Darunavir Population Pharmacokinetic Model Based on HIV Outpatient Data.

Background: Darunavir is a second-generation protease inhibitor and is registered for the treatment of HIV-1 infection. The aim of this study was to develop and validate a darunavir population pharmacokinetic model based on data from daily practice.

Methods: Data sets were obtained from 2 hospitals: ASST Fatebenefratelli Sacco University Hospital, Italy (hospital A), and University Medical Center Groningen, the Netherlands (hospital B).

Pharmacokinetics and Pharmacodynamics of Cabotegravir, a Long-Acting HIV Integrase Strand Transfer Inhibitor.

Available antiretroviral drugs have demonstrated effectiveness in both pre-exposure prophylaxis and treatment of HIV infection. However, some concerns still persist regarding these therapies, mainly related to patient adherence, drug toxicity and dosing convenience. Cabotegravir is a potent integrase strand transfer inhibitor with a chemical structure similar to dolutegravir that is under clinical evaluation both as oral and long-acting injectable (LAI) formulations for both the prevention or treatment of HIV infection.

Impact of Obesity and Hyperglycemia on Placental Mitochondria.

A lipotoxic placental environment is recognized in maternal obesity, with increased inflammation and oxidative stress. These changes might alter mitochondrial function, with excessive production of reactive oxygen species, in a vicious cycle leading to placental dysfunction and impaired pregnancy outcomes. Here, we hypothesize that maternal pregestational body mass index (BMI) and glycemic levels can alter placental mitochondria.

Loss of Control of HIV Viremia With OTC Weight-Loss Drugs: A Call for Caution?

Improved survival achieved by HIV-infected patients has complicated their medical care, as increasing numbers of comorbidities have led to polypharmacy and a higher risk of drug-drug interactions. Here, evidence is provided that weight-loss drugs should be used with caution in HIV-infected patients treated with lipophilic antiretroviral drugs because of the risk of virologic failure. This is particularly relevant considering that these agents are available on the market as over-the-counter medications, thus escaping the control of the physician.

Appropriateness of oral anticoagulant therapy prescription and its associated factors in hospitalized older people with atrial fibrillation.

Aims: Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65 years or older.

Methods: Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards.

Autoinflammatory diseases as a cause of acute abdominal pain in the emergency department.

Autoinflammatory diseases (AIDs) usually present with acute abdominal pain and fever, both of which are also the main causes of referral in the emergency department. As some patients with acute abdominal pain may be discharged from the emergency department without a definitive diagnosis, it is not surprising that, due to their rarity, most cases of AID remain undiagnosed or are misdiagnosed as acute appendicitis. Indeed, the diagnosis of familial Mediterranean fever and autoinflammatory syndromes requires a high index of suspicion and careful assessment of clinical history.

Metformin: Prevention of genomic instability and cancer: A review.

The diabetes drug metformin can mitigate the genotoxic effects of cytotoxic agents and has been proposed to prevent or even cure certain cancers. Metformin reduces DNA damage by mechanisms that are only incompletely understood. Metformin scavenges free radicals, including reactive oxygen species and nitric oxide, which are produced by genotoxicants such as ionizing or non-ionizing radiation, heavy metals, and chemotherapeutic agents.

Review of the Methods to Obtain Paediatric Drug Safety Information: Spontaneous Reporting and Healthcare Databases, Active Surveillance Programmes, Systematic Reviews and Meta-analyses.

Background: Knowledge of drugs safety collected during the pre-marketing phase is inevitably limited because the randomized clinical trials (RCTs) are rarely designed to evaluate safety. The small and selective groups of enrolled individuals and the limited duration of trials may hamper the ability to characterize fully the safety profiles of drugs. Additionally, information about rare adverse drug reactions (ADRs) in special groups is often incomplete or not available for most of the drugs commonly used in the daily clinical practice.

Comparison of the ARK Immunoassay With High-Performance Liquid Chromatography With Ultraviolet Detection for Therapeutic Drug Monitoring of Linezolid.

Background: An enzymatic immunoassay is under development by ARK Diagnostics, Inc for the quantification of plasma concentrations of linezolid (LZD). In this study, the authors aimed to assess the performance of this immunoassay using a validated high-performance liquid chromatography (HPLC) ultraviolet method as reference.

Methods: Within- and between-day in vitro inaccuracy and imprecision of the ARK LZD assay were firstly tested using spiked quality controls (QC) provided by the kit manufacturer.

Can We Rely on AGNP Therapeutic Targets Also For LAI Antipsychotics?

The updated AGNP Consensus Guidelines for Therapeutic Drug Monitoring (TDM) in Neuropsychopharmacology recently published in the journal have reinforced the key role of TDM to individualize psychoparmacological therapies in clinical practice. However, we believe, that these guidelines have missed the important opportunity to face with, and to provide useful information on, the emerging issue of long-acting injectable formulations of atypical antipsychotics. Specific therapeutic ranges also for these formulations should be included in the next AGNP guidelines.

Generics for the Treatment of Hepatitis C in Monoinfected and HIV-coinfected Patients: Pros and Cons.

The treatment of hepatitis C virus in monoinfected and HIV-coinfected patients has greatly changed over recent years as a result of the introduction of direct-acting antiviral agents (DAAs), which have revolutionized clinical outcomes and led to sustained virological response rates above 90-95%. The discovery of new molecules and the subsequent competition between pharmaceutical companies, together with the negotiated price policies pursued by many national health systems, have led to a gradual reduction in the cost of DAAs, and expand their use to an increasing number of patients, including those with mild liver damage. However, the cost of branded DAAs is still too high for many developing countries, and many patients are still left without therapy.

Effect of N-Desalkylquetiapine/Quetiapine Plasma Level Ratio on Anxiety and Depression in Bipolar Disorder: A Prospective Observational Study.

Background: The aim of this study was to analyze the relationships between quetiapine and N-desalkylquetiapine plasma levels and clinical improvement, particularly, in regard to depressive and anxious symptoms and to hostility.

Methods: This was a prospective observational study that involved 37 outpatients diagnosed as having bipolar disorder I or II. All the patients were observed during a clinical acute and postacute phase.

Novel Antiretroviral Drugs in Patients with Renal Impairment: Clinical and Pharmacokinetic Considerations.

Highly active antiretroviral therapy (HAART) has dramatically increased the survival of HIV-infected patients from Western countries reducing the incidence of opportunistic infections and AIDS-related malignancies, and improving the patients' quality of life compared with the pre-HAART era. HIV is thus now considered in the West as a chronic disease, with the majority of HIV-infected patients successfully reaching an optimal immune and virological outcome a few months after starting HAART. However, this switch from acute to chronic disease has been accompanied by an increased incidence of chronic kidney disease (CKD), reported in up to 60% of HIV-infected patients.