Patients with metastatic urothelial carcinoma (mUC) are typically elderly and often have other comorbidities that require the use of concomitant medications. In our study we evaluated the association of concomitant use of antibiotics (ATBs), proton pump inhibitors (PPIs), corticosteroids, statins, metformin and insulin with patient outcomes and we validated the prognostic role of a concomitant drug score in mUC patients treated with enfortumab vedotin (EV) monotherapy. Data from 436 patients enrolled in the ARON-2EV retrospective study were analyzed according to the concomitant medications used at baseline. Finally, the patients were stratified into three risk groups according to the concomitant drug score based on ATBs, corticosteroids and PPIs. Statistical analysis involved Fisher exact test, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. Inferior survival outcomes were observed in ATB users compared to non-users (OS: 7.3 months, 95%CI 5.0 - 12.3 vs 13.7 months, 95%CI 12.2 - 47.3, p = 0.001; PFS: 5.1 months 95%CI 3.3 - 17.7 vs 8.3 months, 95%CI 7.1 - 47.3, p = 0.001) and also in corticosteroid users compared to non-users (OS: 8.4 months, 95%CI 6.6 - 10.0 vs 14.2 months, 95%CI 12.7 - 47.3, p < 0.001; PFS: 6.0 months 95%CI 4.6 - 7.9 vs 8.9 months, 95%CI 7.2 - 47.3, p = 0.004). In the Cox multivariate analysis, the concomitant drug score was a significant factor predicting both OS (HR = 1.32 [95% CI 1.03 - 1.68], p = 0.026) and PFS (HR = 1.23 [95% CI 1.01 - 1.51], p = 0.044). Our findings suggest detrimental impact of concomitant use of ATBs and corticosteroids on survival outcomes and the prognostic utility of the concomitant drug score in previously treated mUC patients receiving EV.

• MeSH
• Anti-Bacterial Agents therapeutic use   MeSH
• Adrenal Cortex Hormones therapeutic use   MeSH
• Proton Pump Inhibitors therapeutic use   MeSH
• Carcinoma, Transitional Cell drug therapy   secondary   pathology   mortality   MeSH
• Middle Aged MeSH
• Humans MeSH
• Antibodies, Monoclonal * therapeutic use   MeSH
• Urinary Bladder Neoplasms drug therapy   pathology   mortality   MeSH
• Prognosis MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Urologic Neoplasms drug therapy   pathology   mortality   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

The rapid antidepressant effect of ketamine has become a breakthrough in the research and treatment of depression. Although predictive and modulating factors of the response to ketamine are broadly studied, little is known about optimal concurrent medication protocols. Concerning gamma-aminobutyric acid neurotransmission being a shared target for both ketamine and benzodiazepines (BZD), we evaluated the influence of BZD on the antidepressant effect of a single ketamine infusion in depressed patients. Data from 47 patients (27 females) with major depression (MADRS ≥ 20, ≥ 1 prior nonresponse to antidepressant treatment in current episode) who participated in two previous studies (EudraCT Number: 2009-010625-39 and 2013-000952-17) entered the analysis. All of the subjects were given an infusion of a subanesthetic dose of racemic ketamine (0.54 mg per kg) as an add-on medication to ongoing antidepressant treatment. Thirteen patients (28%) reached ≥ 50% reduction in MADRS within one week after ketamine administration. Nineteen (40%) patients took concomitant benzodiazepines on a daily basis. The doses of BZDs were significantly higher in nonresponders (p=0.007). ROC analysis distinguished responders from nonresponders by a criterion of >8mg of diazepam equivalent dose (DZ equivalent) with a sensitivity of 80% and a specificity of 85% (p<0.001). RM-ANOVA revealed a different time pattern of response to ketamine between the BZD+ (>8mg of DZ equivalent) and BZD- (≤8mg of DZ equivalent) groups, with a significantly worse outcome in BZD+ on day 3 (p=0.04) and day 7 (p=0.02). The results of the study indicate that concomitant benzodiazepine treatment in higher doses may attenuate ketamine's antidepressant effect. The pathophysiological, clinical and methodological implications of this finding should be considered in future research and ketamine treatment.

