Treatment patterns and factors associated with adherence in pulmonary arterial hypertension.

Objective: Improving understanding of actual pulmonary hypertension (PH) treatment adherence patterns is crucial to properly treating these patients. We aimed to primarily assess adherence to treatments used for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) specific therapies, identify potential factors related to it and secondly describe its treatment patterns.

Methods: A 6-month observational cross-sectional study in a tertiary care hospital was conducted.

Risk Factors Associated with Antibiotic Exposure Variability in Critically Ill Patients: A Systematic Review.

(1) Background: Knowledge about the behavior of antibiotics in critically ill patients has been increasing in recent years. Some studies have concluded that a high percentage may be outside the therapeutic range. The most likely cause of this is the pharmacokinetic variability of critically ill patients, but it is not clear which factors have the greatest impact.

Peripartum lithium management: Early maternal and neonatal outcomes.

Background: It has been suggested that a 30-50 % lithium dose reduction or lithium discontinuation 24-48 h before delivery could minimize neonatal complications. We investigated the maternal lithemia changes around delivery after a brief discontinuation, the placental transfer of lithium at delivery, and the association between neonatal lithemia at delivery and acute neonatal outcomes.

Methods: A retrospective observational cohort study was conducted in a teaching hospital (November/2006-December/2018).

[Translated article] Conquering the future in hospital pharmacy: Training as a pillar of success.

The training of hospital pharmacists in the coming years must adapt and respond to constant current and future social and technological challenges, without neglecting the basic areas of the profession. It is necessary to acquire knowledge in what is known as digital comprehensive health: artificial intelligence, technology and automation, digital skills, and new forms of communication with patients, such as telemedicine and telepharmacy that are already a reality in many hospitals. We must provide knowledge in automated systems for the distribution and dispensing of medicines, robots for preparing sterile preparations, traceability systems, the use of drones in clinical care, etc.

Tackling the future in hospital pharmacy: Training as a pillar of success.

The training of hospital pharmacists in the coming years must adapt and respond to constant current and future social and technological challenges, without neglecting the basic areas of the profession. It is necessary to acquire knowledge in what is known as digital comprehensive health: Artificial intelligence, technology and automation, digital skills, and new forms of communication with patients, such as telemedicine and telepharmacy that are already a reality in many hospitals. We must provide knowledge in automated systems for the distribution and dispensing of medicines, robots for preparing sterile preparations, traceability systems, the use of drones in clinical care, etc.

Treatment patterns and factors associated with adherence in pulmonary arterial hypertension.

Objective: Improving understanding of actual pulmonary hypertension (PH) treatment adherence patterns is crucial to properly treating these patients. We aimed to primarily assess adherence to treatments used for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) specific therapies, identify potential factors related to it and secondly describe its treatment patterns.

Methods: A 6-month observational cross-sectional study in a tertiary care hospital was conducted.

Towards precision medicine of long-acting aripiprazole through population pharmacokinetic modelling.

Population pharmacokinetic (popPK) models constitute a valuable tool for characterizing the pharmacokinetic properties of once-monthly long-acting injectable aripiprazole (LAI aripiprazole) and quantifying the sources of variability in drug exposure. Our aim is to develop a popPK model of both aripiprazole and its metabolite dehydro-aripiprazole in patients treated with LAI aripiprazole, and to personalize the dosing regimen of aripiprazole across different sub-groups of patients. This is a prospective study investigating the pharmacokinetics of LAI aripiprazole.

Real-world data of the use and experience of caplacizumab for the treatment of acquired thrombotic thrombocytopenic purpura: Case series.

Purpose: Caplacizumab was licensed for acquired thrombotic thrombocytopenic purpura (aTTP) based on prospective controlled trials. Real-world evidence is crucial in rare diseases. We aim to describe a patient population with aTTP, receiving caplacizumab in a real-world setting, reporting their outcomes, including safety and tolerability, and contrasting them with a historical cohort from our center.

Real-Life Data on the Effectiveness and Safety of Cefiderocol in Severely Infected Patients: A Case Series.

