Current Therapeutic Research-clinical and Experimental最新文献

{"title":"The Hepatorenal Syndrome Patient Pathway: Retrospective Analysis of Electronic Health Records","authors":"Khurram Jamil MD ,&nbsp;Xingyue Huang PhD ,&nbsp;David Hayashida MSc ,&nbsp;Kunal Lodaya MD","doi":"10.1016/j.curtheres.2022.100663","DOIUrl":"10.1016/j.curtheres.2022.100663","url":null,"abstract":"<div><h3>Background</h3><p>Hepatorenal syndrome (HRS) is among the leading causes of hospitalization and mortality in patients with chronic liver disease.</p></div><div><h3>Objective</h3><p>To assess the HRS patient journey from preadmission to postdischarge to understand patient characteristics, disease progression, treatment patterns, and outcomes.</p></div><div><h3>Methods</h3><p>We conducted a retrospective study using real-world data from a nationwide electronic health record database (Cerner Health Facts, Kansas City, Missouri). We used ICD-9/10 diagnosis codes to identify patients hospitalized with HRS between January 1, 2009, and January 31, 2018. We assessed patient characteristics and history, clinical presentation, treatment, and outcomes. Regression analysis was conducted to assess the association between patient characteristics and survival while adjusting for demographic and clinical covariates.</p></div><div><h3>Results</h3><p>The study included 3563 patients (62% men). Precipitants of HRS included gastrointestinal bleeding (18%), diuretics and infections (30%), and paracentesis (26%). Although 21% of patients had liver injury exclusively associated with alcohol use, 20% had hepatitis C, 8% had nonalcoholic steatohepatitis, and the etiology of the remainder (51%) was either some combination of conditions or unknown. A total of 42% of patients received vasopressors, including octreotide and midodrine (10%), other combinations of vasopressors (11%), or another single vasopressor (21%). In-hospital mortality was 34%, and 14% of patients were discharged to hospice. Regression analysis showed patients with acute-on-chronic liver failure had higher mortality in acute-on-chronic liver failure grades 1 (odds ratio = 1.59), 2 (odds ratio = 2.49), and 3 (odds ratio = 4.53) versus no acute-on-chronic liver failure. Among survivor patients, 38% were readmitted within 90 days of discharge; 23% of readmissions were HRS-related.</p></div><div><h3>Conclusions</h3><p>The HRS patient journey presented in this study highlights inconsistencies in, and provides insight into, associated hospital-based treatment strategies. A mortality rate of 34% along with a readmission rate of 23% associated with HRS-related complications warrant more disease awareness and effective treatment. Further research is needed to examine the interactions between the etiology of cirrhosis, precipitants, treatment, and outcomes. (<em>Curr Ther Res Clin Exp</em>. 2022; 82:XXX–XXX)</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"96 ","pages":"Article 100663"},"PeriodicalIF":1.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X22000029/pdfft?md5=0484b5a2ef6500a9abbc49195685caa8&pid=1-s2.0-S0011393X22000029-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73222191","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":"Clinical Effectiveness of Regdanvimab Treatment for Mild-to-Moderate COVID-19: A Retrospective Cohort Study","authors":"Young Rock Jang MD ,&nbsp;Yoon Ju Oh MD ,&nbsp;Jin Yong Kim MD, MPH","doi":"10.1016/j.curtheres.2022.100675","DOIUrl":"10.1016/j.curtheres.2022.100675","url":null,"abstract":"<div><h3>Background</h3><p>In a Phase III study, regdanvimab (CT-P59) reduced the risk of hospitalization or death versus placebo in patients with mild-to-moderate coronavirus disease 2019 (COVID-19).</p></div><div><h3>Purpose</h3><p>We performed a retrospective cohort study of patients with COVID-19 to examine the effect of regdanvimab versus standard of care (SoC) on oxygen saturation.</p></div><div><h3>Methods</h3><p>We reviewed patients with mild-to-moderate COVID-19 confirmed by reverse transcription-polymerase chain reaction at a single hospital in the Republic of Korea. The primary efficacy end point was the proportion of patients deteriorating with peripheral capillary oxygen saturation &lt;94% on room air up to day 28.