Pub Date : 2024-12-01Epub Date: 2024-09-09DOI: 10.1007/s41030-024-00270-2
Nathaniel M Hawkins, Alan Kaplan, Dennis T Ko, Erika Penz, Mohit Bhutani
Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) have a syndemic relationship with shared risk factors and complex interplay between genetic, environmental, socioeconomic, and pathophysiological mechanisms. CVD is among the most common comorbidities in patients with COPD and vice versa. Patients with COPD, irrespective of their disease severity, are at increased risk of CVD morbidity and mortality, driven in part by COPD exacerbations. Despite these known interrelationships, CVD is underestimated and undertreated in patients with COPD. Similarly, COPD is an independent risk-enhancing factor for adverse cardiovascular (CV) events, yet it is not incorporated into current CV risk assessment tools, leading to under-recognition and undertreatment. There is a pressing need for systems change in COPD management to move beyond symptom control towards a comprehensive cardiopulmonary disease paradigm with proactive prevention of exacerbations and adverse cardiopulmonary outcomes and mortality. However, there is a dearth of evidence defining optimal cardiopulmonary care pathways. Fortunately, there is a precedent to support systems-level change in the field of diabetes, which evolved from glycemic control to comprehensive multi-organ risk assessment and management. Key elements included integrated multidisciplinary care, intensive risk factor management, coordination between primary and specialist care, care pathways and protocols, education and self management, and disease-modifying therapies. This commentary article draws parallels between the cardiometabolic and cardiopulmonary paradigms and makes a case for systems change towards multidisciplinary, integrated cardiopulmonary care, using the evolution in diabetes care as a potential framework.
{"title":"Is 'Cardiopulmonary' the New 'Cardiometabolic'? Making a Case for Systems Change in COPD.","authors":"Nathaniel M Hawkins, Alan Kaplan, Dennis T Ko, Erika Penz, Mohit Bhutani","doi":"10.1007/s41030-024-00270-2","DOIUrl":"10.1007/s41030-024-00270-2","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) have a syndemic relationship with shared risk factors and complex interplay between genetic, environmental, socioeconomic, and pathophysiological mechanisms. CVD is among the most common comorbidities in patients with COPD and vice versa. Patients with COPD, irrespective of their disease severity, are at increased risk of CVD morbidity and mortality, driven in part by COPD exacerbations. Despite these known interrelationships, CVD is underestimated and undertreated in patients with COPD. Similarly, COPD is an independent risk-enhancing factor for adverse cardiovascular (CV) events, yet it is not incorporated into current CV risk assessment tools, leading to under-recognition and undertreatment. There is a pressing need for systems change in COPD management to move beyond symptom control towards a comprehensive cardiopulmonary disease paradigm with proactive prevention of exacerbations and adverse cardiopulmonary outcomes and mortality. However, there is a dearth of evidence defining optimal cardiopulmonary care pathways. Fortunately, there is a precedent to support systems-level change in the field of diabetes, which evolved from glycemic control to comprehensive multi-organ risk assessment and management. Key elements included integrated multidisciplinary care, intensive risk factor management, coordination between primary and specialist care, care pathways and protocols, education and self management, and disease-modifying therapies. This commentary article draws parallels between the cardiometabolic and cardiopulmonary paradigms and makes a case for systems change towards multidisciplinary, integrated cardiopulmonary care, using the evolution in diabetes care as a potential framework.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"363-376"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154890","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 : 2024-12-01Epub Date: 2024-09-12DOI: 10.1007/s41030-024-00269-9
Christian Merlo, Teja Thorat, Lisa J McGarry, Christina V Scirica, Maral DerSarkissian, Catherine Nguyen, Yuqian M Gu, Aruna Muthukumar, Joe Healy, Jaime L Rubin, M Alan Brookhart
Introduction: Ivacaftor (IVA) has been shown to change the trajectory of cystic fibrosis (CF) disease progression by slowing the rate of lung function decline in clinical studies. Long-term real-world data help to confirm the durability of this response.
Methods: This non-interventional, longitudinal study used data from the US CF Foundation Patient Registry to describe the annualized rate of change in lung function in people with CF receiving IVA. The IVA-treated cohort included people with CF aged ≥ 6 years who had ≥ 1 CF transmembrane conductance regulator (CFTR)-gating mutation and initiated IVA between 31 January 2012 and 31 December 2018. An age-matched comparator cohort included people with CF heterozygous for the F508del-CFTR mutation and a minimal function mutation (R117H excluded) and had not received CFTR modulator therapy. Baseline characteristics were balanced using standardized mortality ratio (SMR) weights computed from estimated propensity scores. The annualized rate of change in percent predicted forced expiratory volume in 1 s (ppFEV1) was estimated over 5 years and used to calculate the relative annualized rate of change in lung function in the IVA-treated versus comparator cohorts.
