Current Therapeutic Research-clinical and Experimental最新文献

{"title":"Cost-effectiveness of Evolocumab in Cardiovascular Disease: A Systematic Review","authors":"Nashmil Ghadimi ,&nbsp;Rajabali Daroudi ,&nbsp;Hosein Shabaninejad ,&nbsp;Mahshad Goharimehr ,&nbsp;Davoud Khodamorzideh ,&nbsp;Sara Kaveh","doi":"10.1016/j.curtheres.2024.100758","DOIUrl":"10.1016/j.curtheres.2024.100758","url":null,"abstract":"<div><h3>Background</h3><div>With the rising burden of cardiovascular disease (CVD) and the need for cost-effective interventions, evaluating the economic implications of Evolocumab becomes crucial.</div></div><div><h3>Objectives</h3><div>This study aimed to systematically review and evaluate the cost-effectiveness of Evolocumab in adults at risk of CVD.</div></div><div><h3>Methods</h3><div>We performed an extensive search in Cochrane Library, EMBASE, PubMed, ProQuest, and Web of Science. The reference lists of chosen literature reviews were also examined to find suitable cost-effectiveness analyses (CEAs) of Evolocumab in patients with CVD published until March 2023. The Consolidated Health Economic Evaluation Reporting Standards statement (CHEERS) was used to assess the reporting quality. Cost-related findings were adjusted to reflect 2023 purchase power parity (PPP) values in US dollars to enable cross-study comparisons.</div></div><div><h3>Results</h3><div>This systematic review comprised 16 studies, published between 2016 and 2023, mostly from the USA and China. Compliance with the CHEERS checklist was high in sections like abstracts, backgrounds, and objectives. However, areas like perspective (71.4%), time horizon (57.1%), and engagement with patients (14.3%) showed lower reporting rates. All studies evaluated the cost-effectiveness of Evolocumab in combination with other lipid-lowering treatments (LLTs). Notably, all studies employed model-based economic evaluations using a Markov cohort state-transition model, with a majority adopting a lifetime horizon. Most studies (10 cases) simultaneously reported both the Incremental Cost-Effectiveness Ratio (ICER) per Quality Adjusted Life Years (QALY) and the ICER per Life-Years Saved (LYS). Four studies exclusively reported ICER/QALY, and 2 studies solely focused on ICER/LYS. The ICER/ QALY exhibited a wide range (3,342.57 to 2,687,920.13 USD), with one study presenting as an outlier. Sensitivity analyses revealed factors influencing cost-effectiveness outcomes, including Low-Density Lipoprotein Cholesterol (LDL-C) levels, Evolocumab costs, and disease type, while several studies reported accepted thresholds for cost-effectiveness analysis.</div></div><div><h3>Conclusions</h3><div>Our systematic review concludes that Evolocumab could be a cost-effective treatment, particularly for high-risk patient groups, but this varies by disease category, risk level, and evaluation methods. Future studies should investigate the economic impact's certainty and uncertainty, and consider different countries' income levels. LDL-C levels, medication costs, and CVD types are important factors affecting cost-effectiveness analysis.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"101 ","pages":"Article 100758"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Low-Dose Glucagon on Subcutaneous Insulin Absorption in Pigs","authors":"Ingrid Anna Teigen M.D., Ph.D. ,&nbsp;Marte Kierulf Åm Ph.D. ,&nbsp;Misbah Riaz M.D. ,&nbsp;Sverre Christian Christiansen M.D., Ph.D. ,&nbsp;Sven Magnus Carlsen M.D., Ph.D.","doi":"10.1016/j.curtheres.2024.100736","DOIUrl":"10.1016/j.curtheres.2024.100736","url":null,"abstract":"<div><h3>Background</h3><p>Slow insulin absorption prevents the development of a fully automated artificial pancreas with subcutaneous insulin delivery.</p></div><div><h3>Objective</h3><p>We have hypothesized that glucagon could be used as a vasodilator to accelerate insulin absorption in a bihormonal subcutaneous artificial pancreas. The present proof-of-concept study is the first study to investigate the pharmacokinetics of insulin after subcutaneous administration of a low dose of glucagon at the site of subcutaneous insulin injection.</p></div><div><h3>Methods</h3><p>Twelve anesthetized pigs were randomized to receive a subcutaneous injection of 10 IU insulin aspart with either 100 µg glucagon or the equivalent volume of placebo (0.9% saline solution) injected at the same site. Arterial samples were collected for 180 minutes to determine insulin, glucagon, and glucose concentrations.