</p></div><div><h3>Results</h3><p>A total of 127 patients were treated for COVID-19 with regdanvimab, 190 with SoC. The proportion of patients deteriorating with peripheral capillary oxygen saturation &lt;94% on room air up to day 28 was 13.4% with regdanvimab and 39.5% with SoC (<em>P &lt;</em> 0.0001); median time (range) until sustained recovery of fever was 2.0 (0.2–14.8) and 4.2 (0.1–17.1) days, respectively. Supplemental oxygen was required by 23.6% of patients with regdanvimab and 52.1% with SoC (<em>P&lt;</em>0.0001) for a mean of 6.3 and 8.7 days, respectively (<em>P =</em> 0.0113); no patients needed mechanical ventilation. Compared with SoC, hospitalization was shorter with regdanvimab (mean = 11.1 vs 13.6 days; 63.8% vs 31.6% discharged within 11 days; both <em>P</em> values <em>&lt;</em> 0.0001). Fewer regdanvimab-treated patients required remdesivir (14.2% vs 43.2%; <em>P &lt;</em> 0.0001). There were no deaths. Two patients had adverse reactions with regdanvimab.</p></div><div><h3>Conclusions</h3><p>This real-world study indicates that regdanvimab can prevent deterioration in patients with mild-to-moderate COVID-19. (<em>Curr Ther Res Clin Exp</em>. 2022; 83:XXX–XXX)</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"96 ","pages":"Article 100675"},"PeriodicalIF":1.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X22000145/pdfft?md5=75c3afe6ceeb8f033d6431a6ec475871&pid=1-s2.0-S0011393X22000145-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80988219","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":"Nilotinib-Induced Elephantine Psoriasis In a Patient With Chronic Myeloid Leukemia: A Rare Case Report and Literature Review","authors":"Seyedeh Fatemeh Sadatmadani ,&nbsp;Zahra Malakoutikhah ,&nbsp;Fatemeh Mohaghegh ,&nbsp;Mohammadsaleh Peikar ,&nbsp;Mahdi Saboktakin","doi":"10.1016/j.curtheres.2022.100676","DOIUrl":"10.1016/j.curtheres.2022.100676","url":null,"abstract":"<div><p>Tyrosine kinase inhibitors are anticancer drugs that disrupt signal transduction pathways in protein kinases by different mechanisms. This group of pharmacologic agents has significantly improved the outcome of patients with chronic myeloid leukemia. However, their effect is not limited to cancer cells, and various complications, particularly cutaneous reactions, have been reported. We report a very rare case of a 35-year-old female with a history of chronic myeloid leukemia who presented with elephantine psoriasis after the treatment with nilotinib.</p><p>Conclusions: This case highlights a critical side effect of tyrosine kinase inhibitors. Awareness of this subject can be useful for better management of similar patients.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"96 ","pages":"Article 100676"},"PeriodicalIF":1.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/aa/ec/main.PMC9249592.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40472770","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":"Dasiglucagon Effects on QTc in Healthy Volunteers: A Randomized, Placebo-Controlled, Dose-Escalation, Double-Blind Study","authors":"Ramin Tehranchi MD, PhD, MBA ,&nbsp;Jonas Pettersson MD, PhD ,&nbsp;Anita E. Melgaard MSc ,&nbsp;Friedeborg Seitz MD ,&nbsp;Anders Valeur PhD ,&nbsp;Stine Just Maarbjerg PhD","doi":"10.1016/j.curtheres.2022.100668","DOIUrl":"10.1016/j.curtheres.2022.100668","url":null,"abstract":"<div><h3>Background</h3><p>Dasiglucagon is a novel glucagon analog that is stable in aqueous formulation and approved for use in severe hypoglycemia. Concentration-QTc analyses are critical for assessing risk of drug-induced QTc prolongation and potential for fatal cardiac arrhythmias such as torsades de pointes.</p></div><div><h3>Objective</h3><p>The aim of this study was to determine whether dasiglucagon treatment resulted in any clinically relevant effect on cardiac repolarization in healthy volunteers.