Introduction: Real-life data about cefiderocol use to treat extensively drug-resistant bacteria are scarce. We aim to report our early experience in patients with difficult-to-treat infections and limited therapeutic options.

Methods: Patients treated with cefiderocol from March 2018 to April 2022 in a tertiary-care hospital in Spain were included.

Adequacy of the 10 mg/kg Daily Dose of Antituberculosis Drug Isoniazid in Infants under 6 Months of Age.

In 2010, the WHO recommended an increase in the daily doses of first-line anti-tuberculosis medicines in children. We aim to characterize the pharmacokinetics of the once-daily isoniazid (INH) dose at 10 mg/kg of body weight in infants <6 months of age. We performed a multicenter pharmacokinetic study in Spain.

Drug-drug interactions of ritonavir-boosted SARS-CoV-2 protease inhibitors in solid organ transplant recipients: experience from the initial use of lopinavir-ritonavir.

Objectives: To review the drug-drug interactions between tacrolimus and lopinavir/ritonavir in 23 patients who received solid organ transplant during the first wave of COVID-19 and to determine the efficacy as well as safety of prednisone monotherapy.

Methods: Observational study performed between March and June 2020 in solid organ transplant recipients admitted with an established diagnosis of SARS-CoV-2 infection who received lopinavir/ritonavir (≥2 doses). Once lopinavir/ritonavir therapy was initiated, calcineurin inhibitor treatment was temporarily switched to prednisone monotherapy (15-20 mg/d) to avoid drug-drug interactions and toxicity.

Personalized antimicrobial therapy in critical and elderly patients.

Objective: Personalized therapy in the treatment of infections is essential to  ensure optimization of antimicrobial drug levels. This strategy, together with an  understanding of the activity of these drugs, decreases the risk of bacterial  resistance and improves the drugs' safety profile. Alternative  outes of administration, such as inhalation, and the information provided by  pharmacokinetic models, are essential given the limitation of antimicrobial  activity allowed by the new antimicrobials.

Tigecycline population pharmacokinetics in critically ill patients with decompensated cirrhosis and severe infections.

Objectives: Physiopathological changes in advanced cirrhosis could alter tigecycline pharmacokinetics (PK), thus affecting serum drug concentrations and compromising target attainment. We aimed to describe tigecycline PK in patients with decompensated cirrhosis and severe bacterial infections, identify the sources of PK variability and assess the performance of different dosing regimens to optimize the PK/pharmacodynamic (PD) target.

Methods: Serum concentrations and covariates were obtained from patients with severe infections under tigecycline treatment.

New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia.

Introduction: Chagas disease (CD) affects ~7 million people worldwide. Benznidazole (BZN) and nifurtimox (NFX) are the only approved drugs for CD chemotherapy. Although both drugs are highly effective in acute and paediatric infections, their efficacy in adults with chronic CD (CCD) is lower and variable.

Neonatal Feeding Trajectories in Mothers With Bipolar Disorder Taking Lithium: Pharmacokinetic Data.

Women who take lithium during pregnancy and continue after delivery may choose to breastfeed, formula feed, or mix these options. The aim of the study was to evaluate the neonatal lithium serum concentrations based on these three feeding trajectories. We followed 24 women with bipolar disorder treated with lithium monotherapy during late pregnancy and postpartum (8 per trajectory).

Case Report: Clinical and Pharmacokinetic Profile of Lithium Monotherapy in Exclusive Breastfeeding. A Follow-Up Case Series.

Most guidelines advise that women taking lithium should not breastfeed. The variation in transfer is just one reason behind this advice. To present clinical and pharmacokinetic data of nine mother-infant pairs exposed to lithium monotherapy during late pregnancy and exclusive breastfeeding at the Perinatal Psychiatric Unit (2006-2018).

Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis.

Objectives: To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits.

Methods: Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-kill studies were performed using standard (105 cfu) and high (108 cfu) inocula of five MRSA, one glycopeptide-intermediate (GISA) and five MSSA strains.

Once-daily 1 g ceftriaxone optimizes exposure in patients with septic shock and hypoalbuminemia receiving continuous veno-venous hemodiafiltration.