Results: In the 5-year follow-up period, 548 people were in the IVA-treated and 541 in the comparator cohorts after SMR weighting. The annualized rate of change in ppFEV1 over 5 years was -1.23 (95% CI -1.45, -1.03) and -2.03 (-2.16, -1.90) percentage points in the IVA-treated and comparator cohorts, respectively. There was a 39% reduction (95% CI: 28, 50) in the rate of lung function decline in the IVA-treated versus comparator cohort over 5 years. Findings were generally consistent with those of shorter follow-up periods.
Conclusion: IVA showed a durable clinical benefit by slowing the rate of lung function decline over 5 years. Results support a sustained and consistent impact of IVA on lung function trajectory in people with CF. Word count: 300 (limit: 300 words).
简介在临床研究中,伊伐卡夫托(IVA)通过减缓肺功能下降的速度,改变了囊性纤维化(CF)疾病的发展轨迹。长期实际数据有助于证实这种反应的持久性:这项非干预性纵向研究利用美国CF基金会患者登记处的数据,描述了接受IVA治疗的CF患者肺功能的年变化率。接受IVA治疗的队列包括年龄≥6岁、CF跨膜传导调节器(CFTR)-门控突变≥1个且在2012年1月31日至2018年12月31日期间开始接受IVA治疗的CF患者。年龄匹配的参照队列包括杂合子F508del-CFTR突变和最小功能突变(R117H除外)且未接受过CFTR调节剂治疗的CF患者。根据估计的倾向评分计算出的标准化死亡率 (SMR) 权重平衡了基线特征。我们估算了5年中1 s内用力呼气容积预测值百分比(ppFEV1)的年化变化率,并以此计算了IVA治疗组与对照组的肺功能相对年化变化率:结果:在为期5年的随访中,经过SMR加权后,IVA治疗组有548人,对照组有541人。5年间,IVA治疗组和对照组的ppFEV1年化变化率分别为-1.23(95% CI -1.45, -1.03)和-2.03(-2.16, -1.90)个百分点。5年中,IVA治疗组与对照组相比,肺功能下降率降低了39%(95% CI:28,50)。这些结果与较短随访期的结果基本一致:IVA可在5年内减缓肺功能下降的速度,从而显示出持久的临床益处。结果表明,IVA对CF患者的肺功能轨迹具有持续、一致的影响。字数:300(字数限制:300字)。
{"title":"A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis.","authors":"Christian Merlo, Teja Thorat, Lisa J McGarry, Christina V Scirica, Maral DerSarkissian, Catherine Nguyen, Yuqian M Gu, Aruna Muthukumar, Joe Healy, Jaime L Rubin, M Alan Brookhart","doi":"10.1007/s41030-024-00269-9","DOIUrl":"10.1007/s41030-024-00269-9","url":null,"abstract":"<p><strong>Introduction: </strong>Ivacaftor (IVA) has been shown to change the trajectory of cystic fibrosis (CF) disease progression by slowing the rate of lung function decline in clinical studies. Long-term real-world data help to confirm the durability of this response.</p><p><strong>Methods: </strong>This non-interventional, longitudinal study used data from the US CF Foundation Patient Registry to describe the annualized rate of change in lung function in people with CF receiving IVA. The IVA-treated cohort included people with CF aged ≥ 6 years who had ≥ 1 CF transmembrane conductance regulator (CFTR)-gating mutation and initiated IVA between 31 January 2012 and 31 December 2018. An age-matched comparator cohort included people with CF heterozygous for the F508del-CFTR mutation and a minimal function mutation (R117H excluded) and had not received CFTR modulator therapy. Baseline characteristics were balanced using standardized mortality ratio (SMR) weights computed from estimated propensity scores. The annualized rate of change in percent predicted forced expiratory volume in 1 s (ppFEV<sub>1</sub>) was estimated over 5 years and used to calculate the relative annualized rate of change in lung function in the IVA-treated versus comparator cohorts.</p><p><strong>Results: </strong>In the 5-year follow-up period, 548 people were in the IVA-treated and 541 in the comparator cohorts after SMR weighting. The annualized rate of change in ppFEV<sub>1</sub> over 5 years was -1.23 (95% CI -1.45, -1.03) and -2.03 (-2.16, -1.90) percentage points in the IVA-treated and comparator cohorts, respectively. There was a 39% reduction (95% CI: 28, 50) in the rate of lung function decline in the IVA-treated versus comparator cohort over 5 years. Findings were generally consistent with those of shorter follow-up periods.</p><p><strong>Conclusion: </strong>IVA showed a durable clinical benefit by slowing the rate of lung function decline over 5 years. Results support a sustained and consistent impact of IVA on lung function trajectory in people with CF. Word count: 300 (limit: 300 words).</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"483-494"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294087","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 : 2024-12-01Epub Date: 2024-10-18DOI: 10.1007/s41030-024-00272-0
Sy Duong-Quy, Duc Huynh-Truong-Anh, Tram Tang-Thi-Thao, Thu Nguyen-Ngoc-Phuong, Phung Hoang-Phi-Tuyet, Anh Nguyen-Tuan, Toi Nguyen-Van, Thanh Nguyen-Chi, Thanh Nguyen-Thi-Kim, Tien Nguyen-Quang, Thuy Tran-Ngoc-Anh, Nam Nguyen-Van-Hoai, Mai Do-Thi-Thu, Huong Hoang-Thi-Xuan, Thai Nguyen-Duy, Cong Nguyen-Hai, Tuan Huynh-Anh, Quan Vu-Tran-Thien, Khue Bui-Diem, Giang Nguyen-Mong, Hieu Nguyen-Lan, Giap Vu-Van, Phuong Phan-Thu, Long Nguyen-Viet, Chuong Nguyen-Hong, Sy Dinh-Ngoc, Trong Nguyen-Duc, Dung Truong-Viet, Thu Vo-Pham-Minh, Bao Le-Khac, Duc Nguyen-Hong, Timothy Craig, Vinh Nguyen-Nhu
Introduction: Most hospitalized patients required invasive or non-invasive ventilation and High Flow Nasal Cannula (HFNC). Therefore, this study was conducted to describe the characteristics of patients with severe Coronavirus Disease-2019 (COVID-19) treated by HFNC and its effectiveness for reducing the rate of intubated-mechanical ventilation in the Intensive Care Unit (ICU) of Phu Chanh COVID-19 Department-Binh Duong General Hospital.