• Publication type
• Journal Article MeSH

BACKGROUND: This research article delves into the battle against the COVID-19 pandemic, focusing on the efficacy and, particularly, the safety of the combination of nirmatrelvir with ritonavir, which is found in the pharmaceutical product Paxlovid®. This study aims to analyze the potential interactions of commonly prescribed medicinal products with Paxlovid®, shedding light on its utilization in specific medical fields. METHODS: Prescription data from the Czech Republic's Institute of Health Information and Statistics (IHIS CR) was analyzed, covering 4 million COVID-19 patients and 87.5 million medication records from September 2019 to February 2022. This study focused on potential drug interactions with Paxlovid among the 50 most frequently prescribed medications, with particular attention to four specialties: general medicine, internal medicine, infectious diseases, and diabetology. RESULTS: In this study of the 50 most commonly prescribed drugs, 56% showed no interaction with Paxlovid, 30% had a potential for interaction, and 14% were not specifically mentioned in relation to Paxlovid, with no drugs found to be contraindicated overall. However, in specific medical fields, including diabetology, infectious diseases, internal medicine, and general medicine, certain drugs had potential interactions when co-administered with Paxlovid. CONCLUSIONS: Paxlovid remains a valuable option for early COVID-19 treatment but requires a careful consideration of potential drug interactions, especially in high-risk specialties. A thorough assessment of concurrent medications is essential to optimize safety and efficacy in patients receiving Paxlovid.

• MeSH
• Antiviral Agents adverse effects   therapeutic use   MeSH
• COVID-19 epidemiology   MeSH
• COVID-19 Drug Treatment * MeSH
• Drug Combinations * MeSH
• Drug Interactions * MeSH
• Humans MeSH
• Ritonavir * therapeutic use   adverse effects   MeSH
• SARS-CoV-2 drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

Although immune checkpoint inhibitors (ICI) and/or tyrosine kinase inhibitors (TKI) are the standard treatment of advanced unresectable or metastatic renal cell carcinoma (RCC), the impact of concomitant medications remains unclear. We aimed to evaluate the impact of concomitant medications on survival outcomes in patients treated with systemic therapy for advanced unresectable or metastatic RCC. In August 2024, PubMed, Scopus, and Web of Science were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic RCC (PROSPERO: CRD42024573252). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis according to heterogeneity. We identified 22 eligible studies (5 prospective and 17 retrospective) comprising 16,072 patients. Concomitant medications included proton pump inhibitors (PPI) (n = 3959), antibiotics (n = 571), statins (n = 5466), renin-angiotensin system inhibitors (RASi) (n = 6615), and beta-blockers (n = 1964). Both concomitant PPI and antibiotics were significantly associated with worse OS in patients treated with ICI (PPI: HR: 1.22, P = .01, and antibiotics: HR: 2.09, P < .001). Concomitant statins, RASi, or beta-blocker were significantly associated with improved OS in patients treated with TKI (statins: HR: 0.81, P = .03, RASi: HR: 0.63, P < .001, beta-blocker: HR: 0.69, P < .001, respectively). In patients treated with ICI, RASi was significantly associated with improved OS (HR: 0.64, P = .02). Concomitant use of antibiotics or PPI with ICI can reduce its oncologic efficacy. Conversely, concomitant statins, RASi, or beta-blockers can enhance the oncologic efficacy of TKI. When initiating systemic therapy for metastatic RCC, it may be important for clinicians to assess baseline co-medications and recognize their possible positive or negative effects.

• MeSH
• Survival Analysis MeSH
• Adrenergic beta-Antagonists therapeutic use   MeSH
• Immune Checkpoint Inhibitors therapeutic use   MeSH
• Protein Kinase Inhibitors therapeutic use   MeSH
• Proton Pump Inhibitors therapeutic use   administration & dosage   MeSH
• Carcinoma, Renal Cell * drug therapy   mortality   secondary   MeSH
• Drug Interactions MeSH
• Humans MeSH
• Kidney Neoplasms * drug therapy   mortality   pathology   MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Review MeSH
• Systematic Review MeSH