</p></div><div><h3>Results</h3><p>Glucagon did not influence the insulin concentration T_max in plasma. The plasma insulin AUC_0–∞ was significantly larger after glucagon administration (<em>P</em> &lt; 0.01). The glucagon group had significantly higher glucose concentrations in the first 30 minutes after insulin administration (<em>P</em> &lt; 0.05).</p></div><div><h3>Conclusions</h3><p>This proof-of-concept study indicates that glucagon may increase the total absorption of a single dose of subcutaneously injected insulin. This is a novel observation. However, we did not observe any reduction in insulin concentration T_max, as we had hypothesized. Further, glucagon induced a significant, undesirable increase in early blood glucose concentrations.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"100 ","pages":"Article 100736"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X24000067/pdfft?md5=c0b24e6ee8160e4af109627f08fc13fb&pid=1-s2.0-S0011393X24000067-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139879991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Triple Therapy of Telmisartan/Amlodipine/Rosuvastatin in Patients with Dyslipidemia and Hypertension: A Multicenter Randomized Clinical Trial","authors":"Sungjoon Park MD ,&nbsp;Doyeon Hwang MD ,&nbsp;Jeehoon Kang MD ,&nbsp;Jung-Kyu Han MD ,&nbsp;Han-Mo Yang MD ,&nbsp;Kyung Woo Park MD ,&nbsp;Hyun-Jae Kang MD ,&nbsp;Bon-Kwon Koo MD ,&nbsp;Jin-Man Cho MD ,&nbsp;Byung-Ryul Cho MD ,&nbsp;Sung Gyun Ahn MD ,&nbsp;Seok-Min Kang MD ,&nbsp;Jung-Hoon Sung MD ,&nbsp;Ung Kim MD ,&nbsp;Namho Lee MD ,&nbsp;Hyo-Soo Kim MD","doi":"10.1016/j.curtheres.2024.100735","DOIUrl":"10.1016/j.curtheres.2024.100735","url":null,"abstract":"<div><h3>Background</h3><p>Hypertension and dyslipidemia significantly contribute to cardiovascular disease development. Their coexistence poses challenges in managing multiple medications, influencing treatment adherence.</p></div><div><h3>Objective</h3><p>This study aimed to assess the efficacy and safety of a combined treatment approach using a fixed-dose combination therapy.</p></div><div><h3>Methods</h3><p>This multicenter, 8-week, randomized, double-blind, Phase IV trial was named Telmisartan/Amlodipine/Rosuvastatin from Samjin Pharmaceuticals and evaluated the efficacy and safety of fixed-dose combination treatment in patients with essential hypertension and dyslipidemia. They were randomly assigned to 2 fixed-dose combination therapy groups, telmisartan 40 mg/amlodipine 5 mg/rosuvastatin 10 mg (TEL/ALD/RSV) or amlodipine 5 mg/atorvastatin 10 mg (ALD/ATV) after washout/run-in period. The primary outcomes were the change in mean sitting systolic blood pressure and the percentage change of LDL-C after 8 weeks of medical treatment. Adverse drug reactions and events were assessed.</p></div><div><h3>Results</h3><p>Of a total of 304 patients who underwent screening, 252 were randomized to the TEL/ALD/RSV group (125 patients) and the ALD/ATV group (127 patients). The mean (SD) ages of the TEL/ALD/RSV group and the ALD/ATV group were 67.4 (11.3) and 68.2 (10.6) years, respectively (<em>P</em> = 0.563). The least-squares mean (SE) in mean sitting systolic blood pressure changes between the 2 groups were –16.27 (0.93) mm Hg in the TEL/ALD/RSV group, –6.85 (0.92) mm Hg in the ALD/ATV group (LSM difference = –9.42 mm Hg; 95% CI, –11.99 to –6.84; <em>P</em> &lt; .001). For LDL-C level changes, a significant difference was noted between the 2 groups: –50.03% (1.18%) in the TEL/ALD/RSV group, –39.60% (1.17%) in the ALD/ATV group (LSM difference = –10.43%; 95% CI, –13.70 to –7.16; <em>P</em> &lt; .001). No severe adverse events were observed.</p></div><div><h3>Conclusions</h3><p>TEL/ALD/RSV proved to be more efficient than ALD/ATV in lowering blood pressure and reducing LDL-C levels among patients with hypertension and dyslipidemia, with no notable safety concerns. (<em>Curr Ther Res Clin Exp</em>. 2024; XX:XXX–XXX). ClinicalTrials.gov identifier: NCT03860220.