Future Perspectives of Pulmonary Arterial Hypertension: A Review of Novel Pipeline Treatments and Indications.

Pulmonary arterial hypertension is characterized by elevated blood pressure and pathological changes in the pulmonary arterioles, leading to the development of right-heart failure and potentially fatal outcomes if left untreated. This review aims to provide an overview of novel drugs or formulations and new drug indications for pulmonary arterial hypertension that are currently in phases II-III of randomized controlled trials, and describe the rationale for the use of these targeted therapies, as well as their efficacy, safety profile, and impact on quality of life and survival. The literature research was conducted using data from ClinicalTrials.gov for the period between 1 January 2016 up to 31 December 2022. The population of interest includes individuals aged ≥ 18 years who have been diagnosed with pulmonary arterial hypertension. The review selection criteria included trials with recruiting, enrolling by invitation, active, terminated or completed status in 2022 and 2023. A total of 24 studies were selected for evaluation based on the inclusion and exclusion criteria. This review summarizes the updated information from randomized clinical trials involving novel therapies for pulmonary arterial hypertension. However, larger clinical trials are required to validate their clinical safety and effects. In the future, clinicians should choose therapies based on the patient's individual situation and requirements when developing treatment strategies.

[A prospective observational study on daily intake of drugs, supplements and herbal products and detection of adverse drug reactions in elderly patients.] / Studio osservazionale prospettico relativo all'assunzione giornaliera di farmaci, integratori e prodotti erboristici nei pazienti anziani e rilevazione delle reazioni avverse ai farmaci.

Polytherapy is a common condition in the elderly patient and represents a risk factor for the onset of adverse drug reactions (ADRs). The objectives of this prospective study were the verification of the compliance with implicit criteria (Lipton, MAI and POM) to geriatric prescriptions, the identification of ADRs and the estimatation of the intake of drugs, over-the-counter (OTC) drugs, supplements and herbal products through the administration of a questionnaire. A total of 400 elderly patients (average age 73 years) were analyzed between September 2018 and September 2019. 79.5% of them were in polytherapy (≥4 drugs). The most frequently prescribed drugs were antihypertensives (75%). The use of OTC drugs was reported for 12% patients; the use of supplements for 25% of patients and the use of herbal products only for 2% patients. The prescriptions analysed resulted in compliance with the implicit criteria in terms of dosage, therapeutic indications and the presence of any drug allergies. ADRs were reported for 10% of patients: those related to nintedanib (53%) and pirfenidone (34%) were the most frequent.

Systematic Review and Meta-analysis of Pirfenidone, Nintedanib, and Pamrevlumab for the Treatment of Idiopathic Pulmonary Fibrosis.

BACKGROUND: The comparative efficacy of pirfenidone, nintedanib, and pamrevlumab in slowing the rate of forced vital capacity (FVC) decline and mortality in patients with idiopathic pulmonary fibrosis (IPF) is unknown. OBJECTIVE: To perform a systematic review and meta-analysis (MA) of these drugs for IPF. METHODS: We searched CENTRAL, PubMed, EMBASE, ClincalTrials.gov, and the World Health Organization's registry databases up to March 2020. Phase II/III randomized controlled trials in adults with IPF were eligible. The random-effect model was implemented calculating the effect size and respective 95% CI as Cohen's d for change from baseline FVC (in percentage predicted and liters) and odds ratio (OR) for 10% reduction in FVC and all-cause mortality (ACM). RESULTS: Six studies were included in the MA. For change from baseline in percentage predicted FVC, the MA indicated that the 3 drugs were more effective than placebo (pirfenidone: d=3.30%, 95% CI=2.15-4.45; nintedanib: d=3.15%, 95% CI=2.35-3.95; pamrevlumab: d=4.30%, 95% CI=0.45-8.15). These results are superimposable to those relating to change from baseline FVC in liters (pirfenidone: d=0.09L, 95% CI=0.04-0.14; nintedanib: d=0.13L, 95% CI=0.10-0.16; pamrevlumab: d=0.20L, 95% CI=0.05-0.35). Each drug had a positive effect on 10% reduction in FVC (pirfenidone: OR=0.57, 95% CI=0.45-0.74; nintedanib: OR=0.66, 95% CI=0.51-0.85; pamrevlumab: OR=0.24, 95% CI=0.08-0.73), but only pirfenidone showed an effect on ACM (OR=0.50; 95% CI=0.31-0.83). CONCLUSION AND RELEVANCE: This MA provided encouraging results on pamrevlumab efficacy in slowing the decline in FVC compared with pirfenidone and nintedanib. Actually, in phase 3, it could become a potential IPF treatment.

Evidence-based application of explicit criteria to assess the appropriateness of geriatric prescriptions at admission and hospital stay.

BACKGROUND: Inappropriate prescribing in the elderly is a critical issue in primary care, causing a higher risk of Adverse Drug Reactions (ADRs) and resulting in major patient safety concerns. At international level, many tools have been developed to identify Potentially Inappropriate Medications (PIMs). OBJECTIVE: The aim of this study was the application of Beers, Screening Tool of Older People's Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) and Improving Prescribing in the Elderly Tool (IPET) criteria as key tool to improve the quality of prescribing. METHODS: A retrospective study was conducted using the aforementioned criteria. Two different cohorts of elderly patients were enrolled between January 2015 and December 2016, 1800 at admission and 1466 at hospital stay. The index of each criterion divided by politherapy were correlated with comorbidities (Pearson correlation). A comparison was made between admission and hospital stay through a Student's t test of the average of the index. RESULTS: The Proton Pump Inhibitors (PPIs) were the most prescribed PIMs according Beers criteria in both patient cohorts (56%). The most detected drug-drug and drug-disease interactions at admission and at hospital stay were 3 or more drugs active on the Central Nervous System (CNS) as they can predispose to fall-risk. The most detected PIMs with STOPP criteria at admission were PPIs administered for more than 8 weeks. Inhaled ß2-agonists or antimuscarinics were the most prescribed Potential Prescription Omissions (PPOs) according to START criteria. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in patients with high blood pressure were the most detected PIMs according to IPET criteria during hospital stay. A significant correlation between the comorbidities and the all index at hospital stay, while at admission there was no significant correlation for Beers and IPET index. CONCLUSION: The prescriptive criteria were a useful tool for assessing the quality of prescriptions in the geriatric population and identifying their critical issues.

Essential oil components of orange peels and antimicrobial activity.

In this study, the orange peel of 12 cultivars of Citrus sinensis from central-eastern Sicily was employed to obtain essential oils and extracts. The ones were extracted through steam distillation, the others through extraction in hexane. Chemical constituents were evaluated in terms of qualitative and quantitative analyses by gas chromatography/mass spectrometry. Fifty-four components were identified in the steam essential oils and 44 in the extracts. In all the cultivars, the main component is d-limonene (73.9-97%); discrete percentages of linalool, geraniol and nerol were also found. Cluster analysis based on essential oils composition showed a certain degree of affinity between cultivars of the same type. The antimicrobial activity was investigated against three micro-organisms (Staphylococcus aureus, Listeria monocytogens and Pseudomonas aeruginosa). 'Sanguinello' and 'Solarino Moro' essential oils are significantly active against L. monocytogenes, while 'Valencia' hexanic extract against all the tested micro-organisms.