Exploring the opportunities for alignment of regulatory postauthorization requirements and data required for performance-based managed entry agreements.

Performance-based managed entry agreements (PB-MEAs) might allow patient access to new medicines, but practical hurdles make competent authorities for pricing and reimbursement (CAPR) reluctant to implement PB-MEAs. We explored if the feasibility of PB-MEAs might improve by better aligning regulatory postauthorization requirements with the data generation of PB-MEAs and by active collaboration and data sharing. Reviewers from seven CAPRs provided structured assessments of the information available at the European Medicines Agency (EMA) Web site on regulatory postauthorization requirements for fifteen recently authorized products.

Improving uptake of Fracture Prevention drug treatments: a protocol for Development of a consultation intervention (iFraP-D).

Introduction: Prevention of fragility fractures, a source of significant economic and personal burden, is hindered by poor uptake of fracture prevention medicines. Enhancing communication of scientific evidence and elicitation of patient medication-related beliefs has the potential to increase patient commitment to treatment. The mproving uptake of cture revention drug treatments (iFraP) programme aims to develop and evaluate a theoretically informed, complex intervention consisting of a computerised web-based decision support tool, training package and information resources, to facilitate informed decision-making about fracture prevention treatment, with a long-term aim of improving informed treatment adherence.

Evaluation of Clinical and Economic Outcomes Following Implementation of a Medicare Pay-for-Performance Program for Surgical Procedures.

Importance: Surgical complications increase hospital costs by approximately $20 000 per admission and extend hospital stays by 9.7 days. Improving surgical care quality and reducing costs is needed for patients undergoing surgery, health care professionals, hospitals, and payers.

Salt Marsh Plant Community Structure Influences Success of During Poleward Encroachment.

Along the Florida coast, decreasing freeze events are promoting the range shift of the mangrove species northward into temperate salt marsh wetlands. Although plant species' ranges are tightly linked with their climatic tolerances, there is considerable variability in the magnitude by which biotic factors like competition and facilitation may also influence range shifts. Changes in mangrove and marsh plant abundance can alter both the above and belowground environment, which may in turn influence ecosystem services typically associated with these systems such as storm surge abatement and carbon storage.

Non-invasive, vagus nerve stimulation to reduce ileus after colorectal surgery: protocol for a feasibility trial with nested mechanistic studies.

Introduction: Ileus is a common and distressing condition characterised by gut dysfunction after surgery. While a number of interventions have aimed to curtail its impact on patients and healthcare systems, ileus is still an unmet challenge. Electrical stimulation of the vagus nerve is a promising new treatment due to its role in modulating the neuro-immune axis through a novel anti-inflammatory reflex.

Effect of Bone Quality and Leg Depth on the Biomechanical Performance of a Nitinol Staple.

The use of Nitinol compression staples has increased in foot and ankle procedures due to their ease of delivery and ability to offer sustained, dynamic compression. Prior biomechanical studies have predominantly examined mechanical performance in healthy bone models without investigating the effect of unicortical versus bicortical fixation. The purpose of this study was to examine the effect of bone quality and staple leg depth on the biomechanical performance of Nitinol staples in a bicortical bone model.

How urbanisation alters the intensity of the urban heat island in a tropical African city.

Due to the combined effects of urban growth and climate change, rapid urbanisation is particularly challenging in African cities. Areas that will house a large proportion of the urban population in the future coincide with where natural hazards are expected to occur, and where hazard risk management institutions, knowledge, and capacity are often lacking. One of the challenges posed by rapid urbanisation is the Urban Heat Island (UHI) effect, whereby urban areas are warmer than the surrounding rural areas.

Janus kinase inhibitors in dermatology: Part I. A comprehensive review.

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) intracellular signaling pathway is utilized by many proinflammatory molecules to mediate downstream effects and activate gene transcription. Activation of the JAK-STAT pathway contributes to a number of inflammatory dermatoses. Clinical trials and smaller studies have demonstrated the efficacy of JAK inhibitors in the treatment of a variety of dermatologic conditions.

Using a gene-based phenology model to identify optimal flowering periods of spring wheat in irrigated mega-environments.

To maximize the grain yield of spring wheat, flowering needs to coincide with the optimal flowering period (OFP) by minimizing frost and heat stress on reproductive development. This global study conducted a comprehensive modelling analysis of genotype, environment, and management to identify the OFPs for sites in irrigated mega-environments of spring wheat where the crop matures during a period of increasing temperatures. We used a gene-based phenology model to conduct long-term simulation analysis with parameterized genotypes to identify OFPs and optimal sowing dates for sites in irrigated mega-environments, considering the impacts of frost and heat stress on yield.

Janus kinase inhibitors in dermatology: Part II. A comprehensive review.

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) intracellular signaling pathway is implicated in the pathogenesis of a number of inflammatory dermatoses. Clinical trials and other studies have demonstrated the efficacy of JAK inhibitors in the treatment of a variety of dermatologic conditions. Here we review JAK inhibitors currently under investigation for the treatment of alopecia areata, vitiligo, sarcoidosis, necrobiosis lipoidica, granuloma annulare, and systemic lupus erythematosus with a special emphasis on safety and the implications of JAK inhibitors during the novel coronavirus 2019 pandemic.

A Systematic Review of the Roles and Contributions of Peer Providers in the Behavioral Health Workforce.

Context: Peer providers with lived experiences of mental health and substance use are a growing component of the workforce responsible for the prevention and treatment of behavioral health disorders. This systematic literature review aims to better define the roles of peers and their unique contributions to behavioral health care.

Evidence Acquisition: Researchers searched MEDLINE, CINAHL Complete, PsycINFO, Cochrane Central, and Scopus databases for studies published between January 1, 2013 and April 3, 2020.

