European Journal of Clinical Pharmacology最新文献

{"title":"Efficacy of cannabis-based medicine in the treatment of Tourette syndrome: a systematic review and meta-analysis.","authors":"Ibrahim Serag, Mona Mahmoud Elsakka, Mostafa Hossam El Din Moawad, Hossam Tharwat Ali, Khalid Sarhan, Sally Shayeb, Islam Nadim, Mohamed Abouzid","doi":"10.1007/s00228-024-03710-9","DOIUrl":"10.1007/s00228-024-03710-9","url":null,"abstract":"<p><strong>Background: </strong>Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and phonic tics. It is a condition that affects between 0.3% and 0.7% of children, and its pathophysiology remains largely elusive. TS is associated with structural and functional alterations in corticostriatal circuits and neurochemical imbalances. Even though TS is currently incurable, there are established treatment options available, including behavioral therapy and neuroleptics. The use of cannabis-based medicine for tic management is an emerging therapeutic strategy, although its efficacy is still under investigation. It is hypothesized to interact with the endogenous cannabinoid system, but further research is required to ascertain its safety and effectiveness in TS.</p><p><strong>Aim: </strong>In our systematic review and meta-analysis, we aim to assess the effectiveness of cannabis-based medicine in the treatment of TS.</p><p><strong>Methods: </strong>We searched PubMed, Cochrane, Scopus, and Web of Sciences until February 2024. We included clinical trials and cohort studies investigating the efficacy of cannabis-based medicine in the treatment of TS. Data extraction focused on baseline characteristics of the included studies and efficacy outcomes, including scores on the Yale Global Tic Severity Scale (YGTSS), Premonitory Urge for Tics Scale (PUTS), and Yale-Brown Obsessive Compulsive Scale (Y-BOCS). We conducted the meta-analysis using Review Manager version 5.4. software. We compared the measurements before and after drug intake using mean difference (MD) and 95% confidence interval (CI).</p><p><strong>Results: </strong>In total, 357 articles were identified for screening, with nine studies included in the systematic review and 3 in the meta-analysis. These studies involved 401 adult patients with TS treated with cannabis. YGTSS revealed a significant reduction in total scores (MD = -23.71, 95% CI [-43.86 to -3.55], P = 0.02), PUTS revealed a significant decrease in scores (MD = -5.36, 95% CI [-8.46 to -2.27], P = 0.0007), and Y-BOCS revealed no significant difference in score reduction (MD = -6.22, 95% CI [-12.68 to 0.23], P = 0.06).</p><p><strong>Conclusion: </strong>The current study indicates promising and potentially effective outcomes with the use of cannabis-based medicine in mitigating the severity of tics and premonitory urges. However, there is a need for larger, placebo-controlled studies with more representative samples to validate these findings.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis.","authors":"Xing Liu, Yichen Liu, Peimin Zheng, Xun Xie, Zhouzhou Li, Rui Yang, Lie Jin, Ziwei Mei, Peipei Chen, Limei Zhou","doi":"10.1007/s00228-024-03730-5","DOIUrl":"10.1007/s00228-024-03730-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, - 3.72 to - 0.15) and etelcalcetide (- 7.80, - 11.80 to - 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, - 9.73 to - 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (- 3.66, - 6.72 to - 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (- 5.64, - 8.91 to - 2.37), calcitriol (- 9.36, - 14.81 to - 3.92), and paricalcitol (- 9.30, - 13.78 to - 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of agranulocytosis with metamizole in comparison with alternative medications based on health records in Spain.","authors":"Miguel-Ángel Maciá-Martínez, Belén Castillo-Cano, Patricia García-Poza, Elisa Martín-Merino","doi":"10.1007/s00228-024-03706-5","DOIUrl":"10.1007/s00228-024-03706-5","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to estimate the absolute (incidence) and relative (hazard ratio; HR) risk of agranulocytosis associated with metamizole in comparison with non-steroidal antiinflammatory drugs (NSAIDs).