular degeneration. Understanding the role of these agents and the existing pathways for their neutralization may lead to novel therapeutic approaches.

Recent Findings: The human eye is now known to produce significant quantities of 7-ketocholesterol and related substances as a direct result of photoreceptor function.

Joint assessment of intended and unintended effects of medications: an example using vascular endothelial growth factor inhibitors for neovascular age-related macular degeneration.

Objective. To estimate the net health benefits of pegaptanib and ranibizumab by considering the impact of visual acuity and unintended effects (cardiovascular and hemorrhagic events) on quality-of-life among persons with neovascular age-related macular degeneration. Methods.

Information technology and medical missteps: evidence from a randomized trial.

We analyze the effect of a decision support tool designed to help physicians detect and correct medical "missteps". The data comes from a randomized trial of the technology on a population of commercial HMO patients. The key findings are that the new information technology lowers average charges by 6% relative to the control group.

Cost-effectiveness model for neovascular age-related macular degeneration: comparing early and late treatment with pegaptanib sodium based on visual acuity.

Objective: To compare the cost-effectiveness of pegaptanib and usual care within three distinct cohorts of subfoveal neovascular age-related macular degeneration (NV-AMD) patients, that is, those with early, moderate, and late disease, using a comprehensive economic model.

Methods: A Markov framework was used to model lifetime movement of a subfoveal NV-AMD cohort through health states based on visual acuity. The model takes a US payer perspective of patients over the age of 65 years.

Comparison of comorbid conditions between neovascular age-related macular degeneration patients and a control cohort in the medicare population.

Purpose: To determine whether comorbidities are more prevalent among individuals with neovascular age-related macular degeneration (NV-AMD) than individuals without AMD.

Methods: This 2-year, retrospective, case-control study included Medicare beneficiaries (standard 5% analytic sample) continuously enrolled from January 1, 2003, to December 31, 2004, excluding those in managed care plans. The NV-AMD cohort included individuals >or=65 at baseline with a diagnosis of NV-AMD in 2003 and 2004.

Association between vision loss and higher medical care costs in Medicare beneficiaries costs are greater for those with progressive vision loss.

Purpose: To identify the cost to the Medicare program for patients with either stable or progressive vision loss and to estimate the impact on eye-related and non-eye related care.

Design: Retrospective cohort study.

Participants: The study population was Medicare beneficiaries included in the standard 5% analytic sample and continuously enrolled from 1999 to 2003, excluding Medicare managed-care enrollees.

Using a claims data-based sentinel system to improve compliance with clinical guidelines: results of a randomized prospective study.

Objective: To demonstrate the potential effect of deploying a sentinel system that scans administrative claims information and clinical data to detect and mitigate errors in care and deviations from best medical practices.

Methods: Members (n = 39 462; age range, 12-64 years) of a midwestern managed care plan were randomly assigned to an intervention or a control group. The sentinel system was programmed with more than 1000 decision rules that were capable of generating clinical recommendations.

How to succeed in health information technology.

The United States is poised to move the debate over electronic information systems for health care beyond the question of whether to computerize to how to computerize. Developers should heed the experiences of those who have already attempted similar efforts in vertically integrated environments. A key lesson is that the expertise and design perspectives of IT professionals should be supplemented with practical input from the caregivers and administrators who will actually use these systems.

Incidence of exudative age-related macular degeneration among elderly Americans.

Purpose: To estimate the 3-year incidence of exudative age-related macular degeneration (AMD) and its treatment by laser photocoagulation in elderly Americans.

Design: Population-based cohort study using insurance claims data.

Participants: A random 5% sample of Medicare beneficiaries, age 65 and older.