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The Pan African Medical Journal 2024people living with HIV/AIDS using antiretroviral therapy sometimes present with comorbid conditions or co-infections. This could lead to an increased risk of drug...
INTRODUCTION
people living with HIV/AIDS using antiretroviral therapy sometimes present with comorbid conditions or co-infections. This could lead to an increased risk of drug interactions due to the concomitant use of drugs. The aim of the study was to explore the overall impact of dolutegravir on such comorbidities and the effect of concomitant medication on the safety and efficacy of dolutegravir.
METHODS
data was collected using a survey questionnaire and a retrospective review of medical records of a prospective study sample. Medical records were retrospectively reviewed for up to 12 months after dolutegravir initiation. Concomitantly used drugs and supplements that were identified to have a potential interaction with dolutegravir were further characterized. Descriptive and summary statistics were used to describe the data, t-tests were performed on blood glucose levels and cross-tabulations were done on some variables.
RESULTS
of the 461 participants enrolled into the study, 172 (37.3%) and 54 (11.7%) experienced comorbidity and coinfection respectively. More than 50% of the participants used concomitant medicines. Metformin use led to increased blood glucose levels (p=0.009); participants on rifampicin (n=8) received an additional daily dose of dolutegravir. Virological outcomes in participants on sodium valproate (n=2) and St John´s wort (n=1) did not show safety concerns, whilst 3 dolutegravir discontinuations were observed in participants using supplements and antacids containing divalent cations.
CONCLUSION
even though dolutegravir was safe and effective in the study population, with possible drug interactions leading to treatment discontinuations in only 3(0.7%) participants, further investigation into dolutegravir-induced hyperglycemia needs investigation.
Topics: Humans; Pyridones; Oxazines; HIV Infections; Heterocyclic Compounds, 3-Ring; Piperazines; Female; Male; Retrospective Studies; Adult; Middle Aged; Drug Interactions; HIV Integrase Inhibitors; Prospective Studies; Comorbidity; Surveys and Questionnaires; Cohort Studies; Coinfection; Blood Glucose; Anti-HIV Agents
PubMed: 38881766
DOI: 10.11604/pamj.2024.47.137.40726 -
Medicine Jun 2024As a subtype of the 5-hydroxytryptamine (5-HT) receptor, 5-HT1A receptors are involved in the pathological process of psychiatric disorders and is an important target... (Review)
Review
As a subtype of the 5-hydroxytryptamine (5-HT) receptor, 5-HT1A receptors are involved in the pathological process of psychiatric disorders and is an important target for antidepressants. The research groups focus on these area have tried to design novel compounds to alleviate depression by targeting 5-HT1A receptor. The heterocyclic structures is an important scaffold to enhance the antidepressant activity of ligands, including piperazine, piperidine, benzothiazole, and pyrrolidone. The current review highlights the function and significance of nitrogen-based heterocyclics 5-HT1AR represented by piperazine, piperidine, benzothiazole, and pyrrolidone in the development of antidepressant.
Topics: Humans; Serotonin 5-HT1 Receptor Agonists; Antidepressive Agents; Receptor, Serotonin, 5-HT1A; Piperazines; Benzothiazoles; Heterocyclic Compounds; Piperidines; Pyrrolidinones; Depression
PubMed: 38875413
DOI: 10.1097/MD.0000000000038496 -
Frontiers in Public Health 2024In Europe, the combination of cabotegravir (CAB) with rilpivirine (RPV) has been approved as a dual injection long-acting (LA) therapy for the treatment of human...
BACKGROUND
In Europe, the combination of cabotegravir (CAB) with rilpivirine (RPV) has been approved as a dual injection long-acting (LA) therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in adults since December 2020. Studies have shown that between 36 and 61% of people living with HIV (PLWHIV) prefer LA therapy. However, there are no real-world data on the number of people receiving LA therapy, in Germany or internationally. The aim of this study was to assess the current situation and trends in usage of LA therapy for the treatment of HIV-1 in Germany.
METHODS
Based on pharmacy prescription data derived from Insight Health, the monthly number of prescriptions for oral CAB, CAB-LA, and RPV-LA over the entire period of availability in Germany was analyzed and evaluated (May 2021 to December 2023). The number of 1st and 2nd initiation injections and subsequent maintenance injections was calculated on the basis of the prescriptions for oral CAB initiation.
RESULTS
The bimonthly schedule resulted in two growing cohorts from September 2021 with an estimated 14,523 CAB-LA prescriptions over the entire period. Accordingly, in December 2023, there were approximately 1,364 PLWHIV receiving LA therapy, of whom 1,318 were receiving maintenance therapy. Only treatments with bimonthly regimens were carried out. Accounting for people not covered by statutory health insurance (~13%), a total of ~1,600 PLWHIV were receiving LA therapy in Germany in December 2023. The average rounded annual cost of therapy in 2023 was €11,940 (maintenance therapy with initiation) and €10,950 (maintenance therapy without initiation).
CONCLUSION
To our knowledge, this is the first study of real-world use and number of people receiving LA therapy. A strength of our study is the nearly complete coverage of people with statutory health insurance in Germany. The predicted demand for LA therapy does not match the actual number of people receiving LA therapy. Although the number of PLWHIV receiving LA therapy increased steadily, they accounted for just under 2% of the estimated total number of people receiving HIV therapy in Germany in 2023, almost 2 years after the market launch. No significant increase in prescriptions is expected; on the contrary, the trend is leveling off and is unlikely to change drastically in the near future. Hence, the need for this mode of therapy in Germany appears to be limited. Follow-up studies at regular intervals on the further course would be useful and are recommended, as well as investigations into the possible reasons for the slow uptake to inform public health experts and possibly broaden treatment options.