</p></div><div><h3>Methods</h3><p>This double-blind, placebo-controlled, dose-escalation Phase I trial was conducted at a single center in Germany between November 2018 and June 2019. Sixty healthy volunteers aged 18 to 45 years were randomized within dose cohorts to receive intravenous dasiglucagon, intravenous placebo, or subcutaneous dasiglucagon. In the intravenous administration cohorts, doses ranged from 0.03 mg to 1.5 mg. The subcutaneous administration cohort received the approved 0.6 mg dose. In the intravenous administration cohorts, serial electrocardiograms were extracted from continuous Holter monitors at prespecified time points beginning the day before dosing and through 24 hours postdose. Heart rate, PR interval, and QRS duration were evaluated. Concentration-QT analyses corrected by Fridericia's formula (QTcF) were performed using both a linear mixed-effects and an estimated maximum effect (E_max) model.</p></div><div><h3>Results</h3><p>At the doses studied, dasiglucagon did not have any clinically relevant effect on heart rate, PR interval, or QRS duration. A minor prolongation of the QTcF interval was observed without any clear dose or concentration dependency. Both the linear and E_max models predicted mean and 90% CIs of placebo-corrected change in QTcF remained below 10 ms (the threshold of regulatory concern), although the linear model did not fit the data well at low dasiglucagon plasma concentrations. In the E_max model, the E_max of dasiglucagon was 3.6 ms (90% CI, 1.23–5.95 ms), and the amount to produce half the effect of E_max) was 426.0 pmol/L (90% CI, −48.8 to 900.71 pmol/L). The treatment effect-specific intercept was −0.44 ms (90% CI, −2.37 to 1.49 ms). The most frequently observed treatment-emergent adverse events reported in the trial were gastrointestinal disorders such as nausea and vomiting.</p></div><div><h3>Conclusions</h3><p>Dasiglucagon does not cause clinically relevant QTc prolongation in concentrations up to ≈30,000 pmol/L, a level 5-fold higher than the highest observed plasma concentrations in clinical trials investigating use of the approved 0.6 mg SC dose. ClinicalTrials.gov Identifier: NCT03735225; EudraCT identifier: 2018-002025-32. (<em>Curr Ther Res Clin Exp</em>. 2022; 83:XXX–XXX)</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"96 ","pages":"Article 100668"},"PeriodicalIF":1.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X22000078/pdfft?md5=9899cbd7b90dd5d8062b9ab6d3ca009e&pid=1-s2.0-S0011393X22000078-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54106428","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":"Nanoformulation of Plant-Based Natural Products for Type 2 Diabetes Mellitus: From Formulation Design to Therapeutic Applications","authors":"Akurange Sujeevi Dammadinna Wickramasinghe ,&nbsp;Pabasara Kalansuriya ,&nbsp;Anoja Priyadarshani Attanayake","doi":"10.1016/j.curtheres.2022.100672","DOIUrl":"https://doi.org/10.1016/j.curtheres.2022.100672","url":null,"abstract":"<div><h3>Background</h3><p>Herbal remedies are used to manage type 2 diabetes mellitus (type 2 DM) as the sole treatment or as a complementary therapy. Limitations of herbal remedies, such as poor stability and limited absorption, impede their development as therapeutic agents, which could be overcome by nanoformulations.</p></div><div><h3>Objectives</h3><p>This review attempts to summarize the studies reported between 2009 and 2020 in the development of medicinal plant-based nanoformulations for the management of type 2 DM, discuss formulation methods, mechanisms of action, and identify gaps in the literature to conduct future research on nanoparticle-based herbal treatment options targeting type 2 DM.</p></div><div><h3>Methods</h3><p>To retrieve articles published between January 2009 and December 2020, the electronic databases PubMed, Science Direct, and Google Scholar were searched with the keywords <em>nanoparticle, plant</em>, and <em>diabetes</em> in the entire text. Peer-reviewed research articles on herbal nanoformulations published in English-language based on <em>in vitro</em> and/or <em>in vivo</em> models of type 2 DM and/or its complications were included. The literature search and selection of titles/abstracts were carried out independently by 2 authors. The list of full-text articles was selected considering inclusion and exclusion criteria, with the agreement of all the authors.