</p><p><strong>Methods: </strong>A cohort study of new users of metamizole versus NSAIDs was performed with BIFAP (Pharmacoepidemiologic Research Database in Public Health Systems; Spain). Patients aged ≥ 2 years in 2005-2022 were followed up from the day after their first metamizole or NSAID dispensation till the end of the treatment period to identify patients hospitalized due to idiosyncratic agranulocytosis. Incidence rate (IR) and adjusted HR of agranulocytosis with metamizole versus NSAID were estimated assuming the onset date of agranulocytosis was the date of hospitalization sensitivity analysis or 7 days before (main analysis). In secondary analyses, we used (1) opioids-paracetamol as negative control and (2) any hospitalized neutropenia as outcome (assuming the onset was 7 days before).</p><p><strong>Results: </strong>The cohorts included 444,972 new users of metamizole, 3,814,367 NSAID, and 3,129,221 opioids-paracetamol on continuous treatment during a median of 37-40 days. Overall, 26 hospitalized agranulocytosis occurred, 5 in the first week (and so removed in main analysis) and 21 thereafter. IR of agranulocytosis was 14.20 (N = 5 cases) and 8.52 (N = 3), 1.95 (N = 6) and 1.62 (N = 5), and 4.29 (N = 15) and 3.72 (N = 13)/10⁷ person-weeks of continuous treatment using the date of hospitalization or 7 days before, respectively. Two, 0 and 2 of cases identified in both analyses had neoplasia in every cohort, respectively. HR of agranulocytosis associated with metamizole was 7.20 [95% CI: 1.92-26.99] and 4.40 [0.90-21.57] versus NSAID, and 3.31 [1.17-9.34] and 2.45 [0.68-8.83] versus opioid-paracetamol, respectively. HR of neutropenia with metamizole was 2.98 [1.57-5.65] versus NSAID.</p><p><strong>Conclusions: </strong>Agranulocytosis was very rare but more common (above 4 times more) with metamizole than other analgesics. The impact of the drug-induced agranulocytosis was less precise with metamizole than the comparators due to its lower use, which precluded to find statistical differences in main analysis. The increased risk of hospitalized neutropenias with metamizole supports the link with its severity although triggers unavailable during the follow-up (ex. cytotoxic medication) can not be discarded.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world safety and effectiveness of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.","authors":"Mengjia Kou, Yang Jiao, Zhipeng Li, Bin Wei, Yang Li, Yaodong Cai, Wan Wei","doi":"10.1007/s00228-024-03720-7","DOIUrl":"10.1007/s00228-024-03720-7","url":null,"abstract":"<p><strong>Background and objective: </strong>Multiple randomized controlled studies have shown that pirfenidone and nintedanib are effective and safe for treating idiopathic pulmonary fibrosis. This study aimed to evaluate their efficacy, safety, and tolerability in a real-world setting.</p><p><strong>Methods: </strong>We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases for real-world studies published up to March 3, 2023, on pirfenidone and nintedanib for idiopathic pulmonary fibrosis.</p><p><strong>Results: </strong>A total of 74 studies with 23,119 participants were included. After 12 months of treatment, the change from baseline in percent predicted FVC (%FVC) was - 0.75% for pirfenidone and - 1.43% for nintedanib. The change from baseline in percent predicted DLCO (%DCLO) was - 2.32% for pirfenidone and - 3.95% for nintedanib. The incidence of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) was 12.5% for pirfenidone and 14.4% for nintedanib. The IPF-related mortality rates of pirfenidone and nintedanib were 13.4% and 7.2%, respectively. The all-cause mortality was 20.1% for pirfenidone and 16.6% for nintedanib. In the pirfenidone group, 16.6% of patients discontinued treatment because of adverse events, and in the nintedanib group, 16.2% of patients discontinued treatment because of adverse events. The incidence of adverse events was 56.4% and 69.7% for pirfenidone and nintedanib, respectively.