European Journal of Epidemiology最新文献

{"title":"Use of the instrumental inequalities in simulated mendelian randomization analyses with coarsened exposures.","authors":"Elizabeth W Diemer, Joy Shi, Miguel A Hernan, Sonja A Swanson","doi":"10.1007/s10654-024-01130-8","DOIUrl":"10.1007/s10654-024-01130-8","url":null,"abstract":"<p><p>Mendelian randomization (MR) requires strong unverifiable assumptions to estimate causal effects. However, for categorical exposures, the MR assumptions can be falsified using a method known as the instrumental inequalities. To apply the instrumental inequalities to a continuous exposure, investigators must coarsen the exposure, a process which can itself violate the MR conditions. Violations of the instrumental inequalities for an MR model with a coarsened exposure might therefore reflect the effect of coarsening rather than other sources of bias. We aim to evaluate how exposure coarsening affects the ability of the instrumental inequalities to detect bias in MR models with multiple proposed instruments under various causal structures. To do so, we simulated data mirroring existing studies of the effect of alcohol consumption on cardiovascular disease under a variety of exposure-outcome effects in which the MR assumptions were met for a continuous exposure. We categorized the exposure based on subject matter knowledge or the observed data distribution and applied the instrumental inequalities to MR models for the effects of the coarsened exposure. In simulations of multiple binary instruments, the instrumental inequalities did not detect bias under any magnitude of exposure outcome effect when the exposure was coarsened into more than 2 categories. However, in simulations of both single and multiple proposed instruments, the instrumental inequalities were violated in some scenarios when the exposure was dichotomized. The results of these simulations suggest that the instrumental inequalities are largely insensitive to bias due to exposure coarsening with greater than 2 categories, and could be used with coarsened exposures to evaluate the required assumptions in applied MR studies, even when the underlying exposure is truly continuous.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":"491-499"},"PeriodicalIF":7.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review.","authors":"Grace M Power, Eleanor Sanderson, Panagiota Pagoni, Abigail Fraser, Tim Morris, Claire Prince, Timothy M Frayling, Jon Heron, Tom G Richardson, Rebecca Richmond, Jessica Tyrrell, Nicole Warrington, George Davey Smith, Laura D Howe, Kate M Tilling","doi":"10.1007/s10654-023-01032-1","DOIUrl":"10.1007/s10654-023-01032-1","url":null,"abstract":"<p><p>Diseases diagnosed in adulthood may have antecedents throughout (including prenatal) life. Gaining a better understanding of how exposures at different stages in the lifecourse influence health outcomes is key to elucidating the potential benefits of disease prevention strategies. Mendelian randomisation (MR) is increasingly used to estimate causal effects of exposures across the lifecourse on later life outcomes. This systematic literature review explores MR methods used to perform lifecourse investigations and reviews previous work that has utilised MR to elucidate the effects of factors acting at different stages of the lifecourse. We conducted searches in PubMed, Embase, Medline and MedRXiv databases. Thirteen methodological studies were identified. Four studies focused on the impact of time-varying exposures in the interpretation of \"standard\" MR techniques, five presented methods for repeat measures of the same exposure, and four described methodological approaches to handling multigenerational exposures. A further 127 studies presented the results of an applied research question. Over half of these estimated effects in a single generation and were largely confined to the exploration of questions regarding body composition. The remaining mostly estimated maternal effects. There is a growing body of research focused on the development and application of MR methods to address lifecourse research questions. The underlying assumptions require careful consideration and the interpretation of results rely on select conditions. Whilst we do not advocate for a particular strategy, we encourage practitioners to make informed decisions on how to approach a research question in this field with a solid understanding of the limitations present and how these may be affected by the research question, modelling approach, instrument selection, and data availability.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":"501-520"},"PeriodicalIF":7.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-linear Mendelian randomization: detection of biases using negative controls with a focus on BMI, Vitamin D and LDL cholesterol.","authors":"Fergus W Hamilton, David A Hughes, Wes Spiller, Kate Tilling, George Davey Smith","doi":"10.1007/s10654-024-01113-9","DOIUrl":"10.1007/s10654-024-01113-9","url":null,"abstract":"<p><p>Mendelian randomisation (MR) is an established technique in epidemiological investigation, using the principle of random allocation of genetic variants at conception to estimate the causal linear effect of an exposure on an outcome. Extensions to this technique include non-linear approaches that allow for differential effects of the exposure on the outcome depending on the level of the exposure. A widely used non-linear method is the residual approach, which estimates the causal effect within different strata of the non-genetically predicted exposure (i.e. the \"residual\" exposure). These \"local\" causal estimates are then used to make inferences about non-linear effects. Recent work has identified that this method can lead to estimates that are seriously biased, and a new method-the doubly-ranked method-has been introduced as a possibly more robust approach. In this paper, we perform negative control outcome analyses in the MR context. These are analyses with outcomes onto which the exposure should have no predicted causal effect. Using both methods we find clearly biased estimates in certain situations. We additionally examined a situation for which there are robust randomised controlled trial estimates of effects-that of low-density lipoprotein cholesterol (LDL-C) reduction onto myocardial infarction, where randomised trials have provided strong evidence of the shape of the relationship. The doubly-ranked method did not identify the same shape as the trial data, and for LDL-C and other lipids they generated some highly implausible findings. Therefore, we suggest there should be extensive simulation and empirical methodological examination of performance of both methods for NLMR under different conditions before further use of these methods. In the interim, use of NLMR methods needs justification, and a number of sanity checks (such as analysis of negative and positive control outcomes, sensitivity analyses excluding removal of strata at the extremes of the distribution, examination of biological plausibility and triangulation of results) should be performed.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":"451-465"},"PeriodicalIF":7.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D and human health: evidence from Mendelian randomization studies.","authors":"Aiping Fang, Yue Zhao, Ping Yang, Xuehong Zhang, Edward L Giovannucci","doi":"10.1007/s10654-023-01075-4","DOIUrl":"10.1007/s10654-023-01075-4","url":null,"abstract":"<p><p>We summarized the current evidence on vitamin D and major health outcomes from Mendelian randomization (MR) studies. PubMed and Embase were searched for original MR studies on vitamin D in relation to any health outcome from inception to September 1, 2022. Nonlinear MR findings were excluded due to concerns about the validity of the statistical methods used. A meta-analysis was preformed to synthesize study-specific estimates after excluding overlapping samples, where applicable. The methodological quality of the included studies was evaluated according to the STROBE-MR checklist. A total of 133 MR publications were eligible for inclusion in the analyses. The causal association between vitamin D status and 275 individual outcomes was examined. Linear MR analyses showed genetically high 25-hydroxyvitamin D (25(OH)D) concentrations were associated with reduced risk of multiple sclerosis incidence and relapse, non-infectious uveitis and scleritis, psoriasis, femur fracture, leg fracture, amyotrophic lateral sclerosis, anorexia nervosa, delirium, heart failure, ovarian cancer, non-alcoholic fatty liver disease, dyslipidemia, and bacterial pneumonia, but increased risk of Behçet's disease, Graves' disease, kidney stone disease, fracture of radium/ulna, basal cell carcinoma, and overall cataracts. Stratified analyses showed that the inverse association between genetically predisposed 25(OH)D concentrations and multiple sclerosis risk was significant and consistent regardless of the genetic instruments GIs selected. However, the associations with most of the other outcomes were only pronounced when using genetic variants not limited to those in the vitamin D pathway as GIs. The methodological quality of the included MR studies was substantially heterogeneous. Current evidence from linear MR studies strongly supports a causal role of vitamin D in the development of multiple sclerosis. Suggestive support for a number of other health conditions could help prioritize conditions where vitamin D may be beneficial or harmful.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":"467-490"},"PeriodicalIF":7.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards more reliable non-linear mendelian randomization investigations.","authors":"Stephen Burgess","doi":"10.1007/s10654-024-01121-9","DOIUrl":"10.1007/s10654-024-01121-9","url":null,"abstract":"","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":" ","pages":"447-449"},"PeriodicalIF":7.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multidisciplinary and structured investigation of three suspected clusters of transverse upper limb reduction defects in France","authors":"Julie Boudet-Berquier, Christophe Demattei, Laurence Guldner, Anne Gallay, Sylvie Manouvrier, Jérémie Botton, Claire Philippat, Fleur Delva, Juliette Bloch, Caroline Semaille, Sylvie Odent, Isabelle Perthus, Hanitra Randrianaivo, Sylvie Babajko, Tiphaine Barjat, Claire Beneteau, Naima Brennetot, Ester Garne, Georges Haddad, Mounia Hocine, Isabelle Lacroix, Klervi Leuraud, Michel Mench, Joan Morris, Sophie Patrier, Arnaud Sartelet, Alain Verloes, Christophe Bonaldi, Mélina Le Barbier, Bertrand Gagnière, Philippe Pépin, Ronan Ollivier, Monique Bitoun, Lisa King, Andrea Guajardo-Villar, Eugenia Gomes, Jean-Claude Desenclos, Nolwenn Regnault, Alexandra Benachi","doi":"10.1007/s10654-024-01125-5","DOIUrl":"https://doi.org/10.1007/s10654-024-01125-5","url":null,"abstract":"<p><b>Introduction</b>: Between 2019–2021, facing public concern, a scientific expert committee (SEC) reanalysed suspected clusters of transverse upper limb reduction defects (TULRD) in three administrative areas in France<i>,</i> where initial investigations had not identified any risk exposure. We share here the national approach we developed for managing suspicious clusters of the same group of congenital anomalies occurring in several areas. <b>Methods: </b>The SEC analysed the medical records of TURLD suspected cases and performed spatiotemporal analyses on confirmed cases. If the cluster was statistically significant and included at least three cases, the SEC reviewed exposures obtained from questionnaires, environmental databases, and a survey among farmers living near to cases’ homes concerning their plant product use. <b>Results: </b>After case re-ascertainment, no statistically significant cluster was observed in the first administrative areas. In the second area, a cluster of four children born in two nearby towns over two years was confirmed, but as with the initial investigations, no exposure to a known risk factor explaining the number of cases in excess was identified. In the third area, a cluster including just two cases born the same year in the same town was confirmed. <b>Discussion: </b>Our experience highlights that in the event of suspicious clusters occurring in different areas of a country, a coordinated and standardised approach should be preferred.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"22 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140807369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continued decline in the incidence of myocardial infarction beyond the COVID-19 pandemic: a nationwide study of the Swedish population aged 60 and older during 2015–2022","authors":"Anna C. Meyer, Marcus Ebeling, Enrique Acosta, Karin Modig","doi":"10.1007/s10654-024-01118-4","DOIUrl":"https://doi.org/10.1007/s10654-024-01118-4","url":null,"abstract":"<p>The number of myocardial infarctions declined during the early COVID-19 pandemic but mechanisms behind these declines are poorly understood. COVID-19 infection is also associated with an increased risk of myocardial infarction which could lead to higher incidence rates in the population. This study aims to shed light on the seemingly paradoxical relationship between COVID-19 and myocardial infarction occurrence on the population level by exploring long-term trends in incidence rates, case fatality, and proportion of patients dying before reaching a hospital. Our work is based on a linkage of administrative registers covering the entire population aged 60 + in Sweden. Considering both long-term trends since 2015 and seasonal variability, we compared observed incidence, case fatality, and proportions of patients hospitalized to expected values during 2020–2022. Despite more than 200 laboratory-confirmed COVID-19 cases per 1000 inhabitants by the end of 2022, incidence rates of myocardial infarction continued to decline, thus following the long-term trend observed already before 2020. During the first pandemic wave there was an additional incidence decline corresponding to 13% fewer myocardial infarctions than expected. This decline was neither accompanied by increasing case fatality nor by lower shares of patients being hospitalized. We found no increase in the population-level incidence of myocardial infarction despite large-scale exposure to COVID-19, which suggests that the effect of COVID-19 on myocardial infarction risk is not substantial. Increased pressure on the Swedish health care system has not led to increased risks or poorer outcomes for patients presenting with acute myocardial infarction.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"23 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The underestimated preventive effects of flexible sigmoidoscopy screening: re-analysis and meta-analysis of randomized trials","authors":"Hermann Brenner, Thomas Heisser, Rafael Cardoso, Michael Hoffmeister","doi":"10.1007/s10654-024-01120-w","DOIUrl":"https://doi.org/10.1007/s10654-024-01120-w","url":null,"abstract":"<p>Flexible sigmoidoscopy (FS), which is less invasive, resource intensive and costly than colonoscopy, is among the recommended screening options for colorectal cancer (CRC). Four large randomized trials consistently reported statistically significant, albeit modest effects of screening by FS on CRC incidence. However, their effect estimates included cancers that were already prevalent at recruitment and could not have been prevented by screening. We performed a re-analysis and meta-analysis of two of the trials (including the largest one) to estimate reduction of truly incident cases by a single FS offered between 55 and 64 years of age among the “at risk study population” without prevalent CRC at recruitment. In meta-analyses of data reported after more than 15 years of follow-up, relative risk (95% CI) in intention-to-screen and per-protocol analyses were 0.71 (0.66–0.76) and 0.59 (0.55–0.65) for any CRC, and 0.52 (0.47–0.57) and 0.34 (0.30–0.39) for distal CRC, respectively. These results indicate much stronger effects than those suggested by the original reports and imply that a single screening FS can prevent approximately two out of three distal incident CRC cases within 15 + years of follow-up.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"19 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140622727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, cohort profile and comparison of the KTD-Innov study: a prospective multidimensional biomarker validation study in kidney allograft rejection","authors":"Valentin Goutaudier, Marta Sablik, Maud Racapé, Olivia Rousseau, Benoit Audry, Nassim Kamar, Marc Raynaud, Olivier Aubert, Béatrice Charreau, Emmanuelle Papuchon, Richard Danger, Laurence Letertre, Lionel Couzi, Emmanuel Morelon, Moglie Le Quintrec, Jean-Luc Taupin, Eric Vicaut, Christophe Legendre, Hoa Le Mai, Vishnu Potluri, Thi-Van-Ha Nguyen, Marie-Eliane Azoury, Alice Pinheiro, Georges Nouadje, Pierre Sonigo, Dany Anglicheau, Ineke Tieken, Serge Vogelaar, Christian Jacquelinet, Peter Reese, Pierre-Antoine Gourraud, Sophie Brouard, Carmen Lefaucheur, Alexandre Loupy","doi":"10.1007/s10654-024-01112-w","DOIUrl":"https://doi.org/10.1007/s10654-024-01112-w","url":null,"abstract":"<p>There is an unmet need for robust and clinically validated biomarkers of kidney allograft rejection. Here we present the KTD-Innov study (ClinicalTrials.gov, NCT03582436), an unselected deeply phenotyped cohort of kidney transplant recipients with a holistic approach to validate the clinical utility of precision diagnostic biomarkers. In 2018–2019, we prospectively enrolled consecutive adult patients who received a kidney allograft at seven French centers and followed them for a year. We performed multimodal phenotyping at follow-up visits, by collecting clinical, biological, immunological, and histological parameters, and analyzing a panel of 147 blood, urinary and kidney tissue biomarkers. The primary outcome was allograft rejection, assessed at each visit according to the international Banff 2019 classification. We evaluated the representativeness of participants by comparing them with patients from French, European, and American transplant programs transplanted during the same period. A total of 733 kidney transplant recipients (64.1% male and 35.9% female) were included during the study. The median follow-up after transplantation was 12.3 months (interquartile range, 11.9–13.1 months). The cumulative incidence of rejection was 9.7% at one year post-transplant. We developed a distributed and secured data repository in compliance with the general data protection regulation. We established a multimodal biomarker biobank of 16,736 samples, including 9331 blood, 4425 urinary and 2980 kidney tissue samples, managed and secured in a collaborative network involving 7 clinical centers, 4 analytical platforms and 2 industrial partners. Patients' characteristics, immune profiles and treatments closely resembled those of 41,238 French, European and American kidney transplant recipients. The KTD-Innov study is a unique holistic and multidimensional biomarker validation cohort of kidney transplant recipients representative of the real-world transplant population. Future findings from this cohort are likely to be robust and generalizable.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"2012 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140604000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital anomalies during Covid-19: artifact of surveillance or a real TORCH?","authors":"Nathalie Auger, Laura Arbour, Antoine Lewin, Émilie Brousseau, Jessica Healy-Profitós, Thuy Mai Luu","doi":"10.1007/s10654-024-01122-8","DOIUrl":"https://doi.org/10.1007/s10654-024-01122-8","url":null,"abstract":"<p>Infections in the first trimester of pregnancy can be teratogenic, but the possibility that Covid-19 could lead to birth defects is unclear. We examined whether SARS-CoV-2 infection during pregnancy or exposure to pandemic conditions were associated with the risk of congenital anomalies. We carried out a retrospective study of 420,222 neonates born in Quebec, Canada in two time periods: prepandemic (January 1, 2017 to March 12, 2020) vs. pandemic (March 13, 2020 to March 31, 2022). We classified pandemic births as early (first trimester completed before the pandemic) or late (first trimester during the pandemic), and identified patients with SARS-CoV-2 infections during pregnancy. We applied (1) adjusted log-binomial regression models to assess the association between SARS-CoV-2 infection and congenital anomalies, and (2) autoregressive interrupted time series regression to analyze temporal trends in the monthly number of defects in all patients regardless of infection. In total, 29,263 newborns (7.0%) had a congenital anomaly. First trimester SARS-CoV-2 infections were not associated with a greater risk of birth defects compared with no infection (RR 1.07, 95% CI 0.59–1.95). However, births during the late pandemic period were more likely to be diagnosed with congenital microcephaly compared with prepandemic births (RR 1.44, 95% CI 1.21–1.71). Interrupted time series analysis confirmed that the frequency of microcephaly increased during the late pandemic period, whereas other anomalies did not. We conclude that Covid-19 is likely not teratogenic, but enhanced surveillance of anomalies among late pandemic births may have heightened the detection of infants with microcephaly.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"39 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140538334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}