</p></div><div><h3>Results</h3><p>Among the reported studies, 68% of the studies were on inorganic herbal nanoformulations, whereas 17% and 8% were of polymer-based and lipid-based herbal nanoformulations, respectively. Some of the important biological properties of nanoformulations included improvement in glycemic control and insulin levels, inhibition of the formation of advanced glycation end products, and regeneration of pancreatic β cells. The aforementioned properties were observed by screening nanoformulations using <em>in vitro</em> cellular and noncellular models, as well as <em>in vivo</em> animal models of type 2 DM studied for acute or subacute durations. Only 2 clinical trials with patients with diabetes were reported, indicating the need for further research on medicinal plant-based nanoformulations as a therapeutic option for the management of type 2 DM.</p></div><div><h3>Conclusions</h3><p>Medicinal plant extracts and isolated compounds have been nanoformulated using various methods. The properties of the nanoformulations were found superior to those of the corresponding herbal extracts and isolated compounds. At both the preclinical and clinical levels, there are a number of poorly explored research areas in the development and bioactivity assessment of herbal nanoformulations. (<em>Curr Ther Res Clin Exp</em>. 2022; 83:XXX–XXX) © 2022 Elsevier HS Journals, Inc.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"96 ","pages":"Article 100672"},"PeriodicalIF":1.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X2200011X/pdfft?md5=e98826a85ec645e0afd27656d5cb7fa3&pid=1-s2.0-S0011393X2200011X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91728017","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 Ramosetron on Nausea and Vomiting Following Spinal Surgery: A Meta-Analysis","authors":"Yiyun Lin MD,&nbsp;Sun Tiansheng MMS,&nbsp;Zhang Zhicheng,&nbsp;Chen Xiaobin,&nbsp;Li Fang","doi":"10.1016/j.curtheres.2022.100666","DOIUrl":"https://doi.org/10.1016/j.curtheres.2022.100666","url":null,"abstract":"<div><h3>Background</h3><p>Spinal surgery is associated with severe pain within the first few days after surgery. Opioids are commonly used to control postoperative pain, but these can lead to postoperative nausea and vomiting (PONV). Therefore, use of more effective and better-tolerated agents would be beneficial for these patients. Serotonin receptor antagonists, such as ramosetron, have been used to reduce PONV in patients receiving anesthesia.</p></div><div><h3>Objective</h3><p>We conducted a meta-analysis of published randomized controlled trials (RCTs) to compare the efficacy and tolerance of ramosetron to prevent PONV after spinal surgery.</p></div><div><h3>Methods</h3><p>Medline, Embase, Cochrane Library, and Science Citation Index databases were systematically searched for relevant RCT articles published between January 1979 and November 2020. Full text articles restricted to English language that described RCTs comparing the use of ramosetron with other serotonin antagonists to treat PONV following spinal surgery in adult patients were considered for meta-analysis. Two reviewers independently performed study selection, quality assessment, and data extraction of all articles. Differences were resolved by a third reviewer.</p></div><div><h3>Results</h3><p>The search identified 88 potentially relevant articles, of which only 3 met our selection criteria. Study drugs were administered at the end of spinal surgery in all 3 included articles. The meta-analysis revealed that ramosetron (0.3 mg) reduced the pain score (mean difference = −0.66; 95% CI −1.02 to −0.30), lowered the risk of PONV (risk ratio = 0.86; 95% CI, 0.76–0.97), and postoperative vomiting (risk ratio = 0.32; 95% CI, 0.17–0.60), and limited the use of rescue antiemetics (risk ratio = 0.66; 95% CI, 0.45–0.96) after spinal surgery. However, there were no significant differences in the incidence of postoperative nausea, the use of rescue pain medications, the number of rescue analgesics required, and the risk of discontinuation of patient-controlled analgesia between ramosetron and palonosetron (0.075 mg) or ondansetron (4 mg). There were no statistically significant differences in the risk of adverse events among the 3 medications.