</p><p><strong>Conclusion: </strong>The results of this study indicate that pirfenidone and nintedanib are both effective in slowing down the decline of lung function in IPF patients in real-world settings. The incidence of adverse events with pirfenidone is lower than that with nintedanib, but both are below the clinical trial data, and no new major adverse events have been observed. The discontinuation rates due to adverse reactions of the two drugs are consistent with clinical trial data, indicating good tolerability. However, the mortality rates and AE-IPF incidence rates of these two drugs in real-world settings are higher than those in previous clinical trials, with pirfenidone patients showing a higher mortality rate. Further large-sample studies are needed to investigate the risks of these drugs in these aspects. Additionally, we recommend that future real-world studies pay more attention to patients' subjective symptoms and conduct stratified analyses of the efficacy and safety of pirfenidone and nintedanib based on factors such as patients' baseline lung function, comorbidities, and age, in order to provide more personalized medication advice for IPF patients in clinical practice.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statin treatment for primary and secondary prevention in elderly patients-a cross-sectional study in Stockholm, Sweden.","authors":"Björn Wettermark, Camelia Kalantaripour, Tomas Forslund, Paul Hjemdahl","doi":"10.1007/s00228-024-03724-3","DOIUrl":"10.1007/s00228-024-03724-3","url":null,"abstract":"<p><strong>Background: </strong>Age is a major risk factor for atherosclerotic cardiovascular disease (CVD) and death, but there has been a debate about benefit-risk of statin treatment in the elderly with limited evidence on benefits for primary prevention, while there is strong evidence for its use in secondary prevention.</p><p><strong>Aim: </strong>The aim of this study was to provide an overview of statin utilization in primary and secondary prevention for patients 75-84 years and ≥ 85 years in the Swedish capital Region Stockholm in 2019.</p><p><strong>Methods: </strong>This is a cross-sectional study based on the regional healthcare database VAL containing all diagnoses and dispensed prescription drugs for all 174,950 inhabitants ≥ 75 years old in the Stockholm Region. Prevalence and incidence were analyzed by sex, age, cardiovascular risk, substance, and the intensity of treatment.</p><p><strong>Results: </strong>A total of 35% of all individuals above the age of 75 in the region were treated with statins in 2019. The overall incidence in this age group was 31 patients per 1000 inhabitants. Men, individuals 75-84 compared to ≥ 85 years of age, and those with higher cardiovascular risk were treated to a greater extent. Simvastatin was used primarily by prevalent users and atorvastatin by incident users. The majority was treated with moderate-intensity dosages and fewer women received high intensity treatment.</p><p><strong>Conclusions: </strong>Statins are widely prescribed in the elderly. Physicians seem to consider individual cardiovascular risk when deciding to initiate statin treatment for elderly patients, but here may still be some undertreatment among high-risk patients (especially women and elderly 85 + years) and some overtreatment among patients with low-risk for CVD.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of different pharmacological interventions in the treatment of tardive dyskinesia: a systematic review and network meta-analysis.","authors":"Omar Ismail, Karam Albdour, Yazan Jaber, Kamel Jaber, Ameen Alsaras","doi":"10.1007/s00228-024-03722-5","DOIUrl":"10.1007/s00228-024-03722-5","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study is to indirectly compare and rank the different drugs that have been studied in randomized clinical trials (RCTs) in patients with tardive dyskinesia (TD) in terms of their efficacy in ameliorating the symptoms of TD and safety.</p><p><strong>Design: </strong>A network meta-analysis and a systematic review were registered prospectively on PROSPERO under the ID: CRD42023407823 and were conducted in accordance with the PRISMA-NMA guidelines.</p><p><strong>Data sources: </strong>PubMed, Scopus, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Sciences, and Clinicaltrials.gov were searched to identify relevant records.</p><p><strong>Eligibility criteria for selecting studies: </strong>Any parallel randomized blinded controlled clinical trials that studied the use of any medications in treating TD and assessed the symptoms using a functional scale that has been previously validated.</p><p><strong>Data extraction: </strong>The standardized mean difference of improvement along with the reported adverse events for each drug was extracted from each trial, and a network meta-analysis was conducted using a random-effects model.