Purpose: Ceftriaxone total and unbound pharmacokinetics (PK) can be altered in critically ill patients with septic shock and hypoalbuminemia receiving continuous veno-venous hemodiafiltration (CVVHDF). The objective of this study was to determine the dosing strategy of ceftriaxone that maximizes the probability of maintaining the concentration above the MIC of the susceptible bacteria (≤2 mg/L by the EUCAST) for a 100% of the dosing interval (100% ƒT).

Methods: In a prospective PK study in the intensive care units of two tertiary Spanish hospitals, six timed blood samples were collected per patient; for each sample, ceftriaxone total and unbound concentrations were measured using a liquid chromatography coupled to tandem mass spectrometry method.

Meropenem population pharmacokinetics in patients with decompensated cirrhosis and severe infections.

Objectives: Meropenem pharmacokinetics (PK) may be altered in patients with cirrhosis, hampering target attainment. We aimed to describe meropenem PK in patients with decompensated cirrhosis and severe bacterial infections, identify the sources of PK variability and assess the performance of different dosing regimens to optimize the PK/pharmacodynamic (PD) target.

Methods: Serum concentrations and covariates were obtained from patients with severe infections under meropenem treatment.

Cloxacillin or fosfomycin plus daptomycin combinations are more active than cloxacillin monotherapy or combined with gentamicin against MSSA in a rabbit model of experimental endocarditis.

Background: In vitro and in vivo activity of daptomycin alone or plus either cloxacillin or fosfomycin compared with cloxacillin alone and cloxacillin plus gentamicin were evaluated in a rabbit model of MSSA experimental endocarditis (EE).

Methods: Five MSSA strains were used in the in vitro time-kill studies at standard (105-106 cfu/mL) and high (108 cfu/mL) inocula. In the in vivo EE model, the following antibiotic combinations were evaluated: cloxacillin (2 g/4 h) alone or combined with gentamicin (1 mg/kg/8 h) or daptomycin (6 mg/kg once daily); and daptomycin (6 mg/kg/day) alone or combined with fosfomycin (2 g/6 h).

mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer.

Trastuzumab emtansine (T-DM1) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (BC) and for residual disease after neoadjuvant therapy; however, not all patients benefit. Here, we hypothesized that the heterogeneity in the response seen in patients is partly explained by the levels of human epidermal growth factor receptor 2 gene mRNA. We analyzed expression using a clinically applicable assay in formalin-fixed paraffin-embedded (FFPE) tumors (primary or metastatic) from a retrospective series of 77 patients with advanced HER2+ BC treated with T-DM1.

Evaluation of dose-tapering strategies for intravenous tocilizumab in rheumatoid arthritis patients using model-based pharmacokinetic/pharmacodynamic simulations.

Purpose: Tocilizumab is a humanized monoclonal antibody approved for rheumatoid arthritis treatment. In clinical practice, empirical dose-tapering strategies are implemented in patients showing sustained remission or low disease activity (LDA) to avoid overtreatment and reduce costs. Since rational adaptive-dosing algorithms taking the full pharmacokinetic (PK)/pharmacodynamic (PD) characteristics into account are currently lacking, we aimed to develop novel tapering strategies and compare them with currently used empirical ones.

Anticholinergic Burden and Safety Outcomes in Older Patients with Chronic Hepatitis C: A Retrospective Cohort Study.

Aim: Older patients with chronic hepatitis C infection starting direct-acting antivirals (DAAs) are frequently prescribed multiple medications that may be categorized as inappropriate. Anticholinergic burden has been shown to be a predictor of adverse health and functional outcomes. Different scales are available to calculate anticholinergic burden.

The safety of antimicrobials for the treatment of community-acquired pneumonia.

: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide, and its prevalence continues to increase. Despite the efficacy of antimicrobials, their safety and tolerability remain topics of interest and concern for clinicians and patients alike.: This review outlines the main antimicrobial classes recommended for the empirical treatment of CAP in current guidelines, together with a potential new class.