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"100 ","pages":"Article 100735"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X24000055/pdfft?md5=e2b898a8aaa84b6faae79ae87558da24&pid=1-s2.0-S0011393X24000055-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139885412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioequivalence of a New Pediatric Paracetamol Oral Suspension Compared With a Marketed Formulation in Healthy Adults: A Randomized, Open-Label Study","authors":"Jiri Grim MD, PhD ,&nbsp;Marianna Armogida MD ,&nbsp;Preeti Kachroo BAMS, MD(AM) ,&nbsp;Kamran Siddiqui MBBS, MBA ,&nbsp;Mauro Cavinato PhD ,&nbsp;Mako Araga MS","doi":"10.1016/j.curtheres.2024.100734","DOIUrl":"10.1016/j.curtheres.2024.100734","url":null,"abstract":"<div><h3>Background</h3><p>A new oral paracetamol formulation with the same paracetamol quantity (24 mg/mL) as a marketed formulation but with finer active ingredient particle size and lower amounts of maltitol (5.85 g/dose in the test formulation vs 7.25 g/dose in the reference formulation) and sorbitol (2.4 g/dose vs 2.83 g/dose) was developed.</p></div><div><h3>Objective</h3><p>Establish the bioequivalence of the new pediatric formulation (test treatment) compared with the marketed formulation (reference treatment).</p></div><div><h3>Methods</h3><p>This Phase I, open-label trial assigned healthy adult volunteers to a single 42-mL (1 g para-cetamol) dose of test or reference treatment. Participants received both treatments in a randomized order separated by a 72-hour washout period. The primary endpoints were AUC_0–tlast (AUC vs time curve from time 0 to last measurable sampling timepoint), C_max, and t_max. Safety assessments included adverse event, clinical laboratory, and physical examination data.</p></div><div><h3>Results</h3><p>Thirty-five participants were randomized and treated. The study population was 42.9% women (57.1% men) with a median age of 30 years; most participants were non-Hispanic White. Mean C_max values were comparable between test and reference products, with a median t_max of 1.00 hour for both. The test/reference ratios (%) (90% CI) for AUC_0–tlast and C_max were 98.69% (96.46, 100.97) and 100.73% (95.63, 106.10), respectively. There were no adverse events or deaths.</p></div><div><h3>Conclusions</h3><p>The new paracetamol formulation is bioequivalent to the marketed formulation.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"100 ","pages":"Article 100734"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X24000043/pdfft?md5=47ca70cb77c917b984528fd3d13b1234&pid=1-s2.0-S0011393X24000043-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139887502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Usefulness of Belimumab in Adult Patients With Systemic Lupus Erythematosus Evaluated Using Single Indexes: A Meta-Analysis and Systematic Review","authors":"Chisato Yoshijima BSPharm ,&nbsp;Yosuke Suzuki PhD ,&nbsp;Ayako Oda BSPharm ,&nbsp;Ryota Tanaka PhD ,&nbsp;Hiroyuki Ono BSPharm ,&nbsp;Hiroki Itoh PhD ,&nbsp;Keiko Ohno PhD","doi":"10.1016/j.curtheres.2024.100738","DOIUrl":"10.1016/j.curtheres.2024.100738","url":null,"abstract":"<div><h3>Background</h3><p>Belimumab is the first antibody drug approved for systemic lupus erythematosus (SLE), and is a fully human monoclonal antibody that inhibits soluble B lymphocyte stimulator protein. In clinical trials, a composite index was used to assess efficacy of belimumab. However, clinical guidelines on SLE treatment currently use single efficacy indexes.</p></div><div><h3>Objective</h3><p>The main objective of this study was to perform a meta-analysis to evaluate the efficacy of belimumab utilizing single indexes used in routine clinical practice, rather than the composite efficacy index used in clinical trials during the development phase. As a secondary endpoint, safety was also evaluated.</p></div><div><h3>Methods</h3><p>Several databases were searched to identify reports published up to December 1, 2021 on randomized controlled trials examining the efficacy of belimumab in adult patients with SLE. From the clinical trial data, efficacy was evaluated using single indexes including the SLE Disease Activity Index (SLEDAI), British Isles Lupus Assessment Group Index, and Physician Global Assessment. Safety was also assessed. Data were synthesized and analyzed using Review Manager 5.4. This study protocol was registered in the UMIN Clinical Trials Registry (Registration number: UMIN000052846).</p></div><div><h3>Results</h3><p>The search identified 12 reports that met the inclusion criteria. Five reports were included in efficacy evaluation and 9 in safety evaluation. The primary endpoint was SLEDAI. Significantly more belimumab-treated patients achieved a ≥4-point reduction in SLEDAI (relative risk 1.28; 95% confidence interval, 1.16–1.40; <em>P</em> &lt; 0.00001) compared with placebo. Other efficacy endpoints were also improved significantly in the belimumab group. No difference in safety was found between belimumab and placebo.