Effect of midazolam co-administered with oxycodone on ventilation: a randomised clinical trial in healthy volunteers.

Background: Benzodiazepines can exacerbate opioid-induced respiratory depression by furthering the decrease in central respiratory drive and causing loss of upper airway patency potentially leading to airway obstruction. This study aimed to determine if co-administration of benzodiazepines and opioids significantly decreases hypercapnic ventilation compared with opioids alone.

Methods: We conducted a randomised, double-blind, four-period crossover trial in 20 healthy participants to assess whether i.

Predictive modelling of the effectiveness of vaccines against COVID-19 in Bogotá: Methodological innovation involving different variants and computational optimisation efficiency.

The uncertainty associated with the future of viruses such as SARS-CoV-2 poses a challenge to public health officials because of its implications for welfare, economics and population health. In this document, we develop an age-stratified epidemiological-mathematical model to predict various health outcomes, considering the effectiveness of COVID-19 vaccines. The analytical model proposed and developed for this research is based on the approach constructed by the COVID-19 International Modelling Consortium.

Monitoring Anesthetic Depth Using the Patient State Index in Electroconvulsive Therapy Improves Seizure Quality.

Objectives: The determination of anesthetic depth has been used to assess the optimal moment for applying electrical stimuli in electroconvulsive therapy (ECT), as some of the anesthetics used can reduce its effectiveness. In this study, seizure quality was assessed using anesthetic depth measurement with the patient state index (PSI).

Methods: A prospective experimental study was conducted with a control group, including a sample of 346 stimulations (PSI=134; Control=212) in 51 patients admitted and diagnosed with major depressive disorders.

Predictive models for health outcomes due to SARS-CoV-2, including the effect of vaccination: a systematic review.

Background: The interaction between modelers and policymakers is becoming more common due to the increase in computing speed seen in recent decades. The recent pandemic caused by the SARS-CoV-2 virus was no exception. Thus, this study aims to identify and assess epidemiological mathematical models of SARS-CoV-2 applied to real-world data, including immunization for coronavirus 2019 (COVID-19).

Detecting unexpected growths in health technologies expenditures: the case of MIPRES in Colombia.

We developed an algorithm to explore unexpected growth in the usage and costs of health technologies. We exploit data from the expenditures on technologies funded by the Colombian government under the compulsory insurance system, where all prescriptions for technologies not included in an explicit list must be registered in a centralized information system, covering the period from 2017 to 2022. The algorithm consists of two steps: an outlier detection method based on the density of the expenditures for selecting a first set of technologies to consider (39 technologies out of 106,957), and two anomaly detection models for time series to determine which insurance companies, health providers, and regions have the most notorious increases.

Preliminary clinical pharmacokinetic evaluation of bemotrizinol - A new sunscreen active ingredient being considered for inclusion under FDA's over-the-counter (OTC) sunscreen monograph.

Protection against sunburn, skin damage and the carcinogenic effects of ultraviolet light are the primary health benefits associated with UV filters used in topical sunscreen drug products. Countries such as Europe have 30+ UV filters approved for sunscreen products while the US has about 10, greatly reducing the options to provide diverse, effective sun protection products. Bemotrizinol (BEMT) is the first new sunscreen active ingredient to be evaluated for inclusion in the Over-The-Counter (OTC) sunscreen monograph using FDA's new Generally Recognized as Safe and Effective (GRASE) testing guidelines.

Considerations for Use of Pharmacodynamic Biomarkers to Support Biosimilar Development - (III) A Randomized Trial with Interferon Beta-1a Products.

The US Food and Drug Administration (FDA) has taken steps to bring efficiency to the development of biosimilars, including establishing guidance for the use of pharmacokinetic and pharmacodynamic (PD) similarity study data without a comparative clinical study with efficacy end point(s). To better understand the potential role for PD biomarkers in biosimilar development and inform best practices for biomarker selection and analysis, we conducted a randomized, double-blinded, placebo-controlled, single-dose, parallel-arm clinical study in healthy participants. Eighty-four healthy participants (n = 12 per dose arm) received either placebo or one of three doses of either interferon β-1a (7.

Evaluating the Utility of Proteomics for the Identification of Circulating Pharmacodynamic Biomarkers of IFNβ-1a Biologics.

