Journal of studies on alcohol. Supplement最新文献

{"title":"Design and analysis of trials of combination therapies.","authors":"James D Hosking,&nbsp;Ron A Cisler,&nbsp;David J Couper,&nbsp;David R Gastfriend,&nbsp;Daniel R Kivlahan,&nbsp;Raymond F Anton","doi":"10.15288/jsas.2005.s15.34","DOIUrl":"https://doi.org/10.15288/jsas.2005.s15.34","url":null,"abstract":"<p><strong>Objective: </strong>Combination therapies can have significant advantages over monotherapies. Combinations of therapies can provide additive (or even synergistic) effects on efficacy. They may permit use of lower doses of each component to achieve a given level of efficacy, improving tolerability and reducing adverse effects. A multicomponent treatment may facilitate tailoring of therapy to the needs of individual patients (e.g., treatment augmentation in nonresponders). These characteristics seem highly attractive in developing treatment strategies for alcohol abuse and dependence, because existing monotherapies have shown modest efficacy, at best.</p><p><strong>Method: </strong>However, trials of combination therapies present challenges in design, execution and interpretation, including: (1) choice of the treatment combinations to be compared; (2) definition of primary and secondary hypotheses; (3) differences between interventions in the duration of treatment, the time lag from the start of treatment to an observable effect on outcomes and interval for assessment of efficacy; (4) study power/sample size; (5) logistics of treatment delivery, masking and outcome assessment; and (6) attribution of adverse events.</p><p><strong>Results: </strong>Most of these issues arose in the COMBINE project, a sequence of trials intended to explore the use of combinations of behavioral and pharmacological approaches in the treatment of alcohol dependence. The resolution and impact of the challenges above for the COMBINE trial will be described.</p><p><strong>Conclusions: </strong>Trials of combination therapies address many important clinical questions; however, their level of complexity requires considerable forethought, pilot investigations and organization.</p>","PeriodicalId":17056,"journal":{"name":"Journal of studies on alcohol. Supplement","volume":" 15","pages":"34-42; discussion 33"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.15288/jsas.2005.s15.34","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25646335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost methodology of COMBINE.","authors":"Gary A Zarkin,&nbsp;Jeremy W Bray,&nbsp;Debanjali Mitra,&nbsp;Ron A Cisler,&nbsp;Daniel R Kivlahan","doi":"10.15288/jsas.2005.s15.50","DOIUrl":"https://doi.org/10.15288/jsas.2005.s15.50","url":null,"abstract":"<p><strong>Objective: </strong>This article describes the methodology used in estimating the mean cost per patient of the interventions delivered in COMBINE, a randomized controlled trial (RCT) comparing pharmacotherapies and behavioral interventions for outpatient treatment of alcohol dependence.</p><p><strong>Method: </strong>Our methodology identifies a broad list of nonresearch activities necessary to implement the COMBINE interventions in standard clinical practice. For each activity, we include the time costs of clinical assessments and interventions by staff, the cost of space, laboratory charges and the cost of medical supplies. We also estimate the patients' time used for each of these activities.</p><p><strong>Results: </strong>We present the estimated cost per activity for 15 intake assessments plus the Medical Management (MM) and Combined Behavioral Intervention (CBI) sessions for 9 of the 11 COMBINE sites. Labor costs represent the bulk of the total cost for all activities. The Form 90 AIR/ED is the most expensive intake activity both in terms of labor and space costs. The CBI session is more expensive than the MM session.</p><p><strong>Conclusions: </strong>Our methodology estimates the cost to treatment providers and to patients of implementing the COMBINE intervention in standard practice. Compared with previous methods, the prospective design of our methodology allows for higher quality data, and the detailed activity costing helps identify key cost drivers. Future analyses will present actual COMBINE intervention cost estimates based on trial data. Although this cost study is specific to the COMBINE interventions, the concepts, instruments and methods used here can be applied to any RCT.