BACKGROUND: The introduction of novel hormonal therapies represented by enzalutamide (ENZ) and abiraterone acetate (ABI) has reached a great progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The majority of mCRPC patients are elderly suffering from chronic co-morbidities requiring use of various concomitant medications. In the present study, we focused on impact of concomitant antihypertensive medication on the outcomes of mCRPC patients treated with ENZ or ABI. METHODS: In total, 300 patients were included and their clinical data were retrospectively analyzed. RESULTS: Angiotensin-converting enzyme inhibitors (ACEIs) represented the only concomitant medication significantly associated with survival. The median radiographic progression-free survival (rPFS) and overall survival (OS) for patients using ACEIs were 15.5 and 32.3 months compared to 10.7 and 24.0 months for those not using ACEIs (p = 0.0053 and p = 0.0238, respectively). Cox multivariable analysis revealed the use of ACEIs a significant predictive factor for both rPFS (HR = 0.704, p = 0.0364) and OS (HR = 0.592, p = 0.0185). CONCLUSION: The findings of this study suggest an association between the concomitant use of ACEIs and longer survival of mCRPC patients receiving ENZ or ABI therapy.

• MeSH
• Abiraterone Acetate * therapeutic use   administration & dosage   MeSH
• Antihypertensive Agents * therapeutic use   MeSH
• Benzamides * therapeutic use   MeSH
• Progression-Free Survival MeSH
• Phenylthiohydantoin * therapeutic use   MeSH
• Angiotensin-Converting Enzyme Inhibitors therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Prostatic Neoplasms, Castration-Resistant * drug therapy   mortality   pathology   MeSH
• Nitriles * therapeutic use   MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   adverse effects   MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH

Výskyt srdečního selhání má neustále vzrůstající tendenci především v důsledku stárnutí populace a výrazně zlepšené péči o akutní koronární syndromy. Ekonomická náročnost léčby srdečního selhání dnes ve vyspělých evropských zemích představuje 1–2 % veškerých nákladů do zdravotnictví. Akutní srdeční selhání je klinický syndrom s nízkým minutovým výdejem, hypoperfuzí tkání, zvýšeným plicním tlakem v zaklínění a s městnáním v tkáních. Příčina může být kardiální i nekardiální, trvalá i přechodná a může vést k trvalému poškození srdce s následným rozvojem chronického srdečního selhání. Prognóza onemocnění je závažná. U nemocných s akutním srdečním selháním při infarktu miokardu je hospitalizační mortalita 17 % a roční mortalita 30 %. Prognózu nemocného samozřejmě nejvíce určuje závažnost srdečního selhání. Významnou roli ale hrají i přidružená onemocnění. Popisujeme tzv. AHEAD klasifikaci, která pomocí hodnocení nejzávažnějších komorbidit klasifikuje nemocné do šesti skupin, kdy nemocní s jednou a méně komorbiditami mají relativně příznivou prognózu s roční mortalitou do 20 % (vč. hospitalizační) a nemocní se čtyřmi a více komorbiditami naopak velmi špatnou prognózu s roční mortalitou nad 50 %. Klíčová slova: srdeční selhání – komorbidity – AHEAD skóre

The incidence of heart failure is increasing, mainly due to the increasing age of the population and the improvement of care for patients with acute coronary syndromes. The costs of heart failure treatment form approximately 1–2% of the total costs of medical care in developed European countries. Acute heart fail­­ure is a clinical syndrome with low cardiac output, hypoperfusion, increased pulmonary pressure and congestion. The cause can be cardiac or non‑cardiac, permanent or temporary and the condition can develop into chronic heart failure. The prognosis of the disease is poor and the in‑hospital mortality of patients with acute coronary syndrome and acute heart failure is 17%, while one‑year mortality is 30%. The most important factor is the severity of heart failure, but concomitant diseases also play an important role. We describe the AHEAD classification, which categorises patients into six groups based on the concomitant diseases. Group 0 and 1 have the best prognosis, with one‑year mortality of less than 20%, while group 4 and 5 have the worst prognosis, with one‑year mortality of over 50%. Keywords: heart failure – comorbidities – AHEAD score

• Keywords
• AHEAD skóre,
• MeSH
• Acute Disease * MeSH
• Risk Assessment * methods   MeSH
• Humans MeSH
• Decision Support Techniques MeSH
• Hospital Mortality MeSH
• Odds Ratio MeSH
• Prognosis MeSH
• Proportional Hazards Models MeSH
• Registries MeSH
• Risk Factors MeSH
• Heart Failure * etiology   classification   complications   mortality   MeSH
• Severity of Illness Index MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

