Drugs in Context最新文献

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in atrial fibrillation. At the Asia Pacific Advancing Patient care with EdoXaban 2023 meeting, experts shared insights on gastrointestinal bleeding with NOACs for stroke prevention in atrial fibrillation in Asian clinical practice, where NOACs have gained widespread acceptance due to their favourable profiles. Gastrointestinal bleeding risk varies amongst NOACs, emphasizing the importance of diligent patient assessment, dosage selection and vigilant monitoring. Edoxaban emerged as a viable option with a low gastrointestinal bleeding risk profile in Asian compared with non-Asian patients, supporting its continued clinical utilization for appropriate patients.

This review discusses available evidence on the mechanisms of action of bacterial lysates, and the clinical effects of their sublingual administration. Bacterial lysates act through many immunological effects, including dendritic cell activation, modification of circulating lymphocyte subsets and antibody production. The production of salivary IgA was repeatedly shown to be induced by the sublingual administration of a prototype bacterial lysate containing soluble and corpuscular antigens. Bacterial lysates are a useful tool for the prevention of recurrent respiratory tract infections. Sublingual administration should be the preferred option.

The management of schizophrenia necessitates a comprehensive treatment paradigm that considers individual patient nuances and the efficacy of lurasidone in addressing schizophrenia symptoms, particularly at elevated dosages. Numerous randomized trials have affirmed the efficacy of lurasidone across various dimensions of schizophrenia, demonstrating marked enhancements in positive, negative and cognitive symptoms compared to a placebo. In addition, lurasidone exhibits potential in ameliorating agitation amongst acutely ill patients, showcasing greater efficacy at higher doses. However, despite the favourable outcomes observed with higher lurasidone doses, routine clinical practice often opts for lower doses, potentially limiting its maximal therapeutic impact. Furthermore, lurasidone also shows efficacy in reducing post-psychotic depression in dual psychosis. Moreover, practical insights into lurasidone usage encompass swift dose escalation within a 1-5-day span and recommended combination strategies with other medications such as benzodiazepines for insomnia or agitation, beta-blockers for akathisia, and antihistamines or antimuscarinic drugs for patients transitioning rapidly from antipsychotics with substantial antihistamine and/or anticholinergic effects. Finally, a series of clinical cases is presented, highlighting benefits of lurasidone in terms of cognitive function, functional recovery and other therapeutic aspects for the management of schizophrenia.

Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the global population. Traditional systemic treatments, such as methotrexate, cyclosporine, acitretin and fumaric acid esters, have limited efficacy and are associated with significant adverse effects, necessitating regular monitoring and posing risks of long-term toxicity. Recent advancements have introduced biologic drugs that offer improved efficacy and safety profiles. However, their high cost and the inconvenience of parenteral administration limit their accessibility. Consequently, there is a growing interest in developing new, targeted oral therapies. Small molecules, such as phosphodiesterase 4 inhibitors (e.g. apremilast) and TYK2 inhibitor (e.g. deucravacitinib), have shown promising results with favourable safety profiles. Additionally, other novel oral agents targeting specific pathways, including IL-17, IL-23, TNF, S1PR1 and A3AR, are under investigation. These treatments aim to combine the efficacy of biologics with the convenience and accessibility of oral administration, addressing the limitations of current therapies. This narrative review synthesizes the emerging oral therapeutic agents for psoriasis, focusing on their mechanisms of action, stages of development and clinical trial results.

Bullous pemphigoid (BP) is an autoimmune bullous disease, typically affecting the elderly, characterized by the production of autoantibodies directed against structural components of the dermal-epidermal junction. An association between BP and psoriasis has been described several times, but the mechanisms underlying this association have yet to be clearly defined. The pathophysiological mechanism underlying psoriasis may be implicated in the pathogenesis of BP, as psoriasis precedes BP in most cases; in particular, a promoting role has been hypothesized by biologic therapies, which may induce a switch from a T helper 1 (T_H1)/T_H17-dominant cytokine milieu, typical of patients with psoriasis, to a T_H2-dominant one, typical of patients with BP. IL-17 inhibitors, in particular, have also been successfully used to treat BP in patients with psoriasis. The use of these drugs in these patients has been based on in vitro studies. However, cases of new-onset BP or relapses of BP already diagnosed in patients with psoriasis treated with biologic drugs have also been reported, and they occurred mainly in patients on anti-TNF drugs, yet very few cases with anti-IL-17A drugs have been described. We hereby describe two cases of new-onset BP in two patients treated with anti-IL-17 drugs for psoriasis.

