Search Results (22)

Background: Fixed-dose combination medications (FDCs) are recognized methods of increasing adherence to polytherapy in chronic diseases. However, the role of FDCs in patients with benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms (LUTS) remains uncertain. We designed this study to assess persistence, adherence, and patient satisfaction with FDCs recently introduced to the Polish pharmaceutical market, which contain tamsulosin (an α1-adrenergic receptor antagonist) in combination with solifenacin (a muscarinic receptor antagonist) or dutasteride (a 5-α reductase inhibitor). Methods: The analysis included 50,435 men (67.8 ± 8.8 years old) managed by urologists for BPH-associated LUTS, who had been on combination therapies for at least 3 months. Two study visits, with an interval of 2.1 ± 1.4 months, were conducted between February and December 2024. Results: Single-component drugs (83.1%) were more common forms of therapy compared to FDCs (16.9%). ARAs (α1-adrenergic receptor antagonists) with 5-α reductase inhibitors comprised 70.2%, while ARAs with muscarinic receptor antagonists or β3-adrenergic agonists comprised 29.5%. Persistence with therapy across two visits was 82.0% for single-component drugs and 93.6% for FDCs (p < 0.001); OR = 1.31 (95% CI: 1.02–1.63). Similarly, adherence was better in patients treated with FDCs (96.6% vs. 91.0% at visit 1, p < 0.001; 99.3% vs. 97.9% at visit 2, p < 0.05). Patients prescribed FDCs were satisfied with therapy more often than those prescribed single-component drugs (62.6% and 76.8% vs. 50.6% and 67.5% at visits 1 and 2, respectively; p < 0.001). Conclusions: 1. Combination therapies are still more commonly administered as separate tablets than FDCs in patients with BPH-associated LUTS. 2. The use of FDCs increases short-term satisfaction and persistence with therapy, with a mild effect on adherence. Full article

Background: Oxidative stress is associated with the pathogenesis of epilepsy. Long-term treatment with anti-seizure medications (ASMs) may reduce antioxidant levels, which consequently impairs the brain’s ability to counteract oxidative damage. This study aimed to assess the concentrations of selected antioxidants (i.e., glutathione, retinol, and α- and γ-tocopherols) in children with epilepsy treated with polytherapy. Methods: The study included 21 children with epilepsy treated with ≥2 ASMs for at least 6 months (mean age 7.1 ± 4.4 years) and 23 control children without epilepsy (mean age 7.4 ± 3.9 years). Both groups were recruited at the Department of Pediatric Neurology, the Medical University of Silesia in Katowice (Poland). The concentrations of glutathione, retinol, and α- and γ-tocopherols were determined in blood serum by HPLC. The antioxidant levels were compared between sex and age subgroups of individuals with epilepsy. Results: In the group of individuals with epilepsy, the percentage of females was 38% and in the control group it was 30%. There were no differences in antioxidant levels between female and male individuals with epilepsy, nor between younger epileptic children (0–6 years) and older children (>6 years). Individuals with epilepsy had significantly lower glutathione levels than the control group (1.5 ± 0.3 µmol/L vs. 2.4 ± 1.2 µmol/L, respectively, p < 0.001). In turn, the ratios of both α-tocopherol/glutathione and γ-tocopherol/glutathione were higher in individuals with epilepsy than in the control group (p = 0.042 and p = 0.004, respectively). Individuals with epilepsy taking ASM combinations other than valproic acid (VPA) and levetiracetam (LEV) had a lower level of both retinol and glutathione than individuals on VPA and LEV treatment (for retinol 0.44 ± 0.13 µmol/L vs. 0.6 ± 0.1 µmol/L, respectively, p = 0.047, and for glutathione 1.3 ± 0.3 µmol/L vs. 1.8 ± 0.3 µmol/L, respectively, p = 0.003). In the individuals with epilepsy, the level of α-tocopherol decreased with age (r = −0.505, p = 0.019). In turn, in the control group, the levels of retinol and γ-tocopherol increased with age (r = 0.573, p = 0.004 and r = 0.461, p = 0.027, respectively). Conclusions: Glutathione levels significantly differed between children with and without epilepsy. The concentration of α-tocopherol decreased with age in pediatric individuals with epilepsy. The levels of both retinol and glutathione were higher in individuals with epilepsy taking VPA and LEV treatment compared to individuals on ASMs combination other than VPA and LEV. Full article

