Registry versus publication: discrepancy of primary outcomes and possible outcome reporting bias in child and adolescent mental health

Outcome reporting bias is one of the fundamental forms of publication bias. It implies publishing only outcomes that have positive results. The aim of this observational study was to explore primary outcome discrepancies between registry of clinical trials and their corresponding publications, since these can indicate outcome reporting bias in child mental health. Data were extracted from completed interventional clinical trials from ClinicalTrial.gov registry and its Archive site. Trials were registered under “Behaviours and Mental Disorders” category, and conducted on underage participants (0–17 years). Their primary outcomes were compared to those published in publication which had a corresponding NCT number stated in the text. Sixteen percent of trials did not have the minimum information on primary outcome stated in the registry—neither the measure used nor the measurement time points; 38.9% of trials had the minimum information stated to describe primary outcome, while only 3.3% of trials had all the necessary elements stated in the registry. Most of the publication in our sample had positive results (66.4%). Half of the trials registered before completion had non-matching primary outcomes in the registry and publication; 85.4% of trials with non-matching outcomes indicated possible outcome reporting bias for some of the primary outcome. Middle-sized trials and industry-funded trials were related with higher quality of primary outcome registration. Industry funding was related with positive findings in publication. Non-industry funding proved to be the only significant predictor of discrepancy between registered and published primary outcomes, and possible outcome reporting bias. Journal impact factor was not related with any of the outcome measures. The main limitation of the study is that it primarily offers an insight into discrepancy of registered and published outcomes. The methodology does not imply an access to results of unpublished outcomes — therefore, it was not possible to determine the presence of the bias with sufficient certainty in large number of trials. Further research should be done with improved methodology and additional data.

     

No publication bias in industry funded clinical trials of degenerative diseases of the spine

Industry sponsorship of clinical research of degenerative diseases of the spine has been associated with excessive positive published results as compared to research carried out without industry funding. We sought the rates of publication of clinical trials of degenerative diseases of the spine based on funding source as a possible explanation for this phenomenon. We reviewed all clinical trials registered at clinicaltrials.gov relating to degenerative diseases of the spine as categorized under six medical subject heading terms (spinal stenosis, spondylolisthesis, spondylolysis, spondylosis, failed back surgery syndrome, intervertebral disc degeneration) and with statuses of completed or terminated. These collected studies were categorized as having, or not having, industry funding. Published results for these studies were then sought within the clinicaltrials.gov database itself, PubMed and Google Scholar. One hundred sixty-one clinical trials met these criteria. One hundred nineteen of these trials had industry funding and 42 did not. Of those with industry funding, 45 (37.8%) had identifiable results. Of those without industry funding, 17 (40.5%) had identifiable results. There was no difference in the rates of publication of results from clinical trials of degenerative diseases of the spine no matter the funding source.     

Defining the hidden evidence in autism research. Forty per cent of rigorously designed clinical trials remain unpublished ‐ a cross‐sectional analysis

Autism spectrum disorders (ASD) have a prevalence of up to 2.7% and show significant rates of comorbidities. Pharmacological treatment can be difficult. New treatment options are needed, several are currently under investigation. Publication bias presents a major problem in current clinical research. This study was designed to quantify publication bias in rigorously designed ASD research. The database at ClinicalTrials.gov was searched for all completed randomized controlled clinical trials investigating interventions in ASD and their results made public. If results could neither be retrieved through search of the database, nor of scientific databases nor by enquiries of the responsible parties or sponsors listed, a trial was defined as not published. The search delivered N  = 30 (60%) trials were published, N  = 20 (40%) remained unpublished, N  = 2,421 (59%) patients were enrolled in the published trials, N  = 1,664 (41%) patients in the unpublished trials, time to publication was 21.4 months [standard deviation (SD) = 18.48; range = ?5 to 80 months]. Results of N  = 22 trials were available through ClinicalTrials.gov . Characteristics of published compared to unpublished trials did not show apparent differences. The majority of trials investigated drugs. The results emphasize the serious issue of publication bias. The large proportion of unpublished results precludes valuable information and has the potential to distort evidence for treatment approaches in ASD.     