</p></div><div><h3>Conclusions</h3><p>The present meta-analysis evaluating clinical trial data using various single indexes recommended by clinical guidelines for SLE verifies that addition of belimumab to standard of care is efficacious for moderate-to-severe SLE.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"100 ","pages":"Article 100738"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X24000080/pdfft?md5=eb9bf6e5cf8f97a106df5ebcde529663&pid=1-s2.0-S0011393X24000080-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139967046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Narrative Review of the Coronavirus Disease 2019 Response in the Kingdom of Bahrain","authors":"Manaf AlQahtani MD, FRCPC, FRCPI ,&nbsp;Jaleela Sayed Jawad MD, MSc ,&nbsp;Abdulla AlAwadhi MSc ,&nbsp;Basma Mahmood Al Saffar MD, MSc ,&nbsp;Ejlal Faisal AlAlawi MD, MSc ,&nbsp;Hashim Hadi Sayed Adnan MPH ,&nbsp;Hammam Haridy MD ,&nbsp;Jean Joury BSPharm, CMD ,&nbsp;Graciela del Carmen Morales MD","doi":"10.1016/j.curtheres.2024.100733","DOIUrl":"10.1016/j.curtheres.2024.100733","url":null,"abstract":"<div><h3>Background</h3><p>The Kingdom of Bahrain has reported more than 696,000 cases of coronavirus disease 2019 (COVID-19) and 1548 associated deaths as of December 26, 2022.</p></div><div><h3>Objectives</h3><p>To better inform responses to future public health threats, this narrative review documents the challenges and responses to the COVID-19 pandemic in the Kingdom of Bahrain.</p></div><div><h3>Methods</h3><p>A PubMed search was conducted focusing on severe acute respiratory syndrome or COVID-19 in Bahrain. Additional relevant references were also included from the authors’ personal reference collections.</p></div><div><h3>Results</h3><p>The search indicated that Bahrain achieved well-established control of the pandemic through robust public health measures, including an early, comprehensive vaccination program. Bahrain was among the first countries to grant emergency authorization for COVID-19 vaccines; as of December 2022, nearly 73% of the eligible population has been fully vaccinated, and approximately 60% has been boosted. Low case rates in recent months highlight Bahrain's successful response to the COVID-19 pandemic.</p></div><div><h3>Conclusions</h3><p>Early organization, robust and systematic protective measures, and a comprehensive vaccination program were key components of the Kingdom's response to the pandemic; traveler quarantines and attempts to combat misinformation were of little or no benefit. These lessons provide guidance for future preparedness to minimize the public health impacts of another pandemic. (<em>Curr Ther Res Clin Exp</em>. 2024; XX:XXX–XXX).</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"100 ","pages":"Article 100733"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X24000031/pdfft?md5=de87cf74fc105a19560ec04c0c6c322f&pid=1-s2.0-S0011393X24000031-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139686641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Complementary and Alternative Medicine in Patients With Idiopathic Inflammatory Demyelinating Diseases of the Central Nervous System: A Cross-Sectional Study in Thailand","authors":"Punchika Kosiyakul MD ,&nbsp;Jiraporn Jitprapaikulsan MD ,&nbsp;Natthapon Rattanathamsakul MD ,&nbsp;Sasitorn Siritho MD ,&nbsp;Onpawee Sangsai MSc ,&nbsp;Kamonchanok Aueaphatthanawong BSc ,&nbsp;Montira Engchuan BNS ,&nbsp;Naraporn Prayoonwiwat MD","doi":"10.1016/j.curtheres.2024.100749","DOIUrl":"https://doi.org/10.1016/j.curtheres.2024.100749","url":null,"abstract":"<div><h3>Background</h3><p>Complementary and alternative medications (CAM) are common among patients with multiple sclerosis (MS) for physical and psychological support. However, there is insufficient data regarding the application of CAM in the different cultures and beliefs of each community as well as patient's status.</p></div><div><h3>Objective</h3><p>To evaluate the prevalence and modalities of the use of CAM among patients with central nervous system idiopathic inflammatory demyelinating diseases (CNS-IIDD) in a tertiary care hospital</p></div><div><h3>Methods</h3><p>A cross-sectional study was conducted at Siriraj Hospital from June to December 2021 involving patients with MS, neuromyelitis optic spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), idiopathic transverse myelitis (iTM), and optic neuritis (ON) to examine the prevalence and mode of CAM use and its correlation with patient characteristics.