</p><p><strong>Results: </strong>One thousand eight hundred seventeen patients in 33 RCTs were included in the analysis. Twenty-three different drugs were compared to placebo in terms of reduction in TD symptoms. Among these, valbenazine 80 mg (SMD =  - 1.66, 95%CI = [- 2.55; - 0.78]), valbenazine 40 mg (- 1.00, [- 1.89; - 0.11]), and vitamin E (- 0.77, [- 1.45; - 0.1]) significantly reduced TD symptoms in comparison to placebo, while deutetrabenazine 36 mg (- 1.00, [- 2.12; 0.11]) and reserpine (- 0.54, [- 1.09; 0.02]) did not significantly reduce symptoms. Some serious adverse events were reported for valbenazine and deutetrabenazine, which included mainly psychiatric symptoms such as depression, worsening of schizophrenia, and suicidal ideation, while mild adverse events were reported for other drugs, and their incidence in the treatment arms was comparable to those in the placebo arm.</p><p><strong>Conclusions: </strong>Valbenazine (80 and 40 mg) and vitamin E demonstrated efficacy in treating tardive dyskinesia. However, the significant side effects of valbenazine should prompt further investigation of alternative treatment modalities.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Use of statins and risks of ovarian, uterine, and cervical diseases: a cohort study in the UK Biobank\".","authors":"Pei-Ying Chung, Kuan-Fu Liao, Shih-Wei Lai","doi":"10.1007/s00228-024-03760-z","DOIUrl":"https://doi.org/10.1007/s00228-024-03760-z","url":null,"abstract":"","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of age and renal function on the pharmacokinetics and protein binding characteristics of fludarabine in paediatric and adult patients undergoing allogeneic haematopoietic stem cell transplantation conditioning.","authors":"Christa E Nath, Sebastian P A Rosser, Kiran K Nath, Jason Chung, Stephen Larsen, John Gibson, Melissa Gabriel, Peter J Shaw, Steven J Keogh","doi":"10.1007/s00228-024-03751-0","DOIUrl":"https://doi.org/10.1007/s00228-024-03751-0","url":null,"abstract":"<p><strong>Aim: </strong>To evaluate the population pharmacokinetics of unbound F-Ara-A (the circulating metabolite of fludarabine) in 211 patients (age range, 0.1-63.4 years) undergoing allogeneic haematopoietic stem cell transplantation conditioning.</p><p><strong>Methods: </strong>Total (n = 2480) and unbound (n = 1403) F-Ara-A concentrations were measured in blood samples collected at timed intervals after fludarabine doses ranging from 10 to 50 mg/m² and infused over 0.42-1.5 h. A three-compartment population pharmacokinetic model was developed based on unbound plasma concentrations and used to estimate F-Ara-A unbound pharmacokinetic parameters and fraction unbound (fu). A number of covariates, including glomerular filtration rate (GFR) and post-menstrual age (PMA), were evaluated for inclusion in the model.</p><p><strong>Results: </strong>The base population mean estimates ± relative standard error (%RSE) for unbound clearance from the central compartment (CLu) and inter-compartmental clearances (Q2u, Q3u) were 3.42 ± 3%, 6.54 ± 24% and 1.47 ± 16% L/h/70 kg, respectively. The population mean estimates (%RSE) for the unbound volume of distribution into the central (V1u) and peripheral compartments (V2u, V3u) were 9.65 ± 8%, 8.17 ± 9% and 16.4 ± 10% L/70 kg, respectively, and that for fu was 0.877 ± 1%. Covariate model development involved differentiating F-Ara-A CLu into non-renal (1.81 ± 9% L/h/70 kg) and renal components (1.02 ± 9%*GFR L/h/70 kg). A sigmoidal maturation factor was applied to renal CLu, with population mean estimates for the Hill exponent and PMA at 50% mature of 2.97 ± 4% and 69.1 ± 8% weeks, respectively.</p><p><strong>Conclusion: </strong>Patient age and GFR are predictors of unbound F-Ara-A CLu. This has the potential to impact dose requirements. Dose individualisation by target concentration intervention will be facilitated by this model once it is externally validated.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium-glucose cotransporter 2 inhibitors and renal cancer in the US FDA adverse event reporting system","authors":"Bo Xu, Jiecan Zhou","doi":"10.1007/s00228-024-03759-6","DOIUrl":"https://doi.org/10.1007/s00228-024-03759-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Recent evidence suggests an association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and a higher risk of renal cancer.