Background: Feeding and Eating Disorders (FEDs) are severe mental health conditions often emerging during childhood or adolescence, with rising prevalence. They are frequently associated with psychiatric and organic comorbidities, including anxiety symptoms and insomnia. Phytotherapy, particularly Passiflora incarnata L. Herba, has been suggested as a potential treatment option for anxiety and insomnia in youth. Methods: this is an observational and retrospective study that includes patients assessed in a third-level Italian Regional Centre for Feeding and Eating Disorders in Children and Adolescents between 1 January 2020 and 31 December 2023. Eligible patients had a confirmed diagnosis of a FED, along with either an anxiety or a sleep disorder. During follow-up, the clinical efficacy of Passiflora incarnata L. Herba was assessed using the Clinical Global Impression–Improvement scale (CGI-I). Comparative analyses were conducted by stratifying the sample based on the target symptoms (sleep disorders/insomnia and anxiety), FED subtype, and whether polytherapy was used. Results: this study includes 94 patients, with most diagnosed with anorexia nervosa (71.3%). Passiflora incarnata L. Herba was administered at a dosage of 200 mg (1–2 tablets for day). It was often combined with selective serotonin reuptake inhibitors (SSRIs) (56.5%), atypical antipsychotics (27.7%), or benzodiazepines (7.4%). Treatment was initiated for anxiety symptoms (75.5%) or insomnia (28.7%). No side effects were reported. Among patients with specific outcome data, 53.3% reported improvements in anxiety symptoms, and 45.4% reported improvements in insomnia. Conclusions: this is the first study to evaluate the use of Passiflora incarnata L. Herba for anxiety and insomnia in children and adolescents with FEDs. Our findings suggest that Passiflora incarnata L. Herba may serve as a well-tolerated adjunctive treatment, showing symptomatic improvement in up to 53% of the patients with data on treatment outcomes. Notably, 53.3% and 45.4% of participants, with specific outcome data, reported reduced anxiety and insomnia symptoms, respectively. Given its excellent safety profile and preliminary efficacy, Passiflora incarnata L. Herba may represent a promising alternative for patients with mild symptoms or for caregivers hesitant about conventional pharmacotherapy. Full article

Status epilepticus (SE) is a neurological emergency. Current evidence dictates a step-by-step approach with a first line of therapy consisting of benzodiazepines (BDZs). In many situations, the currently approved approach does not terminate a BDZ-resistant SE. This happens in Stage 1 Plus, a framework designed by the author to recognize cases of probable benzodiazepine-resistant status epilepticus even before treatment initiation. These cases include Prolonged SE (SE lasting > 10 min), the absence of prominent motor phenomena, and acute etiology (primary central nervous system etiologies most of all). BDZ-refractory SE cases (Stage 1 Plus) might require a different approach, one targeting the unresponsive GABA signaling state mediated by NMDA/AMPA receptors, such as combined polytherapy with Ketamine from the start. These considerations stem from the receptor trafficking hypotheses: in prolonged seizure activity and primary central nervous system etiologies, GABA receptors get internalized and move away from synapses, and therefore, SE becomes resistant to BDZ. A rational polytherapy that might restore the unresponsiveness to BDZ in SE should include NMDA antagonists, such as Ketamine. Ketamine has proven effective in many experimental models of status epilepticus, and much evidence is gathering supporting its use in humans, especially in refractory and super-refractory SE. We lack studies evaluating combined polytherapy in SE, especially in the early phases. The author suggests here that Ketamine should be used along with first-line BDZ in the early SE stage falling in the category of Stage 1 Plus and as a first-line anesthetic infusion drug in refractory SE, especially in cases progressing from Stage 1 Plus, eventually adding continuous midazolam/propofol infusion in later phases. This systematic review’s objective is to summarize the presently available evidence of the early use of combined polytherapy that includes Ketamine, along with the currently available evidence of Ketamine use in early, established, and refractory SE. Nine studies were included. Boluses of Ketamine and Midazolam are effective in pediatric convulsive Stage 1 Plus SE. The results show that earlier Ketamine administration (especially within 12 h of SE onset) was significantly associated with improved seizure control, with a more favorable safety profile than Midazolam in refractory SE. Notably, a dosage of less than 0.9 mg/kg/h proves ineffective in terminating SE. Ketamine has the advantage of preventing intubation, possibly shortening the length of stay in the intensive care unit. Full article