</p></div><div><h3>Conclusions</h3><p>This meta-analysis of 3 RCTs showed that ramosetron reduced the risk of PONV and POV, limited the use of rescue antiemetics, reduced the postoperative pain score, and did not increase the risk of discontinuing patient-controlled analgesia compared with palonosetron or ondansetron after spinal surgery in 3 RCTs. Therefore, this meta-analysis indicates that ramosetron is an effective and well tolerated antiemetic that can be used to prevent PONV following spinal surgery in adult patients. PROSPERO identifier: CRD42020223596 (<em>Curr Ther Res Clin Exp</em>. 2022; 83:XXX–XXX)</p><p>© 2022 Elsevier HS Journals, Inc.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"96 ","pages":"Article 100666"},"PeriodicalIF":1.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X22000054/pdfft?md5=e679d10988df7b8bbd3a5c39ce686b14&pid=1-s2.0-S0011393X22000054-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91728018","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":"Selectivity and Maximum Response of Vibegron and Mirabegron for β3-Adrenergic Receptors","authors":"Benjamin M. Brucker MD ,&nbsp;Jennifer King PharmD ,&nbsp;Paul N. Mudd Jr PharmD, MBA ,&nbsp;Kimberly McHale PhD","doi":"10.1016/j.curtheres.2022.100674","DOIUrl":"10.1016/j.curtheres.2022.100674","url":null,"abstract":"<div><h3>Background</h3><p>The β₃-adrenergic agonists vibegron and mirabegron have shown favorable safety profiles and efficacy for the treatment of overactive bladder. However, β-adrenergic receptors are also found outside the bladder, which could lead to off-target activity.</p></div><div><h3>Objective</h3><p>This study assessed the selectivity of vibegron and mirabegron for β-adrenergic receptors and the maximal effect and potency for β₃-adrenergic receptors.</p></div><div><h3>Methods</h3><p>Functional cellular assays were performed using Chinese hamster ovary-K1 cells expressing β₁-, Chinese hamster ovary cells expressing β₂-, and human embryonic kidney 293 cells expressing β₃-adrenergic receptors. Cells were incubated with vibegron, mirabegron, or control (β₁ and β₃, isoproterenol; β₂, procaterol). Responses were quantified using homogeneous time-resolved fluorescence of cyclic adenosine monophosphate and were normalized to the respective control. Half-maximal effective concentration and maximum response values were determined by nonlinear least-squares regression analysis.</p></div><div><h3>Results</h3><p>Activation of β₃-adrenergic receptors with vibegron or mirabegron resulted in concentration-dependent β₃-adrenergic receptor responses. Mean (SEM) half-maximal effective concentration values at β₃-adrenergic receptors were 2.13 (0.25) nM for vibegron and 10.0 (0.56) nM for mirabegron. At a concentration of 10 µM, β₃-adrenergic activity relative to isoproterenol was 104% for vibegron and 88% for mirabegron. Maximum response at β₃-adrenergic receptors was 99.2% for vibegron and 80.4% for mirabegron. β₁-adrenergic activity was 0% and 3% for vibegron and mirabegron, respectively; β₂-adrenergic activity was 2% and 15%, respectively.</p></div><div><h3>Conclusions</h3><p>Vibegron showed no measurable β₁ and low β₂ activity compared with mirabegron, which showed low β₁ and some β₂ activity. Both showed considerable selectivity at β₃-adrenergic receptors; however, vibegron demonstrated near-exclusive β₃ activity and a higher maximum β₃ response.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"96 ","pages":"Article 100674"},"PeriodicalIF":1.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X22000133/pdfft?md5=fc54efeb449cd62aea76d2446cbb04b7&pid=1-s2.0-S0011393X22000133-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91344274","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":"Drugs Currently Undergoing Preclinical or Clinical Trials for the Treatment of Overactive Bladder: A Review","authors":"Silvia Joseph MBBS,&nbsp;Steffi A. Maria MD,&nbsp;Jacob Peedicayil MD","doi":"10.1016/j.curtheres.2022.100669","DOIUrl":"https://doi.org/10.1016/j.curtheres.2022.100669","url":null,"abstract":"<div><h3>Background</h3><p>Overactive bladder (OAB) is a common clinical condition for which current drug treatment comprises drugs blocking the cholinergic nerve supply, or augmenting the adrenergic nerve supply, to the detrusor muscle of the urinary bladder. Current treatments have drawbacks, including lack of efficacy and the development of adverse effects in some patients. Hence, new and better drugs for treating OAB will be clinically useful.