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>We conducted a pharmacovigilance analysis using the US FDA Adverse Event Reporting System (FAERS) to investigate the disproportionate association between SGLT2 inhibitors and renal cancer.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We used AERSMine to mine data from FAERS, covering the period from 2014 Q1 to 2023 Q3. The control group was treated with other glucose-lowering medications (ATC-A10B). Disproportionality analysis results were performed using a proportional reporting ratio (PRR) with a 95% confidence interval (CI) and an information component (IC) with 95% credible interval.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Compared to the control group, the SGLT2 inhibitor group had a higher disproportionate renal cancer reporting frequency (0.92 vs 0.27/1000 reports; PRR 3.38; 95% CI 2.68–4.25; <i>p</i> &lt; 0.001) with an IC of 1.36 (0.60–2.06), comprising dapagliflozin (PRR 4.14; 2.95–5.80; <i>p</i> &lt; 0.001), empagliflozin (PRR 2.74; 1.94–3.89; <i>p</i> &lt; 0.001), and canagliflozin (PRR 3.56; 2.48–5.12; <i>p</i> &lt; 0.001). Consistent results were obtained in the diabetes indication with the primary outcomes only for the SGLT2 inhibitors group (not individual molecule). The results of the sensitivity analysis (excluding hypertension indication or antihypertensive drugs, obesity, smoking, alpha-1 blockers, or anti-renal cancer drugs) were highly consistent with the main outcomes, indicating good robustness of the results. The results from 2004 Q1 to 2023 Q3 were similar to those from 2014 Q1 to 2023 Q3, with the exception of empagliflozin.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>There was a disproportionate association between SGLT2 inhibitors and renal cancer, which supports the current meta-analysis results indicating an increased risk of renal cancer associated with SGLT2 inhibitors.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics-pharmacodynamics of first-line antitubercular drugs: a comparative study in tuberculosis patients with and without concomitant diabetes mellitus","authors":"Sourav Mondal, Vandana Roy, Girish Gulab Meshram, Ashwani Khanna, Thirumurthy Velpandian, Sandeep Garg","doi":"10.1007/s00228-024-03754-x","DOIUrl":"https://doi.org/10.1007/s00228-024-03754-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>To observe the variability in the plasma concentrations and pharmacokinetic-pharmacodynamic (PK-PD) profiles of first-line antitubercular drugs in pulmonary tuberculosis (TB) patients with and without diabetes mellitus (DM).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Newly diagnosed pulmonary TB patients aged 18–60 years with or without DM were included in the study. Group I (<i>n</i> = 20) included patients with TB, whereas group II (<i>n</i> = 20) included patients with both TB and DM. After 2 weeks of therapy, plasma concentrations and other PK-PD parameters were determined. Improvements in clinical features, X-ray findings, sputum conversion, and adverse drug reactions (ADRs) were assessed after 2 months of therapy.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Isoniazid displayed non-significantly higher plasma concentrations in diabetic patients, along with a significantly (<i>P</i> &lt; 0.05) longer elimination half-life (t_1/2). Rifampicin plasma concentrations at 4, 8, and 12 h were significantly (<i>P</i> &lt; 0.05) lower, and it displayed significantly (<i>P</i> &lt; 0.05) lower area under the curve (AUC_0-12 and AUC_0-∞), shorter t_1/2, higher clearance (Cl), and a lower AUC_0-∞/MIC ratio in diabetic patients. Pyrazinamide and ethambutol showed non-significantly higher plasma concentrations, AUC_0-12, AUC_0-∞, and t_1/2 in diabetic patients. The improvements in clinical features, X-ray findings, sputum conversion, and ADRs were comparable in both groups.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The presence of DM in TB patients affects the PK-PD parameters of isoniazid, rifampicin, pyrazinamide, and ethambutol variably in the Indian population. Studies with a larger number of patients are required to further elucidate the role of DM on the PK-PD profile of first-line antitubercular drugs and treatment outcomes in TB patients with concomitant DM.</p><h3 data-test=\"abstract-sub-heading\">Trial registration</h3><p>CTRI/2021/08/035578 dated 11/08/2021.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}