Pharmacovigilance of Drug-Drug Interactions with Nirmatrelvir/Ritonavir.

Introduction: Nirmatrelvir/ritonavir (NMV/r) is approved in the United States (US) and more than 70 other countries for the treatment of mild to moderate COVID-19 in nonhospitalized adults at high risk for severe disease. Because ritonavir inhibits several drug metabolizing enzymes, potential drug-drug interactions (DDIs) between ritonavir and concomitant medications are an important consideration for prescribers. Here, we conducted a real-world analysis of data from Pfizer's global safety database regarding adverse events (AEs) reported during use of NMV/r concomitantly with potentially interacting drugs.

Oral Nirmatrelvir-Ritonavir as Postexposure Prophylaxis for Covid-19.

Background: Clinical trials of treatments for coronavirus disease 2019 (Covid-19) have not shown a significant benefit of postexposure prophylaxis.

Methods: We conducted a phase 2-3 double-blind trial to assess the efficacy and safety of nirmatrelvir-ritonavir in asymptomatic, rapid antigen test-negative adults who had been exposed to a household contact with Covid-19 within 96 hours before randomization. The participants were randomly assigned in a 1:1:1 ratio to receive nirmatrelvir-ritonavir (300 mg of nirmatrelvir and 100 mg of ritonavir) every 12 hours for 5 days or for 10 days or matching placebo for 5 or 10 days.

Viral SARS-CoV-2 Rebound Rates in Linked Commercial Pharmacy-Based Testing and Health Care Claims.

Background: Viral SARS-CoV-2 rebound (viral RNA rebound) is challenging to characterize in large cohorts due to the logistics of collecting frequent and regular diagnostic test results. Pharmacy-based testing data provide an opportunity to study the phenomenon in a large population, also enabling subgroup analyses. The current real-world evidence approach complements approaches focused on smaller, prospective study designs.

Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19.

Background: Nirmatrelvir in combination with ritonavir is an antiviral treatment for mild-to-moderate coronavirus disease 2019 (Covid-19). The efficacy of this treatment in patients who are at standard risk for severe Covid-19 or who are fully vaccinated and have at least one risk factor for severe Covid-19 has not been established.

Methods: In this phase 2-3 trial, we randomly assigned adults who had confirmed Covid-19 with symptom onset within the past 5 days in a 1:1 ratio to receive nirmatrelvir-ritonavir or placebo every 12 hours for 5 days.

Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.

Background: Nirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (M) inhibitor with potent pan-human-coronavirus activity in vitro.

Methods: We conducted a phase 2-3 double-blind, randomized, controlled trial in which symptomatic, unvaccinated, nonhospitalized adults at high risk for progression to severe coronavirus disease 2019 (Covid-19) were assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir (a pharmacokinetic enhancer) or placebo every 12 hours for 5 days. Covid-19-related hospitalization or death from any cause through day 28, viral load, and safety were evaluated.

The use of extrapolation based on modeling and simulation to support high-dose regimens of ceftaroline fosamil in pediatric patients with complicated skin and soft-tissue infections.

A model-informed drug development approach was used to select ceftaroline fosamil high-dose regimens for pediatric patients with complicated skin and soft-tissue infections caused by Staphylococcus aureus with a ceftaroline minimum inhibitory concentration (MIC) of 2 or 4 mg/L. Steady-state ceftaroline concentrations were simulated using a population pharmacokinetics (PK) model for ceftaroline fosamil and ceftaroline including data from 304 pediatric subjects and 944 adults. Probability of target attainment (PTA) for various simulated pediatric high-dose regimens and renal function categories were calculated based on patients achieving 35% fT>MIC (S.

Phase 2 Study of the Safety, Pharmacokinetics and Efficacy of Ceftaroline Fosamil in Neonates and Very Young Infants With Late-onset Sepsis.

Background: With increasing antimicrobial resistance, antibiotic treatment options for neonatal late-onset sepsis (LOS) are becoming limited. Primary objective of this study was assessment of the safety of ceftaroline fosamil in LOS.

