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      Issues and Solutions in Psychiatric Clinical Trial with Case Studies

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          Abstract

          The coronavirus disease-2019 pandemic resulted in a major increase in depression and anxiety disorders worldwide, which increased the demand for mental health services. However, clinical interventions for treating mental disorders are currently insufficient to meet this growing demand. There is an urgent need to conduct scientific and standardized clinical research that are consistent with the features of mental disorders in order to deliver more effective and safer therapies in the clinic. Our study aimed to expose the challenges, complexities of study design, ethical issues, sample selection, and efficacy evaluation in clinical research for mental disorders. The reliance on subjective symptom presentation and rating scales for diagnosing mental diseases was discovered, emphasizing the lack of clear biological standards, which hampers the construction of rigorous research criteria. We underlined the possibility of psychotherapy in efficacy evaluation alongside medication treatment, proposing for a multidisciplinary approach comprising psychiatrists, neuroscientists, and statisticians. To comprehend mental disorders progression, we recommend the development of artificial intelligence integrated evaluation tools, the use of precise biomarkers, and the strengthening of longitudinal designs. In addition, we advocate for international collaboration to diversity samples and increase the dependability of findings, with the goal of improving clinical research quality in mental disorders through sample representativeness, accurate medical history gathering, and adherence to ethical principles.

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          Most cited references36

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          Biological Insights From 108 Schizophrenia-Associated Genetic Loci

          Summary Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here, we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain providing biological plausibility for the findings. Many findings have the potential to provide entirely novel insights into aetiology, but associations at DRD2 and multiple genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that play important roles in immunity, providing support for the hypothesized link between the immune system and schizophrenia.
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            Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls

            Most studies have some missing data. Jonathan Sterne and colleagues describe the appropriate use and reporting of the multiple imputation approach to dealing with them
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              1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study

              Background The full range of long-term health consequences of COVID-19 in patients who are discharged from hospital is largely unclear. The aim of our study was to comprehensively compare consequences between 6 months and 12 months after symptom onset among hospital survivors with COVID-19. Methods We undertook an ambidirectional cohort study of COVID-19 survivors who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. At 6-month and 12-month follow-up visit, survivors were interviewed with questionnaires on symptoms and health-related quality of life (HRQoL), and received a physical examination, a 6-min walking test, and laboratory tests. They were required to report their health-care use after discharge and work status at the 12-month visit. Survivors who had completed pulmonary function tests or had lung radiographic abnormality at 6 months were given the corresponding tests at 12 months. Non-COVID-19 participants (controls) matched for age, sex, and comorbidities were interviewed and completed questionnaires to assess prevalent symptoms and HRQoL. The primary outcomes were symptoms, modified British Medical Research Council (mMRC) score, HRQoL, and distance walked in 6 min (6MWD). Multivariable adjusted logistic regression models were used to evaluate the risk factors of 12-month outcomes. Findings 1276 COVID-19 survivors completed both visits. The median age of patients was 59·0 years (IQR 49·0–67·0) and 681 (53%) were men. The median follow-up time was 185·0 days (IQR 175·0–198·0) for the 6-month visit and 349·0 days (337·0–361·0) for the 12-month visit after symptom onset. The proportion of patients with at least one sequelae symptom decreased from 68% (831/1227) at 6 months to 49% (620/1272) at 12 months (p<0·0001). The proportion of patients with dyspnoea, characterised by mMRC score of 1 or more, slightly increased from 26% (313/1185) at 6-month visit to 30% (380/1271) at 12-month visit (p=0·014). Additionally, more patients had anxiety or depression at 12-month visit (26% [331/1271] at 12-month visit vs 23% [274/1187] at 6-month visit; p=0·015). No significant difference on 6MWD was observed between 6 months and 12 months. 88% (422/479) of patients who were employed before COVID-19 had returned to their original work at 12 months. Compared with men, women had an odds ratio of 1·43 (95% CI 1·04–1·96) for fatigue or muscle weakness, 2·00 (1·48–2·69) for anxiety or depression, and 2·97 (1·50–5·88) for diffusion impairment. Matched COVID-19 survivors at 12 months had more problems with mobility, pain or discomfort, and anxiety or depression, and had more prevalent symptoms than did controls. Interpretation Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work and life. The health status in our cohort of COVID-19 survivors at 12 months was still lower than that in the control population. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                ndt
                Neuropsychiatric Disease and Treatment
                Dove
                1176-6328
                1178-2021
                04 June 2024
                2024
                : 20
                : 1191-1200
                Affiliations
                [1 ]Clinical Research Institute & School of Public Health, Shanghai Jiao Tong University School of Medicine , Shanghai, People’s Republic of China
                [2 ]Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine , Shanghai, People’s Republic of China
                [3 ]School of Life Sciences and Biotechnology, Shanghai Jiao Tong University , Shanghai, People’s Republic of China
                Author notes
                Correspondence: Hongsheng Tan, Clinical Research Institute & School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Email tanhs@shsmu.edu.cn
                Zhangsheng Yu, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 210240, People’s Republic of China, Email yuzhangsheng@sjtu.edu.cn
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-3837-2761
                Article
                454813
                10.2147/NDT.S454813
                11162181
                38855383
                0c408f41-1d43-46c6-8211-41457ef3bda1
                © 2024 Chen et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 13 December 2023
                : 22 May 2024
                Page count
                Figures: 0, Tables: 1, References: 38, Pages: 10
                Funding
                Funded by: the Fundamental Research Funds for the Central Universities;
                Funded by: Shanghai Jiao Tong University School of Medicine, open-funder-registry 10.13039/501100008233;
                This study was sponsored by the Fundamental Research Funds for the Central Universities (YG2021ZD02); Shanghai Jiao Tong University School of Medicine (BJ1-7000-21-8102); Shanghai Jiao Tong University Trans-med Awards Research (STAR 20230101); Shanghai Committee of Science and Technology (23DZ2290600).
                Categories
                Perspectives

                Neurology
                clinical efficacy assessment,clinical trials,mental health,research design,statistical analysis

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