Antibiotics are amongst the most prescribed medications globally in both inpatient and outpatient settings. Antibiotic-induced neuropsychiatric toxicity is relatively uncommon; yet, when it occurs, it can lead to severe morbidity ranging from dizziness and confusion to seizure and psychosis. However, the actual incidence rate of these adverse events may be higher due to underdiagnosis or misdiagnosis as they are commonly confused with clinical manifestations of different neuropsychiatric conditions. The incidence and mechanism of antibiotic-induced neuropsychiatric toxicity vary between different antibiotic classes and clinical presentation (i.e. neurotoxicity versus psychiatric toxicity). However, the exact mechanism by which antibiotics can cause neuropsychiatric toxicity remains unclear. This article reviews the epidemiology of antibiotic-induced neuropsychiatric toxicity, explores potential mechanisms of this adverse event, investigates variations in frequency and clinical presentations between different antibiotic classes causing neuropsychiatric toxicity, and discusses management strategies.

Background: Patients with severe asthma are often dependent on oral corticosteroids (OCS) and have frequent exacerbations. This article aims to report very long-term data of patients with severe eosinophilic asthma assessing asthma control, lung function, inhaled corticosteroid (ICS) dose reduction, and clinical and biological parameters of patients treated with mepolizumab.

Methods: Four cases of adult patients with severe eosinophilic asthma who were treated for 60 months or more with mepolizumab 100 mg/4 weeks, leading to the stable discontinuation of OCS, are presented. ICS dose, OCS dose and withdrawal date, lung function, eosinophil count, fractional exhaled nitric oxide, and asthma control test were recorded as well as exacerbations in the 12 months before commencing mepolizumab and in the 12 months before the last follow-up visit.

Results: Three of the patients were men, median age was 52.5 years (range 79-53), median length of asthma before mepolizumab start was 67.5 months (range 24-240), three had chronic rhinosinusitis without nasal polyposis and two were atopic. All had eosinophil counts >300 cells/μL at baseline. The median follow-up was 73.5 months (range 71-74), and OCS withdrawal from baseline occurred after a median of 13 months of mepolizumab treatment (range 12-39). A substantial reduction of ICS treatment was registered as well as improvement in asthma control test, fractional exhaled nitric oxide and functional parameters, and a significant reduction of exacerbations in the last 12 months before last visit was observed as compared to the 12 months before baseline (from a median of 4 (range 3-6) to 0; p=0.0286).

Conclusions: Mepolizumab could be a 'disease-modifying' agent, with high tolerability and a good efficacy profile in the long term.

The advent of immunotherapy, and in particular the use of immune-checkpoint inhibitors, has profoundly revolutionized the treatment of different cancers, including lung cancer. The use of immune-checkpoint inhibitors has prolonged survival in lung cancer with a strong benefit in a significant percentage of patients with non-small-cell lung cancer. Here, a clinical case of a patient who, despite testing negative for PD-L1, displayed a sustained complete response to immunotherapy treatment in advanced metastatic non-small-cell lung cancer is presented. Additionally, recent findings concerning the application of immunotherapy in this context are reviewed.

Background: Epilepsy is a persistent tendency to experience epileptic seizures and can lead to various neurobiological disorders, with an elevated risk of premature mortality. This study evaluates the efficacy of brivaracetam adjuvant therapy in patients with epilepsy.

Methods: A prospective observational multicentre study that was conducted in Pakistan from March to September 2022, by using a non-probability convenience sampling technique. The population consisted of 543 individuals with a diagnosis of epilepsy for whom adjunctive brivaracetam (Brivera; manufactured by Helix Pharma Pvt Ltd., Sindh, Pakistan) was recommended by the treating physician. The research sample was drawn from various private neurology clinics of Karachi, Lahore, Rawalpindi, Islamabad and Peshawar. Data originating from routine patient visits, and assessments at three study time points, were recorded in the study case report form.

Results: Across 18 clinical sites, 543 individuals participated, with a mean age of 32.9 years. The most prescribed dosages were 50 mg BD, followed by 100 mg BD. Notably, brivaracetam combined with divalproex sodium was the most prevalent treatment, followed by brivaracetam with levetiracetam. At both the 14th and 90th day assessments, a significant reduction in seizure frequency was observed, with 63.1% of individuals showing a favourable response by day 90. Treatment-naive individuals exhibited higher rates of seizure freedom and response compared with treatment-resistant individuals.

Conclusions: The study demonstrates the effectiveness of brivaracetam combination therapy in epilepsy management, with notable reductions in seizure frequency and favourable clinical responses observed, particularly in treatment-naive individuals.