Low dissemination rates,non-transparency of trial premature cessation and late registration in child mental health: observational study of registered interventional trials

The aim of this observational study was to explore trial premature cessation, non-publication and trial registration time in child mental health. Data were extracted for “closed” trials in Clinicaltrials.gov registry and European Union Clinical Trial Register (EUCTR) and corresponding publications of completed trials indexed in three data bases (PubMed, Scopus and Google Scholar). We restricted the extraction to the ‘Behaviours and Mental Disorders’ category and participants’ age of 0–17 years. Outcome measures were trial completion, results reporting within a year after the trial completion, publishing an article in a peer-reviewed journal within an average time to publish (729 days), and registration time. The number of EUCTR trials was relatively small (n?=?35) and with many inconsistencies. Out of 827 “closed” trials extracted from ClinicalTrials.gov, 69% were completed, 24.2% of prematurely ceased trials did not report reasons for early termination, 12.2% of the completed trials had results reported within a year, and 29.3% had an article published within 24 months after completion. Middle-sized (100–499 participants) and behavioural trials had higher chances of being successfully completed. Middle-sized and industry-funded trials were associated with results reporting. Chances for publishing an article were lower for industry-funded trials. Industry funding and drug interventions were related to timely registration. Large sample and non-industry funding were related to retrospective registration, which was recorded more often in recent years than before (we observed trials registered from 2002 until 2017). This study found low dissemination rates in the field of child mental health, with worrying under-reporting of premature termination causes. These findings indicate that more children are being subjected to unnecessary risk that comes with trial participation.

     

Acupuncture in stroke rehabilitation Literature retrieval based on international databases

OBJECTIVE: To identify global research trends of acupuncture in stroke rehabilitation using a bibliometric analysis of the Web of Science and the Clinical Trials registry database (ClinicalTrials.gov). DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for acupuncture in stroke rehabilitation from 1992 to 2011 using the Web of Science and ClinicalTrials.gov. SELECTION CRITERIA: Inclusion criteria: (1) Web of Science: (a) Peer-reviewed articles on acupuncture in stroke rehabilitation that were published and indexed in the Web of Science. (b) Type of articles: original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material and news items. (c) Year of publication: 1992-2011. (2) ClinicalTrials.gov: All clinical trials relating to acupuncture in stroke rehabilitation were searched in this database. Exclusion criteria: (1) Web of Science: (a) Articles that required manual searching or telephone access. (b) We excluded documents that were not published in the public domain. (c) We excluded a number of corrected papers from the total number of articles. (2) ClinicalTrials.gov: (a) We excluded clinical trials that were not in the ClinicalTrials.gov database. (b) We excluded clinical trials that dealt with magnetic stimulation other than acupuncture in stroke rehabilitation in the ClinicalTrials.gov database. MAIN OUTCOME MEASURES: (1) Type of literature; (2) annual publication output; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) top cited articles over the last 20 years; and (7) clinical trials registered. RESULTS: (1) In all, 92 studies on acupuncture in stroke rehabilitation appeared in the Web of Science from 1992 to 2011, almost half of which derived from Chinese and American authors and institutes. The number of studies addressing acupuncture in stroke rehabilitation has gradually increased over the past 20 years. Most papers on acupuncture in stroke rehabilitation appeared in journals with a particular focus on rehabilitation research, such as Stroke, Archives of Physical Medicine, Cochrane Database of Systematic Reviews and Journal of Alternative and Complementary Medicine. (2) In the ClinicalTrials.gov, three studies can be searched on acupuncture and stroke, all of which were registered and sponsored by Chinese institutions since February 2009. CONCLUSION: From our analysis of the literature and research trends, we found that acupuncture in stroke rehabilitation may offer further benefits in regenerative medicine.     

Neuromodulatory treatments for psychiatric disease: A comprehensive survey of the clinical trial landscape

BackgroundNumerous neuromodulatory therapies are currently under investigation or in clinical use for the treatment of psychiatric conditions.Objective/hypothesisWe sought to catalogue past and present human research studies on psychiatric neuromodulation and identify relevant trends in this field.MethodsClinicalTrials.gov (https://www.clinicaltrials.gov/) and the International Clinical Trials Registry Platform (https://www.who.int/ictrp/en/) were queried in March 2020 for trials assessing the outcome of neuromodulation for psychiatric disorders. Relevant trials were categorized by variables such as neuromodulation modality, country, brain target, publication status, design, and funding source.ResultsFrom 72,086 initial search results, 1252 unique trials were identified. The number of trials registered annually has consistently increased. Half of all trials were active and a quarter have translated to publications. The largest proportion of trials involved depression (45%), schizophrenia (18%), and substance use disorders (14%). Trials spanned 37 countries; China, the second largest contributor (13%) after the United States (28%), has increased its output substantially in recent years. Over 75% of trials involved non-convulsive non-invasive modalities (e.g., transcranial magnetic stimulation), while convulsive (e.g., electroconvulsive therapy) and invasive modalities (e.g., deep brain stimulation) were less represented. 72% of trials featured approved or cleared interventions. Characteristic inter-modality differences were observed with respect to enrollment size, trial design/phase, and funding. Dorsolateral prefrontal cortex accounted for over half of focal neuromodulation trial targets. The proportion of trials examining biological correlates of neuromodulation has increased.Conclusion(s)These results provide a comprehensive overview of the state of psychiatric neuromodulation research, revealing the growing scope and internationalism of this field.     