</p></div><div><h3>Objective</h3><p>This review is meant to provide information on drugs currently undergoing preclinical or clinical trials for the treatment of OAB published in journal articles or elsewhere.</p></div><div><h3>Methods</h3><p>The cited articles were retrieved from PubMed and Google Scholar from January 1, 1990, to December 31, 2021. The search terms used were <em>contraction</em> or <em>contractility, detrusor, inhibition, isolated</em> or <em>in vitro, in vivo, overactive bladder</em>, and <em>relaxant effect</em> or <em>relaxation</em>.</p></div><div><h3>Results</h3><p>There are 4 classes of new drugs under various stages of development for the treatment of OAB. These are drugs acting on the autonomic nerve supply to the detrusor muscle of the urinary bladder that include the anticholinergics tarafenacin and afacifenacin and the β₃ adrenoceptor agonists solabegron and ritobegron; drugs acting on ion channels in the detrusor muscle (eg, potassium channel openers and calcium channel blockers), drugs acting on cellular enzymes like phosphodiesterase-5 inhibitors and Rho kinase inhibitors, and drugs acting on miscellaneous targets (eg, pregabalin and trimetazidine).</p></div><div><h3>Conclusions</h3><p>Drugs currently used to treat OAB target only the cholinergic and adrenergic cellular signalling pathways. There are many other drugs under trial targeting other cellular pathways that may be useful for treating OAB. Their approval for clinical use might improve the treatment of patients with OAB. (<em>Curr Ther Res Clin Exp</em>. 2022; 83:XXX–XXX)</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"96 ","pages":"Article 100669"},"PeriodicalIF":1.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X2200008X/pdfft?md5=0dd817fbf247b933f733ccead9a27768&pid=1-s2.0-S0011393X2200008X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91728226","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":"Associations Between Cessation of Second-Line Therapies and Relapse Rates of Childhood Refractory Minimal-Change Nephrotic Syndrome: A Single-Center, Retrospective Chart Review","authors":"Jing Jin MSc,&nbsp;Yufeng Li MD, PhD,&nbsp;Yaju Zhu MSc,&nbsp;Jiajia Ni MD, PhD","doi":"10.1016/j.curtheres.2022.100671","DOIUrl":"10.1016/j.curtheres.2022.100671","url":null,"abstract":"<div><h3>Background</h3><p>Most patients (≥85%) with minimal-change nephrotic syndrome (MCNS) respond to corticosteroid treatment. However, about 10% to 20% of patients with MCNS have steroid-resistant nephrotic syndrome and 25% to 43% of patients have steroid-dependent nephrotic syndrome or frequent-relapse steroid-sensitive nephrotic syndrome. Patients with refractory MCNS are treated with various second-line therapies.</p></div><div><h3>Objectives</h3><p>This study aimed to evaluate the associations between the use of various second-line therapies and relapse rates in Chinese patients with childhood refractory MCNS.</p></div><div><h3>Methods</h3><p>In this study, patients with childhood nephrotic syndrome renal biopsy proved to be “minimal change” from a single tertiary-care center between January 2002 and July 2018 were identified. A Total of 56 medical charts of patients treated with 1 of these second-line immunosuppressors: cyclophosphamide (CYC), mycophenolate mofetil (MMF), or tacrolimus (TAC) were reviewed. Patients were divided into CYC (n = 24), MMF (n = 20), and TAC (n = 12) groups according to the second-line therapy administered. Baseline characteristics, immune status, immunocomplex deposition in the renal tissue, and treatment outcomes were analyzed.</p></div><div><h3>Results</h3><p>The ratio of patients with steroid-resistant nephrotic syndrome and steroid-dependent nephrotic syndrome in the CYC, MMF, and TAC groups did not differ significantly (<em>P</em> = 0.721). The immunofluorescence assay did not show any significant differences in immunocomplex deposition identified in renal biopsy specimens among the 3 groups. The rate of steroid-free remission in the TAC group (75%) was higher than that in the MMF (55%) and CYC (25%) groups (<em>P</em> = 0.012). At the last follow-up, two-thirds of children in the TAC group had a relapse following discontinuation of therapy. In the TAC group, patients for whom steroids were withdrawn had significantly higher levels of immunoglobulin G at the onset of nephrotic syndrome than those for whom steroids were continued (<em>P</em> = 0.017). In the MMF group, children with relapse had a significantly higher percentage of CD16⁺CD56⁺-positive cells than those without relapse (<em>P</em> = 0.042). The relapse rate after treatment discontinuation was significantly different among the 3 groups (<em>P</em> = 0.035). Notably, the relapse rate after treatment discontinuation in the CYC group was lower than those in the other 2 groups (<em>P</em> = 0.035).</p></div><div><h3>Conclusions</h3><p>In this small population of Chinese patients with childhood refractory MCNS, the relapse rate following TAC therapy was higher than that following MMF or CYC therapy. Different proportions of CD16⁺CD56⁺-positive cells might be associated with relapse rates in patients with MCNS receiving MMF treatment. (<em>Curr Ther Res Clin Exp</em>. 2022; 83:XXX–XXX)</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"96 ","pages":"Article 100671"},"PeriodicalIF":1.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X22000108/pdfft?md5=915977ab55f1a3b9b7c71297d1b524ff&pid=1-s2.0-S0011393X22000108-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54106445","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":"Safety Profile and Tolerability of Topical Phosphodiesterase 4 Inhibitors for the Treatment of Atopic Dermatitis: A Systematic Review and Meta-Analysis","authors":"Ana Martín-Santiago MD ,&nbsp;Susana Puig MD PhD ,&nbsp;Daniel Arumi MD PhD ,&nbsp;Francisco Jose Rebollo Laserna MD","doi":"10.1016/j.curtheres.2022.100679","DOIUrl":"10.1016/j.curtheres.2022.100679","url":null,"abstract":"<div><h3>Objective</h3><p>Evaluate the safety profile and tolerability of topical phosphodiesterase 4 (PDE4) inhibitors versus vehicle as treatment for atopic dermatitis in published studies.</p></div><div><h3>Methods</h3><p>A search was performed in Medline/PubMed, Web of Science, and Cochrane Library databases on September 27, 2021, by 1 evaluator, without restrictions on publication dates or languages. Terms such as <em>atopic dermatitis, phosphodiesterase 4 inhibitors, calcineurin inhibitors</em>, and <em>randomized controlled trials</em> were included. The database searches were carried out by 1 evaluator. The titles and abstracts were reviewed for the identification and evaluation of potentially eligible studies. Study selection was made by two reviewers, so there was no intra-examiner statistic at the study selection step. The full-text articles were reviewed to determine whether or not they would be included in the systematic review. Global analyses, which included studies with both unclear and low risk of bias and subanalyses of studies with a low risk of bias were performed.</p></div><div><h3>Results</h3><p>Out of 237 identified articles, 14 clinical trials were included in the meta-analysis. In global analyses of studies with low and unclear risk of bias, topical treatment with PDE4 inhibitors did not differ from vehicle treatment in global treatment emergent adverse events (relative risk = 0.99; 95% CI, 0.87–1.14; <em>P</em> = 0.94) or in serious emergent adverse events appearance (relative risk = 0.92; 95% CI, 0.39–2.20; <em>P</em> = 0.86). In subanalyses of studies with a low risk of bias, a reduced rate of atopic dermatitis exacerbation was observed in PDE4 inhibitors compared with the vehicle (relative risk = 0.62; 95% CI, 0.39-0.98; <em>P</em> = 0.04) and risk of pain at the application site was confirmed (relative risk = 2.59; 95% CI, 1.27–5.28; <em>P</em> = 0.01).</p></div><div><h3>Conclusions</h3><p>PDE4 inhibitors did not show differences from vehicle treatment in treatment emergent adverse events or serious emergent adverse events incidence. In studies with low risk of bias, PDE4 inhibitors had a statistically significant risk of producing pain and reduced occurrence of atopic dermatitis exacerbation.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"96 ","pages":"Article 100679"},"PeriodicalIF":1.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2f/c4/main.PMC9278032.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40513934","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}