Effectiveness of an image analyzing AI-based Digital Health Technology to identify Non-Melanoma Skin Cancer and other skin lesions: results of the DERM-003 study.

Introduction: Identification of skin cancer by an Artificial Intelligence (AI)-based Digital Health Technology could help improve the triage and management of suspicious skin lesions.

Methods: The DERM-003 study (NCT04116983) was a prospective, multi-center, single-arm, masked study that aimed to demonstrate the effectiveness of an AI as a Medical Device (AIaMD) to identify Squamous Cell Carcinoma (SCC), Basal Cell Carcinoma (BCC), pre-malignant and benign lesions from dermoscopic images of suspicious skin lesions. Suspicious skin lesions that were suitable for photography were photographed with 3 smartphone cameras (iPhone 6S, iPhone 11, Samsung 10) with a DL1 dermoscopic lens attachment.

Folate-Dependent Cognitive Impairment Associated With Specific Gene Networks in the Adult Mouse Hippocampus.

Short-term folate deficiency has been linked to cognitive defects. Given folate's role in regulating nucleotide synthesis and DNA and histone methylation, these changes are often linked to altered gene expression and might be controlled by specific regulatory networks. In our study we examined the effects of folic acid (FA) deficient or replete diets in mice, containing either no source of folate or normal FA intake, beginning post-weaning and persisting through the end of adult life at 18 months.

Views and Experiences of Adults who are Overweight and Obese on the Barriers and Facilitators to Weight Loss in Southeast Brazil: A Qualitative Study.

: Obesity in Brazil is increasing with 54% of the Brazilian population being overweight, of which 20% is obese. Obesity is a risk factor for non-communicable diseases such as cardiovascular disease: the leading cause of mortality in Brazil. This study aims to identify the barriers and facilitators to weight loss as perceived by patients with a view to reducing the burden of obesity-related diseases on patients and healthcare services.

Adaptive Designs: Results of 2016 Survey on Perception and Use.

Background: The DIA Adaptive Designs Scientific Working Group has a devoted subteam to performing surveys, literature reviews, and registry reviews every 4 years to assess the perception and use of adaptive designs (ADs) in the development of drugs and biologics.

Methods: A survey was distributed to pharmaceutical companies, academic institutions, and contract research organizations to collect information about the usage of ADs of different types and perception of challenges for their use. Literature and registry reviews were conducted to assess the prevalence of ADs of different types in drug and biologics development.

A randomized, controlled trial of oral propranolol in infantile hemangioma.

Background: Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited.

Methods: We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months).

Adaptive Design: Results of 2012 Survey on Perception and Use.

Adaptive designs are increasingly used in clinical trials. The Drug Information Association's Adaptive Design Scientific Working Group (ADSWG) works to foster collaboration among regulatory agencies, academia, and pharmaceutical and biotech companies to further the science of adaptive clinical development. The ADSWG Survey Subteam has collected data on the usage of adaptive designs in clinical research from multiple sources, including a recent ADSWG survey regarding the perception and usage of adaptive designs in academia and industry for studies between 2008 and 2011, as well as barriers to usage; a literature review examining publications of adaptive design methodology and usage between 2000 and 2011; and a trial registry review of adaptive design references from 1996 to 2011.

Views on Emerging Issues Pertaining to Data Monitoring Committees for Adaptive Trials.

In this paper, the authors express their views on a range of topics related to data monitoring committees (DMCs) for adaptive trials that have emerged recently. The topics pertain to DMC roles and responsibilities, membership, training, and communication. DMCs have been monitoring trials using the group sequential design (GSD) for over 30 years.

An adaptive confirmatory trial with interim treatment selection: practical experiences and unbalanced randomization.

This article has been motivated by an ongoing international adaptive confirmatory trial. At the interim analysis of this two-stage trial, none, one or two active treatment regimens are selected for further study in the second stage. A combination test approach is used in this practical setting with an extension of the theory to unbalanced randomization.

Impact of the control of symptomatic paroxysmal atrial fibrillation on health-related quality of life.

Aims: Patients with atrial fibrillation (AF) consider the related symptoms disruptive to their quality of life (QoL). This study aimed to evaluate the impact of the control of symptomatic paroxysmal AF (PAF) on QoL.

Methods And Results: Patients with symptomatic PAF were treated for 48 weeks with open-label flecainide acetate controlled release (Flec CR).

Population pharmacokinetics of artesunate and amodiaquine in African children.