Obesity, oxidative DNA damage and vitamin D as predictors of genomic instability in children and adolescents.

Background/objectives: Epidemiological evidence indicates obesity in childhood and adolescence to be an independent risk factor for cancer and premature mortality in adulthood. Pathological implications from excess adiposity may begin early in life. Obesity is concurrent with a state of chronic inflammation, a well-known aetiological factor for DNA damage.

Feasibility and Acceptability of a mHealth Self-Management Intervention for Pediatric Transplant Families.

Families of pediatric solid organ transplant recipients need ongoing education and support in the first 30 days following hospital discharge for the transplantation. The purpose of this report is to describe the feasibility, acceptability, and preliminary efficacy of a mHealth family-self management intervention, (), designed to improve post-discharge outcomes of coping, family quality of life, self-efficacy, family self-management, and utilization of health care resources. We enrolled 46 primary family members.

IMI2-PainCare-BioPain-RCT3: a randomized, double-blind, placebo-controlled, crossover, multi-center trial in healthy subjects to investigate the effects of lacosamide, pregabalin, and tapentadol on biomarkers of pain processing observed by electroencephalography (EEG).

Background: IMI2-PainCare-BioPain-RCT3 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on the nociceptive system that could serve to accelerate the future development of analgesics, by providing a quantitative understanding between drug exposure and effects of the drug on nociceptive signal processing in human volunteers. IMI2-PainCare-BioPain-RCT3 will focus on biomarkers derived from non-invasive electroencephalographic (EEG) measures of brain activity.

Methods: This is a multisite single-dose, double-blind, randomized, placebo-controlled, 4-period, 4-way crossover, pharmacodynamic (PD) and pharmacokinetic (PK) study in healthy subjects.

Shared Decision-Making With a Virtual Patient in Medical Education: Mixed Methods Evaluation Study.

Background: Shared decision-making (SDM) is a process in which clinicians and patients work together to select tests, treatments, management, or support packages based on clinical evidence and the patient's informed preferences. Similar to any skill, SDM requires practice to improve. Virtual patients (VPs) are simulations that allow one to practice a variety of clinical skills, including communication.

Physical Activity as a Predictor of Cognitive Decline in an Elderly Essential Tremor Cohort: A Prospective, Longitudinal Study.

Essential tremor (ET), one of the most common neurological diseases, is associated with cognitive impairment. Surprisingly, predictors of cognitive decline in ET remain largely unidentified, as longitudinal studies are rare. In the general population, however, lower physical activity has been linked to cognitive decline.

Quantifying groundwater flow variability in a poorly cemented fractured sandstone aquifer to inform in situ remediation.

This study applies innovative methods to characterize and quantify the magnitude of groundwater flow in a fractured and variably cemented sandstone aquifer to inform an in-situ remediation strategy for trichloroethene (TCE) contamination. A modified active-distributed temperature sensing (A-DTS) approach in which fiber optic cables were permanently grouted in the borehole was used to quantify groundwater flow rates. Two additional tracer tests were conducted: 1) fluorescein tracer injection followed by rock coring and sampling for visual mapping and porewater analysis, and 2) deployment of passive flux meters in conventional monitoring wells to evaluate groundwater velocity and mass flux distributions.

Scaling up high-throughput phenotyping for abiotic stress selection in the field.

High-throughput phenotyping (HTP) is in its infancy for deployment in large-scale breeding programmes. With the ability to measure correlated traits associated with physiological ideotypes, in-field phenotyping methods are available for screening of abiotic stress responses. As cropping environments become more hostile and unpredictable due to the effects of climate change, the need to characterise variability across spatial and temporal scales will become increasingly important.

Identification of SARS-CoV-2 Receptor Binding Inhibitors by In Vitro Screening of Drug Libraries.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) global pandemic. The first step of viral infection is cell attachment, which is mediated by the binding of the SARS-CoV-2 receptor binding domain (RBD), part of the virus spike protein, to human angiotensin-converting enzyme 2 (ACE2). Therefore, drug repurposing to discover RBD-ACE2 binding inhibitors may provide a rapid and safe approach for COVID-19 therapy.

The anaerobic oxidation of methane in paddy soil by ferric iron and nitrate, and the microbial communities involved.

The anaerobic oxidation of methane (AOM) mediated by microorganisms is a key process in the reduction of methane emissions, and AOM-coupled electron acceptors have been shown to regulate methane emissions into the atmosphere in marine systems. Paddy fields are a significant source of methane and account for 20% of global methane emissions, but the effect of electron acceptors on the methane emission process in flooded paddy fields has been poorly characterized. This study aimed to determine whether the electron acceptors ferric iron and nitrate, and biochar, acting as an electron shuttle, can regulate the AOM process in paddy soil, with or without interaction between biochar and these two electron acceptors.

Baseline Infection Burden and Cognitive Function in Elders with Essential Tremor.

Background: Patients with essential tremor (ET) have an increased risk of cognitive impairment, yet little is known about the predictors of cognitive decline in these patients. Exposures to infectious agents throughout the lifespan may impact the later development of cognitive impairment. For example, high Infection exposure has been associated with lower cognitive performance in Alzheimer's and Parkinson's disease.

Separating the wheat from the chaff: Observations on the analysis of lysergamides LSD, MIPLA, and LAMPA.

Lysergic acid diethylamide (LSD) is a potent psychoactive substance that has attracted great interest in clinical research. As the pharmacological exploration of LSD analogs continues to grow, some of those analogs have appeared on the street market. Given that LSD analogs are uncontrolled in many jurisdictions, it is important that these analogs be differentiated from LSD.