A maturity model for the scientific review of clinical trial designs and their informativeness.

Background: Informativeness, in the context of clinical trials, defines whether a study's results definitively answer its research questions with meaningful next steps. Many clinical trials end uninformatively. Clinical trial protocols are required to go through reviews in regulatory and ethical domains: areas that focus on specifics outside of trial design, biostatistics, and research methods.

Totality of evidence of the effectiveness of repurposed therapies for COVID-19: Can we use real-world studies alongside randomized controlled trials?

Rapid and robust strategies to evaluate the efficacy and effectiveness of novel and existing pharmacotherapeutic interventions (repurposed treatments) in future pandemics are required. Observational "real-world studies" (RWS) can report more quickly than randomized controlled trials (RCTs) and would have value were they to yield reliable results. Both RCTs and RWS were deployed during the coronavirus disease 2019 (COVID-19) pandemic.

Coming full circle: The potential utility of real-world evidence to discern predictions from a physiologically based pharmacokinetic model.

Today real word data (RWD) are playing a greater role in informing health care decisions. A physiologically based pharmacokinetic model (PBPK) and observed exposure-risk relationship predicted an increased bleeding risk induced by rivaroxaban (RXB) in patients with mild to moderate chronic kidney disease (CKD) taking concomitant medications that are combined Pgp-CYP3A inhibitors. In this commentary, we explore the potential use of RWD to assess the clinical consequence of this complex drug-drug interaction predicted from PBPK.

Artificial Intelligence and Machine Learning for Lead-to-Candidate Decision-Making and Beyond.

The use of artificial intelligence (AI) and machine learning (ML) in pharmaceutical research and development has to date focused on research: target identification; docking-, fragment-, and motif-based generation of compound libraries; modeling of synthesis feasibility; rank-ordering likely hits according to structural and chemometric similarity to compounds having known activity and affinity to the target(s); optimizing a smaller library for synthesis and high-throughput screening; and combining evidence from screening to support hit-to-lead decisions. Applying AI/ML methods to lead optimization and lead-to-candidate (L2C) decision-making has shown slower progress, especially regarding predicting absorption, distribution, metabolism, excretion, and toxicology properties. The present review surveys reasons why this is so, reports progress that has occurred in recent years, and summarizes some of the issues that remain.

Systemic quinolones and risk of retinal detachment III: a nested case-control study using a US electronic health records database.

Background: Quinolones are popular antibiotics that are known for their potency, broad coverage, and reasonable safety. Concerns have been raised about a possible association between quinolones and retinal detachment (RD).

Methods: We conducted a nested case-control study using electronic health records (EHR) from the Health Facts® Database.

Application of exposure bracketing to streamline the development of contraceptive products.

Developing new long-acting products of well-characterized contraceptive drugs is one way to address some of the reasons for unmet need for modern methods of family planning among women in low- and middle-income countries. Development and approval of such products traditionally follow a conventional paradigm that includes large Phase 3 clinical trials to evaluate efficacy (pregnancy prevention) and safety of the investigational product. Exposure-bracketing is a concept that applies known pharmacokinetics and pharmacodynamics of a drug substance to inform its safe and efficacious use in humans.

Association of treatments for acute appendicitis with pregnancy outcomes in the United States from 2000 to 2016: Results from a multi-level analysis.

Background: Open appendectomy, laparoscopic appendectomy, and non-surgical treatment are three options to treat acute appendicitis during pregnancy. Previous studies on the association of different treatment methods for acute appendicitis with pregnancy outcomes have been limited by small sample sizes and residual confounding, especially with respect to hospital-level factors. This study aimed to investigate the association of treatment method for acute appendicitis with pregnancy outcomes using a multi-level analysis.

Use of RWE to Inform Regulatory, Public Health Policy, and Intervention Priorities for the Developing World.

For low- and middle-income countries (LMICs) to benefit from real-world evidence (RWE)/real-world data (RWD) in both product registration ("regulatory") decision making and in product utilization policy ("policy") decision making, they need to overcome several challenges. They need to deploy more electronic health records systems (EHRs), adjust for confounder variables, build trust between stakeholders, and create laws and regulations for local generation of data that are assented for secondary use. The role of procurers and their use of RWE/RWD in the LMIC context likewise is in a state of ongoing development.

Systemic quinolones and risk of acute liver failure III: A nested case-control study using a US electronic health records database.

Background And Aim: Quinolones are globally popular antibiotics with proven potency, broad coverage, and reasonable safety. However, some concerns were raised as to their possible association with acute liver failure (ALF). The aim of this study is to assess ALF risk within 30 days of receiving a systemically administered quinolone antibiotic, in individuals with no history of liver/diseases.

Risk of Adverse Cardiovascular Events Following a Myocardial Infarction in Patients Receiving Combined Clopidogrel and Proton Pump Inhibitor Treatment: A Nested Case-Control Study.

Background: The clinical implications of potential interactions between proton pump inhibitors (PPIs) and clopidogrel have been debated for over a decade.

Objective: We assessed the association between combined clopidogrel-PPI treatment and the risk of recurrent myocardial infarction (MI) and three secondary outcomes.