Background: Pharmacokinetic (PK) data on amodiaquine (AQ) and artesunate (AS) are limited in children, an important risk group for malaria. The aim of this study was to evaluate the PK properties of a newly developed and registered fixed dose combination (FDC) of artesunate and amodiaquine.

Methods: A prospective population pharmacokinetic study of AS and AQ was conducted in children aged six months to five years.

The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum.

Background: Artesunate (AS) plus amodiaquine (AQ) is one artemisinin-based combination (ACT) recommended by the WHO for treating Plasmodium falciparum malaria. Fixed-dose AS/AQ is new, but its safety and efficacy are hitherto untested.

Methods: A randomized, open-label trial was conducted comparing the efficacy (non-inferiority design) and safety of fixed (F) dose AS (25 mg)/AQ (67.

Reduced glutathione levels and expression of the enzymes of glutathione synthesis in cryopreserved hepatocyte monolayer cultures.

Cryopreservation of monolayers of hepatocytes in a freezing medium containing 10% (v/v) dimethylsulfoxide, 90% (v/v) foetal calf serum retains cell morphology and viability, but cells lose up to 50% of their intracellular reduced glutathione. This is accompanied by a small increase in glutamate cysteine ligase expression in cryopreserved cultures, but glutathione synthetase expression is undetectable post-cryopreservation. Inclusion of ascorbic acid and alpha-tocopherol in the freezing medium improves maintenance of reduced glutathione content post-cryopreservation at 84% of the levels in non-cryopreserved monolayer cultures, but does not restore glutathione synthetase expression.

A comparison of adaptive allocation rules for group-sequential binary response clinical trials.

In clinical trials to compare two or more treatments with dichotomous responses, group-sequential designs may reduce the total number of patients involved in the trial and response-adaptive designs may result in fewer patients being assigned to the inferior treatments. In this paper, we combine group-sequential and response-adaptive designs, extending recent work on sample size re-estimation in trials to compare two treatments with normally distributed responses, to analogous binary response trials. We consider the use of two parameters of interest in the group-sequential design, the log odds ratio and the simple difference between the probabilities of success.

Prognostic factors for death due to invasive aspergillosis after hematopoietic stem cell transplantation: a 1-year retrospective study of consecutive patients at French transplantation centers.

Background: Invasive aspergillosis (IA) is a major cause of death after hematopoietic stem cell transplantation (HSCT). The goal of this retrospective and consecutive survey was to assess prognostic factors of death due to IA after HSCT at the time of diagnosis of IA.

Methods: All 64 health care centers affiliated with the Société Française de Greffe de Moelle et de Thérapie Cellulaire were contacted to participate in this study of all proven or probable cases of IA that occurred among HSCT recipients in 2002.

Cutaneous microdialysis as a novel means of continuously stimulating eccrine sweat glands in vivo.

Previous studies of the pharmacological regulation of sweat gland function in humans have administered agonists or antagonists systemically, by local intradermal injection or by iontophoresis. This has not allowed prolonged or steady-state activation of sweat glands to be examined. In this study, we used the technique of dermal microdialysis to administer pharmacological agents singly and in combination for up to 5 hours.

The viability and function of primary rat hepatocytes cultured on polymeric membranes developed for hybrid artificial liver devices.

Bioartificial liver devices require membranes to support the function and viability of hepatocytes because they are anchorage-dependent cells. This study investigated the ability of several polymeric membranes to support the functions of primary hepatocyte cultures. Tailor-made membranes were sought by synthesizing acrylonitrile copolymers with different comonomers resulting in ionic, hydrophilic, or reactive functional groups on the polymer surface.

Sample size re-estimation in group-sequential response-adaptive clinical trials.

In clinical trials where the variances of the response variables are unknown, in accurate estimates of these can affect the type II error rate considerably. More accurate estimates of the variances may be obtained by taking a look at the data available part way through the trial and re-calculating the required sample size based on these new estimates. The main impetus for sample size re-estimation came from a two-stage procedure developed by Stein in 1945 and the literature is now replete with variations on this approach.

Estimation following group-sequential response-adaptive clinical trials.

A sequential clinical trial model is considered in which two treatments with immediate normally distributed responses are to be compared. The class of one-sided group-sequential tests with response-adaptive sampling developed by Jennison and Turnbull is used to investigate which of the treatments has the larger mean response. The power function for this class of tests is the same as that under nonadaptive sampling, and significant decreases in the inferior treatment number can be achieved with only minor increases in the average total sample number.