Probability of Regulatory Approval Over Time: A Cohort Study of Cancer Therapies.

Purpose: New cancer therapies are frequently evaluated in multiple disease indications. We evaluated whether the probability of achieving US Food and Drug Administration (FDA) approval for a new cancer therapy changes with time.

Methods: We identified a cohort of anticancer drugs with a first registered efficacy trial from 2007 to 2011 on ClinicalTrials.

Engineered as oral probiotics to enhance clearance of blood lactate.

Elevated lactate concentrations are implicated in various acute and chronic diseases such as sepsis and mitochondrial dysfunction, respectively. Conversely, ineffective lactate clearance is associated with poor clinical prognoses and high mortality in these diseases. While several groups have proposed using small molecule inhibitors and enzyme replacement to reduce circulating lactate, there are few practical and effective ways to manage this condition.

Large numbers of patients are needed to obtain additional approvals for new cancer drugs: A retrospective cohort study.

Patients endure risk and uncertainty when they participate in clinical trials. We previously estimated that 12,217 patient-participants are required to bring a new cancer drug to market. However, many development efforts are aimed at extending the label of already approved drugs.

Timing for First-in-Minor Clinical Trials of New Cancer Drugs.

Objectives: To describe the delay for first-in-minor cancer clinical trials and its relationship with the Food and Drug Administration (FDA) approval.

Study Design: We used ClinicalTrials.gov to create a sample of pediatric-relevant cancer drugs starting efficacy testing in adults from 2006 through 2011.

How to limit uninformative trials: Results from a Delphi working group.

To be justifiable, clinical trials must test novel hypotheses and produce informative results. However, many trials fail on this score. A Delphi process was used to establish consensus on 35 recommendations across five domains related to the role of scientific review in preventing uninformative trials.

Effects of an inulin fiber diet on the gut microbiome, colon, and inflammatory biomarkers in aged mice.

Due to the increasing human life expectancy and limited supply of healthcare resources, strategies to promote healthy aging and reduce associated functional deficits are of public health importance. The gut microbiota, which remodels with age, has been identified as a significant contributor to the aging process that is modifiable by diet. Since prebiotic dietary components such as inulin have been shown to impart positive benefits with regards to aging, this study used C57Bl6 mice to investigate whether 8 weeks on a 2.

Inhibition of inflammatory microglia by dietary fiber and short-chain fatty acids.

Microglia play a vital role maintaining brain homeostasis but can also cause persistent neuroinflammation. Short-chain fatty acids (SCFAs) produced by the intestinal microbiota have been suggested to regulate microglia inflammation indirectly by signaling through the gut-brain axis or directly by reaching the brain. The present work evaluated the anti-inflammatory effects of SCFAs on lipopolysaccharide (LPS)-stimulated microglia from mice fed inulin, a soluble fiber that is fermented by intestinal microbiota to produce SCFAs in vivo, and SCFAs applied to primary microglia in vitro.

Competition for recruitment in SARS-CoV-2 Trials in the United States: a longitudinal cohort analysis.

Objective: Competition among trials for patient enrollment can impede recruitment. We hypothesized that this occurred early in the COVID-19 pandemic, when an unprecedented number of clinical trials were launched. We performed a simple and multivariable regression analysis evaluating the relationship between the proportion of SARS-CoV-2 investigational trial sites within each USA state with unsuccessful patient-participant recruitment and: (i) the proportion of cases required to reach state recruitment goals; (ii) state population based on data from the US Census; and, (iii) number of trial sites per state.

Effects of Broad-Spectrum Antibiotic Treatment or Germ-Free Status on Endurance Performance and Exercise Adaptations in Mice.

Purpose: Endurance exercise alters the gut microbiome independently of diet. The extent to which gut microbes are responsible for physiologic adaptations to exercise training is unknown. The purpose of these experiments was to determine the role of gut microbes in performance and muscle adaptation to 6 wk of voluntary wheel running (VWR) in mice.

The proportion of randomized controlled trials that inform clinical practice.

Prior studies suggest that clinical trials are often hampered by problems in design, conduct, and reporting that limit their uptake in clinical practice. We have described 'informativeness' as the ability of a trial to guide clinical, policy, or research decisions. Little is known about the proportion of initiated trials that inform clinical practice.

Quantifying Patient Investment in Novel Neurological Drug Development.

While the drug development literature provides numerous estimates of the financial costs to bring a new drug to market, the investment of patient-participants in the research process has not been described. Trial participants and their caregivers, like companies, invest time and undertake risk when they participate in prelicense trials. We determined the average number of patient-participants needed to develop a novel neurological drug.

Status of Southeast Asia's marine sharks and rays.

In Southeast Asia, elasmobranchs are particularly threatened. We synthesized knowledge from the peer-reviewed and gray literature on elasmobranchs in the region, including their fisheries, status, trade, biology, and management. We found that 59% of assessed species are threatened with extinction and 72.