Research progress in rehabilitation treatment of stroke patients A bibliometric analysis

BACKGROUND: Stroke presents as a transient or chronic brain dysfunction and is associated with high morbidity and high mortality. The doctors and scientists would like to argue how to enhance the validity of the rehabilitation treatment and how to further improve the level of treatment on stroke. OBJECTIVE: The aim of this study was to quantitatively analyze the current worldwide progress in research on stroke rehabilitation treatment based on Web of Science database and ClinicalTrial.gov in the past 10 years. METHODS: We conducted a quantitative analysis of clinical trial articles regarding stroke rehabilitation published in English from 2003 to 2013 and indexed in the National Institutes of Health Clinical Trials registry and Web of Science databases. Data were downloaded on March 15, 2013. RESULTS: (1) From 2003 to 2013, 2 654 clinical trials investigating stroke were indexed in ClinicalTrials.gov. There were only 58 clinical trials registered in 2003, and there was a marked increase from 2005. A total of 605 clinical trials on the rehabilitation of stroke were conducted in the past 10 years. (2) The analysis showed that most of the trials in the field were registered by North American institutions. With respect to the Asian countries, China and Taiwan area of China also published a reasonable proportion of the trials, but comparatively speaking, the number of trials is really rare. Most of the interventions were drugs, followed by the devices, and behavioral interventions were ranked third. (3) In the past 10 years, there were 4 052 studies on stroke indexed by Web of Science database. CONCLUSION: From perspective of research progress, we found that the number of clinical trials and papers on stroke rehabilitation has increased significantly in the past 10 years, between them a remarkable positive correlation exists.     

Research progress in muscle-derived stem cells Literature retrieval results based on international database

OBJECTIVE: To identify global research trends of muscle-derived stem cells (MDSCs) using a bibliometric analysis of the Web of Science, Research Portfolio Online Reporting Tools of the National Institutes of Health (NIH), and the Clinical Trials registry database (ClinicalTrials.gov). DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for MDSCs from 2002 to 2011 using the Web of Science, NIH, and ClinicalTrials.gov. SELECTION CRITERIA: Inclusion criteria: (1) Web of Science: (a) peer-reviewed articles on MDSCs that were published and indexed in the Web of Science. (b) Type of articles: original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material and news items. (c) Year of publication: 2002-2011. (d) Citation databases: Science Citation Index-Expanded (SCI-E), 1899-present; Conference Proceedings Citation Index-Science (CPCI-S), 1991-present; Book Citation Index-Science (BKCI-S), 2005-present. (2) NIH: (a) Projects on MDSCs supported by the NIH. (b) Fiscal year: 1988-present. (3) ClinicalTrials.gov: All clinical trials relating to MDSCs were searched in this database. Exclusion criteria: (1) Web of Science: (a) Articles that required manual searching or telephone access. (b) We excluded documents that were not published in the public domain. (c) We excluded a number of corrected papers from the total number of articles. (d) We excluded articles from the following databases: Social Sciences Citation Index (SSCI), 1898-present; Arts & Humanities Citation Index (A&HCI), 1975-present; Conference Proceedings Citation Index - Social Science & Humanities (CPCI-SSH), 1991-present; Book Citation Index - Social Sciences & Humanities (BKCI-SSH), 2005-present; Current Chemical Reactions (CCR-EXPANDED), 1985-present; Index Chemicus (IC), 1993-present. (2) NIH: (a) We excluded publications related to MDSCs that were supported by the NIH. (b) We limited the keyword search to studies that included MDSCs within the title or abstract. (3) ClinicalTrials.gov: (a) We excluded clinical trials that were not in the ClinicalTrials.gov database. (b) We excluded clinical trials that dealt with stem cells other than MDSCs in the ClinicalTrials.gov database. MAIN OUTCOME MEASURES: (1) Type of literature; (2) annual publication output; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) top cited authors over the last 10 years; (7) projects financially supported by the NIH; and (8) clinical trials registered. RESULTS: (1) In all, 802 studies on MDSCs appeared in the Web of Science from 2002 to 2011, almost half of which derived from American authors and institutes. The number of studies on MDSCs has gradually increased over the past 10 years. Most papers on MDSCs appeared in journals with a particular focus on cell biology research, such as Experimental Cell Research, Journal of Cell Science, and PLoS One. (2) Eight MDSC research projects have received over US$6 billion in funding from the NIH. The current project led by Dr. Johnny Huard of the University of Pittsburgh-"Muscle-Based Tissue Engineering to Improve Bone Healing"-is supported by the NIH. Dr. Huard has been the most productive and top-cited author in the field of gene therapy and adult stem cell research in the Web of Science over last 10 years. (3) On ClinicalTrials.gov, "Muscle Derived Cell Therapy for Bladder Exstrophy Epispadias Induced Incontinence" Phase 1 is registered and sponsored by Johns Hopkins University and has been led by Dr. John P. Gearhart since November 2009. CONCLUSION: From our analysis of the literature and research trends, we found that MDSCs may offer further benefits in regenerative medicine.     