Methods: It was a cross-sectional and descriptive study. All severe patients with COVID-19 with acute respiratory failure eligible for the study were included. Patient characteristics, clinical symptoms, laboratory results, and treatment methods were collected for analysis; parameters and data related to HFNC treatment and follow-up were analysed.
Results: 80 patients, aged of 49.7 ± 16.6 years, were treated with HFNC at admission in ICU. 14 patients had type 2 diabetes (17.5%), 3 patients had chronic respiratory disease (3.8%), 19 patients had high blood pressure (23.8%), and 5 patients with other comorbidities (7.4%). The majority of patients with severe COVID-19 had typical symptoms of COVID-19 such as shortness of breath (97.5%), intensive tired (81.3%), cough (73.7%), anosmia (48.3%), ageusia (41.3%), and fever (26.3%). The results of arterial blood gases demonstrated severe hypoxia under optimal conventional oxygen therapy (PaO2 = 52.5 ± 17.4 mmHg). Respiratory rate, SpO2, PaO2 were significantly improved after using HFNC at 1st day, 3rd day and 7th day (P < 0.05; P < 0.05; P < 0.01; respectively). Receiver operating characteristics (ROC) index was significantly increased after treating with HFNC vs before HFNC treatment (4.79 ± 1.86, 5.53 ± 2.39, and 7.41 ± 4.24 vs 2.97 ± 0.39; P < 0.05, P < 0.05 and P < 0.01, respectively). 54 (67.5%) patients were success with HFNC treatment and 26 (32.5%) patients with HFNC failure needed to treat with Continuous Positive Airway Pressure (CPAP) (13 patients; 50%) or intubated ventilation (13 patients; 50%).
Conclusion: HFNC therapy could be considered as a useful and effective alternative treatment for patients with acute respiratory failure. HFNC might help to delay the intubated ventilation for patients with respiratory failure and to minimise the risk of invasive ventilation complications and mortality. However, it is crucial to closely monitor the evolution of patient's respiratory status and responsiveness of HFNC treatment to avoid unintended delay of intubation-mechanical ventilation.
Trial registration: An independent ethics committee approved the study (The Ethics Committee of Binh Duong General Hospital; No. HDDD-BVDK BINH DUONG 9.2021), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.
{"title":"Efficacy of High Flow Nasal Cannula in the Treatment of Patients with COVID-19 with Acute Respiratory Distress Syndrome: Results of Single Centre Study in Vietnam.","authors":"Sy Duong-Quy, Duc Huynh-Truong-Anh, Tram Tang-Thi-Thao, Thu Nguyen-Ngoc-Phuong, Phung Hoang-Phi-Tuyet, Anh Nguyen-Tuan, Toi Nguyen-Van, Thanh Nguyen-Chi, Thanh Nguyen-Thi-Kim, Tien Nguyen-Quang, Thuy Tran-Ngoc-Anh, Nam Nguyen-Van-Hoai, Mai Do-Thi-Thu, Huong Hoang-Thi-Xuan, Thai Nguyen-Duy, Cong Nguyen-Hai, Tuan Huynh-Anh, Quan Vu-Tran-Thien, Khue Bui-Diem, Giang Nguyen-Mong, Hieu Nguyen-Lan, Giap Vu-Van, Phuong Phan-Thu, Long Nguyen-Viet, Chuong Nguyen-Hong, Sy Dinh-Ngoc, Trong Nguyen-Duc, Dung Truong-Viet, Thu Vo-Pham-Minh, Bao Le-Khac, Duc Nguyen-Hong, Timothy Craig, Vinh Nguyen-Nhu","doi":"10.1007/s41030-024-00272-0","DOIUrl":"10.1007/s41030-024-00272-0","url":null,"abstract":"<p><strong>Introduction: </strong>Most hospitalized patients required invasive or non-invasive ventilation and High Flow Nasal Cannula (HFNC). Therefore, this study was conducted to describe the characteristics of patients with severe Coronavirus Disease-2019 (COVID-19) treated by HFNC and its effectiveness for reducing the rate of intubated-mechanical ventilation in the Intensive Care Unit (ICU) of Phu Chanh COVID-19 Department-Binh Duong General Hospital.</p><p><strong>Methods: </strong>It was a cross-sectional and descriptive study. All severe patients with COVID-19 with acute respiratory failure eligible for the study were included. Patient characteristics, clinical symptoms, laboratory results, and treatment methods were collected for analysis; parameters and data related to HFNC treatment and follow-up were analysed.