Background: The use of complementary integrative medicine (CIM) by cancer patients is currently very common. The main reasons why patients turn to CIM are to improve quality of life (QoL) and support the immune system. Unfortunately, many patients rely on CIM self-prescription, neglecting the risk of interactions with anticancer treatments (ACTs). The primary objective is to demonstrate the feasibility of combining CIM and ACT in a multidisciplinary approach to improve the QoL of cancer patients and to reduce ACT’s adverse events. Methods: Cancer patients were treated with CIM by expert physicians. CIM mainly consisted of vitamins C and D, the medicinal mushrooms blend U-CARE, and probiotics administered alone or in combination. The patients were followed-up by physicians and data were recorded in a detailed shared file. Results: A total of 54 cancer patients were treated with an integrative approach, especially during ACTs. The combination showed a good safety profile. No adverse events occurred in 92.6% of patients, whereas only 7.4% of patients experienced gastrointestinal or liver toxicity from the CIM approach. The main benefit of the CIM approach was improved fatigue and QoL, and this was mainly achieved by the concomitant use of polytherapy-based complementary medicine (PCM) and U-CARE. The toxicity improvement was mainly associated with the use of solely U-CARE. Conclusions: These results highlight the feasibility of the CIM approach in cancer patients addressed by a multidisciplinary team of experts in the field. The patient-centered and evidence-based approach of CIM is an example of the comprehensive and coordinated strategy pursued by the EU in its programmatic document against cancer aiming to focus on the QoL of patients and to avoid potentially harmful CIM self-prescription. Full article

Stage 1 Plus is defined here as a naïve, previously untreated, status epilepticus (SE) that is probably refractory to Benzodiazepines (BDZ). These cases include not only prolonged SE as previously proposed by the author (SE lasting > 10 min) but also other cases notoriously associated with BDZ refractoriness such as the absence of prominent motor phenomena and acute etiology (especially primary central nervous system etiology). Interestingly, the absence of prominent motor phenomena as is the case of non convulsive SE might implicitly fall in the category of prolonged SE due to the delay in recognition and treatment. Future studies should help identify other factors associated with BDZ refractoriness, therefore widening the definition of Stage 1 Plus. The appropriate timing for defining prolonged SE may also differ depending on different etiology. Consequently, in future tailored models of SE, the definition of prolonged SE could be enhanced by defining it for a longer duration than Tx, a time point that changes based on different etiologies (x), Tx being much shorter than 10 min in acute etiologies. These cases of naïve probably BDZ refractory SE (Stage 1 Plus) might require a different approach: combined polytherapy from the start. The objective of this review is to provide pathophysiological and pre-clinical evidence, mostly from animal studies, for the different approach of combined polytherapy from the start for those cases of SE falling in the definition of Stage 1 Plus. Full article

Cystic fibrosis (CF) is a life-threatening genetic disease characterised by chronic lung infections sustained by opportunistic pathogens such as Pseudomonas aeruginosa. During the chronic long-lasting lung infections, P. aeruginosa adapts to the host environment. Hypermutability, mainly due to defects in the DNA repair system, resulting in an increased spontaneous mutation rate, represents a way to boost the rapid adaptation frequently encountered in CF P. aeruginosa isolates. We selected 609 isolates from 51 patients with CF chronically colonised by P. aeruginosa to study, by full-length genome sequencing, the longitudinal evolution of the bacterium. We recovered at least one hypermutable (mutator) isolate in 57% of patients. By combining genomic information and phenotypic analyses, we followed the evolutionary pathways of the P. aeruginosa mutator strains, identifying their contribution to multi-drug resistance and the emergence of new sub-lineages. By implementing patient clinical data, we observed that mutators preferentially follow a specific evolutionary trajectory in patients with a negative clinical outcome and that maintenance antibiotic polytherapy, based on alternating molecules, apparently reduces the occurrence of hypermutability. Finally, we draw attention to the possibility that modulator-induced changes in the pulmonary environment may be associated with the onset of hypermutability. Full article