Clinical trials for deep brain stimulation: Current state of affairs

BackgroundDeep brain stimulation (DBS) is a surgical neuromodulation procedure with a historically wide range of possible therapeutic indications, including movement disorders, neuropsychiatric conditions, and cognitive disorders. Ongoing research in this field is critical to gain further insights into the mechanisms of DBS, to discover novel brain targets for new and existing indications, and to refine targeting and post-operative programming techniques for the optimization of therapeutic outcomes.ObjectiveTo update on the state of DBS-related clinical human research by cataloging and summarizing clinical trials that have been completed or are currently ongoing in this field worldwide.MethodsA search was conducted for clinical trials pertaining to DBS, currently listed on the ClinicalTrials.gov database. Trials were analyzed to generate a detailed overview of ongoing DBS-related research. Specifically, trials were categorized by trial start date, study completion status, clinical phase, projected subject enrollment, disorder, brain target, country of origin, device manufacturer, funding source, and study topic.ResultsIn total, 384 relevant clinical trials were identified. The trials spanned 28 different disorders across 26 distinct brain targets, with almost 40% of trials being for conditions other than movement disorders. The majority of DBS trials have been US-based (41.9% of studies) but many countries are becoming increasingly active. The ratio of investigator-sponsored to industry-sponsored trials was 3:1. Emphasizing the need to better understand the mechanism of action of DBS, one-third of the studies predominantly focus on imaging or electrophysiological changes associated with DBS.ConclusionsThis overview of current DBS-related clinical trials provides insight into the status of DBS research and what we can anticipate in the future concerning new brain targets, indications, techniques, and developing a better understanding of the mechanisms of action of DBS.     

Recent randomized controlled trials of psychological interventions in healthcare: A review of their quantity,scope, and characteristics

Objective

This study aimed to describe the quantity, scope, and fundamental characteristics of recently published randomized controlled trials (RCTs) of psychological interventions.

Methods

We queried two major databases (PsycINFO and PubMeD) for primary reports published in 2010 of RCTs of psychological interventions for participants with a medical condition. We collected data on the characteristics of the trials, participants, interventions, outcomes, and reports.

Results

Of 3696 retrieved reports 295 primary publications were included. About half (53%) of trials included participants with a mental disorder and more than half evaluated interventions based on a cognitive behavioral therapy (CBT) framework. A majority of trials recruited participants in North America and Europe (79%). A minority of the trials focused on children and adolescents (17%) or the elderly (8%). The median sample size of the intervention arm was n = 41. Thirty-nine percent of trials reported solely patient-reported outcomes. Only 5% of reports indicated funding from for-profit organizations. The median 2010 impact factor of the journals in which reports were published was 2.96.

Conclusion

This snapshot of the research on psychological interventions suggests that the evidence base for psychological interventions is expanding mainly for CBT interventions for adults in high-income countries. Although the restrictive inclusion criteria limit the generalizability of these results, researchers and funding agencies might be advised to strive for greater diversity regarding interventions, geographical/cultural settings and age groups. Regularly updated reviews of this research field, with gradually refined methodology and increased scope, may further inform funders and researchers.     