</p><p><strong>Results: </strong>80 patients, aged of 49.7 ± 16.6 years, were treated with HFNC at admission in ICU. 14 patients had type 2 diabetes (17.5%), 3 patients had chronic respiratory disease (3.8%), 19 patients had high blood pressure (23.8%), and 5 patients with other comorbidities (7.4%). The majority of patients with severe COVID-19 had typical symptoms of COVID-19 such as shortness of breath (97.5%), intensive tired (81.3%), cough (73.7%), anosmia (48.3%), ageusia (41.3%), and fever (26.3%). The results of arterial blood gases demonstrated severe hypoxia under optimal conventional oxygen therapy (PaO<sub>2</sub> = 52.5 ± 17.4 mmHg). Respiratory rate, SpO2, PaO2 were significantly improved after using HFNC at 1st day, 3rd day and 7th day (P < 0.05; P < 0.05; P < 0.01; respectively). Receiver operating characteristics (ROC) index was significantly increased after treating with HFNC vs before HFNC treatment (4.79 ± 1.86, 5.53 ± 2.39, and 7.41 ± 4.24 vs 2.97 ± 0.39; P < 0.05, P < 0.05 and P < 0.01, respectively). 54 (67.5%) patients were success with HFNC treatment and 26 (32.5%) patients with HFNC failure needed to treat with Continuous Positive Airway Pressure (CPAP) (13 patients; 50%) or intubated ventilation (13 patients; 50%).</p><p><strong>Conclusion: </strong>HFNC therapy could be considered as a useful and effective alternative treatment for patients with acute respiratory failure. HFNC might help to delay the intubated ventilation for patients with respiratory failure and to minimise the risk of invasive ventilation complications and mortality. However, it is crucial to closely monitor the evolution of patient's respiratory status and responsiveness of HFNC treatment to avoid unintended delay of intubation-mechanical ventilation.</p><p><strong>Trial registration: </strong>An independent ethics committee approved the study (The Ethics Committee of Binh Duong General Hospital; No. HDDD-BVDK BINH DUONG 9.2021), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"451-468"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473398","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 : 2024-12-01Epub Date: 2024-09-28DOI: 10.1007/s41030-024-00271-1
Vinod K Viswanathan, Aloke G Ghoshal, Anant Mohan, Ketaki Patil, Chaitanya Bhargave, Sanjay Choudhari, Suyog Mehta
A severe and progressive interstitial lung disease (ILD) known as idiopathic pulmonary fibrosis (IPF) has an unknown etiology with poorly defined mechanisms of development. Among the currently prescribed pharmacological interventions for IPF, nintedanib demonstrates the ability to decelerate the deterioration of lung function and yield positive clinical outcomes. Multiple randomized placebo-controlled trials have confirmed the efficacy and acceptable safety profile of nintedanib. Real-world evidence studies also support the use of nintedanib in IPF, being an efficient and well-tolerated treatment option. It has the potential to stabilize the disease progression in patients with ILD. Patients with IPF frequently have comorbidities like diabetes and hypertension, which can exacerbate the course of disease, reduce quality of life, and decrease treatment adherence. For well-informed decision-making, it is important for healthcare professionals to recognize the position of nintedanib therapy in IPF with comorbidities. The gastrointestinal adverse effects, notably diarrhea, dominate the nintedanib safety profile. These can be effectively controlled by closely monitoring side effects, administering anti-diarrheal and anti-emetic drugs, reducing the nintedanib dose, and discontinuing it in case of severe symptoms with an option to reintroduce the treatment after side effects subside. Symptomatic interventions and monitoring of liver enzymes may reduce the occurrence of permanent treatment discontinuations.
{"title":"Patient Profile-Based Management with Nintedanib in Patients with Idiopathic Pulmonary Fibrosis.","authors":"Vinod K Viswanathan, Aloke G Ghoshal, Anant Mohan, Ketaki Patil, Chaitanya Bhargave, Sanjay Choudhari, Suyog Mehta","doi":"10.1007/s41030-024-00271-1","DOIUrl":"10.1007/s41030-024-00271-1","url":null,"abstract":"<p><p>A severe and progressive interstitial lung disease (ILD) known as idiopathic pulmonary fibrosis (IPF) has an unknown etiology with poorly defined mechanisms of development. Among the currently prescribed pharmacological interventions for IPF, nintedanib demonstrates the ability to decelerate the deterioration of lung function and yield positive clinical outcomes. Multiple randomized placebo-controlled trials have confirmed the efficacy and acceptable safety profile of nintedanib. Real-world evidence studies also support the use of nintedanib in IPF, being an efficient and well-tolerated treatment option. It has the potential to stabilize the disease progression in patients with ILD. Patients with IPF frequently have comorbidities like diabetes and hypertension, which can exacerbate the course of disease, reduce quality of life, and decrease treatment adherence. For well-informed decision-making, it is important for healthcare professionals to recognize the position of nintedanib therapy in IPF with comorbidities. The gastrointestinal adverse effects, notably diarrhea, dominate the nintedanib safety profile. These can be effectively controlled by closely monitoring side effects, administering anti-diarrheal and anti-emetic drugs, reducing the nintedanib dose, and discontinuing it in case of severe symptoms with an option to reintroduce the treatment after side effects subside. Symptomatic interventions and monitoring of liver enzymes may reduce the occurrence of permanent treatment discontinuations.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"377-409"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352768","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 : 2024-12-01Epub Date: 2024-11-08DOI: 10.1007/s41030-024-00277-9
Alan G Kaplan
The coexistence of depression with chronic obstructive pulmonary disease (COPD) has been associated with poorer outcomes. Studies have questioned the safety of antidepressants in patients with COPD. This review shows the potential relationships and the possible mechanisms and gives us good warnings on how to approach this problem. Treatment should be both non-pharmacological and pharmacological, but importantly tailored to the individual patient.
{"title":"Do Antidepressants Worsen COPD Outcomes in Depressed Patients with COPD?","authors":"Alan G Kaplan","doi":"10.1007/s41030-024-00277-9","DOIUrl":"10.1007/s41030-024-00277-9","url":null,"abstract":"<p><p>The coexistence of depression with chronic obstructive pulmonary disease (COPD) has been associated with poorer outcomes. Studies have questioned the safety of antidepressants in patients with COPD. This review shows the potential relationships and the possible mechanisms and gives us good warnings on how to approach this problem. Treatment should be both non-pharmacological and pharmacological, but importantly tailored to the individual patient.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"411-426"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626899","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 : 2024-12-01Epub Date: 2024-09-27DOI: 10.1007/s41030-024-00274-y
Owen W Tomlinson, Philip Mitchelmore, Craig A Williams
Introduction: Advances in development of cystic fibrosis transmembrane conductance regulator modulator (CFTRm) therapies mean that now people who are heterozygous (instead of having to be homozygous) for the common F508del variant can benefit from these therapies. Recent economic estimates suggest only approximately 15% of the global population have CFTRm access, yet it is unknown how prevalence of F508del and economic factors may affect this availability.
Methods: Data related to prevalence of cystic fibrosis (CF), CFTRm usage, and prevalence of F508del in 10 countries were extracted from publicly accessible registry reports from 2021. National gross domestic product (GDP) was obtained via open access World Bank data. Descriptive statistics and correlation coefficients assessed relationships.
Results: Notable discrepancies were noted in the equity of availability of data between national registries-only four countries reported number of patients eligible for CFTRm. Registry data represented 70,694 patients, with 42,858 found to be using CFTRm (60.6%). Prevalence of CFTRm usage ranged from 1.8% to 76.7% and prevalence of F508del ranged from 35.2% to 94.4%. The correlation between prevalence of CFTRm usage and F508del is positive (r = 0.56, p = 0.10), and the correlation between CFTRm usage and GDP (per capita) was also positive, and significant (r = 0.72, p = 0.02).
Conclusion: Both F508del prevalence and GDP are associated with variable CFTRm usage rates, although a predominant reason is unclear as a result of poor consistency in registry reporting. Urgent action is needed to create uniform reporting of registry data and increase availability of novel CFTRm therapies to the global CF population.
{"title":"Comparison of Reporting Quality in National Cystic Fibrosis Patient Registries: Implications for Identifying Use of Novel CFTR Modulators.","authors":"Owen W Tomlinson, Philip Mitchelmore, Craig A Williams","doi":"10.1007/s41030-024-00274-y","DOIUrl":"10.1007/s41030-024-00274-y","url":null,"abstract":"<p><strong>Introduction: </strong>Advances in development of cystic fibrosis transmembrane conductance regulator modulator (CFTRm) therapies mean that now people who are heterozygous (instead of having to be homozygous) for the common F508del variant can benefit from these therapies. Recent economic estimates suggest only approximately 15% of the global population have CFTRm access, yet it is unknown how prevalence of F508del and economic factors may affect this availability.</p><p><strong>Methods: </strong>Data related to prevalence of cystic fibrosis (CF), CFTRm usage, and prevalence of F508del in 10 countries were extracted from publicly accessible registry reports from 2021. National gross domestic product (GDP) was obtained via open access World Bank data. Descriptive statistics and correlation coefficients assessed relationships.</p><p><strong>Results: </strong>Notable discrepancies were noted in the equity of availability of data between national registries-only four countries reported number of patients eligible for CFTRm. Registry data represented 70,694 patients, with 42,858 found to be using CFTRm (60.6%). Prevalence of CFTRm usage ranged from 1.8% to 76.7% and prevalence of F508del ranged from 35.2% to 94.4%. The correlation between prevalence of CFTRm usage and F508del is positive (r = 0.56, p = 0.10), and the correlation between CFTRm usage and GDP (per capita) was also positive, and significant (r = 0.72, p = 0.02).</p><p><strong>Conclusion: </strong>Both F508del prevalence and GDP are associated with variable CFTRm usage rates, although a predominant reason is unclear as a result of poor consistency in registry reporting. Urgent action is needed to create uniform reporting of registry data and increase availability of novel CFTRm therapies to the global CF population.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"427-438"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352767","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}
Introduction: The pathogenesis and clinical profiles of patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD-PH) are poorly understood. Whether and to what extent pulmonary arterial hypertension (PAH)-specific therapy improves hemodynamic and outcome in ILD-PH are also unknown.
Study objective: This study aims to clarify the characteristics, clinical course and response to PAH-specific therapy of ILD and/or PH by enrolling three unique subsets: PAH, ILD-PH, and ILD.
Methods: The proposed study is a retrospective and prospective, multi-centre, observational cohort study of patients treated at any of three university hospitals in the Hokkaido region of Japan who have any one of the following: PAH; ILD-PH with or without PAH features; or ILD without PH. We aim to enrol 250 patients in total. For the retrospective observation period, data obtained after 1 January 2010, will be analysed, and the prospective observation period will be 1 year. We will compare the clinical data of patients with ILD-PH with those of patients with PAH and those of patients with ILD without PH in the real-world clinical setting. In addition, within the cohort of patients with ILD-PH, we will explore the subset with "ILD-PH with PAH features" and compare the response to PAH-specific therapy with that of PAH. The primary outcome will be the change in pulmonary vascular resistance from first treatment to follow-up in patients with PAH and ILD-PH with PAH features (excluding ILD-PH without PAH feature and ILD-no-PH for the primary outcome). The exploratory outcomes will include analyses of PH-associated biomarkers, right ventricular function and patient-reported outcomes.
Results: This is a protocol article and the results will be presented after data collection is completed.
Conclusion: The POPLAR study will provide data that help better understand the pathophysiology of ILD-PH and improve the quality of life and outcome of patients with PH and/or ILD.
Trial registration: Japan Registry of Clinical Trials: jRCT1010230018.
{"title":"A PrOsPective Cohort Study on Interstitial Lung Disease-Associated Pulmonary Hypertension with a ParticulaR Focus on the Subset with Pulmonary Arterial Hypertension Features (POPLAR Study).","authors":"Ichizo Tsujino, Kazuki Kitahara, Junichi Omura, Toshiyuki Iwahori, Satoshi Konno","doi":"10.1007/s41030-024-00264-0","DOIUrl":"10.1007/s41030-024-00264-0","url":null,"abstract":"<p><strong>Introduction: </strong>The pathogenesis and clinical profiles of patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD-PH) are poorly understood. Whether and to what extent pulmonary arterial hypertension (PAH)-specific therapy improves hemodynamic and outcome in ILD-PH are also unknown.</p><p><strong>Study objective: </strong>This study aims to clarify the characteristics, clinical course and response to PAH-specific therapy of ILD and/or PH by enrolling three unique subsets: PAH, ILD-PH, and ILD.</p><p><strong>Methods: </strong>The proposed study is a retrospective and prospective, multi-centre, observational cohort study of patients treated at any of three university hospitals in the Hokkaido region of Japan who have any one of the following: PAH; ILD-PH with or without PAH features; or ILD without PH. We aim to enrol 250 patients in total. For the retrospective observation period, data obtained after 1 January 2010, will be analysed, and the prospective observation period will be 1 year. We will compare the clinical data of patients with ILD-PH with those of patients with PAH and those of patients with ILD without PH in the real-world clinical setting. In addition, within the cohort of patients with ILD-PH, we will explore the subset with \"ILD-PH with PAH features\" and compare the response to PAH-specific therapy with that of PAH. The primary outcome will be the change in pulmonary vascular resistance from first treatment to follow-up in patients with PAH and ILD-PH with PAH features (excluding ILD-PH without PAH feature and ILD-no-PH for the primary outcome). The exploratory outcomes will include analyses of PH-associated biomarkers, right ventricular function and patient-reported outcomes.</p><p><strong>Results: </strong>This is a protocol article and the results will be presented after data collection is completed.</p><p><strong>Conclusion: </strong>The POPLAR study will provide data that help better understand the pathophysiology of ILD-PH and improve the quality of life and outcome of patients with PH and/or ILD.</p><p><strong>Trial registration: </strong>Japan Registry of Clinical Trials: jRCT1010230018.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"297-313"},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443205","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 : 2024-09-01Epub Date: 2024-06-04DOI: 10.1007/s41030-024-00262-2
Kittipong Maneechotesuwan, Bhumika Aggarwal, Gabriel Garcia, Daniel Tan, Hugo Neffen, Ramon Jason M Javier, Mona Al-Ahmad, Mousa Khadada, Vu Tran Thien Quan, Krittika Teerapuncharoen, Mario Soto Ramos, Gur Levy, Maximilian Plank, Abhay Phansalkar, Peter G Gibson
Introduction: Clinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with asthma.
Methods: In this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants.
Results: Surveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4-6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12 months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice.
Conclusions: In line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy.
{"title":"Exploring Clinical Remission in Moderate Asthma - Perspectives from Asia, the Middle East, and South America.","authors":"Kittipong Maneechotesuwan, Bhumika Aggarwal, Gabriel Garcia, Daniel Tan, Hugo Neffen, Ramon Jason M Javier, Mona Al-Ahmad, Mousa Khadada, Vu Tran Thien Quan, Krittika Teerapuncharoen, Mario Soto Ramos, Gur Levy, Maximilian Plank, Abhay Phansalkar, Peter G Gibson","doi":"10.1007/s41030-024-00262-2","DOIUrl":"10.1007/s41030-024-00262-2","url":null,"abstract":"<p><strong>Introduction: </strong>Clinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with asthma.</p><p><strong>Methods: </strong>In this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants.</p><p><strong>Results: </strong>Surveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4-6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12 months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice.</p><p><strong>Conclusions: </strong>In line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"279-295"},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238078","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 : 2024-09-01Epub Date: 2024-07-16DOI: 10.1007/s41030-024-00263-1
Juzar Ali, Jasmanda Wu, Mariam Hassan, Jui-Hua Tsai, Nancy Touba, Kelly McCarrier, Mark Ballard, Anjan Chatterjee
Introduction: This study aimed to gain insight from patients with refractory Mycobacterium avium complex lung disease (MAC-LD) into strategies used to manage adverse events (AEs) associated with amikacin liposome inhalation suspension (ALIS).
Methods: We conducted semi-structured interviews with US patients with refractory MAC-LD prescribed ALIS in a real-world setting. Interview transcripts were analyzed and coded to identify patterns in participants' descriptions of their ALIS treatment experiences, including AEs and their disruptiveness, and AE mitigation strategies, including participants' ratings of strategies' effectiveness. Concept saturation was also assessed.
Results: Twenty participants (mean age 48.7 years; 80% women; mean ALIS duration 5.45 months) were interviewed. At the time of the interview, 15 participants (75%) had received ALIS for > 1 month and 13 (65%) were currently receiving ALIS. Participants described 44 unique AE mitigation strategies, which can be categorized into three groups: prepare for treatment; prevent increased emergence of AEs; and persist on treatment by mitigating AEs. Common strategies (reported by ≥ 50% of participants) included use of educational materials from the patient support program, localized management of throat irritation, and symptom management to reduce fatigue. Evidence of concept saturation was observed: no new strategies were identified in the last five interviews, which suggests the sample was robust enough to identify all mitigation strategies likely to be used by the broader patient population.
Conclusions: This real-world study identified a diverse set of potential AE mitigation strategies intended to help individual patients prepare for ALIS treatment, prevent the increased emergence of certain AEs, and mitigate the impact of AEs on treatment persistence. Developing a comprehensive accounting of the types of mitigation strategies in use among patients in real-world settings can inform future investigation of the effectiveness of such strategies, and support evidence-based recommendations for treatment management.
{"title":"Qualitative Interviews Exploring Adverse Event Mitigation Strategies in Adults Receiving Amikacin Liposome Inhalation Suspension.","authors":"Juzar Ali, Jasmanda Wu, Mariam Hassan, Jui-Hua Tsai, Nancy Touba, Kelly McCarrier, Mark Ballard, Anjan Chatterjee","doi":"10.1007/s41030-024-00263-1","DOIUrl":"10.1007/s41030-024-00263-1","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to gain insight from patients with refractory Mycobacterium avium complex lung disease (MAC-LD) into strategies used to manage adverse events (AEs) associated with amikacin liposome inhalation suspension (ALIS).</p><p><strong>Methods: </strong>We conducted semi-structured interviews with US patients with refractory MAC-LD prescribed ALIS in a real-world setting. Interview transcripts were analyzed and coded to identify patterns in participants' descriptions of their ALIS treatment experiences, including AEs and their disruptiveness, and AE mitigation strategies, including participants' ratings of strategies' effectiveness. Concept saturation was also assessed.</p><p><strong>Results: </strong>Twenty participants (mean age 48.7 years; 80% women; mean ALIS duration 5.45 months) were interviewed. At the time of the interview, 15 participants (75%) had received ALIS for > 1 month and 13 (65%) were currently receiving ALIS. Participants described 44 unique AE mitigation strategies, which can be categorized into three groups: prepare for treatment; prevent increased emergence of AEs; and persist on treatment by mitigating AEs. Common strategies (reported by ≥ 50% of participants) included use of educational materials from the patient support program, localized management of throat irritation, and symptom management to reduce fatigue. Evidence of concept saturation was observed: no new strategies were identified in the last five interviews, which suggests the sample was robust enough to identify all mitigation strategies likely to be used by the broader patient population.</p><p><strong>Conclusions: </strong>This real-world study identified a diverse set of potential AE mitigation strategies intended to help individual patients prepare for ALIS treatment, prevent the increased emergence of certain AEs, and mitigate the impact of AEs on treatment persistence. Developing a comprehensive accounting of the types of mitigation strategies in use among patients in real-world settings can inform future investigation of the effectiveness of such strategies, and support evidence-based recommendations for treatment management.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"315-330"},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620813","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 : 2024-09-01Epub Date: 2024-08-10DOI: 10.1007/s41030-024-00268-w
Alberto Fantin, Nadia Castaldo, Ernesto Crisafulli, Giulia Sartori, Avinash Aujayeb, Paolo Vailati, Giuseppe Morana, Filippo Patrucco, Maria de Martino, Miriam Isola, Vincenzo Patruno
Introduction: Medical thoracoscopy is a minimally invasive and safe procedure mostly performed for unexplained exudative pleural effusions but may be considered for pneumothorax (PNX).
Methods: This retrospective study included participants affected by PNX who underwent medical thoracoscopy with talc poudrage at a single academic hospital from 2008 to 2021. The primary endpoint was the observation of complete radiographical lung re-expansion and absence of air supply from the chest drain within 7 days of medical thoracoscopy. The secondary endpoint was achieving no recurrence of ipsilateral PNX at 24 months post-discharge.
Results: A total of 95 patients affected by primary spontaneous PNX (PSP), secondary spontaneous PNX (SSP), iatrogenic, and traumatic PNX were enrolled. An additional procedure was required by 17.89% of patients, and only one patient with SSP required subsequent surgery. Recurrence of PNX occurred on the same side within 24 months after discharge in 9.47% of patients, with a median time to recurrence of 13.5 months. The PSP group was significantly more likely to achieve the primary endpoint. Pleural morphology was significantly associated with reaching the primary endpoint, while receiving a cumulative dose of talc greater than or equal to 4 g during hospitalization was associated with a lower risk of meeting it. Receiving a cumulative dose of talc greater than or equal to 4 g led in all cases to the achievement of the secondary endpoint. Patients with iatrogenic and traumatic PNX had an excellent prognosis in both the short- and long-term evaluation.
Conclusion: Medical thoracoscopy is an effective procedure for treating PNX in the acute setting in selected cases while preventing long-term relapses. Large prospective clinical studies are needed to support and better define the role of medical thoracoscopy in current clinical practice.
{"title":"The Role of Medical Thoracoscopy with Talc Poudrage in Spontaneous, Iatrogenic, and Traumatic Pneumothorax: A Prolonged Experience of a Tertiary Care Center.","authors":"Alberto Fantin, Nadia Castaldo, Ernesto Crisafulli, Giulia Sartori, Avinash Aujayeb, Paolo Vailati, Giuseppe Morana, Filippo Patrucco, Maria de Martino, Miriam Isola, Vincenzo Patruno","doi":"10.1007/s41030-024-00268-w","DOIUrl":"10.1007/s41030-024-00268-w","url":null,"abstract":"<p><strong>Introduction: </strong>Medical thoracoscopy is a minimally invasive and safe procedure mostly performed for unexplained exudative pleural effusions but may be considered for pneumothorax (PNX).</p><p><strong>Methods: </strong>This retrospective study included participants affected by PNX who underwent medical thoracoscopy with talc poudrage at a single academic hospital from 2008 to 2021. The primary endpoint was the observation of complete radiographical lung re-expansion and absence of air supply from the chest drain within 7 days of medical thoracoscopy. The secondary endpoint was achieving no recurrence of ipsilateral PNX at 24 months post-discharge.</p><p><strong>Results: </strong>A total of 95 patients affected by primary spontaneous PNX (PSP), secondary spontaneous PNX (SSP), iatrogenic, and traumatic PNX were enrolled. An additional procedure was required by 17.89% of patients, and only one patient with SSP required subsequent surgery. Recurrence of PNX occurred on the same side within 24 months after discharge in 9.47% of patients, with a median time to recurrence of 13.5 months. The PSP group was significantly more likely to achieve the primary endpoint. Pleural morphology was significantly associated with reaching the primary endpoint, while receiving a cumulative dose of talc greater than or equal to 4 g during hospitalization was associated with a lower risk of meeting it. Receiving a cumulative dose of talc greater than or equal to 4 g led in all cases to the achievement of the secondary endpoint. Patients with iatrogenic and traumatic PNX had an excellent prognosis in both the short- and long-term evaluation.</p><p><strong>Conclusion: </strong>Medical thoracoscopy is an effective procedure for treating PNX in the acute setting in selected cases while preventing long-term relapses. Large prospective clinical studies are needed to support and better define the role of medical thoracoscopy in current clinical practice.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"347-362"},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913720","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}