Memory is one of the most important abilities of our brain. The process of memory and learning is necessary for the proper existence of humans in the surrounding environment. However, sometimes there are unfavourable changes in the functioning of the brain and memory deficits occur, which may be associated with various diseases. Disturbances in the cholinergic system lead to abnormalities in memory functioning and are an essential part of clinical symptoms of many neurodegenerative diseases. However, their treatment is difficult and still unsatisfactory; thus, it is necessary to search for new drugs and their targets, being an alternative method of mono- or polypharmacotherapy. One of the possible strategies for the modulation of memory-related cognitive disorders is connected with the endocannabinoid system (ECS). The aim of the present study was to determine for the first time the effect of administration of natural cannabinoid compound (cannabidiol, CBD) and rivastigmine alone and in combination on the memory disorders connected with cholinergic dysfunctions in mice, provoked by using an antagonist of muscarinic cholinergic receptor—scopolamine. To assess and understand the memory-related effects in animals, we used the passive avoidance (PA) test, commonly used to examine the different stages of memory. An acute administration of CBD (1 mg/kg) or rivastigmine (0.5 mg/kg) significantly affected changes in scopolamine-induced disturbances in three different memory stages (acquisition, consolidation, and retrieval). Interestingly, co-administration of CBD (1 mg/kg) and rivastigmine (0.5 mg/kg) also attenuated memory impairment provoked by scopolamine (1 mg/kg) injection in the PA test in mice, but at a much greater extent than administered alone. The combination therapy of these two compounds, CBD and rivastigmine, appears to be more beneficial than substances administered alone in reducing scopolamine-induced cognitive impairment. This polytherapy seems to be favourable in the pharmacotherapy of various cognitive disorders, especially those in which cholinergic pathways are implicated. Full article

Whilst monotherapy is traditionally the preferred treatment starting point for chronic conditions such as hypertension and diabetes, other diseases require the use of multiple drugs (polytherapy) from the onset of treatment (e.g., human immunodeficiency virus acquired immunodeficiency syndrome, tuberculosis, and malaria). Successful treatment of these chronic conditions is sometimes hampered by patient non-adherence to polytherapy. The options available for polytherapy are either the sequential addition of individual drug products to deliver an effective multi-drug regimen or the use of a single fixed-dose combination (FDC) therapy product. This article intends to critically review the use of FDC drug therapy and provide an insight into FDC products which are already commercially available. Shortcomings of FDC formulations are discussed from multiple perspectives and research gaps are identified. Moreover, an overview of fundamental formulation considerations is provided to aid formulation scientists in the design and development of new FDC products. Full article

Recently, bombesin (BN) and its analogs have attracted much attention as excellent anticancer agents because they interact with specific receptors widely distributed on the surface of various cancer cells. However, their biological properties proceed far beyond this, given a broad spectrum of activity. Bombesin receptor ligands are effective drugs for the treatment of rheumatoid arthritis or gastrointestinal diseases. However, most diseases are complex, and the use of polytherapy may lead to pharmacokinetic and pharmacodynamic drug–drug interactions, resulting in side effects. Therefore, there is a need to develop effective compounds that also contain BN or its analogs, which are combined with other structural entities, thus generating a so-called hybrid drug. Hybrid drugs that contain bombesin pharmacophore(s) may be proposed as a solution to the problem of polytherapy or the lack of an effective cure. Such structures have now demonstrated the desired efficacy, though information on these aforementioned compounds is relatively scarce. Therefore, our paper aims to encourage researchers to focus on bombesins. Herein, we indicate that the hybrid approach should also be firmly applied to bombesins and the BN receptor family. This paper’s structure is divided into two main sections demonstrating bombesins and their properties, as well as recent data on bombesin-based hybrid compounds and their potential usefulness in medicine. Overall, it refers to the discovery and synthesis of modified bombesin-based hybrid compounds. Full article

The proper drug choice determines the treatment quality for a disease. The pharmacotherapeutic strategy for respiratory diseases often involves the combination of different drugs with different mechanisms of action. Salbutamol is a short-acting β2-agonist (SABA) used as a reliever in the treatment of asthma and is frequently paired with inhaled corticosteroids (ICS). Indeed, drug–drug interactions (DDI) receive special attention as they are some of the most common causes of adverse effects and can lead to increased morbidity and mortality. DDIs can occur in patients undergoing polytherapy at the pharmacokinetic (PK) or pharmacodynamic (PD) level. Given this, the interaction of salbutamol with other drugs has been extensively explored in terms of PD and PK since its introduction into the pharmaceutical market. To date, more than a thousand salbutamol interactions have been reported. Here, we propose to review some interactions of salbutamol with other drugs such as beta-blockers, anticholinergics, other classes of bronchodilators, corticosteroids, and others, and point out significant gaps in the knowledge of DDI. Full article