Methods: Eligible neonates and very young infants 7 to <60 days of age with LOS were enrolled in this phase 2, open-label, multicenter study (NCT02424734) and received ceftaroline fosamil 4 or 6 mg/kg every 8 hours by 1-hour intravenous infusion plus intravenous ampicillin and optional aminoglycoside for 48 hours-14 days.

Bupropion Use During Pregnancy: A Systematic Review.

Objective: To evaluate data on birth outcomes following bupropion use during pregnancy.

Data Sources: A systematic literature review of PubMed and PsycINFO was performed through June 2017 for clinical studies published in English. The following keywords were used: bupropion, pregnancy, depression, smoking cessation, birth outcomes, miscarriage, and spontaneous abortion.

Minimizing weight gain for patients taking antipsychotic medications: The potential role for early use of metformin.

Background: Patients taking antipsychotic medications are at high risk for weight gain, which in turn leads to poor health outcomes, nonadherence with treatment, and low self-esteem.

Methods: We reviewed published studies of pharmacologic interventions aimed at minimizing antipsychotic-induced weight gain. Treatments initiated prior to onset of weight gain were compared with those that started once weight gain already had occurred.

Lethal and sub-lethal responses of the biogenic reef forming polychaete Sabellaria alveolata to aqueous chlorine and temperature.

Sabellaria alveolata, a reef-forming marine polychaete, was exposed to aqueous chlorine which is routinely used as an anti-fouling agent in power station cooling water. Worms were treated to a range of chlorination levels (0, 0.02, 0.

Buried Alive: The Behavioural Response of the Mussels, Modiolus modiolus and Mytilus edulis to Sudden Burial by Sediment.

Sedimentation in the sea occurs through natural processes, such as wave and tidal action, which can be exacerbated during storms and floods. Changes in terrestrial land use, marine aggregate extraction, dredging, drilling and mining are known to result in substantial sediment deposition. Research suggests that deposition will also occur due to the modern development of marine renewable energy.

Sediment Burial Intolerance of Marine Macroinvertebrates.

The marine environment contains suspended particulate matter which originates from natural and anthropogenic sources. Settlement of this material can leave benthic organisms susceptible to smothering, especially if burial is sudden i.e.

Selective estrogen receptor modulators in clinical practice: a safety overview.

Introduction: Selective estrogen receptor (ER) modulators (SERMs) are a class of nonsteroidal compounds that interact with ERs, each with a distinct tissue-specific profile. Depending upon the degree of ER agonism/antagonism at the target tissue, SERMs show efficacy for various indications including osteoporosis, dyspareunia, and breast cancer, and are associated with safety risks.

Areas Covered: This review describes the safety profile of SERMs (tamoxifen, raloxifene, toremifene, bazedoxifene, lasofoxifene, and ospemifene) and fulvestrant (a pure ER antagonist) from Phase III trials, long-term extension studies, and active comparator studies.

Antidepressant use during pregnancy and childhood autism spectrum disorders.

Context: The prevalence of autism spectrum disorders (ASDs) has increased over recent years. Use of antidepressant medications during pregnancy also shows a secular increase in recent decades, prompting concerns that prenatal exposure may contribute to increased risk of ASD.

Objective: To systematically evaluate whether prenatal exposure to antidepressant medications is associated with increased risk of ASD.

Ephemeral bio-engineers or reef-building polychaetes: how stable are aggregations of the tube worm Lanice conchilega (Pallas, 1766)?

Dense aggregations of tube-worms can stabilize sediments and generate oases for benthic communities that are different and often more diverse and abundant than those of the surroundings. If these features are to qualify as biogenic reefs under nature-conservation legislation such as the EC Habitats Directive, a level of stability and longevity is desirable aside from physical and biological attributes. Lanice conchilega (Pallas, 1766) is widely distributed around the European coast and aggregations of this tube-dwelling polychaete are known to have a positive effect on the biodiversity of associated species in inter- and sub-tidal areas.

