Time-to-event outcomes are a key component in survival analyses. Effect modification by time, also known as interaction between effect and time, can exist in time-to-event data and influence the analysis process. Our objective is to discuss the proper methods to conduct evidence synthesis of time-to-event data when effect modification by time exists.
In the study of real-world data, the pragmatic randomized controlled trial can provide the optimal evidence for clinical decisions. Although randomization protects against confounding, post-randomization confounding may still arise due to non-compliance. Traditional intention-to-treat analysis will drift apart from true estimation and lead to deviation of clinical decisions. Meanwhile, the alternative traditional methods would subject to bias and confounding. Thus, new methods are required for revolution, i.e., instrument variable method and modern per-protocol analysis. Our study reviews the defects of traditional methods in pragmatic randomized controlled trials, and then refers to two new methods with a detailed discussion of strengths and weaknesses. We aim to provide researches with insights on choosing the statistical methods for pragmatic trial.
ObjectivesTo systematically review the efficacy and safety of autologous bone marrow cells therapy for patients with diabetic foot. GRADE system was used to evaluate the evidence quality of outcomes.MethodsWe searched databases including PubMed, EMbase, The Cochrane Library, CBM, WanFang Data and CNKI for randomized controlled trials (RCTs) about bone marrow cell transplantation in patients with diabetic foot from inception to February 28th 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was performed using RevMan 5.3 software. The evidence quality was evaluated by using GRADE profiler 3.6 software.ResultsFour RCTs were included. Meta-analysis showed that the bone marrow cell transplantation could decrease the rate of amputation (RR=0.08, 95%CI 0.00 to 1.32, P=0.08) and rest pain score (MD=–1.89, 95%CI –2.24 to –1.55, P<0.000 01), increase the rate of ameliorate ulcer healing (RR=2.01, 95%CI 1.45 to 2.79,P<0.000 1) and the quantity of new collateral vessels (MD=1.33, 95%CI 0.60 to 2.05,P<0.000 3). Besides, bone marrow cell transplantation could improve ankle-brachial index (MD=0.16, 95%CI 0.10 to 0.22,P<0.000 01) and transcutaneous arterial oxygen tension (MD=18.81, 95%CI 16.06 to 21.57,P<0.000 01). No adverse event was reported for all included studies. The qualities of evidence for all outcomes were rated as "low" to "very low".ConclusionBased on the current evidence, autologous bone marrow cells transplantation therapy has a certain effect and it is safe for patients with diabetic foot. However, due to the limited quantity and quality of included studies, the above conclusions are still needed more multicenter clinical trials with large sample size to confirm.
Objective When making causal inferences in observational studies, in order to improve the robustness of the results of observational studies, statistical analysis techniques are often used to estimate the impact of unmeasured potential confounding factors. By systematically reviewing the application progress of the E-value, one of the sensitivity analysis methods, the advantages and limitations of using the E-value were discussed, to provide references for the application, reporting and interpretation of the E-value. Methods In the PubMed database, E-value was used as a keyword for title, abstract and key paper citation retrieval, and the literature that used the E-value analysis method for sensitivity analysis during 2016-2021 was screened. Results The E-value was widely used not only in cohort studies (n=215) and case-control studies (n=15), but also in cross-sectional studies (n=28), randomized controlled trials (n=6) and meta-analysis (n=16). The E-value was often combined with other sensitivity analysis methods, such as hierarchical analysis, instrumental variables, and multiple statistical regression models that correct different covariates, to further explore the reliability and robustness of the results. Conclusion When the E-value is used to evaluate the confounding factors in observational studies, the confidence interval and P value can be combined to evaluate the sensitivity of the results more comprehensively.