Proteomics has the potential to identify pharmacodynamic (PD) biomarkers for similarity assessment of proposed biosimilars without relying on clinical efficacy end points. In this study, with 36 healthy participants randomized to therapeutic doses of interferon-beta 1a products (IFNβ-1a) or pegylated-IFNβ-1a (pegIFNβ-1a) approved to treat multiple sclerosis or placebo, we evaluated the utility of a proteomic assay that profiles > 7,000 plasma proteins. IFNβ-1a and pegIFNβ-1a resulted in 248 and 528 differentially expressed protein analytes, respectively, between treatment and placebo groups over the time course.

Temperature and strain sensitivities of a groove bonded fiber Bragg grating at room and cryogenic temperatures.

Optical fiber Bragg gratings (FBGs) are well suited for applications as temperature or/and strain sensors in harsh environments, e.g., detecting thermal hot spots in high-temperature superconductor (HTS) fusion energy magnets at cryogenic temperatures and high radiation environments.

Effect of Paroxetine or Quetiapine Combined With Oxycodone vs Oxycodone Alone on Ventilation During Hypercapnia: A Randomized Clinical Trial.

Importance: Opioids can cause severe respiratory depression by suppressing feedback mechanisms that increase ventilation in response to hypercapnia. Following the addition of boxed warnings to benzodiazepine and opioid products about increased respiratory depression risk with simultaneous use, the US Food and Drug Administration evaluated whether other drugs that might be used in place of benzodiazepines may cause similar effects.

Objective: To study whether combining paroxetine or quetiapine with oxycodone, compared with oxycodone alone, decreases the ventilatory response to hypercapnia.

Promoter Methylation Status and and Expression in Patients With Wild-type KRAS Gene in Colorectal Cancer.

Background/aim: Although some mutations of KRAS proto-oncogene, GTPase (KRAS) have been associated with the prognosis and therapeutic management of colorectal cancer (CRC), the epigenetic mechanisms (DNA methylation and microRNA expression) that regulate wild-type KRAS expression in patients with CRC are poorly known. The aim of this study was to establish whether there is a relationship between the expression of the wild-type KRAS gene, the methylation status of its distal promoter, and miR-143 and miR-18a-3p levels in samples of sporadic CRC.

Patients And Methods: A total of 51 cases of sporadic CRC with wild-type KRAS were analyzed.

The Consumption of Food-Based Iodine in the Immediate Pre-Pregnancy Period in Madrid Is Insufficient. San Carlos and Pregnancy Cohort Study.

A pre-gestational thyroid reserve of iodine is crucial to guarantee the increased demand for thyroid hormone production of early pregnancy. An iodine intake ≥150 µg/day is currently recommended. The objective of this study was to assess average pre-gestational food-based iodine consumption in pregnant women at their first prenatal visit (<12 gestational weeks), and its association with adverse materno-fetal events (history of miscarriages, early fetal losses, Gestational Diabetes, prematurity, caesarean sections, and new-borns large/small for gestational age).

Early Levothyroxine Treatment for Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy: The St Carlos Gestational and Thyroid Protocol.

Unlabelled: The optimal maternal levels of thyroid hormones (TH) during the first trimester of gestation have not been established, nor has the ideal moment to initiate levothyroxine treatment (LT) to improve the evolution of gestation and fetal development. Cut-off points for Thyroid-stimulating hormone (TSH) <2.5 µIU/mL and free thyroxine (FT4)>7.

How should we define cure after parathyroidectomy for normocalcemic primary hyperparathyroidism? A retrospective cohort study.

Cure after surgery for normocalcemic primary hyperparathyroidism (NHPT) is defined as parathyroid hormone (PTH) normalization. However, an increase of PTH is frequently observed in cured patients with hypercalcemic primary hyperparathyroidism (HHPT). Therefore, this criterion must be redefined.

Social and professional consequences of COVID-19 lockdown in patients with multiple sclerosis from two very different populations.

Unlabelled: The global lockdown measures implemented due to the COVID-19 pandemic have nearly always had negative consequences for patients with multiple sclerosis (MS).

Objective: We compared the social and professional effects of confinement on patients with MS in 2 very different populations, from Spain and China.

Methods: Questionnaires were administered to a group of patients with MS who consulted at the MS unit of Vithas hospital (DINAC Foundation) in Seville, and patients with MS attended in several provinces of China in April 2020, with the aim of analysing the differences and similarities between populations in the social and professional effects of confinement.

Effect of Sunscreen Application on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial.

Importance: A prior pilot study demonstrated the systemic absorption of 4 sunscreen active ingredients; additional studies are needed to determine the systemic absorption of additional active ingredients and how quickly systemic exposure exceeds 0.5 ng/mL as recommended by the US Food and Drug Administration (FDA).