Dietary Fiber as a Counterbalance to Age-Related Microglial Cell Dysfunction.

With increasing age, microglia shift toward a pro-inflammatory phenotype that may predispose individuals to neurodegenerative disease. Because fiber fermentation in the colon produces bioactive short-chain fatty acids (SCFAs; e.g.

Randomised open-label trial comparing intravenous iron and an erythropoiesis-stimulating agent versus oral iron to treat preoperative anaemia in cardiac surgery (INITIATE trial).

Background: Preoperative anaemia is a risk factor for adverse postoperative outcomes after cardiac surgery. Iron deficiency is a frequent cause of low preoperative haemoglobin. An effective treatment for preoperative anaemia associated with iron deficiency has not been determined.

How informative were early SARS-CoV-2 treatment and prevention trials? a longitudinal cohort analysis of trials registered on ClinicalTrials.gov.

Background: Early in the SARS-CoV-2 pandemic, commentators warned that some COVID trials were inadequately conceived, designed and reported. Here, we retrospectively assess the prevalence of informative COVID trials launched in the first 6 months of the pandemic.

Methods: Based on prespecified eligibility criteria, we created a cohort of Phase 1/2, Phase 2, Phase 2/3 and Phase 3 SARS-CoV-2 treatment and prevention efficacy trials that were initiated from 2020-01-01 to 2020-06-30 using ClinicalTrials.

Green Synthesis of Gold Nanoparticles Using Upland Cress and Their Biochemical Characterization and Assessment.

This research focuses on the plant-mediated green synthesis process to produce gold nanoparticles (Au NPs) using upland cress (Barbarea verna), as various biomolecules within the upland cress act as both reducing and capping agents. The synthesized gold nanoparticles were thoroughly characterized using UV-vis spectroscopy, surface charge (zeta potential) analysis, scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX), atomic force microscopy (AFM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and X-ray diffraction (XRD). The results indicated the synthesized Au NPs are spherical and well-dispersed with an average diameter ~11 nm and a characteristic absorbance peak at ~529 nm.

Development of Gelatin-Coated Microspheres for Novel Bioink Design.

A major challenge in tissue engineering is the formation of vasculature in tissue and organs. Recent studies have shown that positively charged microspheres promote vascularization, while also supporting the controlled release of bioactive molecules. This study investigated the development of gelatin-coated pectin microspheres for incorporation into a novel bioink.

The COVID-19 pandemic and physical activity.

The SARS-CoV-2-caused COVID-19 pandemic has resulted in a devastating threat to human society in terms of health, economy, and lifestyle. Although the virus usually first invades and infects the lung and respiratory track tissue, in extreme cases, almost all major organs in the body are now known to be negatively impacted often leading to severe systemic failure in some people. Unfortunately, there is currently no effective treatment for this disease.

Behavioral strategies to prevent and mitigate COVID-19 infection.

The single stranded RNA virus SARS-CoV-2 has caused a massive addition to the already leading global cause of mortality, viral respiratory tract infections. Characterized by and associated with early and deleteriously enhanced production of pro-inflammatory cytokines by respiratory epithelial cells, severe COVID-19 illness has the potential to inflict acute respiratory distress syndrome and even death. Due to the fast spreading nature of COVID-19 and the current lack of a vaccine or specific pharmaceutical treatments, understanding of viral pathogenesis, behavioral prophylaxis, and mitigation tactics are of great public health concern.

Behavioral repertoire of high-shore littorinid snails reveals novel adaptations to an extreme environment.

Species that inhabit high-shore environments on rocky shores survive prolonged periods of emersion and thermal stress. Using two Hong Kong high-shore littorinids ( and . ) as models, we examined their behavioral repertoire to survive these variable and extreme conditions.

Patient Participation in Clinical Trials of Oncology Drugs and Biologics Preceding Approval by the US Food and Drug Administration.

Importance: Several studies have estimated the financial inputs for successful drug development. Such analyses do not capture the large investment that patient study participants commit to drug development.

Objective: To estimate the volume of patients required to achieve a first US Food and Drug Administration (FDA) approval for a new anticancer drug or biologic therapy.

Mothers' experience of Intensive Interaction.

There is limited research into parents' experiences of Intensive Interaction. Despite this, there are parents who use it and may hold unique experiences. Exploring this could provide insight into how to support parents using Intensive Interaction.

Probability of Success and Timelines for the Development of Vaccines for Emerging and Reemerged Viral Infectious Diseases.

Background: Anticipated success rates and timelines for COVID-19 vaccine development vary. Recent experience with developing and testing viral vaccine candidates can inform expectations regarding the development of safe and effective vaccines.

Objective: To estimate timelines and probabilities of success for recent vaccine candidates.