Patients And Methods: A nested case-control study was conducted within Cerner Corporation's Health Facts database.

Pressure Ulcer Risk Factors in Persons with Mobility-Related Disabilities.

Objective: To assess pressure ulcer (PU) risk in persons with mobility impairments using a large data set to identify demographic, laboratory, hemodynamic, and pharmacologic risk factors.

Methods: The cohort of interest was persons with disabilities who have mobility impairments and are diagnostically at risk of PUs. To define this cohort, diagnoses that qualify patients for skin protection wheelchair cushions were used.

Seasonal Differences in Light Exposure and the Associations With Health and Well-Being in Older Adults: An Exploratory Study.

Objective: This article reports summer verses winter seasonal variations across a suite of blue light, illuminance levels and health and well-being indicators.

Background: The quality of lighting in care homes has been assessed previously, yet seasonal comparisons and the associations with sleep quality are limited. This exploratory study investigates light exposure in two seasons to determine the changes over time and the associations with health and well-being.

Successful treatment of multifocal pedal infection in a feline immunodeficiency virus-positive cat with multiple Bowenoid in situ carcinomas containing papillomaviral DNA sequences.

Case Summary: A 16-year-old, castrated male, feline immunodeficiency virus (FIV)-positive, domestic shorthair cat developed multiple skin lesions. Most of these were Bowenoid carcinoma in situ and contained DNA sequences consistent with papillomavirus type 2. Two additional lesions that developed in the skin and subcutaneous tissues between the digital and carpal pads on the left forelimb and right hindlimb were shown by cytology, histology and culture to be caused by .

External validation and comparison of two variants of the Elixhauser comorbidity measures for all-cause mortality.

Unlabelled: Assessing prevalent comorbidities is a common approach in health research for identifying clinical differences between individuals. The objective of this study was to validate and compare the predictive performance of two variants of the Elixhauser comorbidity measures (ECM) for inhospital mortality at index and at 1-year in the Cerner Health Facts® (HF) U.S.

Associations between Anticholinergic Burden and Adverse Health Outcomes in Parkinson Disease.

Background: Elderly adults should avoid medications with anticholinergic effects since they may increase the risk of adverse events, including falls, delirium, and cognitive impairment. However, data on anticholinergic burden are limited in subpopulations, such as individuals with Parkinson disease (PD). The objective of this study was to determine whether anticholinergic burden was associated with adverse outcomes in a PD inpatient population.

Enhancing Nursing Staffing Forecasting With Safety Stock Over Lead Time Modeling.

In balancing competing priorities, it is essential that nursing staffing provide enough nurses to safely and effectively care for the patients. Mathematical models to predict optimal "safety stocks" have been routine in supply chain management for many years but have up to now not been applied in nursing workforce management. There are various aspects that exhibit similarities between the 2 disciplines, such as an evolving demand forecast according to acuity and the fact that provisioning "stock" to meet demand in a future period has nonzero variable lead time.

Off-label use of cancer therapies in women diagnosed with breast cancer in the United States.

Purpose: To determine the level of off-label cancer therapy use in a population of female breast cancer patients and to establish whether this use was evidence-based.

Methods: A study was conducted by sampling Cerner's data warehouse for all women diagnosed with breast cancer between January 2000 and June 2009 who received at least one cancer therapy approved by the US-FDA during the study period. Drug encounters were considered off-label if the circumstances of use did not match the age or medical diagnoses specified on the product label at the time of study.

Statistical methods for active pharmacovigilance, with applications to diabetes drugs.

Pharmacovigilance aims to identify adverse drug reactions using postmarket surveillance data under real-world conditions of use. Unlike passive pharmacovigilance, which is based on largely voluntary (and hence incomplete) spontaneous reports of adverse drug reactions with limited information on patient characteristics, active pharmacovigilance is based on electronic health records containing detailed information about patient populations, thereby allowing consideration of modifying factors such as polypharmacy and comorbidity, as well as sociodemographic characteristics. With the present shift toward active pharmacovigilance, statistical methods capable of addressing the complexities of such data are needed.

A continuous quality improvement program to focus a college of pharmacy on programmatic advancement.

Objective: To enhance the achievement of a college of pharmacy's goals for education, research, and service missions by implementing an excellence program based on the Studer Group model for continuous quality improvement.

Methods: The Studer model was combined with university strategic planning for a comprehensive quality-improvement program that was implemented over 5 years. The program included identifying and measuring key performance indicators, establishing specific "pillar" goals, aligning behaviors with goals and values, and training leaders.

Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.

Background: Iatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed urine-derived gonadotropins for infertility. Although menopausal urine donors are screened for symptomatic neurological disease, incubation of Creutzfeldt-Jakob disease (CJD) is impossible to exclude by non-invasive testing.

A novel dry powder inhaler: Effect of device design on dispersion performance.

The effect of device geometry and film characteristics on the performance of several passive flutter-induced dispersion DPI prototypes was investigated. Device resistance measurements indicated that the type of films, type of device geometry and specific device dimensions significantly affects the airflow resistance of the device. It was found that airflow resistance was positively correlated to the turbulence generated within the device.