Objective To analyze the current state, evaluate the accuracy, and determine the influencing factors of diabetes-related subscriptions on the WeChat platform. Methods The top 100 WeChat platforms on the "China WeChat Platform New Rank Annual List 2020" were searched using the term "diabetes". We identified diabetes-related subscriptions published from June 1, 2021 to August 31, 2021. The accuracy of subscriptions was analyzed according to the consistency with clinical practice guidelines, and was independently assessed by two specialists. SPSS 22.0 software was used for data analysis. Results Sixty-eight subscriptions from 26 WeChat platforms were included. Twenty-five (36.8%) subscriptions were evaluated as inconsistent. The numbers of "wow" per thousand reads and "like" per thousand reads of inconsistent diabetic subscriptions were statistically higher than those of consistent diabetic subscriptions (P<0.05). Subscriptions with expert support (80.8% vs. 52.4%) and evidence support (91.7% vs. 57.1%) shared a higher consistency (P<0.05). Subscriptions with commercial promotion (16.7% vs. 67.7%) had a lower consistency (P=0.02). Conclusion Although some content is inconsistent with guidelines, diabetes-related subscriptions have a certain dissemination ability on the WeChat platform. Moreover, readers are more likely to "wow" or "like" for inconsistent subscriptions. Diabetes-related subscriptions on the WeChat public platform need supervision and can be further regulated by providing evidence support and regulating commercial promotion.
Randomized controlled trials (RCTs) are considered the “gold standard” for evaluating the causal effects of interventions on outcome measures. However, due to high research costs and ethical constraints, conducting RCTs in clinical practice, especially in the surgical field, faces numerous challenges such as difficulties in subject recruitment, implementation of blinding, and standardization of interventions. In such cases, using real-world data to perform causal inference under the framework of target trial emulation (TTE), based on the principles of RCT design, helps to identify and reduce biases arising from design flaws in traditional observational studies, such as immortal time bias, confounding, selection bias, or collider bias. This approach can produce high-quality evidence comparable to that of RCTs, thereby enhancing the clinical guidance value of real-world data studies. However, TTE has limitations, such as the inability to completely eliminate confounding, high quality requirements for source data, and the current lack of reporting standards. Therefore, researchers should be fully aware of these limitations to avoid making incorrect causal inferences. This article intends to provide an overview of the TTE framework, implementation points, application scope, application cases, and advantages and disadvantages of the framework.
Objective To investigate the financial burden of in-patients with thyroid diseases in the West China Hospital in Chengdu, Sichuan province, from January 2011 to December 2012, so as to provide baseline data for further research. Methods The data of in-patients (who had been discharged from the department of endocrinology and metabolism or discharged after being transferred to other departments for diagnosis and treatment in the West China Hospital in 2011) were collected from the Hospital Information System (HIS) of the West China Hospital, including basic information, initial diagnosis when the patients were discharged, hospital costs, the information about whether the patients had been registered the insurance in hospital, etc. We classified diseases according to ICD-10 based on the initial diagnosis when the patients were discharged on the first page of case reports. The data were input using Excel 2010 software, and statistical analysis was performed using SPSS 13.0 software. Results The results showed that: a) in 2011, 205 person-times were hospitalized in the department of endocrinology and metabolism, of which, 84 were male and 121 were female, with mean age of 45.3±15.7 years; b) for patients with thyroid diseases, median hospital stay was 10 days, the average cost of hospital stay for each patient was RMB 2 881.43 yuan, most of which was for lab tests and examination; c) the person-times of patients with hyperthyroidism was 162, accounting for 79.5% of the total of thyroid diseases, median hospital stay was 10 days, and the average cost of hospital stay was RMB 2 958.36 yuan; and d) there was no association between the number of hyperthyroidism complications and hospital stay and costs. Conclusion Thyroid diseases are a commonly-seen disease in the department of endocrinology and metabolism, of which, hyperthyroidism accounts for the most. There is no association between the number of hyperthyroidism complications and hospital stay/costs.