Increased productivity of recombinant tissular plasminogen activator (t-PA) by butyrate and shift of temperature: a cell cycle phases analysis.

Directed control of cell metabolism by a modification of the physicochemical conditions (presence of Na-butyrate and modification of the temperature) was used to modulate the productivity of human recombinant tissular plasminogen activator (t-PA) expressed under control of SV40 promoter in Chinese Hamster Ovary (CHO) cell lines. We showed that both by adding Na-butyrate or lowering temperature from 37 degrees C to 32 degrees C there is an increase in the amount of t-PA excreted, while cell growth is significantly reduced. The treatments also increased the intracellular amount of t-PA.

A general artificial neural network for the modelization of culture kinetics of different CHO strains.

Animal cell cultures are characterized by very complex nonlinear behaviors, difficult to simulate by analytical modeling. Artificial Neural Networks, while being black box models, possess learning and generalizing capacities that could lead to better results. We first trained a three-layer perceptron to simulate the kinetics of five important parameters (biomass, lactate, glucose, glutamine and ammonia concentrations) for a series of CHO K1(Chinese Hamster Ovary, type K1) batch cultures.

Adhesion, growth and detachment of cells on modified polystyrene surface.

By adsorbing poly(N-isopropylacrylamide) (PNIPAAm) from an aqueous solution onto oxidised polystyrene without the need for grafting the polymer to the surface, we showed here that cells(CHO-K1) adhere and grow well at 37 degrees C and are detached by lowering the temperature to 10 degrees C without any other deleterious treatment. Both bacterial culture grade polystyrene Petri dishes and polystyrene beads (120 to 250mum diameters) commercially available used in static conditions of growth were tested with similar results. The contact angle of modified Petri dishes with a water droplet increases from 36 to 58 degrees when the temperature is raised from 25 to 37 degrees C indicating change in hydrophilicity of the surface as a function of temperature.

Detection and quantification of ATP and heavy metal with electronical micro-circuits.

In order to use whole eukaryotic cells as an active element in the detection and amplification of biological signals, for both in vitro and in vivo applications, we have undertaken a first approach to interface live cells and integrated circuit, and evaluate the possibility to develop a microbioreactor. An amplified photodiode system was designed and built as an electronical circuit in a way that it could easily be miniaturised. In parallel micro-chips with silicium chambers were used as microbioreactors to adhere cells.

Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment.

Context: Pregnancy has historically been described as a time of emotional well-being, providing "protection" against psychiatric disorder. However, systematic delineation of risk of relapse in women who maintain or discontinue pharmacological treatment during pregnancy is necessary.

Objective: To describe risk of relapse in pregnant women who discontinued antidepressant medication proximate to conception compared with those who maintained treatment with these medications.

The impact of depression and fluoxetine treatment on obstetrical outcome.

Introduction: This study prospectively followed women over the course of pregnancy to assess the impact of depression and/or antidepressant treatment on obstetrical outcome.

Method: Sixty-four outpatient women with an Axis I diagnosis of major depressive disorder or no psychiatric history were followed in each trimester of pregnancy with administration of the CES-D. A subset of the women with depression received treatment with fluoxetine during pregnancy.

An Update on Mood and Anxiety Disorders During Pregnancy and the Postpartum Period.

Because women in the childbearing years are vulnerable to mood and anxiety disorders, physicians in all patient care specialties need to be familiar with the prevalence and course of these disorders, particularly during pregnancy and the postpartum period. Systematic prospective data are limited on the onset of mood and anxiety disorders during pregnancy and the postpartum period as well as on the risk of relapse during these time periods in women with prior histories of the disorders. The literature on mood and anxiety disorders during pregnancy is frequently complicated by the use of various methodologies, procedures, and study populations, and inconsistencies in the postpartum time frame (up to 6 months after delivery) make the literature on epidemiology of postpartum disorders difficult to interpret.