AIM: To investigate potential association between administration of corticosteroids, antibiotics, probiotics, proton pump inhibitors, non-steroidal anti-inflammatory drugs (NSAID), statins and metformin and outcome in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. PATIENTS AND METHODS: A total of 224 patients with advanced NSCLC treated at nine comprehensive cancer centers were analyzed in this national retrospective study. Survival statistics were evaluated using Kaplan-Meier method and Cox analysis. RESULTS: Only corticosteroid use had a significant negative effect on the objective response rate. In the univariate analysis, there was no significant effect of the studied concomitant medications on the efficacy of nivolumab. In a subsequent multifactorial analysis, a possible positive effect of the concomitant use of NSAID at the initiation of nivolumab treatment was revealed. CONCLUSION: The results of the present retrospective exploratory analysis underscore the importance of knowing the exact type of concomitant medication, the route of administration, the dose of medication, and the region of the ongoing study. The present data indicated a significantly higher rate of progression in patients treated with corticosteroids and the possible positive effect of NSAID use at the initiation of nivolumab treatment.

• MeSH
• Anti-Bacterial Agents administration & dosage   MeSH
• Anti-Inflammatory Agents, Non-Steroidal administration & dosage   MeSH
• Outcome Assessment, Health Care methods   statistics & numerical data   MeSH
• Adrenal Cortex Hormones administration & dosage   MeSH
• Proton Pump Inhibitors administration & dosage   MeSH
• Kaplan-Meier Estimate MeSH
• Middle Aged MeSH
• Humans MeSH
• Metformin administration & dosage   MeSH
• Lung Neoplasms drug therapy   MeSH
• Carcinoma, Non-Small-Cell Lung drug therapy   MeSH
• Nivolumab administration & dosage   MeSH
• Probiotics administration & dosage   MeSH
• Proportional Hazards Models MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is administered directly to the small intestine of patients with advanced Parkinson's disease (APD) to help maintain stable plasma levodopa levels. OBJECTIVE: The objective of this study was to investigate the effect of LCIG in reducing polypharmacy for the treatment of APD. METHODS: The COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS) is a large, real-world, multinational observational study investigating comedication use with LCIG. All enrolled patients had used LCIG for ≥12 months and data were collected cross-sectionally (study visit) and retrospectively. The primary endpoint was the percentage of patients using LCIG as monotherapy (without add-on PD medications) at initiation and at 3, 6, 9, and 12 months thereafter. RESULTS: Overall, 409 patients were enrolled from 14 countries and were treated with LCIG for a mean of 35.8 ± 23.2 months. A total of 15.2% of patients initiated LCIG as monotherapy and 31.7% were receiving monotherapy at 12 months after initiation. The mean duration of LCIG monotherapy was 39.3 ± 25.6 months. Use of add-on medications decreased over time with all LCIG regimens. From LCIG initiation to the patient visit, mean off time decreased by 3.8, 4.6, and 3.9 hours/day for LCIG monotherapy, LCIG daytime monotherapy, and LCIG polytherapy groups, respectively, while duration of dyskinesia decreased by 1.7, 2.0, and 1.9 hours/day, respectively. Adverse events likely related to study treatment occurred in 112 patients (27.4%) during LCIG treatment. CONCLUSIONS: LCIG is an effective long-term monotherapy option with a positive risk-benefit profile and contributes to reduced polypharmacy for patients with APD. © 2021 The AbbVie Inc. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

• MeSH
• Antiparkinson Agents MeSH
• Drug Combinations MeSH
• Gels MeSH
• Carbidopa * MeSH
• Levodopa MeSH
• Humans MeSH
• Parkinson Disease * drug therapy   MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Research Support, Non-U.S. Gov't MeSH