</p></div><div><h3>Results</h3><p>There were 107 patients. The diagnoses were MS (38), NMOSD (55), MOGAD (5), iTM (7), and ON (2). Most of the patients were female (89.7%), and 61.7% were diagnosed over 5 years. The mean Expanded Disability Status Scale was 2.63 (S.D., 2.38), and the median ambulation index was 0 (range 0–8.5). There were 68 patients (63.6%) with a history of CAM use for at least 3 months, while those with current use decreased to 62 (58.5%). Vitamins and minerals were the most commonly used, particularly vitamin D (97.1%) and calcium (47.7%). Both treatments were primarily prescribed (95.3%) rather than self-administered (24.3%). The main reasons for the use of CAM were to strengthen their health (48.6%) and relieve existing symptoms (28.0%).</p></div><div><h3>Conclusions</h3><p>The use of CAM is common among patients with Thai CNS-IIDD. Further exploration of patient perspectives and preferences regarding CAM usage may contribute to a more comprehensive management approach for patients with CNS-IIDD.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"100 ","pages":"Article 100749"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X24000195/pdfft?md5=fb9b38632a0a5e14ddab786818a943a8&pid=1-s2.0-S0011393X24000195-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141068026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Remission With Upadacitinib in a Child With Refractory Crohn's Disease and ATM Mutation: A Case Report","authors":"Yan Liu MD,&nbsp;XiaoMei Song MD,&nbsp;LingYa Xiang MD,&nbsp;Wei Tan MD,&nbsp;Min Zou MD,&nbsp;Hong Guo MD","doi":"10.1016/j.curtheres.2024.100756","DOIUrl":"10.1016/j.curtheres.2024.100756","url":null,"abstract":"<div><p>Managing pediatric Crohn's disease (PCD) presents challenges due to severe complications and higher biologic therapy needs. Transitioning from anti–tumor necrosis factor agents to off-label therapies adds complexity. Although upadacitinib has demonstrated efficacy and tolerability in adult inflammatory bowel disease and pediatric atopic dermatitis, there are limited data for its application in PCD. This case report delineates successful remission with upadacitinib in a child with CD refractory to infliximab, ustekinumab, adalimumab, thalidomide, and prednisone. Notably, the patient carried an <em>ataxia telangiectasia mutated</em> (<em>ATM</em>) gene mutation. These findings provide valuable evidence for PCD management and highlight the potential benefits of upadacitinib in this population.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"101 ","pages":"Article 100756"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X24000262/pdfft?md5=38a12349069328845dcd8ec630763297&pid=1-s2.0-S0011393X24000262-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Study on the Prognostic Value and Clinicopathological Significance of Different Immune Checkpoints in Patients With Colorectal Cancer: A Systematic Review and Meta-Analysis","authors":"Mahdieh Azizi PhD ,&nbsp;Zahra Mokhtari MSc ,&nbsp;Shirin Tavana MSc ,&nbsp;Peyman Bemani PhD ,&nbsp;Zahra Heidari PhD ,&nbsp;Roghayeh Ghazavi PhD ,&nbsp;Marzieh Rezaei PhD","doi":"10.1016/j.curtheres.2024.100760","DOIUrl":"10.1016/j.curtheres.2024.100760","url":null,"abstract":"<div><h3>Background</h3><div>The prognostic significance of immune checkpoint expression in the tumor microenvironment has been widely investigated in colorectal cancers. However, the results of these studies are inconsistent and limited to some immune checkpoints.</div></div><div><h3>Objective</h3><div>The study aimed to investigate the correlation between different immune checkpoint expression and clinicopathological features and prognostic parameters.</div></div><div><h3>Methods</h3><div>We conducted a systematic review and meta-analysis of the published literature in PubMed, Web of Science-Core Collection, Scopus, Embase, and Cochrane databases to summarize the association between various immune checkpoints expression on both tumor cells and immune cells with clinicopathological features and prognostic parameters in patients with colorectal cancer.