Objective: To assess the systemic absorption and pharmacokinetics of the 6 active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate) in 4 sunscreen products under single- and maximal-use conditions.

Effect of Cefiderocol, a Siderophore Cephalosporin, on QT/QTc Interval in Healthy Adult Subjects.

Purpose: Cefiderocol is a novel siderophore cephalosporin with potent activity against gram-negative bacteria, including multidrug-resistant strains. This Phase I study was conducted to assess the tolerability of single-ascending doses of cefiderocol (part 1) and the effect of cefiderocol on cardiac repolarization, assessed using the electrocardiographic corrected QT interval (QTcF) and other ECG parameters (part 2), in healthy adult subjects.

Methods: Part 1 was a randomized, double-blind, placebo-controlled, single-ascending dose study in healthy adult male and female subjects.

Distribution of cervical lesions in young and older women.

Introduction: Age range for cervical screening varies widely between countries. In addition, sexual behavior has changed, life expectancy is increasing, and new insights have been gained into the pathogenesis of HPV infection. Our aim is to evaluate the distribution of cervical lesions in young and older patients.

Effect of Sunscreen Application Under Maximal Use Conditions on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial.

Importance: The US Food and Drug Administration (FDA) has provided guidance that sunscreen active ingredients with systemic absorption greater than 0.5 ng/mL or with safety concerns should undergo nonclinical toxicology assessment including systemic carcinogenicity and additional developmental and reproductive studies.

Objective: To determine whether the active ingredients (avobenzone, oxybenzone, octocrylene, and ecamsule) of 4 commercially available sunscreens are absorbed into systemic circulation.

Anal cytology in women: Experience from a single tertiary center.

Introduction: Anal cytology (AC) can be used as a screening tool for detection of anal HPV associated lesions, mainly in men who have sex with men and in immunosuppressed patients. Our aim is to review our experience with AC in women.

Material & Methods: We have retrospectively reviewed all AC diagnosed between 2010-2017 in a single tertiary hospital (n = 644) and selected those performed in women (n = 158).

Assessment of Multi-Ion Channel Block in a Phase I Randomized Study Design: Results of the CiPA Phase I ECG Biomarker Validation Study.

Balanced multi-ion channel-blocking drugs have low torsade risk because they block inward currents. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative proposes to use an in silico cardiomyocyte model to determine the presence of balanced block, and absence of heart rate corrected J-T (J-T c) prolongation would be expected for balanced blockers. This study included three balanced blockers in a 10-subject-per-drug parallel design; lopinavir/ritonavir and verapamil met the primary end point of ΔΔJ-T c upper bound < 10 ms, whereas ranolazine did not (upper bounds of 8.

NYX-2925, A Novel N-methyl-D-aspartate Receptor Modulator: A First-in-Human, Randomized, Double-blind Study of Safety and Pharmacokinetics in Adults.

NYX-2925, a new chemical entity, acts as a co-agonist to glutamate at the N-methyl-D-aspartate receptor (NMDAR). At low concentrations of endogenous agonists (glycine/D-serine), NYX-2925 partially activates NMDARs, modulating neural pathways relevant for chronic pain. NYX-2925 is being developed for the treatment of chronic pain conditions, including painful diabetic peripheral neuropathy and fibromyalgia.

Evaluation of the Cardiac Safety of Long-Acting Endectocide Moxidectin in a Randomized Concentration-QT Study.

Potential effects on cardiac repolarization of single doses of moxidectin, a potent long-acting macrocyclic lactone endectocide, were assessed in a concentration-QT (c-QT; exposure-response) study. This double-blind, placebo-controlled, parallel-group study in healthy male volunteers (n = 60) randomized subjects to a single oral dose of moxidectin (4 mg, 8 mg, 16 mg, 24 mg, or 36 mg) or matching placebo. Serial plasma samples for pharmacokinetic (PK) analysis and concurrent triplicate electrocardiogram measurements were taken at baseline and 14 prespecified time points over 72 hours, yielding 900 QT interval-plasma concentration time-matched pairs.

[Cost-Fffectiveness of Two Antiviral Therapies for Chronic Hepatitis B in Peru: Entecavir and Tenofovir].

Objetives: To compare in terms of cost-effectiveness to entecavir (ETV) and tenofovir (TDF) in the treatment of hepatitis B virus (HBV) in public hospitals in Peru.

Materials And Methods: We structured a Markov model. We define effectiveness adjusted life years for quality (QALY).