Clinical Drug Investigation最新文献

{"title":"Diagnosis and Management of Drug-Induced Interstitial Lung Disease in the context of Anti-Cancer Therapy: a Multidisciplinary Viewpoint by Portuguese Experts.","authors":"Mário Fontes E Sousa, Sérgio Campainha, Inês Dias Marques, Rui Dinis, João Rodrigues Inácio, João João Mendes, Rita Luís, Ana Magalhães Ferreira, Ricardo Racha-Pacheco, Rui Rolo, Gabriela Sousa, Paulo Cortes","doi":"10.1007/s40261-024-01400-z","DOIUrl":"10.1007/s40261-024-01400-z","url":null,"abstract":"<p><p>Drug-induced interstitial lung disease (DI-ILD) is a significant complication in patients undergoing treatment with certain anti-cancer therapies, with incidence rates rising, particularly with newer drugs such as trastuzumab-deruxtecan, which may impact their safe and effective use. Although the exact pathophysiological mechanisms remain unknown, and different drugs may induce lung damage through different pathways, the most recognized mechanisms are cytotoxic- and immune-mediated effects. Multidisciplinary teams play a crucial role in the diagnosis, management, and prevention of DI-ILD. Given the wide variability in the onset of DI-ILD, which may occur within the first few days of treatment or months after, patient education and clinician training are essential for early detection and improved outcomes. Moreover, the diagnostic confirmation requires the exclusion of alternative causes through clinical, imaging and bronchoscopy evaluation. Treatment strategies largely depend on the grade of severity of the clinical manifestations of DI-ILD, ranging from interruption or discontinuation of the offending drug to corticosteroid therapy and hospitalization for appropriate monitoring. Nonetheless, further research is needed to better understand the impact of emerging anti-cancer drugs on DI-ILD and to establish standardized management protocols.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"801-810"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in the Adverse Event Profiles of Sodium-Glucose Cotransporter 2 Inhibitors used in Patients with Diabetes Mellitus and Heart Failure: An Analysis Using the Japanese Adverse Drug Event Report Database.","authors":"Toshiaki Sakamoto, Hirotaka Miyamoto, Junya Hashizume, Hayato Akamatsu, Tomoaki Akagi, Yukinobu Kodama, Hirofumi Hamano, Yoshito Zamami, Kaname Ohyama","doi":"10.1007/s40261-024-01394-8","DOIUrl":"10.1007/s40261-024-01394-8","url":null,"abstract":"<p><strong>Background and objectives: </strong>Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently become a standard treatment for heart failure and renal failure. The number of patients using these drugs is expected to increase further. However, no adverse drug event profiles have been published for the use of SGLT2i in patients without diabetes. To analyze and clarify the differences in adverse event profiles associated with the use of SGLT2i in patients with diabetes or heart failure using the Japanese Adverse Drug Event Report (JADER) database, a Japanese reporting system for adverse events.</p><p><strong>Methods: </strong>The JADER database, containing reports submitted between April 2004 and January 2024, was used. Our study focused on patients with diabetes or heart failure, analyzing adverse events associated with empagliflozin and dapagliflozin. The reporting odds ratio (ROR) and 95% confidence interval (CI) were calculated for signal detection.</p><p><strong>Results: </strong>We identified risks of adverse drug events such as ketoacidosis, urinary tract infection, dehydration, and acidosis in both patient groups. However, the risks of cerebral infarction and ischemic heart disease were identified only in patients with diabetes, while risks of renal dysfunction, hypoglycemia, and sepsis were identified only in those with heart failure.</p><p><strong>Conclusion: </strong>Adverse events should be managed appropriately for patients using SGLT2i, as the adverse event profiles differ between those with diabetes and those with heart failure. Understanding these differences is crucial for improving patient safety and optimizing treatment outcomes.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"761-771"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Cost-Effectiveness of Atezolizumab Versus Durvalumab as First-Line Combination Treatment with Chemotherapy for Patients with Extensive-Disease Small-Cell Lung Cancer in Japan.","authors":"Munenobu Kashiwa, Miho Tsukada, Ryo Matsushita","doi":"10.1007/s40261-024-01383-x","DOIUrl":"10.1007/s40261-024-01383-x","url":null,"abstract":"<p><p>BACKGROUND AND OBJECTIVE: Recent trials have shown that immune checkpoint inhibitors (ICIs), atezolizumab and durvalumab, in combination with chemotherapy, are effective in treating extensive-disease small-cell lung cancer (ED-SCLC). However, owing to the expensiveness of ICIs, monetary issues arise. The cost-effectiveness of ICI combination treatment with carboplatin plus etoposide (CE) as first-line therapy for patients with ED-SCLC was examined to aid public health policy in Japan.</p><p><strong>Methods: </strong>IMpower 133 and CASPIAN data were used to create a partitioned survival model. Medical expenses and quality-adjusted life years (QALYs) were considered. The analysis period, discount rate, and threshold were set at 20 years, 2%, and 15 million Japanese yen (JPY) [114,068 US dollars (USD)] per QALY, respectively. The incremental cost-effectiveness ratio (ICER) was calculated by gathering reasonable parameters from published reports and combining the costs and effects using parametric models. Monte Carlo simulations, scenario analysis, and one-way sensitivity analyses were employed to quantify uncertainty.</p><p><strong>Results: </strong>After comparing atezolizumab plus CE (ACE) and durvalumab plus CE (DCE) with CE, it was found that the ICERs exceeded the threshold at 35,048,299 JPY (266,527 USD) and 36,665,583 JPY (278,826 USD) per QALY, respectively. For one-way sensitivity and scenario assessments, the ICERs exceeded the threshold, even with considerably adjusted parameters. For the probabilistic sensitivity analyses, there was no probability that the ICER of the ICI combination treatment with chemotherapy would fall below the threshold.</p><p><strong>Conclusion: </strong>ACE and DCE were not cost-effective compared with CE as first-line therapy for ED-SCLC in Japan. Both these therapies exhibited high ICERs.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"749-759"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurological and Psychiatric Adverse Events Associated with Cyclin-Dependent Kinase 4/6 Inhibitors in Breast Cancer Patients: Insights from a Pharmacovigilance Study via the FDA Adverse Event Reporting System.","authors":"Zicheng Yu, Mengying Guan, Xiaolan Liao","doi":"10.1007/s40261-024-01396-6","DOIUrl":"10.1007/s40261-024-01396-6","url":null,"abstract":"<p><strong>Background and objective: </strong>Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have revolutionised cancer therapy, particularly breast cancer therapy. However, concerns about their potential to cause neurological and psychiatric adverse events (AEs) have emerged, and these concerns remain underexplored. This study aimed to investigate the signals related to neurological and psychiatric AEs associated with CDK4/6 inhibitor use.</p><p><strong>Methods: </strong>A retrospective study was performed to analyse reports of AEs associated with the use of CDK4/6 inhibitors (abemaciclib, ribociclib and palbociclib) from the first quarter of 2015 to the fourth quarter of 2023 on the basis of the FDA Adverse Event Reporting System (FAERS). Both the reporting odds ratio (ROR) and the multi-item gamma Poisson shrinker (MGPS) were used for signal detection. The timing of events was assessed with the Weibull shape parameter (WSP). The management, analysis and presentation of the data were performed via Python (version 3.8) and R software (version 4.3.2).</p><p><strong>Results: </strong>A total of 19,001 AE reports in which CDK4/6 inhibitors were identified as the 'primary suspect drug' were included in this study. These events were predominantly observed in patients aged 65 to 85 years. Through an ROR analysis, 85 positive signals for neurological and psychiatric AEs associated with CDK4/6 inhibitors were identified. The MGPS method revealed 61 positive AE signals for neurological and psychiatric AEs associated with CDK4/6 inhibitors. A total of 34 positive AE signals were identified by both the ROR and MGPS analyses. The WSP indicated that the onset times for AEs associated with all three CDK4/6 inhibitors tended to be early in drug therapy, suggesting a propensity for early failure type.</p><p><strong>Conclusion: </strong>The present study revealed neurological and psychiatric AEs associated with CDK4/6 inhibitors that often occur early in treatment. Significant signals include spinal cord herniation and cerebral microangiopathy. Close monitoring of these AEs is crucial. Further studies are necessary to verify the connection between CDK4/6 inhibitors and neurological and psychiatric AEs.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"789-798"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcipotriol and 5-Fluorouracil Combination Therapy for the Treatment of Actinic Keratosis in the Clinic: A Review Article.","authors":"Anna H Dlott, Sara A Spencer, Anthony J Di Pasqua","doi":"10.1007/s40261-024-01392-w","DOIUrl":"10.1007/s40261-024-01392-w","url":null,"abstract":"<p><p>This review examines the pharmacology, efficacy and safety, dosage and administration, and place in therapy of the combination of 5-fluorouracil (5-FU) and calcipotriol for the treatment of actinic keratosis. Currently, 5% 5-FU topical cream is approved for actinic keratosis treatment, while calcipotriol is indicated for plaque psoriasis in adults. The typical administration of 5-FU involves topical application twice daily for up to 4 weeks, whereas calcipotriol is applied in a thin layer once or twice daily as directed by a physician. Adverse effects of 5-FU are primarily localized, including skin irritation, ulceration, pruritus, erythema, crusting, and eczematous reactions due to minimal systemic absorption. Calcipotriol may cause burning, itching, and skin irritation. This review details clinical trials that investigate the innovative approach of combining topical 5-FU with calcipotriol for actinic keratosis treatment, highlighting the significant outcomes. Notably, the clinical trials indicate that all participants experienced either a reduction in lesion size or complete lesion clearance, with minimal adverse effects impacting treatment success. The combination of 5-FU and calcipotriol effectively treats actinic keratosis by enhancing the immune response and targeting cell overgrowth, while reducing local site reactions and the lengthy treatment time often associated with existing therapies.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"733-737"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: AVT04: An Ustekinumab Biosimilar.","authors":"Hannah A Blair","doi":"10.1007/s40261-024-01393-9","DOIUrl":"10.1007/s40261-024-01393-9","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"799"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single‑Dose Pharmacokinetics and Safety of the Oral Galectin‑3 Inhibitor, Selvigaltin (GB1211), in Participants with Hepatic Impairment.","authors":"Vassilios Aslanis, Michael Gray, Robert J Slack, Fredrik R Zetterberg, Dimitar Tonev, De Phung, Becky Smith, Brian Jacoby, Hans Schambye, Zahari Krastev, Anna-Lena Ungell, Bertil Lindmark","doi":"10.1007/s40261-024-01395-7","DOIUrl":"10.1007/s40261-024-01395-7","url":null,"abstract":"<p><strong>Background and objectives: </strong>Selvigaltin (GB1211), an orally available small molecule galectin-3 inhibitor developed as a treatment for liver fibrosis and cirrhosis, was evaluated to assess the effect of hepatic impairment on its pharmacokinetics and safety to address regulatory requirements.</p><p><strong>Methods: </strong>GULLIVER-2 was a Phase Ib/IIa three-part study. Parts 1 and 3 had single-dose, open-label designs assessing pharmacokinetics (plasma [total and unbound] and urine), safety, and tolerability of 100 mg oral selvigaltin in participants with moderate (Child-Pugh B, Part 1) or severe (Child-Pugh C, Part 3) hepatic impairment, compared with healthy-matched participants (n = 6 each).</p><p><strong>Results: </strong>All participants received selvigaltin and completed the study. No adverse events were reported. The median time to reach maximum total plasma concentration following drug administration was of 3.49 and 4.00 h post-dose for Child-Pugh B and C participants, respectively; comparable with controls. Total plasma exposure was higher for participants with hepatic impairment compared with controls. Whilst maximum plasma concentration (C_max) was unaffected in Child-Pugh B participants, area under the plasma concentration-time curve from time zero to infinity (AUC_∞) increased by ~ 1.7-fold compared with controls, and half-life was prolonged (geometric mean 28.15 vs 16.38 h). In Child-Pugh C participants, C_max increased by ~ 1.3-fold, AUC_∞ increased by ~ 1.5-fold, and half-life was prolonged (21.05 vs 16.14 h). No trend was observed in plasma unbound fractions or urinary excretion of unchanged selvigaltin in either group.</p><p><strong>Conclusion: </strong>Hepatic impairment increased selvigaltin exposure without safety concerns. These data can inform dose recommendations for future clinical programmes.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov NCT05009680.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"773-787"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Economic Burden of Atherosclerotic Cardiovascular Disease in Italy.","authors":"Francesco S Mennini, Matteo Scortichini, Furio Colivicchi, Aldo P Maggioni, Paolo Sciattella","doi":"10.1007/s40261-024-01365-z","DOIUrl":"10.1007/s40261-024-01365-z","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerotic cardiovascular diseases remain the primary cause of mortality in Italy. Individuals with a history of acute coronary syndrome, peripheral arterial disease, and ischemic stroke/transient ischemic attack face an elevated risk of recurrent major adverse cardiovascular events, including mortality. The population aging, coupled with increasing risk factors such as diabetes mellitus and obesity, exacerbates the disease's economic impact.</p><p><strong>Objectives: </strong>This study aims to comprehensively assess the economic burden of atherosclerotic cardiovascular diseases in Italy, specifically focusing on direct healthcare costs.</p><p><strong>Methods: </strong>We analyzed real-world data from administrative databases in the Marche region and Local Health Unit Umbria 2. The economic burden of patients discharged with acute coronary syndrome, peripheral arterial disease, and ischemic stroke/transient ischemic attack was evaluated, with a focus on direct costs associated with hospitalizations, drugs, and outpatient visits. Results were stratified by age, sex, comorbidities at baseline, and adherence to lipid-lowering therapy and antihypertensive agents.</p><p><strong>Results: </strong>Annually, nearly 350,000 patients were hospitalized for peripheral arterial disease, acute coronary syndrome, or ischemic stroke/transient ischemic attack. Direct health costs averaged €7190 per patient over a 2-year follow-up, with hospitalizations accounting for nearly 70% of the total. Male patients incurred significantly higher costs (€7467) than female patients (€6625). Costs correlated positively with age and with the number of baseline comorbidities, with a range from €5259 (0-1 comorbidities) to €17,095 (4+ comorbidities). Costs were significantly lower in adherent subjects (€6813) compared with non-adherent subjects (€7757).</p><p><strong>Conclusions: </strong>This study provides valuable insights into the economic implications of atherosclerotic cardiovascular diseases in Italy, emphasizing the necessity of a comprehensive approach to preventive measures, optimal medication adherence, and lifestyle modifications to mitigate its impact.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"739-747"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: PB006: A Natalizumab Biosimilar.","authors":"Matt Shirley","doi":"10.1007/s40261-024-01388-6","DOIUrl":"10.1007/s40261-024-01388-6","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"729"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Placebo on Pruritus in Patients with Chronic Urticaria: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.","authors":"Peiwen Xue, Haiyan Qin, Di Qin, Yunzhou Shi, Huijing Li, Tian Luo, Caiyun Shi, Yeliu Wang, Zihao Zhao, Wei Cao, Zihao Zou, Qian Yang, Rongjiang Jin, Juan Li, Xianjun Xiao","doi":"10.1007/s40261-024-01389-5","DOIUrl":"10.1007/s40261-024-01389-5","url":null,"abstract":"<p><strong>Background: </strong>The anti-pruritic effect of placebo in patients with chronic urticaria has gained increasing attention in clinical research. However, the extent of placebo effect and its influencing factors in the treatment of chronic urticaria are not well understood.</p><p><strong>Objective: </strong>The objective of this systematic review and meta-analysis was to investigate the effect of placebo on pruritus in patients with chronic urticaria and to explore relevant influencing factors.</p><p><strong>Methods: </strong>PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO were searched from inception to 10 July, 2024. Primary outcome included pruritus scores. The secondary outcomes focused on global symptoms and quality of life. Subgroup analyses and meta-regression analyses were conducted based on drug types, sample size, participants' age, and other variables. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and a trial sequential analysis were employed to establish the reliability of evidence.</p><p><strong>Results: </strong>A total of 65 eligible publications (including 67 randomized controlled trials) involving 10,704 patients with chronic urticaria were included. The pruritus scores decreased following placebo treatment (moderate evidence). In addition, favorable results were observed in global symptoms (moderate evidence) and quality of life (low evidence) after placebo treatment. Subgroup analyses indicated that the type of active medication in intervention groups was an influencing factor of placebo effect of pruritus. Meta-regression analyses demonstrated that the anti-pruritic effect of placebo was inversely correlated with sample size and positively correlated with participants' age. A trial sequential analysis provided further support for the anti-pruritic effect of placebo.</p><p><strong>Conclusions: </strong>A substantial improvement of pruritus after placebo treatment was observed in patients with chronic urticaria. The anti-pruritic effect of placebo varied with sample size, participants' age, and type of active medication used. Future research should further investigate the effect size of placebo and clarify the potential mechanism.</p><p><strong>Prospero registration: </strong>The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42023482608.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"635-654"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}