Topics: Humans; Germany; HIV Infections; Anti-HIV Agents; HIV-1; Rilpivirine; Drug Prescriptions; Male; Adult; Female; Pyridones; Diketopiperazines
PubMed: 38873299
DOI: 10.3389/fpubh.2024.1404255 -
Cell Communication and Signaling : CCS Jun 2024KRAS-mutant non-small cell lung cancer (NSCLC) shows a relatively low response rate to chemotherapy, immunotherapy and KRAS-G12C selective inhibitors, leading to short...
BACKGROUND
KRAS-mutant non-small cell lung cancer (NSCLC) shows a relatively low response rate to chemotherapy, immunotherapy and KRAS-G12C selective inhibitors, leading to short median progression-free survival, and overall survival. The MET receptor tyrosine kinase (c-MET), the cognate receptor of hepatocyte growth factor (HGF), was reported to be overexpressed in KRAS-mutant lung cancer cells leading to tumor-growth in anchorage-independent conditions.
METHODS
Cell viability assay and synergy analysis were carried out in native, sotorasib and trametinib-resistant KRAS-mutant NSCLC cell lines. Colony formation assays and Western blot analysis were also performed. RNA isolation from tumors of KRAS-mutant NSCLC patients was performed and KRAS and MET mRNA expression was determined by real-time RT-qPCR. In vivo studies were conducted in NSCLC (NCI-H358) cell-derived tumor xenograft model.
RESULTS
Our research has shown promising activity of omeprazole, a V-ATPase-driven proton pump inhibitor with potential anti-cancer properties, in combination with the MET inhibitor tepotinib in KRAS-mutant G12C and non-G12C NSCLC cell lines, as well as in G12C inhibitor (AMG510, sotorasib) and MEK inhibitor (trametinib)-resistant cell lines. Moreover, in a xenograft mouse model, combination of omeprazole plus tepotinib caused tumor growth regression. We observed that the combination of these two drugs downregulates phosphorylation of the glycolytic enzyme enolase 1 (ENO1) and the low-density lipoprotein receptor-related protein (LRP) 5/6 in the H358 KRAS G12C cell line, but not in the H358 sotorasib resistant, indicating that the effect of the combination could be independent of ENO1. In addition, we examined the probability of recurrence-free survival and overall survival in 40 early lung adenocarcinoma patients with KRAS G12C mutation stratified by KRAS and MET mRNA levels. Significant differences were observed in recurrence-free survival according to high levels of KRAS mRNA expression. Hazard ratio (HR) of recurrence-free survival was 7.291 (p = 0.014) for high levels of KRAS mRNA expression and 3.742 (p = 0.052) for high MET mRNA expression.
CONCLUSIONS
We posit that the combination of the V-ATPase inhibitor omeprazole plus tepotinib warrants further assessment in KRAS-mutant G12C and non G12C cell lines, including those resistant to the covalent KRAS G12C inhibitors.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Proto-Oncogene Proteins p21(ras); Cell Line, Tumor; Animals; Proto-Oncogene Proteins c-met; Mutation; Omeprazole; Mice; Pyridines; Pyrimidines; Xenograft Model Antitumor Assays; Mice, Nude; Pyrimidinones; Female; Triazines; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; Piperazines; Piperidines; Pyridazines; Pyridones
PubMed: 38867255
DOI: 10.1186/s12964-024-01667-x -
Journal of Infection in Developing... May 2024Coenzyme Q10 (CoQ10) is considered to be beneficial for patients with acute viral myocarditis (AVM). In addition, trimetazidine may be also beneficial to patients with... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Coenzyme Q10 (CoQ10) is considered to be beneficial for patients with acute viral myocarditis (AVM). In addition, trimetazidine may be also beneficial to patients with AVM by promoting cardiac energy metabolism. This systematic review and meta-analysis examined the efficacy and safety of combining trimetazidine and CoQ10 with respect to CoQ10 alone in patients suffering from AVM.
METHODOLOGY
PubMed, Embase, the Cochrane Library, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were searched for relevant randomized controlled trials (RCTs). An analysis of random effects was employed to combine the results.
RESULTS
Sixteen RCTs that included 1,364 patients with AVM contributed to the meta-analysis. Overall, 687 patients received the combined treatment, while 677 received the CoQ10 alone for a duration of 2-12 weeks (mean: 5.2 weeks). In contrast to monotherapy with CoQ10, combined treatment with trimetazidine and CoQ10 significantly improved overall therapy effectiveness (risk ratio [RR]: 1.19, 95% confidence interval [CI]: 1.13 to 1.24, p < 0.001; I2 = 0%). Differences in study parameters such as the incidence of heart failure upon admission, dosage of CoQ10, or length of treatment did not significantly alter the outcomes (p for all subgroup analyses > 0.05). The combined treatment was associated with improved myocardial enzyme levels and recovery of cardiac systolic function as compared to CoQ10 alone (p all < 0.05). In addition, trimetazidine combined with CoQ10 caused no greater increase in adverse events than CoQ10 alone.
CONCLUSIONS
Trimetazidine combined with CoQ10 is an effective and safe treatment for AVM.
Topics: Trimetazidine; Humans; Myocarditis; Ubiquinone; Drug Therapy, Combination; Randomized Controlled Trials as Topic; Treatment Outcome; Acute Disease
PubMed: 38865387
DOI: 10.3855/jidc.18776