</div></div><div><h3>Results</h3><div>One hundred four studies incorporating 22,939 patients were included in our meta-analysis. Our results showed that among the B7 family, the high expression of B7H3, B7H4, PD-1, and PD-L1 on tumor cells and tumor tissue was significantly associated with higher T stage, advanced tumor, node, metastasis (TNM) stage, presence of vascular invasion, and lymphatic invasion. In addition, patients with high expression of B7H3, B7H4, PD-1, PD-L1, and PD-L2 were associated with shorter overall survival. High expression of PD-1 and PD-L1 in immune cells correlated with the absence of lymph node metastasis, lower TNM stage, early T stage, poor overall survival, and disease-free survival, respectively. Moreover, we found significant positive correlations between CD70 and Galectin-3 expression with advanced T stage. HLA-II overexpression was correlated with the absence of lymph node metastasis (odds ratio = 0.21, 95% CI = 0.11–0.38, <em>P</em> &lt; 0.001) and early TNM stage (odds ratio = 0.35, 95% CI = 0.26–0.47, <em>P</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Overexpression of B7H3, B7H4, PD-1, PD-L1, PD-L2, CD70, and Galectin-3 on tumors is significantly associated with unfavorable clinicopathological characteristics and poor prognostic factors. Hence, these immune checkpoints can serve as predictive biomarkers for prognosis and the clinicopathological features of colorectal cancer because this is essential to identify patients suitable for anticancer therapy with immune checkpoint inhibitors.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"101 ","pages":"Article 100760"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rate of Polypharmacy and Its Determinants Among Older Adult Cardiovascular Patients at Hiwot Fana Comprehensive Specialized Hospital in Eastern Ethiopia","authors":"Shambel Nigussie MSc ,&nbsp;Fekade Demeke Bayou MPH","doi":"10.1016/j.curtheres.2024.100752","DOIUrl":"10.1016/j.curtheres.2024.100752","url":null,"abstract":"<div><h3>Background</h3><p>Understanding the rate of polypharmacy in cardiovascular patients is crucial because of its increasing occurrence and its association with potentially inappropriate prescribing practices and negative health outcomes, particularly among elderly individuals with cardiovascular conditions. According to the best of the literature search knowledge, the magnitude of polypharmacy and associated factors were not known among older cardiovascular patients in eastern Ethiopia.</p></div><div><h3>Objective</h3><p>The aim of this study was to assess the rate of polypharmacy and its determinants among older adult cardiovascular patients at Hiwot Fana Comprehensive Specialized Hospital in eastern Ethiopia.</p></div><div><h3>Methods</h3><p>A cross-sectional study design was undertaken, involving a cohort of 364 individuals aged 65 years and older who were receiving follow-up care for cardiovascular disease. A data abstraction sheet was used to gather the data. The convenience sampling technique was employed. To identify factors related to the rate of polypharmacy, multivariable logistic regression analysis was employed.</p></div><div><h3>Results</h3><p>The analysis included the medical records of 325 patients, revealing a polypharmacy prevalence rate of 20.7%. Individuals who were 77 years of age or older had a 1.12 times higher likelihood of having polypharmacy than individuals who were 65 to 70 years old. The presence of comorbidities along with cardiovascular diseases was a significant factor related to polypharmacy. Polypharmacy was prevalent among individuals with a larger number of comorbidities.</p></div><div><h3>Conclusions</h3><p>This study reported that 1 in 5 cardiovascular patients at a chronic care clinic experienced polypharmacy. Age (≥77 years), having comorbidities, number of comorbid diseases (≥3), duration of cardiovascular disease (≥5 years), and number of years taking cardiovascular drugs (≥5) were associated with higher odds of polypharmacy. Health care providers should be cautious about prescribing multiple medications to this population. Training in the prevention of inappropriate polypharmacy is crucial to reducing the trend of polypharmacy and its associated burden.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"101 ","pages":"Article 100752"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X24000225/pdfft?md5=a900521557a4a8a112f46fa9d00d35b4&pid=1-s2.0-S0011393X24000225-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141415889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}