Objective To investigate financial burden of in-patients with hypothalamus-pituitary-adrenal gland/gonad diseases in the West China Hospital of Sichuan University, 2011, so as to provide baseline data for further research. Methods The data of in-patients (who had been discharged from the department of endocrinology and metabolism or discharged after being transferred to other departments for diagnosis and treatment in the West China Hospital in 2011) were collected from the Hospital Information System (HIS) of the West China Hospital, including basic information, initial diagnosis when the patients were discharged, hospital costs, the information about whether the patients had been registered the insurance in hospital, etc. We classified diseases according to ICD-10 based on the initial diagnosis when the patients were discharged on the first page of case reports. The data were input using Excel 2010 software, and statistical analysis was performed using SPSS 13.0 software. Results The results showed that: in 2011, 352 person-times of in-patients with hypothalamus-pituitary-adrenal gland/gonad disease as first diagnosis were hospitalized in the department of endocrinology and metabolism, of which, 139 were male and 213 were female, with mean age of 42.9±15.0 years; and b) median hospital stay was 11 days, the average cost of hospital stay for each patient was RMB 4 361.09 yuan, most of which was for lab tests, examination, and biomedicine cost. Conclusion Hypothalamus-pituitary-adrenal gland/gonad diseases are an important health problem in the department of endocrinology and metabolism in a Triple-A Hospital. Most of hospitalization costs are for lab tests, examination, and biomedicine cost.
Objective To investigate the association between costs of hospitalized patients with diabetes mellitus and their complications in the West China Hospital of Sichuan University, so as to provide baseline data for further research. Methods We extracted the hospitalization case data of hospitalized patients with diabetes mellitus who were discharged from the department of endocrinology and metabolism, or discharged after being transferred to other departments for treatment from January 2011 to December 2012, using the hospital information system (HIS) of the West China Hospital of Sichuan University. The data included baseline of hospital patients, discharge diagnosis, hospitalization costs, and if their medical insurance had been registered in hospital. Then, we classified the diseases according to ICD-10 based on discharge diagnosis, coped the data using Excel 2010 software, and conducted statistical analysis using SPSS 13.0. Results a) In 2011, acute and chronic diabetes complication in diabetes inpatients were 11.9% (166/1 396) and 67.1% (930/1 396), respectively. Most of them had peripheral neuropathy and peripheral vascular disease. b) The most frequently-occurred complications were hypertension, followed by dyslipidemia, and osteoporosis. c) The median hospital stay was 13 days (7 to 9 days), and the median total cost of hospital/person-time was 6 578.88 yuan (4 186.93 to 10 953.89 yuan). d) The total cost and duration of hospitalization increased along with the increasing number of the chronic complications of diabetes. e) The diabetic foot patients were 255 person-times, the median duration of hospitalization was 18 days (13 to 29 days), and the median total cost of hospital/person-time was 16 672.19 yuan (10 903.93 to 28 530.37 yuan). Diabetes patients with foot complication had higher total costs and longer duration of hospitalization than those without foot complication. Conclusion Diabetes mellitus is one of the most important diseases in the department of endocrinology and metabolism, which is heavy disease burden. The costs of hospitalization and chronic complications are closely associated. Among these complications, diabetic foot is the heaviest disease burden.
The development of evidence-based clinical practice guidelines is a sophisticated and systematic process, often requiring multidisciplinary efforts. The traditional approach to developing and updating clinical practice guidelines is usually time-consuming. These limitations obstacle the effective use of guideline recommendations and efficient transformation of most recent research evidence into practice. The MAGIC system is a novel method system for rapid creation and dissemination of high-quality clinical recommendations, including rapid creation of trustworthy recommendations, thus ensuring the scientific and efficient production of clinical practice guidelines; facilitating rapid dissemination and dynamic updating of clinical practice guidelines through recommendation release system (i.e., MAGICapp); and helping promote the production of relevant high-quality original research evidence by identifying the insufficiency of evidence in the process of creation of guideline recommendations. Ultimately, a complete closed-loop digital and trustworthy evidence ecosystem is developed. In order to further promote the effective transformation of research evidence into guideline recommendations, MAGIC China Center was established. We anticipate that the Center will assist the further development and effective use of clinical practice guideline in China.