The ECG changes produced by antipsychotics and other psychotropic medications are studied mostly regarding QTc interval prolongation. This study aimed to investigate ECG changes beyond long QTc interval produced by psychotropic medications. A cross-sectional study was conducted to assess the effect of these agents on RR, PR, TpTe intervals and TpTe/QT ratio among Jordanian outpatients. The RR interval was significantly shorter among patients on TCAs versus those not receiving TCAs and among patients on polytherapy versus those on monotherapy (p < 0.05 for both comparisons), when adjusted for age, gender, BMI, caffeine intake, smoking, presence of diabetes mellitus, cardiovascular disease and medications known to produce heart rate changes. Positive correlations were found between the PR interval and age in patients treated with SGAs, SSRIs, citalopram, polytherapy and in the total sample (p < 0.01 for all). Inverse correlations were found between the RR interval and the number of psychotropic medications among patients treated with SSRIs and in the whole study sample (p < 0.01 for both). In conclusion, various ECG changes beyond QTc interval prolongation are observed in patients on antipsychotics and other psychotropic medications, in those on polytherapy. It is recommended to obtain an ECG before starting patients on psychotropic drugs known to produce electrocardiographic changes and their combinations. Full article

EML4-ALK is an oncogenic fusion protein that accounts for approximately 5% of NSCLC cases. Targeted inhibitors of ALK are the standard of care treatment, often leading to a good initial response. Sadly, some patients do not respond well, and most will develop resistance over time, emphasizing the need for alternative treatments. This review discusses recent advances in our understanding of the mechanisms behind EML4-ALK-driven NSCLC progression and the opportunities they present for alternative treatment options to ALK inhibitor monotherapy. Targeting ALK-dependent signalling pathways can overcome resistance that has developed due to mutations in the ALK catalytic domain, as well as through activation of bypass mechanisms that utilise the same pathways. We also consider evidence for polytherapy approaches that combine targeted inhibition of these pathways with ALK inhibitors. Lastly, we review combination approaches that use targeted inhibitors of ALK together with chemotherapy, radiotherapy or immunotherapy. Throughout this article, we highlight the importance of alternative breakpoints in the EML4 gene that result in the generation of distinct EML4-ALK variants with different biological and pathological properties and consider monotherapy and polytherapy approaches that may be selective to particular variants. Full article

The incidence of metabolic diseases such as type 2 diabetes mellitus (DM) and obesity has been increasing dramatically. Both diseases are closely linked and new approaches for type 2 DM treatment aim to enable weight loss. A combined therapy of dapagliflozin and exenatide has been used against type 2 DM, influencing allbody glucose dynamics. Spermatogenesis is highly dependent on the metabolic cooperation established between Sertoli cells (SCs) and developing germ cells. To study the effects of dapagliflozin and exenatide on SC metabolism, mouse SCs were treated in the presence of sub-pharmacologic, pharmacologic, and supra-pharmacologic concentrations of dapagliflozin (50, 500, 5000 nM, respectively) and/or exenatide (2.5, 25, 250 pM, respectively). Cytotoxicity of these compounds was evaluated and the glycolytic profile, glycogen content assay, and lipid accumulation of SCs were determined. Dapagliflozin treatment decreased fat cellular deposits, demonstrating its anti-obesity properties at the cellular level. Polytherapy of exenatide plus dapagliflozin increased lactate production by SCs, which has been reported to improve sperm production and quality. Thus, the results herein suggest that the use of these two pharmacological agents can protect male fertility, while improving their glucose homeostasis and inducing weight loss. Full article

Multiple illness is an increasingly common phenomenon. Its consequence is the need for polytherapy, which is particularly common among people suffering from arterial hypertension. The development of combined preparations (containing at least two API-active pharmaceutical ingredients) dedicated to the treatment of hypertension is a response to increased compliance, especially in elderly patients. In our work, we describe in particular the possibilities of using β-adrenergic receptors blockers and angiotensin-converting enzyme inhibitors in combinations. The combinations of APIs are used as single pills in patients with arterial hypertension with concomitant diseases such as hyperlipidemia; blood coagulation problems and diabetes mellitus were also discussed successively. Pharmacoeconomic analysis for the API combinations shown is also presented. As a final conclusion, numerous benefits of using the combined preparations should be indicated, especially by the elderly and/or in patients with coexistence of other diseases. Full article