</p>","PeriodicalId":17056,"journal":{"name":"Journal of studies on alcohol. Supplement","volume":" 15","pages":"50-5; discussion 33"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.15288/jsas.2005.s15.50","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25646338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How pilot studies improve large-scale clinical trials: lessons learned from the COMBINE Study.","authors":"Stephanie S O'Malley,&nbsp;Daniel J Martin,&nbsp;James D Hosking,&nbsp;Barbara J Mason","doi":"10.15288/jsas.2005.s15.66","DOIUrl":"https://doi.org/10.15288/jsas.2005.s15.66","url":null,"abstract":"<p><strong>Objective: </strong>The design of a clinical trial to evaluate a potential therapy requires decisions about issues that include safety, efficacy, measurement, feasibility and training. Experience from the COMBINE Study, which tests the combination of medications and behavioral therapies for alcohol dependence, is presented as an example of how pilot studies improve large-scale clinical trials.</p><p><strong>Method: </strong>The COMBINE Pilot 1 inpatient study was designed to inform the main trial about the safety and tolerability of the doses of acamprosate (3 g/day) and naltrexone (100 mg/day) selected for study, alone and in combination. Pilot 2 was conducted as a feasibility study for the main trial, with the goals of (1) assessing the length of and compliance with research assessments, (2) developing methods for subject recruitment and staff training and (3) assessing the safety of the medications under less controlled outpatient conditions.</p><p><strong>Results: </strong>Results from Pilot 1 provided safety information to support testing the medications in an outpatient study and contributed to the decision to incorporate dose reductions into the main trial protocol to manage adverse events. The results of Pilot 2 formed a basis for (1) reducing the length of the assessment battery, (2) having staff fully trained and recruitment procedures established for the main trial and (3) extending the drug safety results of Pilot 1 to outpatient conditions similar to those of the main trial.</p><p><strong>Conclusions: </strong>The COMBINE Study provides several examples of the successful application of pilot studies to inform the design of a clinical trial.</p>","PeriodicalId":17056,"journal":{"name":"Journal of studies on alcohol. Supplement","volume":" 15","pages":"66-71; discussion 65"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.15288/jsas.2005.s15.66","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25646340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factorial designs in clinical trials: options for combination treatment studies.","authors":"David J Couper,&nbsp;James D Hosking,&nbsp;Ron A Cisler,&nbsp;David R Gastfriend,&nbsp;Daniel R Kivlahan","doi":"10.15288/jsas.2005.s15.24","DOIUrl":"https://doi.org/10.15288/jsas.2005.s15.24","url":null,"abstract":"<p><strong>Objective: </strong>This study reviews the use of factorial designs in clinical trials investigating combinations of therapies.</p><p><strong>Method: </strong>Factorial designs may be used when (1) the factors are regarded as being independent or (2) the factors are thought to be complementary and a specific aim is to investigate these interactions. We describe what is meant by a factorial design and the issues that need to be addressed when using such a design. We discuss these issues in general and describe how they have been addressed in various prevention trials and in the COMBINE Study, which is a treatment trial of combinations of therapies for alcohol dependence.</p><p><strong>Results: </strong>Trials of type (1) can provide substantial cost savings in conducting multiple unrelated prevention studies in the same group of participants. Such a factorial trial poses few design challenges beyond those of a standard parallel group trial. Trials of type (2) require consideration of aspects that are intrinsic to the factorial design.</p><p><strong>Conclusions: </strong>A factorial design is a useful way to examine the effects of combinations of therapies, but it poses challenges that need to be addressed in determining the appropriate sample size and in conducting interim and final statistical analyses.</p>","PeriodicalId":17056,"journal":{"name":"Journal of studies on alcohol. Supplement","volume":" 15","pages":"24-32; discussion 6-7"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.15288/jsas.2005.s15.24","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25646333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COMBINE genetics study: the pharmacogenetics of alcoholism treatment response: genes and mechanisms.","authors":"David Goldman,&nbsp;Gabor Oroszi,&nbsp;Stephanie O'Malley,&nbsp;Raymond Anton","doi":"10.15288/jsas.2005.s15.56","DOIUrl":"https://doi.org/10.15288/jsas.2005.s15.56","url":null,"abstract":"OBJECTIVE Partial efficacy of treatment and differences in adverse events across individuals are a challenge and an opportunity in the treatment of alcoholism. Individuation of therapy and understanding origins of differential treatment response may require identification of inherited functional variants of genes. The neurobiology of reward, executive cognitive function, anxiety and dysphoria have been identified as critical domains that may have a genetic basis that could predict treatment response. METHOD The COMBINE Study presents a unique opportunity to evaluate specific genetic loci (markers) that affect neurobiology central to addiction and extended withdrawal. The study also addresses variation in drug metabolism and action. Candidate genetic markers are selected for study based on functionality and abundance. RESULTS COMT Vall58Met is a common (minor allele frequency 0.42), functional, catecholamine-metabolizing enzyme polymorphism with threefold relevance. Vall58Met alters executive cognitive function, stress and anxiety responses and brain endogenous opioid function. OPRM1 Asn40Asp is a common (minor allele frequency 0.10), functional polymorphism of the mu-opioid receptor, which may serve as a gatekeeper molecule in naltrexone's actions and was recently reported to affect naltrexone response. HTTLPR (minor allele frequency 0.40) alters serotonin transporter function to affect anxiety, dysphoria and obsessional behavior, which are assessed in COMBINE and may be related to relapse and addictive behavior. CONCLUSIONS All genetic testing is consented through a separate human research protocol, and the testing is conducted nonclinically, confidentially and apart from the clinical record to protect human research participants who have volunteered for this aspect of COMBINE.","PeriodicalId":17056,"journal":{"name":"Journal of studies on alcohol. Supplement","volume":" 15","pages":"56-64; discussion 33"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.15288/jsas.2005.s15.56","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25646339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Choosing pharmacotherapies for the COMBINE Study--process and procedures: an investigational approach to combination pharmacotherapy for the treatment of alcohol dependence.","authors":"Robert Swift,&nbsp;Helen M Pettinati","doi":"10.15288/jsas.2005.s15.141","DOIUrl":"https://doi.org/10.15288/jsas.2005.s15.141","url":null,"abstract":"<p><strong>Objective: </strong>This article describes the process by whichthe COMBINE investigators evaluated and chose the two pharmacotherapies to be studied in COMBINE.</p><p><strong>Method: </strong>The pharmacotherapies were chosen through a consensus process that involved the evaluation of neuropharmacological agents known to modify alcohol consumption or other alcohol-related behaviors in animals and humans. Medications were classified according to the published evidence, with the highest ranking given to those with evidence of efficacy in human clinical trials. The investigators also considered evidence for safety, potential drug-drug interactions, management of side effects, optimal dose, treatment duration, availability of the medication and integration with the psychosocial therapies. The full evaluation required conducting two pilot studies and the development of an instrument to monitor safety, the COMBINE Systematic Assessment for Treatment Emergent Events.</p><p><strong>Results: </strong>Naltrexone, at a dose of 100 mg per day, and acamprosate, at a dose of 3,000 mg per day, were chosen for the study. The medications were administered for a period of 4 months, concurrent with the COMBINE psychosocial therapies</p><p><strong>Conclusions: </strong>The results of the decision making with respect to medications and safety monitoring resulted in a well-planned and well-executed study that minimized risks to the participants.</p>","PeriodicalId":17056,"journal":{"name":"Journal of studies on alcohol. Supplement","volume":" 15","pages":"141-7; discussion 140"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25633694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Origins, issues and options in the development of the combined behavioral intervention.","authors":"Richard Longabaugh,&nbsp;Allen Zweben,&nbsp;Joseph S Locastro,&nbsp;William R Miller","doi":"10.15288/jsas.2005.s15.179","DOIUrl":"https://doi.org/10.15288/jsas.2005.s15.179","url":null,"abstract":"<p><strong>Objective: </strong>The aim of the investigators was to develop a moderate intensity comprehensive behavioral treatment based on the principles of motivational interviewing and Cognitive Behavioral Therapy that, within the confines of a standardized abstinence-oriented treatment, would provide a broad spectrum of modules to assist those seeking treatment to achieve reduction of problematic drinking.</p><p><strong>Method: </strong>The core issue of how to deliver a flexible therapy tailored to the needs of individual clients while at the same time providing a standardized treatment protocol for a randomized clinical trial provided the dilemma out of which this unique standardized protocol arose. By using a single decision tree, client choice, combined with limited options, we were able to reconcile these conflicting demands.</p><p><strong>Results: </strong>Key decisions that were made in developing the treatment protocol and the thinking leading to these decisions are described.</p><p><strong>Conclusions: </strong>Understanding these key issues and the factors that led to the decisions made will assist would-be users in their own clinical and/or clinical research needs.</p>","PeriodicalId":17056,"journal":{"name":"Journal of studies on alcohol. Supplement","volume":" 15","pages":"179-87; discussion 168-9"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.15288/jsas.2005.s15.179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25633637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a baseline assessment battery: balancing patient time burden with essential clinical and research monitoring.","authors":"David R Gastfriend,&nbsp;Dennis Donovan,&nbsp;Rachel Lefebvre,&nbsp;Kelly T Murray","doi":"10.15288/jsas.2005.s15.94","DOIUrl":"https://doi.org/10.15288/jsas.2005.s15.94","url":null,"abstract":"<p><strong>Objective: </strong>Baseline assessment in a multisite alcohol-dependence treatment study has several purposes: addressing inclusion/exclusion criteria and characterizing participants to illuminate subsequent efficacy and safety patterns of the interventions. Combination pharmacotherapy and behavioral therapy trials, however, require more complex assessments than single-modality studies. Medication trials require measures of initial safety for study drug as well as for subsequent side-effect and adverse-effect monitoring (e.g., physical examination, laboratory markers, somatic symptoms, medical conditions and concomitant medications). Behavioral therapy trials (and in some cases medication trials) warrant baseline measurement of mediators of therapy effect (e.g., prior treatment history, motivation for change, self-efficacy, other psychiatric conditions, treatment expectations and network supports). Measures may be needed to interpret interactions that may be discovered between these modalities.</p><p><strong>Method: </strong>The National Institute on Alcohol Abuse and Alcoholism COMBINE Study evaluated the potentially overwhelming number of candidate instruments through an iterative process, using the following sequence to finalize a rational baseline assessment battery: key constructs, representative measures, determination of duration of assessment, risk of assessment reactivity, goal priorities, necessity for measure \"pruning\" and order of measure presentation. After selecting the draft battery, feasibility was evaluated in a pilot study prior to the main trial.</p><p><strong>Results: </strong>The battery was feasible to administer and avoided unintended selection bias. Dropout was substantial, however, and differences across sites in baseline assessment completion rates reflected a tendency of a central intake model to function as an initial filter of dropouts, compared with a direct recruitment model.</p><p><strong>Conclusions: </strong>This process holds several potentially useful lessons for investigators.</p>","PeriodicalId":17056,"journal":{"name":"Journal of studies on alcohol. Supplement","volume":" 15","pages":"94-103; discussion 92-3"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.15288/jsas.2005.s15.94","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25633690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The COMBINE SAFTEE: a structured instrument for collecting adverse events adapted for clinical studies in the alcoholism field.","authors":"Bankole A Johnson,&nbsp;Nassima Ait-Daoud,&nbsp;John D Roache","doi":"10.15288/jsas.2005.s15.157","DOIUrl":"https://doi.org/10.15288/jsas.2005.s15.157","url":null,"abstract":"<p><strong>Objective: </strong>In the many clinical studies conducted in the alcoholism field with psychotropic drugs--and throughout the drug development field in medicine, where evaluation of adverse events can be incomplete, arbitrary or misleading--few standardized methods have been developed for assessing adverse events, whereas defining standardized methods for evaluating clinical efficacy is typical. For the National Institute on Alcohol Abuse and Alcoholism COMBINE Study, testing the safety and efficacy of naltrexone and acamprosate, both alone and in combination, in the treatment of alcohol dependence, we adapted a standardized instrument--the Systematic Assessment for Treatment Emergent Events (SAFTEE)--for assessing adverse events in these Phase 2- to Phase 3-type studies.</p><p><strong>Method: </strong>We standardized use of the SAFTEE with training, supervision and clear guidelines for its implementation, including development of a nomenclature for the typical adverse events associated with these medications and a format for examining symptom severity. Data from the COMBINE SAFTEE include not only frequency of adverse events but also severity level and a composite index taking into account both the severity and duration of symptoms.</p><p><strong>Results: </strong>The COMBINE SAFTEE was incorporated into the Medical Management therapy and showed high fidelity with its utility, consistency of deliverability and flexibility in measuring adverse events in both the human laboratory and clinical trial settings using intervals that varied from daily to weekly use.</p><p><strong>Conclusions: </strong>Due to its high standardization level, the COMBINE SAFTEE could be incorporated into other brief compliance enhancement strategies in clinical studies to assess the efficacy of putative therapeutic drugs.</p>","PeriodicalId":17056,"journal":{"name":"Journal of studies on alcohol. Supplement","volume":" 15","pages":"157-67; discussion 140"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.15288/jsas.2005.s15.157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25633696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A structured approach to medical management: a psychosocial intervention to support pharmacotherapy in the treatment of alcohol dependence.","authors":"Helen M Pettinati,&nbsp;Roger D Weiss,&nbsp;William Dundon,&nbsp;William R Miller,&nbsp;Dennis Donovan,&nbsp;Denise B Ernst,&nbsp;Bruce J Rounsaville","doi":"10.15288/jsas.2005.s15.170","DOIUrl":"https://doi.org/10.15288/jsas.2005.s15.170","url":null,"abstract":"<p><strong>Objective: </strong>Given the national trend toward integrating substance abuse treatment into medical practice, experts in the field of alcoholism designed a psychosocial, medically based intervention to be used with pharmacotherapy in the COMBINE multisite national study, supported by the National Institute on Alcohol Abuse and Alcoholism. A main purpose of the COMBINE Study is to investigate optimal treatment for patients with alcohol dependence by combining pharmacotherapy and psychosocial interventions.</p><p><strong>Method: </strong>The medically based intervention, called Medical Management (MM), was specifically constructed to be implemented by medically trained practitioners in nonspecialty settings. Each visit includes evaluations of medication safety and adherence, monitoring of alcohol use and direct advice to the patient for achieving full recovery.</p><p><strong>Results: </strong>There are several themes implicit in MM. Patient education about the disorder and about the treatment being provided are both essential. The clinician also educates the patient about how he or she has been affected by alcohol dependence. Information is given on how to take the medication(s) as prescribed, what the patient should expect from the medication(s) and what kinds of events the clinician will need to know about during treatment. Finally, the clinician and patient discuss strategies for ensuring medication safety and adherence to the prescribed regimen.</p><p><strong>Conclusions: </strong>MM was easily implemented in the COMBINE Study with the aid of the MM Treatment Manual.</p>","PeriodicalId":17056,"journal":{"name":"Journal of studies on alcohol. Supplement","volume":" 15","pages":"170-8; discussion 168-9"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.15288/jsas.2005.s15.170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25633697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}