Mezi nejčastěji předepisované léky patří nesteroidní antiflogistika, antikoagulancia a antiagregancia. Přes svoji vysokou terapeutickou efektivitu jsou tyto léky příčinou závažných gastrointestinálních komplikací, především krvácení. Jejich indikace proto musí být uvážlivá, se znalostí výhod a nevýhod léčby. V případě, že nemocní jsou těmito léky léčeni v době endoskopického vyšetření, se znalostmi, jak postupovat, aby endoskopický výkon byl bezpečný, tj. aby bylo minimalizováno riziko vzniku krvácivých komplikací. Vždy je třeba zhodnotit, zda při nasazení medikace nesteroidními antiflogistiky se jedná o tzv. rizikové nemocné (vyšší věk, anamnéza vředové nemoci apod.), a v případě že ano, doplnit podávání léků blokátorem protonové pumpy nebo nahradit šetrnějším lékem na bázi inhibice cyklooxygenázy II. U osob léčených agregancii a antikoagulancii je doporučeno zvolit podobnou rozvahu s tím, že podávání kyseliny acetylosalicylové rizikovým osobám by mělo být nahrazeno jiným lékem nebo by měl být podáván současně blokátor protonové pumpy. Při endoskopickém vyšetření u osob se současnou antikoagulační nebo antiagregační terapií je vhodné nemocné stratifikovat, kdy je výkon zatížen vysokým rizikem komplikací a kdy rizikem nízkým. Nejlépe je endoskopii provést jako výkon elektivní po vysazení krvácení indukujících léků, vždy s odpovídajícím zajištěním pacienta z pohledu možných komplikací.

Nonsteroidal anti-inflammatory drugs, anticoagulation and antiplatelet medications belong to the most frequently prescribed medications. In spite of their high therapeutic effectiveness these medications cause serious gastrointestinal complications. Their indication must be carefully considered including the knowledge of their advantages and disadvantages. In the case a patient is on these medications during an endoscopic treatment, this information is important, so that the endoscopic examination is safe and the risk of bleeding complications minimalized. It is always necessary to consider whether patients receiving nonsteroidal anti-inflammatory drugs are in high risk (old age, history of peptic ulcer disease etc.). If so the treatment should include proton pump inhibitor or the medication should be replaced by less dangerous drug based on cyclooxygenase II inhibition. Similar considerations are recommended for patients who are on anti-platelet medications and anticoagulation. Acetylosalicylic acid in patients in high risk should be replaced by another medication or concomitent treatment with proton pump inhibitor should be given. It is recommended to stratify patients undergoing endoscopic examination according their risk of complications. It is optimal to perform the endoscopy as an elective procedure after discontinuation of medications with potential of bleeding and with an adequate support with regard to complications.

• MeSH
• Anti-Inflammatory Agents, Non-Steroidal adverse effects   therapeutic use   MeSH
• Anticoagulants adverse effects   therapeutic use   MeSH
• Platelet Aggregation Inhibitors adverse effects   therapeutic use   MeSH
• Proton Pump Inhibitors MeSH
• Humans MeSH
• Proton Pumps MeSH
• Risk Factors MeSH
• Check Tag
• Humans MeSH

Patients with pulmonary embolism (PE) may have symptomatic or asymptomatic concomitant deep vein thrombosis (DVT). The reported prevalence of PE-associated DVT is variable, and thus, the utility of routine testing is controversial. The aim of our study was to analyze the prevalence of DVT and the factors associated with proximal DVT/whole-leg DVT in patients with symptomatic PE. In 428 consecutive patients (mean age: 59 ± 16.4 years; 52.3% men), we performed clinical examination and complete bilateral compression ultrasound and ascertained medical history and risk factors for DVT/PE. χ2 and t tests were used. Deep vein thrombosis was found in 70.6%; proximal DVT in 49.5%. Sensitivity/specificity of DVT symptoms was 42.7%/93.7% for whole-leg DVT and 47.6%/83.3% for proximal DVT. Male gender significantly prevailed among those with whole-leg DVT and with proximal DVT (58.9% and 61.8%). Active malignancy was significantly more frequent in the patients with proximal DVT than without proximal DVT (10.4% vs 3.7%). In conclusion, the prevalence of PE-associated DVT is quite high but clinical diagnosis is unreliable. In our group, male gender and active malignancy were significantly associated with the presence of concomitant proximal DVT.

• MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Pulmonary Embolism * blood   epidemiology   etiology   MeSH
• Prevalence MeSH
• Risk Factors MeSH
• Aged MeSH
• Sex Factors MeSH
• Venous Thrombosis * blood   complications   epidemiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH