Concomitant therapy and bismuth quadruple therapy are both recommended as first-line treatment regimens for the empiric treatment of Helicobacter pylori infection, especially after the increased resistance to clarithromycin.
Objective
Our goal was to compare both treatment regimens among a sample of the Lebanese population to eventually conclude whether one of these therapies has a higher efficacy than the other one as a first- and second-line treatment regimens.
Methods
It is a randomized, prospective, and crossover study, started from March 2016 to December 2018. Participants were randomly chosen patients diagnosed with active H pylori through histology. Two groups were then formed randomly and equally: patients in the first group received 10 days of concomitant therapy, whereas patients in the second group received 10 days of bismuth quadruple therapy. Eradication was evaluated by the 14C urea breath test done 6 weeks after the end of antibiotic use. A negative breath test indicated a successful eradication. All patients with a positive breath test were then given the other treatment regimen for another 10 days and then re-evaluated for eradication in the same manner.
Results
Both regimens demonstrated similar efficacy as first-line therapies for H pylori eradication. Among 175 patients receiving concomitant therapy, 160 (91.4%) achieved eradication, whereas in the 174 patients treated with bismuth quadruple therapy, 164 (94.2%) were successfully eradicated (P = 0.306). Among patients requiring second-line treatment, 14 of 15 (93.3%) who failed concomitant therapy were successfully treated with bismuth quadruple therapy, whereas all 10 patients (100%) who failed bismuth therapy achieved eradication with concomitant therapy (P < 0.001).
Conclusions
Bismuth quadruple therapy and concomitant therapy are both equally effective first-line treatment regimens for the eradication of H pylori. They are also effective if used as second-line treatment regimens for this purpose. Lebanese Clinical Trials Registry identifier: LBCTR2024095653.
{"title":"A Randomized, Prospective and Crossover Study, Comparing the Eradication Rate After 10 Days of Concomitant Therapy to Bismuth Quadruple Therapy Among a Sample of the Lebanese Population","authors":"Jad Chidiac MD , Reine-Marie Kahwaji MD , Souheil Hallit PharmD, MSc, MPH, PhD , Yara Yazbeck MD , Bassem Akiki MD , Charbel Yazbeck MD","doi":"10.1016/j.curtheres.2025.100791","DOIUrl":"10.1016/j.curtheres.2025.100791","url":null,"abstract":"<div><h3>Background</h3><div>Concomitant therapy and bismuth quadruple therapy are both recommended as first-line treatment regimens for the empiric treatment of <em>Helicobacter pylori</em> infection, especially after the increased resistance to clarithromycin.</div></div><div><h3>Objective</h3><div>Our goal was to compare both treatment regimens among a sample of the Lebanese population to eventually conclude whether one of these therapies has a higher efficacy than the other one as a first- and second-line treatment regimens.</div></div><div><h3>Methods</h3><div>It is a randomized, prospective, and crossover study, started from March 2016 to December 2018. Participants were randomly chosen patients diagnosed with active <em>H pylori</em> through histology. Two groups were then formed randomly and equally: patients in the first group received 10 days of concomitant therapy, whereas patients in the second group received 10 days of bismuth quadruple therapy. Eradication was evaluated by the <sup>14</sup>C urea breath test done 6 weeks after the end of antibiotic use. A negative breath test indicated a successful eradication. All patients with a positive breath test were then given the other treatment regimen for another 10 days and then re-evaluated for eradication in the same manner.</div></div><div><h3>Results</h3><div>Both regimens demonstrated similar efficacy as first-line therapies for <em>H pylori</em> eradication. Among 175 patients receiving concomitant therapy, 160 (91.4%) achieved eradication, whereas in the 174 patients treated with bismuth quadruple therapy, 164 (94.2%) were successfully eradicated (<em>P</em> = 0.306). Among patients requiring second-line treatment, 14 of 15 (93.3%) who failed concomitant therapy were successfully treated with bismuth quadruple therapy, whereas all 10 patients (100%) who failed bismuth therapy achieved eradication with concomitant therapy (<em>P</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>Bismuth quadruple therapy and concomitant therapy are both equally effective first-line treatment regimens for the eradication of <em>H pylori</em>. They are also effective if used as second-line treatment regimens for this purpose. Lebanese Clinical Trials Registry identifier: LBCTR2024095653.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100791"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xerostomia, or dry mouth, is a common and debilitating symptom in patients with Sjögren's syndrome, affecting their quality of life. Although Cevimeline, a muscarinic agonist, has been investigated as a potential treatment, its efficacy and optimal dosage remain uncertain. This study aims to assess the effectiveness of Cevimeline in relieving xerostomia in patients with Sjögren's syndrome by a meta-analysis of randomized clinical trials (RCT).
Method
A comprehensive search was conducted across PubMed, Scopus, Cochrane, and Web of Science databases, utilizing Medical Subject Headings terms and keywords related to “cevimeline,” “xerostomia,” and “Sjögren's syndrome” from inception until January 3, 2024. Studies were selected based on predefined inclusion criteria, focusing on clinical trials involving human subjects treated with cevimeline for xerostomia in Sjögren's syndrome. Data extraction was performed systematically, and statistical analysis was conducted using STATA software.
Result
This meta-analysis included three RCTs with a total of 302 patients with Sjögren's syndrome (Cevimeline = 187; Placebo = 115). The analysis demonstrated that Cevimeline significantly reduces xerostomia (regarded as salivary flow, mouth dryness) in patients with Sjögren's syndrome with a pooled odds ratio –5.79 (95% CI [–10.55, –1.03]; I2 = 39.6%).
Conclusions
In summary, cevimeline significantly increases salivary flow secretion rates in patients with Sjögren's syndrome. With a favorable safety profile at recommended dosages, cevimeline represents a viable therapeutic option for managing xerostomia, particularly in patients with mild to moderate salivary gland destruction.
背景：口干，或口干，是Sjögren综合征患者常见的衰弱症状，影响他们的生活质量。虽然西维美林，一种毒蕈碱激动剂，已经作为一种潜在的治疗方法进行了研究，但其疗效和最佳剂量仍然不确定。本研究旨在通过随机临床试验（RCT）的荟萃分析来评估西维美林缓解Sjögren综合征患者口干症的有效性。方法：综合检索PubMed、Scopus、Cochrane和Web of Science数据库，利用医学主题词和关键词“西维美林”、“口干症”和“Sjögren’s syndrome”，从研究开始到2024年1月3日。研究是根据预先确定的纳入标准选择的，重点是涉及使用西维美林治疗Sjögren综合征口干症的人类受试者的临床试验。系统提取数据，使用STATA软件进行统计分析。结果：本荟萃分析纳入3项随机对照试验，共纳入302例Sjögren综合征患者(塞维米林 = 187；安慰剂 = 115)。分析表明，西维美林可显著减少Sjögren综合征患者的口干症（视为唾液流、口干），合并优势比为-5.79 (95% CI [-10.55, -1.03]；I 2 = 39.6%)。结论：综上所述，西维美林可显著提高Sjögren综合征患者的唾液分泌率。在推荐剂量下，西维美林具有良好的安全性，是治疗口干症的可行治疗选择，特别是在轻度至中度唾液腺破坏的患者中。
{"title":"Efficacy of Cevimeline on Xerostomia in Sjögren's Syndrome Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials","authors":"Mehdi Karimi MD , Fatemeh Ahmadi Hajikolaei MD , Fahime Hoseinpour MD , Seyed-Ali Hashemi MD , Anita Fatehi MD , Seyed-Abbas Pakmehr MD , Niloofar Deravi MD , Mahdyieh Naziri MSc , Mohaddeseh Belbasi MD , Sahar Khoshravesh MD , Seyed Hossein Vaezzadeh MD","doi":"10.1016/j.curtheres.2024.100770","DOIUrl":"10.1016/j.curtheres.2024.100770","url":null,"abstract":"<div><h3>Background</h3><div>Xerostomia, or dry mouth, is a common and debilitating symptom in patients with Sjögren's syndrome, affecting their quality of life. Although Cevimeline, a muscarinic agonist, has been investigated as a potential treatment, its efficacy and optimal dosage remain uncertain. This study aims to assess the effectiveness of Cevimeline in relieving xerostomia in patients with Sjögren's syndrome by a meta-analysis of randomized clinical trials (RCT).</div></div><div><h3>Method</h3><div>A comprehensive search was conducted across PubMed, Scopus, Cochrane, and Web of Science databases, utilizing Medical Subject Headings terms and keywords related to “cevimeline,” “xerostomia,” and “Sjögren's syndrome” from inception until January 3, 2024. Studies were selected based on predefined inclusion criteria, focusing on clinical trials involving human subjects treated with cevimeline for xerostomia in Sjögren's syndrome. Data extraction was performed systematically, and statistical analysis was conducted using STATA software.</div></div><div><h3>Result</h3><div>This meta-analysis included three RCTs with a total of 302 patients with Sjögren's syndrome (Cevimeline = 187; Placebo = 115). The analysis demonstrated that Cevimeline significantly reduces xerostomia (regarded as salivary flow, mouth dryness) in patients with Sjögren's syndrome with a pooled odds ratio –5.79 (95% CI [–10.55, –1.03]; <em>I</em><strong><sup>2</sup></strong> = 39.6%).</div></div><div><h3>Conclusions</h3><div>In summary, cevimeline significantly increases salivary flow secretion rates in patients with Sjögren's syndrome. With a favorable safety profile at recommended dosages, cevimeline represents a viable therapeutic option for managing xerostomia, particularly in patients with mild to moderate salivary gland destruction.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100770"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045872","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}
Pub Date : 2025-01-01DOI: 10.1016/j.curtheres.2025.100801
Mohammad Khairy El-Badrawy MD , Rehab Ahmad Elmorsey MD , Mahmoud Mostafa Elhosiny MD , Mohammed Shehta MD , Tamer Ali El-Hadidy MD , Ibrahim El-Said Abdelwahab MD , Adel El-Badrawy MD , Ahmed A. Shokeir MD
Background
Entry of severe acute respiratory syndrome coronavirus 2 into a host cell is pH-dependent. Hence, intracellular alkalinization by nebulized sodium bicarbonate could elevate endosomal pH and then block viral entry into the host cells.
Objective
To study the efficacy of nebulized sodium bicarbonate as an adjuvant treatment for coronavirus disease 2019 (COVID-19).
Methods
A prospective, randomized, double-blinded trial was conducted in Mansoura University Hospital, Egypt. Eligible patients were >18 years old with all COVID-19 severities. Patients were electronically randomly assigned (1:1) to receive standard treatment only (control group) (274 patients) or standard treatment plus nebulized sodium bicarbonate (272 patients). The primary end points were time to clinical improvement, defined as number of days from diagnosis until reporting of a better feeling by the patients; length of hospital stay for admitted patients; and mortality. This study was registered at ClinicalTrials.gov (NCT05035524) on September 2, 2021, and has been completed.
Results
Between September 2, 2021, and April 30, 2022, 546 patients (215 men and 331 women) were enrolled and randomly allocated for treatment. Mean (SD) age was 50.7 (16.8) years. Study showed a significantly shorter time to clinical improvement and length of hospital stay in the study group (P < 0.001), and the number of deaths was significantly low only in the severe grade of the study group (11 cases in the study group vs 22 cases in the control group, P = 0.014). C-reactive protein and D-dimer levels measured at 1 week were significantly lower in the severe cases of the study group (P = 0.001). The overall median computed tomography score was significantly better in the study group at all points of follow-up (P < 0.05). All patients reported mild irritative cough initially with sodium bicarbonate inhalation. No serious treatment adverse events were observed.
Conclusions
Nebulized sodium bicarbonate (8.4%) could be a possible adjuvant therapy for patients with moderate and severe COVID‑19. ClinicalTrials.gov identifier: NCT05035524.
{"title":"Efficacy and Safety of Nebulized Sodium Bicarbonate in Adults with COVID-19 (SODIC): A Randomized, Single-Center, Double-Blinded, Controlled Trial","authors":"Mohammad Khairy El-Badrawy MD , Rehab Ahmad Elmorsey MD , Mahmoud Mostafa Elhosiny MD , Mohammed Shehta MD , Tamer Ali El-Hadidy MD , Ibrahim El-Said Abdelwahab MD , Adel El-Badrawy MD , Ahmed A. Shokeir MD","doi":"10.1016/j.curtheres.2025.100801","DOIUrl":"10.1016/j.curtheres.2025.100801","url":null,"abstract":"<div><h3>Background</h3><div>Entry of severe acute respiratory syndrome coronavirus 2 into a host cell is pH-dependent. Hence, intracellular alkalinization by nebulized sodium bicarbonate could elevate endosomal pH and then block viral entry into the host cells.</div></div><div><h3>Objective</h3><div>To study the efficacy of nebulized sodium bicarbonate as an adjuvant treatment for coronavirus disease 2019 (COVID-19).</div></div><div><h3>Methods</h3><div>A prospective, randomized, double-blinded trial was conducted in Mansoura University Hospital, Egypt. Eligible patients were >18 years old with all COVID-19 severities. Patients were electronically randomly assigned (1:1) to receive standard treatment only (control group) (274 patients) or standard treatment plus nebulized sodium bicarbonate (272 patients). The primary end points were time to clinical improvement, defined as number of days from diagnosis until reporting of a better feeling by the patients; length of hospital stay for admitted patients; and mortality. This study was registered at ClinicalTrials.gov (NCT05035524) on September 2, 2021, and has been completed.</div></div><div><h3>Results</h3><div>Between September 2, 2021, and April 30, 2022, 546 patients (215 men and 331 women) were enrolled and randomly allocated for treatment. Mean (SD) age was 50.7 (16.8) years. Study showed a significantly shorter time to clinical improvement and length of hospital stay in the study group (<em>P</em> < 0.001), and the number of deaths was significantly low only in the severe grade of the study group (11 cases in the study group vs 22 cases in the control group, <em>P</em> = 0.014). C-reactive protein and D-dimer levels measured at 1 week were significantly lower in the severe cases of the study group (<em>P</em> = 0.001). The overall median computed tomography score was significantly better in the study group at all points of follow-up (<em>P</em> < 0.05). All patients reported mild irritative cough initially with sodium bicarbonate inhalation. No serious treatment adverse events were observed.</div></div><div><h3>Conclusions</h3><div>Nebulized sodium bicarbonate (8.4%) could be a possible adjuvant therapy for patients with moderate and severe COVID‑19. ClinicalTrials.gov identifier: NCT05035524.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100801"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.curtheres.2025.100782
Ahmed Nouri PharmD, MSc
Background
Mobile health applications have become essential tools in modern healthcare, enabling professionals to access real-time drug information, clinical guidelines, and patient management resources. While globally embraced, the adoption of these apps in resource-limited settings like Palestine remains under-researched, particularly among community pharmacists, who are pivotal to the healthcare system.
Aims
This study explores the perceptions, awareness, and challenges faced by Palestinian community pharmacists regarding mobile health applications. It aims to assess the feasibility of integrating these tools into their practice to improve pharmaceutical care and patient outcomes.
Methods
A cross-sectional online survey was conducted in 2023 among community pharmacists in Palestine. A self-administered electronic questionnaire was distributed via social media, targeting registered pharmacists. Data were collected using a structured, validated questionnaire addressing demographics, app usage patterns, perceived benefits, and barriers. Descriptive and inferential analyses were performed using SPSS® software, with P-values ≤0.05 considered statistically significant.
Results
The study included 400 community pharmacists, predominantly female (65.8%). Pharmacists frequently used information resources for verifying drug interactions (89%) and dosages (98%), citing quick access to reliable information as a major advantage. Barriers included time constraints (92.3%) and concerns about patient trust (77.8%). No significant associations were found between demographics (e.g., gender, years of experience) and perceptions of app usefulness or trust. A strong positive correlation (P < 0.001) was observed between community pharmacists’ support for mobile health applications and their perception of the applications’ reliability. This indicates that pharmacists who perceive mobile apps as reliable are more likely to support their use in practice.
Conclusion
Limited app use among Palestinian community pharmacists impacts medication safety, patient trust, and care quality. Adopting mobile tools can improve efficiency, reduce errors, and align pharmacy practice with modern standards, highlighting the need for future research.
{"title":"Exploring the Use of Mobile Health Applications in Palestinian Community Pharmacy Practice","authors":"Ahmed Nouri PharmD, MSc","doi":"10.1016/j.curtheres.2025.100782","DOIUrl":"10.1016/j.curtheres.2025.100782","url":null,"abstract":"<div><h3>Background</h3><div>Mobile health applications have become essential tools in modern healthcare, enabling professionals to access real-time drug information, clinical guidelines, and patient management resources. While globally embraced, the adoption of these apps in resource-limited settings like Palestine remains under-researched, particularly among community pharmacists, who are pivotal to the healthcare system.</div></div><div><h3>Aims</h3><div>This study explores the perceptions, awareness, and challenges faced by Palestinian community pharmacists regarding mobile health applications. It aims to assess the feasibility of integrating these tools into their practice to improve pharmaceutical care and patient outcomes.</div></div><div><h3>Methods</h3><div>A cross-sectional online survey was conducted in 2023 among community pharmacists in Palestine. A self-administered electronic questionnaire was distributed via social media, targeting registered pharmacists. Data were collected using a structured, validated questionnaire addressing demographics, app usage patterns, perceived benefits, and barriers. Descriptive and inferential analyses were performed using SPSS® software, with P-values ≤0.05 considered statistically significant.</div></div><div><h3>Results</h3><div>The study included 400 community pharmacists, predominantly female (65.8%). Pharmacists frequently used information resources for verifying drug interactions (89%) and dosages (98%), citing quick access to reliable information as a major advantage. Barriers included time constraints (92.3%) and concerns about patient trust (77.8%). No significant associations were found between demographics (e.g., gender, years of experience) and perceptions of app usefulness or trust. A strong positive correlation (<em>P</em> < 0.001) was observed between community pharmacists’ support for mobile health applications and their perception of the applications’ reliability. This indicates that pharmacists who perceive mobile apps as reliable are more likely to support their use in practice.</div></div><div><h3>Conclusion</h3><div>Limited app use among Palestinian community pharmacists impacts medication safety, patient trust, and care quality. Adopting mobile tools can improve efficiency, reduce errors, and align pharmacy practice with modern standards, highlighting the need for future research.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100782"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684679","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}
Patients with hereditary transthyretin (ATTRv) amyloidosis experience progressive degeneration of the somatic and peripheral nervous system that can impair ambulation, autonomy, and quality of life (QOL). Tafamidis meglumine (tafamidis) is the first pharmacotherapy approved to slow the progression of peripheral neurological impairment in ATTRv amyloidosis and was well tolerated and efficacious in clinical trials; however, longer-term safety in Japanese patients with ATTRv amyloidosis has not been fully elucidated. Consequently, the present study was conducted to understand the safety and efficacy of long-term use (up to 156 weeks) of tafamidis meglumine under postmarketing conditions in Japan.
Methods
This single-arm observational study (conducted from November 2013 to May 2021) included all patients prescribed tafamidis (20 mg/day) for the treatment of ATTRv amyloidosis in routine clinical practice. The observation period was 156 weeks (3 years) following tafamidis initiation (78 weeks [1.5 years] for patients who initiated treatment after May 2018). The outcomes of interest were clinical characteristics of patients, tafamidis utilization patterns, adverse drug reactions (ADRs), serious ADRs (safety analysis set), and efficacy (Neuropathy Impairment Score–Lower Limbs [NIS-LL] score, total QOL [TQOL] score, modified body mass index [mBMI], and ambulatory status; efficacy analysis set).
Findings
A total of 400 and 397 patients were included in the safety and efficacy analysis sets, respectively. The mean ± standard deviation (SD) age was 61.5 ± 15.0 years, 65.5% were male, 57.3% were aged ≥50 years at disease onset, 71.0% were from nonendemic areas, and 10.3% had Karnofsky Performance Status 40 to 10. A total of 212 (53.0%) patients were treated with tafamidis for >156 weeks (mean ± SD treatment duration: 120.8 ± 56.4 weeks) and 145 (36.3%) patients discontinued the study, with the reasons for discontinuation (duplicate) being adverse events (n = 46), hospital transfer (n = 33), loss to follow-up (n = 15), insufficient clinical response (n = 9), and others (n = 62). ADRs and serious ADRs were reported in 58 (14.5%) and 12 (3.0%) patients, respectively. In the efficacy analysis set, NIS-LL score, TQOL score, mBMI, and ambulatory status after 156 weeks of treatment were comparable to those reported prior to tafamidis initiation.
Implications
The findings of this study indicate that late-onset cases of ATTRv amyloidosis and those that originate from nonendemic areas may be more prevalent in Japan than historically believed. The safety profile of tafamidis was largely consistent with that obtained from previous research, and no new safety concerns were identified. The efficacy of tafamidis was also demonstrated in the real-world clinical setting.
{"title":"Real-World Utilization Patterns, Safety, and Efficacy of Tafamidis in Patients With Hereditary Transthyretin Amyloidosis in Japan","authors":"Hiroaki Konishi PharmD , Hajime Abe MD, PhD , Noriko Matsumoto , Yutaka Endo , Yoshiki Sekijima MD, PhD , Mitsuharu Ueda MD, PhD , Yukio Ando MD, PhD","doi":"10.1016/j.curtheres.2025.100793","DOIUrl":"10.1016/j.curtheres.2025.100793","url":null,"abstract":"<div><h3>Purpose</h3><div>Patients with hereditary transthyretin (ATTRv) amyloidosis experience progressive degeneration of the somatic and peripheral nervous system that can impair ambulation, autonomy, and quality of life (QOL). Tafamidis meglumine (tafamidis) is the first pharmacotherapy approved to slow the progression of peripheral neurological impairment in ATTRv amyloidosis and was well tolerated and efficacious in clinical trials; however, longer-term safety in Japanese patients with ATTRv amyloidosis has not been fully elucidated. Consequently, the present study was conducted to understand the safety and efficacy of long-term use (up to 156 weeks) of tafamidis meglumine under postmarketing conditions in Japan.</div></div><div><h3>Methods</h3><div>This single-arm observational study (conducted from November 2013 to May 2021) included all patients prescribed tafamidis (20 mg/day) for the treatment of ATTRv amyloidosis in routine clinical practice. The observation period was 156 weeks (3 years) following tafamidis initiation (78 weeks [1.5 years] for patients who initiated treatment after May 2018). The outcomes of interest were clinical characteristics of patients, tafamidis utilization patterns, adverse drug reactions (ADRs), serious ADRs (safety analysis set), and efficacy (Neuropathy Impairment Score–Lower Limbs [NIS-LL] score, total QOL [TQOL] score, modified body mass index [mBMI], and ambulatory status; efficacy analysis set).</div></div><div><h3>Findings</h3><div>A total of 400 and 397 patients were included in the safety and efficacy analysis sets, respectively. The mean ± standard deviation (SD) age was 61.5 ± 15.0 years, 65.5% were male, 57.3% were aged ≥50 years at disease onset, 71.0% were from nonendemic areas, and 10.3% had Karnofsky Performance Status 40 to 10. A total of 212 (53.0%) patients were treated with tafamidis for >156 weeks (mean ± SD treatment duration: 120.8 ± 56.4 weeks) and 145 (36.3%) patients discontinued the study, with the reasons for discontinuation (duplicate) being adverse events (<em>n</em> = 46), hospital transfer (<em>n</em> = 33), loss to follow-up (<em>n</em> = 15), insufficient clinical response (<em>n</em> = 9), and others (<em>n</em> = 62). ADRs and serious ADRs were reported in 58 (14.5%) and 12 (3.0%) patients, respectively. In the efficacy analysis set, NIS-LL score, TQOL score, mBMI, and ambulatory status after 156 weeks of treatment were comparable to those reported prior to tafamidis initiation.</div></div><div><h3>Implications</h3><div>The findings of this study indicate that late-onset cases of ATTRv amyloidosis and those that originate from nonendemic areas may be more prevalent in Japan than historically believed. The safety profile of tafamidis was largely consistent with that obtained from previous research, and no new safety concerns were identified. The efficacy of tafamidis was also demonstrated in the real-world clinical setting.</div></div><div><h3>Clinical trial registration","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100793"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.curtheres.2025.100813
Simon Eng MD , Michael Fetell MD , Haitao Gao PhD , Jingning Mei PhD , Jesus Trejos MSc, PhD , Luz Cortes-Burgos MSc , Tina Ho PharmD , Garen Manvelian MD , Yamini Patel PhD , Ngan Trinh MBA , Kenneth C. Turner PhD , Hazem E. Hassan PhD, RPh, FCP , Stephen DiMartino MD, PhD , Pamela Krueger BSc , Gregory P. Geba MD, DrPH , Ned Braunstein MD , Lynn E. Macdonald PhD , Randy Soltys PhD , Susan D. Croll PhD , Paula Dakin MBChB
Purpose
Osteoarthritis (OA) is a chronic disease where breakdown and loss of cartilage leads to pain, primarily in the joints. Nerve growth factor inhibitors (eg, fasinumab) can reduce pain, but have been associated with nervous system adverse events (AEs). Here we describe the results of a Phase 2, randomized, double-blind, placebo-controlled study and a series of nonclinical analyses investigating the effects of fasinumab on peripheral nerve function and ganglion anatomy.
Methods
In the Phase 2 study, 180 adults with knee or hip OA and moderate-to-severe pain inadequately controlled with analgesics, who could not tolerate/were unwilling to take opioids, received subcutaneous fasinumab 1 mg every 4 weeks or placebo for 12 weeks. The primary endpoint was change from baseline to Week 16 in conduction velocity and amplitude for the peroneal, sural, and ulnar nerves. Secondary endpoints included peripheral sensory events. The nonclinical analyses involved adult and developing Sprague-Dawley rats and developing cynomolgus monkeys; endpoints included baseline and isoproterenol‑induced hemodynamic parameters, dorsal root ganglia (DRG) and superior cervical ganglia (SCG) volumes, neuron volumes and counts, and volumes and counts of specific neural subsets.
Findings
In the Phase 2 study, nerve conduction velocities and action potential amplitudes between baseline and Week 16 were generally within normal ranges. There were no compelling differences in nerve conduction tests between fasinumab- and placebo-treated patients. Incidences of AEs, including peripheral sensory AEs, were similar between fasinumab and placebo. In the nonclinical analyses, neither hemodynamic parameters nor DRG and SCG stereological parameters were statistically significantly different between fasinumab-treated and isotype control antibody–treated rats.
Implications
No clinically meaningful differences were observed between fasinumab- and placebo-treated patients for nerve conduction velocities and action potential amplitudes. In the nonclinical studies, no significant changes could be detected in adult rat ganglion anatomical parameters or hemodynamic parameters at a variety of fasinumab doses. Results from these studies demonstrated that fasinumab did not affect the tested nervous system parameters in adult humans or rats.
{"title":"The Effects of Fasinumab on Peripheral Nerve Function and Ganglion Anatomy: Results From a Randomized, Double-Blind, Placebo-Controlled Study in Patients With Pain Due to Osteoarthritis of the Knee or Hip, and a Series of Nonclinical Studies","authors":"Simon Eng MD , Michael Fetell MD , Haitao Gao PhD , Jingning Mei PhD , Jesus Trejos MSc, PhD , Luz Cortes-Burgos MSc , Tina Ho PharmD , Garen Manvelian MD , Yamini Patel PhD , Ngan Trinh MBA , Kenneth C. Turner PhD , Hazem E. Hassan PhD, RPh, FCP , Stephen DiMartino MD, PhD , Pamela Krueger BSc , Gregory P. Geba MD, DrPH , Ned Braunstein MD , Lynn E. Macdonald PhD , Randy Soltys PhD , Susan D. Croll PhD , Paula Dakin MBChB","doi":"10.1016/j.curtheres.2025.100813","DOIUrl":"10.1016/j.curtheres.2025.100813","url":null,"abstract":"<div><h3>Purpose</h3><div>Osteoarthritis (OA) is a chronic disease where breakdown and loss of cartilage leads to pain, primarily in the joints. Nerve growth factor inhibitors (eg, fasinumab) can reduce pain, but have been associated with nervous system adverse events (AEs). Here we describe the results of a Phase 2, randomized, double-blind, placebo-controlled study and a series of nonclinical analyses investigating the effects of fasinumab on peripheral nerve function and ganglion anatomy.</div></div><div><h3>Methods</h3><div>In the Phase 2 study, 180 adults with knee or hip OA and moderate-to-severe pain inadequately controlled with analgesics, who could not tolerate/were unwilling to take opioids, received subcutaneous fasinumab 1 mg every 4 weeks or placebo for 12 weeks. The primary endpoint was change from baseline to Week 16 in conduction velocity and amplitude for the peroneal, sural, and ulnar nerves. Secondary endpoints included peripheral sensory events. The nonclinical analyses involved adult and developing Sprague-Dawley rats and developing cynomolgus monkeys; endpoints included baseline and isoproterenol‑induced hemodynamic parameters, dorsal root ganglia (DRG) and superior cervical ganglia (SCG) volumes, neuron volumes and counts, and volumes and counts of specific neural subsets.</div></div><div><h3>Findings</h3><div>In the Phase 2 study, nerve conduction velocities and action potential amplitudes between baseline and Week 16 were generally within normal ranges. There were no compelling differences in nerve conduction tests between fasinumab- and placebo-treated patients. Incidences of AEs, including peripheral sensory AEs, were similar between fasinumab and placebo. In the nonclinical analyses, neither hemodynamic parameters nor DRG and SCG stereological parameters were statistically significantly different between fasinumab-treated and isotype control antibody–treated rats.</div></div><div><h3>Implications</h3><div>No clinically meaningful differences were observed between fasinumab- and placebo-treated patients for nerve conduction velocities and action potential amplitudes. In the nonclinical studies, no significant changes could be detected in adult rat ganglion anatomical parameters or hemodynamic parameters at a variety of fasinumab doses. Results from these studies demonstrated that fasinumab did not affect the tested nervous system parameters in adult humans or rats.</div><div>Trial registration number: NCT02447276; <span><span>https://clinicaltrials.gov/study/NCT02447276</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100813"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.curtheres.2024.100769
Miaoyu Zhang, Lingling Zhong
Background
As the global population ages, frailty-marked by diminished physiological reserves and increased vulnerability, poses significant health risks such as falls, hospitalization, and mortality. Exercise therapy, enhancing muscle strength and balance, has shown promise in mitigating frailty's effects, while nursing interventions ensure tailored, comprehensive care. However, the combined impact of these interventions remains underexplored. This study investigates the clinical effectiveness of integrating active exercise with nursing interventions to manage frailty in elderly patients, aiming to improve their physical function and quality of life.
Methods
This retrospective study analyzed 100 elderly patients (≥80 years) admitted to our hospital with mild to moderate frailty. Participants were randomly assigned to either a control group (n = 50), receiving a standard exercise program, or an experimental group (n = 50), receiving the same program with personalized interventions under nursing assistance. Assessments were conducted at baseline and at 1, 3, 6, and 12 months. Outcome measures included assessing functional mobility, physical dependence in activities of daily living (ADLs), balance, muscle strength, degree of frailty and patient satisfaction with the nursing care.
Results
There were no significant differences in the baseline characteristics between the two groups (P ˃ 0.05). However, both groups exhibited significant improvements from baseline in functional mobility (P < 0.001), physical dependence in ADLs (P < 0.001), balance (P < 0.001), muscle strength (P < 0.001), and degree of frailty (P < 0.001). Importantly, from 3 months onward, the experimental group showed significantly greater improvements in all these parameters compared to the control group (P < 0.001 for each measure). Additionally, patient satisfaction was higher in the experimental group, with a satisfaction rate of 94.0% compared to 72.0% in the control group (P = 0.013).
Conclusions
This study demonstrates that combining active exercise with nursing interventions significantly improves physical performance, independence, balance, muscle strength, and reduces frailty in elderly patients. Furthermore, the high levels of patient satisfaction underscore the effectiveness and favorable reception of this intervention. These findings suggest that the implemented interventions can be a valuable approach in improving the overall health and well-being of elderly patients with frailty.
{"title":"Assessing the Impact of Frailty Interventions on Older Patients With Frailty","authors":"Miaoyu Zhang, Lingling Zhong","doi":"10.1016/j.curtheres.2024.100769","DOIUrl":"10.1016/j.curtheres.2024.100769","url":null,"abstract":"<div><h3>Background</h3><div>As the global population ages, frailty-marked by diminished physiological reserves and increased vulnerability, poses significant health risks such as falls, hospitalization, and mortality. Exercise therapy, enhancing muscle strength and balance, has shown promise in mitigating frailty's effects, while nursing interventions ensure tailored, comprehensive care. However, the combined impact of these interventions remains underexplored. This study investigates the clinical effectiveness of integrating active exercise with nursing interventions to manage frailty in elderly patients, aiming to improve their physical function and quality of life.</div></div><div><h3>Methods</h3><div>This retrospective study analyzed 100 elderly patients (≥80 years) admitted to our hospital with mild to moderate frailty. Participants were randomly assigned to either a control group (n = 50), receiving a standard exercise program, or an experimental group (n = 50), receiving the same program with personalized interventions under nursing assistance. Assessments were conducted at baseline and at 1, 3, 6, and 12 months. Outcome measures included assessing functional mobility, physical dependence in activities of daily living (ADLs), balance, muscle strength, degree of frailty and patient satisfaction with the nursing care.</div></div><div><h3>Results</h3><div>There were no significant differences in the baseline characteristics between the two groups (<em>P</em> ˃ 0.05). However, both groups exhibited significant improvements from baseline in functional mobility (<em>P</em> < 0.001), physical dependence in ADLs (<em>P</em> < 0.001), balance (<em>P</em> < 0.001), muscle strength (<em>P</em> < 0.001), and degree of frailty (<em>P</em> < 0.001). Importantly, from 3 months onward, the experimental group showed significantly greater improvements in all these parameters compared to the control group (<em>P</em> < 0.001 for each measure). Additionally, patient satisfaction was higher in the experimental group, with a satisfaction rate of 94.0% compared to 72.0% in the control group (<em>P</em> = 0.013).</div></div><div><h3>Conclusions</h3><div>This study demonstrates that combining active exercise with nursing interventions significantly improves physical performance, independence, balance, muscle strength, and reduces frailty in elderly patients. Furthermore, the high levels of patient satisfaction underscore the effectiveness and favorable reception of this intervention. These findings suggest that the implemented interventions can be a valuable approach in improving the overall health and well-being of elderly patients with frailty.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100769"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.curtheres.2025.100806
Sara Aravand MSc , Azam J. Esfahani PhD , Nematollah Gheibi PhD , Saeideh G. Khoei PhD , Shaghayegh P. Dibazar MSc , Leila Zolghadr PhD , Hossein Ahmadpour_Yazdi PhD
Background
Propolis holds great potential in therapeutic development due to the presence of flavonoids, phenolic acids, and esters. However, its chemical composition has restricted its solubility and bioaccessibility. Here, we synthesized responsive Iranian propolis nanoparticles derived from 3 distinct regions of Iran, representing the first comparative investigation of their anticancer effects against AGS gastric cancer cells.
Methods
Propolis was collected from 3 different regions of Iran. Iranian propolis extract (IPE) was prepared using Bosio method. Quantitative and qualitative analyses were performed. Using the probe sonication, Iranian propolis nanoparticles (IPNs) were prepared. Identification tests of IPNs were performed with dynamic light scattering (DLS)-Zetasizer methods. Next, the anticancer potential of IPNs was analyzed by measuring the cell survival rate on the AGS gastric cancer cell line by MTT assay. Also, the IPNs apoptotic activity was evaluated using Annexin V/FITC-propidium iodide (PI) flow cytometry.
Results
Analysis of the IPE showed the presence of paracoumaric acid and caffeic acid predominantly. An average IPNs size was obtained from 8 to 15 nm with good stability and cellular uptake. Compared with IPE, IPNs showed a greater effect on AGS gastric cancer cell survival inhibition after 24 and 48 h. The IC50 values of cancer cells treated with IPE and IPNs were calculated as 76.55 and 43.26 µg/ml for 24 h and 63.26 and 12.14 µg/ml for 48 h respectively. The flow cytometry results showed that the apoptosis induced by IPNs was greater than the control cells.
Conclusions
Our study indicated that the IPNs can be more effective than IPE in reducing AGS cell viability and increasing apoptosis. These results suggest the potential of IPNs as low-toxicity nanocarriers for gastric cancer therapy, although further in vivo studies are required to validate their therapeutic potential and assess their pharmacokinetic properties.
{"title":"Anti-Gastric Cancer Activity of Mixed-Region Iranian Propolis Nanoparticles: Potential Therapeutic Applications","authors":"Sara Aravand MSc , Azam J. Esfahani PhD , Nematollah Gheibi PhD , Saeideh G. Khoei PhD , Shaghayegh P. Dibazar MSc , Leila Zolghadr PhD , Hossein Ahmadpour_Yazdi PhD","doi":"10.1016/j.curtheres.2025.100806","DOIUrl":"10.1016/j.curtheres.2025.100806","url":null,"abstract":"<div><h3>Background</h3><div>Propolis holds great potential in therapeutic development due to the presence of flavonoids, phenolic acids, and esters. However, its chemical composition has restricted its solubility and bioaccessibility. Here, we synthesized responsive Iranian propolis nanoparticles derived from 3 distinct regions of Iran, representing the first comparative investigation of their anticancer effects against AGS gastric cancer cells.</div></div><div><h3>Methods</h3><div>Propolis was collected from 3 different regions of Iran. Iranian propolis extract (IPE) was prepared using Bosio method. Quantitative and qualitative analyses were performed. Using the probe sonication, Iranian propolis nanoparticles (IPNs) were prepared. Identification tests of IPNs were performed with dynamic light scattering (DLS)-Zetasizer methods. Next, the anticancer potential of IPNs was analyzed by measuring the cell survival rate on the AGS gastric cancer cell line by MTT assay. Also, the IPNs apoptotic activity was evaluated using Annexin V/FITC-propidium iodide (PI) flow cytometry.</div></div><div><h3>Results</h3><div>Analysis of the IPE showed the presence of paracoumaric acid and caffeic acid predominantly. An average IPNs size was obtained from 8 to 15 nm with good stability and cellular uptake. Compared with IPE, IPNs showed a greater effect on AGS gastric cancer cell survival inhibition after 24 and 48 h. The IC50 values of cancer cells treated with IPE and IPNs were calculated as 76.55 and 43.26 µg/ml for 24 h and 63.26 and 12.14 µg/ml for 48 h respectively. The flow cytometry results showed that the apoptosis induced by IPNs was greater than the control cells.</div></div><div><h3>Conclusions</h3><div>Our study indicated that the IPNs can be more effective than IPE in reducing AGS cell viability and increasing apoptosis. These results suggest the potential of IPNs as low-toxicity nanocarriers for gastric cancer therapy, although further in vivo studies are required to validate their therapeutic potential and assess their pharmacokinetic properties.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100806"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.curtheres.2025.100814
Randal Goldberg MD , Lucy Norcliffe-Kaufmann PhD , Horacio Kaufmann MD , Ikoa Jeschke-Lopez MD , Yu Guo MS , Judy Zhong PhD , Kenneth I. Berger MD , Roberta M. Goldring MD , David S. Goldstein MD, PhD , Carey Pope PhD , Lara Maxwell DVM, PhD , Manushree Bharadwaj PhD , Alex Reyentovich MD , Stuart D. Katz MD, MS
Background
Pyridostigmine bromide is a short-acting carbamate acetylcholinesterase inhibitor that has been shown to acutely augment parasympathetic signaling in cardiovascular disease populations.
Objective
This study was undertaken to characterize pharmacodynamics, safety, and tolerability of pyridostigmine during repeated dosing in patients with heart failure.
Methods
A prospective ascending-dose, forced titration, double-blind Phase II randomized clinical trial was conducted to compare the effects of pyridostigmine bromide (15, 30, and 60 mg TID over 8 weeks) versus matching placebo on red blood cell (RBC) acetylcholinesterase activity, cholinergic side effects, and physiologic measures of parasympathetic heart rate modulation and sympathovagal balance in ambulatory patients with chronic systolic heart failure.
Results
Fifty subjects were screened, and 33 eligible subjects were randomly assigned (mean age, 55 years; mean left ventricular ejection fraction, 23%). Pyridostigmine bromide significantly decreased RBC acetylcholinesterase activity (P < 0.02 vs placebo) and increased the frequency of participant-reported cholinergic excess symptoms (P < 0.001 vs placebo). Physiologic measures of parasympathetic heart rate modulation and sympathovagal balance did not differ between treatment groups. In the pyridostigmine bromide group, RBC acetylcholinesterase activity was not significantly associated with postexercise parasympathetic heart modulation.
Conclusions
Pyridostigmine bromide administered over 8 weeks was associated with a significant reduction of RBC acetylcholinesterase activity and relatively mild symptoms of cholinergic excess, but changes in parasympathetic signaling in the sinoatrial node previously reported after acute administration were not observed. Further investigations are needed to delineate pharmacodynamic and pathobiological factors contributing to these findings. ClinicalTrials.gov identifier: NCT01415921.
{"title":"Pharmacodynamics, Safety, and Tolerability of Pyridostigmine Bromide in Heart Failure","authors":"Randal Goldberg MD , Lucy Norcliffe-Kaufmann PhD , Horacio Kaufmann MD , Ikoa Jeschke-Lopez MD , Yu Guo MS , Judy Zhong PhD , Kenneth I. Berger MD , Roberta M. Goldring MD , David S. Goldstein MD, PhD , Carey Pope PhD , Lara Maxwell DVM, PhD , Manushree Bharadwaj PhD , Alex Reyentovich MD , Stuart D. Katz MD, MS","doi":"10.1016/j.curtheres.2025.100814","DOIUrl":"10.1016/j.curtheres.2025.100814","url":null,"abstract":"<div><h3>Background</h3><div>Pyridostigmine bromide is a short-acting carbamate acetylcholinesterase inhibitor that has been shown to acutely augment parasympathetic signaling in cardiovascular disease populations.</div></div><div><h3>Objective</h3><div>This study was undertaken to characterize pharmacodynamics, safety, and tolerability of pyridostigmine during repeated dosing in patients with heart failure.</div></div><div><h3>Methods</h3><div>A prospective ascending-dose, forced titration, double-blind Phase II randomized clinical trial was conducted to compare the effects of pyridostigmine bromide (15, 30, and 60 mg TID over 8 weeks) versus matching placebo on red blood cell (RBC) acetylcholinesterase activity, cholinergic side effects, and physiologic measures of parasympathetic heart rate modulation and sympathovagal balance in ambulatory patients with chronic systolic heart failure.</div></div><div><h3>Results</h3><div>Fifty subjects were screened, and 33 eligible subjects were randomly assigned (mean age, 55 years; mean left ventricular ejection fraction, 23%). Pyridostigmine bromide significantly decreased RBC acetylcholinesterase activity (<em>P</em> < 0.02 vs placebo) and increased the frequency of participant-reported cholinergic excess symptoms (<em>P</em> < 0.001 vs placebo). Physiologic measures of parasympathetic heart rate modulation and sympathovagal balance did not differ between treatment groups. In the pyridostigmine bromide group, RBC acetylcholinesterase activity was not significantly associated with postexercise parasympathetic heart modulation.</div></div><div><h3>Conclusions</h3><div>Pyridostigmine bromide administered over 8 weeks was associated with a significant reduction of RBC acetylcholinesterase activity and relatively mild symptoms of cholinergic excess, but changes in parasympathetic signaling in the sinoatrial node previously reported after acute administration were not observed. Further investigations are needed to delineate pharmacodynamic and pathobiological factors contributing to these findings. ClinicalTrials.gov identifier: NCT01415921.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100814"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diabetic wounds, characterized by their chronic nature, represent a critical challenge for patients with diabetes, often leading to amputation and mortality. Although stem cells show great promise, their use is limited by challenges related to stability and tumorigenicity. The secretome of stem cells, comprising molecules released by these cells, offers a potential alternative to the challenges associated with stem cell therapy and provides a promising solution for diabetic wound healing.
Objective
We conducted a systematic review and meta-analysis of relevant preclinical studies to evaluate the effectiveness of stem cell secretomes in treating diabetic wounds.
Methods
The protocol registration for this systematic review and meta-analysis was recorded in the PROSPERO database (CRD42023473726). Databases were searched from their inception until November 20, 2023. The quality assessment of the included studies was performed utilizing the CAMARADES 10-item Quality Checklist. Statistical analyses were conducted using a random-effects model to calculate standardized mean differences (SMD) and 95% confidence intervals (CI), with heterogeneity assessed via the I² statistic. The primary outcome evaluated was the wound closure rate, while secondary outcomes included parameters such as the number of fibroblasts, neutrophils, and macrophages.
Results
Twenty studies were included, comprising 382 animal subjects, and five of which were eligible for quantitative evaluation in a meta-analysis. The stem cell secretome significantly improved the wound closure rate (SMD = 9.63; 95% CI = 2.01 −17.25; P = 0.01, I2 = 76%) and reduced the number of neutrophils (SMD = −8.47; 95% CI = −13.05 to −3.90; P = 0.0003) and macrophages (SMD = −5.32; 95% CI = −9.09 to −1.55; P = 0.006).
Conclusion
This review suggests that stem cell secretomes have potential as a novel therapeutic strategy for diabetic wound healing, enhancing wound closure rates and reducing inflammation. These findings support the use of stem cell secretomes as a safer and more stable alternative to direct stem cell therapy, but further clinical studies are needed to confirm these results in human patients.
糖尿病伤口以其慢性性质为特征，对糖尿病患者来说是一个严峻的挑战，经常导致截肢和死亡。尽管干细胞显示出巨大的前景，但其应用受到稳定性和致瘤性方面的挑战的限制。干细胞分泌组由这些细胞释放的分子组成，为干细胞治疗相关的挑战提供了一个潜在的替代方案，并为糖尿病伤口愈合提供了一个有希望的解决方案。目的对相关临床前研究进行系统回顾和荟萃分析，评价干细胞分泌组治疗糖尿病创面的有效性。方法本系统评价和荟萃分析的方案注册记录在PROSPERO数据库（CRD42023473726）中。数据库从建立到2023年11月20日被搜索。采用CAMARADES 10项质量检查表对纳入的研究进行质量评估。采用随机效应模型进行统计分析，计算标准化平均差异（SMD）和95%置信区间（CI），并通过I²统计量评估异质性。评估的主要结局是伤口愈合率，次要结局包括成纤维细胞、中性粒细胞和巨噬细胞数量等参数。结果纳入20项研究，包括382名动物受试者，其中5项符合meta分析的定量评价标准。干细胞分泌组显著提高创面愈合率(SMD = 9.63；95% ci = 2.01−17.25；P = 0.01, I2 = 76%)，中性粒细胞数量减少(SMD =−8.47；95% CI =−13.05 ~−3.90；P = 0.0003)和巨噬细胞(SMD =−5.32；95% CI =−9.09 ~−1.55；p = 0.006)。结论干细胞分泌组有潜力作为糖尿病创面愈合的新治疗策略，提高创面愈合率，减少炎症。这些发现支持使用干细胞分泌组作为直接干细胞治疗的更安全、更稳定的替代方法，但需要进一步的临床研究来证实这些结果在人类患者中的应用。
{"title":"The Effect of Stem Cell Secretome on the Improvement of Diabetic Wound Recovery: A Systematic Review and Meta-Analysis of In Vivo Studies","authors":"Cecep Suhandi MSc , Gofarana Wilar PhD , Khaled M. Elamin PhD , Audry Rahma Dewayani BSc , Salsabil Ghaliya BSc , Astriani Abdullah BSc , Nasrul Wathoni PhD","doi":"10.1016/j.curtheres.2025.100778","DOIUrl":"10.1016/j.curtheres.2025.100778","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic wounds, characterized by their chronic nature, represent a critical challenge for patients with diabetes, often leading to amputation and mortality. Although stem cells show great promise, their use is limited by challenges related to stability and tumorigenicity. The secretome of stem cells, comprising molecules released by these cells, offers a potential alternative to the challenges associated with stem cell therapy and provides a promising solution for diabetic wound healing.</div></div><div><h3>Objective</h3><div>We conducted a systematic review and meta-analysis of relevant preclinical studies to evaluate the effectiveness of stem cell secretomes in treating diabetic wounds.</div></div><div><h3>Methods</h3><div>The protocol registration for this systematic review and meta-analysis was recorded in the PROSPERO database (CRD42023473726). Databases were searched from their inception until November 20, 2023. The quality assessment of the included studies was performed utilizing the CAMARADES 10-item Quality Checklist. Statistical analyses were conducted using a random-effects model to calculate standardized mean differences (SMD) and 95% confidence intervals (CI), with heterogeneity assessed via the <em>I²</em> statistic. The primary outcome evaluated was the wound closure rate, while secondary outcomes included parameters such as the number of fibroblasts, neutrophils, and macrophages.</div></div><div><h3>Results</h3><div>Twenty studies were included, comprising 382 animal subjects, and five of which were eligible for quantitative evaluation in a meta-analysis. The stem cell secretome significantly improved the wound closure rate (SMD = 9.63; 95% CI = 2.01 −17.25; <em>P</em> = 0.01, I<sup>2</sup> = 76%) and reduced the number of neutrophils (SMD = −8.47; 95% CI = −13.05 to −3.90; <em>P</em> = 0.0003) and macrophages (SMD = −5.32; 95% CI = −9.09 to −1.55; <em>P</em> = 0.006).</div></div><div><h3>Conclusion</h3><div>This review suggests that stem cell secretomes have potential as a novel therapeutic strategy for diabetic wound healing, enhancing wound closure rates and reducing inflammation. These findings support the use of stem cell secretomes as a safer and more stable alternative to direct stem cell therapy, but further clinical studies are needed to confirm these results in human patients.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100778"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526717","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}
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