Human umbilical cord mesenchymal stem cells to treat spinal cord injury in the early chronic phase: study protocol for a prospective,multicenter, randomized,placebo-controlled,single-blinded clinical trial

Human umbilical cord mesenchymal stem cells(hUC-MSCs)support revascularization,inhibition of inflammation,regulation of apoptosis,and promotion of the release of beneficial factors.Thus,they are regarded as a promising candidate for the treatment of intractable spinal cord injury(SCI).Clinical studies on patients with early chronic SCI(from 2 months to 1 year post-injury),which is clinically common,are rare;therefore,we will conduct a prospective,multicenter,randomized,placebo-controlled,single-blinded clinical trial at the Third Affiliated Hospital of Sun Yat-sen University,West China Hospital of Sichuan University,and Shanghai East Hospital,Tongji University School of Medicine,China.The trial plans to recruit 66 early chronic SCI patients.Eligible patients will undergo randomization at a 2:1 ratio to two arms:the observation group and the control group.Subjects in the observation group will receive four intrathecal transplantations of stem cells,with a dosage of 1×106/kg,at one calendar month intervals.Subjects in the control group will receive intrathecal administrations of 10 mL sterile normal saline in place of the stem cell transplantations.Clinical safety will be assessed by the analysis of adverse events and laboratory tests.The American Spinal Injury Association(ASIA)total score will be the primary efficacy endpoint,and the secondary efficacy outcomes will be the following:ASIA impairment scale,International Association of Neural Restoration-Spinal Cord Injury Functional Rating Scale,muscle tension,electromyogram,cortical motor and cortical sensory evoked potentials,residual urine volume,magnetic resonance imaging–diffusion tensor imaging,T cell subtypes in serum,neurotrophic factors and inflammatory factors in both serum and cerebrospinal fluid.All evaluations will be performed at 1,3,6,and 12 months following the final intrathecal administration.During the entire study procedure,all adverse events will be reported as soon as they are noted.This trial is designed to evaluate the clinical safety and efficacy of subarachnoid transplantation of hUC-MSCs to treat early chronic SCI.Moreover,it will establish whether cytotherapy can ameliorate local hostile microenvironments,promote tracking fiber regeneration,and strengthen spinal conduction ability,thus improving overall motor,sensory,and micturition/defecation function in patients with early chronic SCI.This study was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2018]-02)on March 30,2018,and was registered with ClinicalTrials.gov(registration No.NCT03521323)on April 12,2018.The revised trial protocol(protocol version 4.0)was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2019]-10)on February 25,2019,and released on ClinicalTrials.gov on April 29,2019.     

α7-烟碱型乙酰胆碱受体激动剂对精神分裂症认知缺陷和阴性症状治疗:随机双盲对照研究的meta分析

背景:现有α7-烟碱型乙酰胆碱受体激动剂(α7-nAChR受体激动剂)对精神分裂症的认知障碍和阴性症状治疗的临床研究结果不尽一致.目的:评估α7-烟碱型乙酰胆碱受体激动剂在治疗精神分裂症认知缺损和阴性症状的临床疗效和安全性.方法:PubMed、Embase、ClinicalTrials.gov、CochraneLibrary和中国知网、万方、VIP数据库进行文献检索,检索时间截止于2017年5月26日.M eta分析双盲随机对照试验中α7-nAChR受体激动剂的作用,评估α7-nAChR受体激动剂对精神分裂症的总体认知功能和阴性症状的临床疗效.通过计算药物和安慰剂之间的平均差(SMDs),评估α7-nAChR受体激动剂能否作为有效的抗精神病药物.结果:8个低偏倚研究纳入了meta分析.我们没有发现α7乙酰受体激动剂对精神分裂症患者的认知障碍(SMD=-0.10(-0.46,0.25),=88％)和阴性症状(SMD=0.13(-0.04,0.30),I2=64％)有明显疗效.敏感性分析也印证了此结果.药物总体安全且耐受性良好,在不良事件(RR=1.02,[0.85,1.23])和脱落率(RR=1.04,[0.61,1.78])与安慰剂对照无显著差异.根据GRADE评级,该meta分析结果的证据强度为“中”.结论:α7-nAChR受体激动剂可能不是有效地改善精神分裂症患者总体认知障碍和的阴性症状的药物.     

Surgical intervention combined with weight-bearing walking training improves neurological recoveries in 320 patients with clinically complete spinal cord injury:a prospective self-controlled study

Although a large number of trials in the SCI field have been conducted, few proven gains have been realized for patients. In the present study, we determined the efficacy of a novel combination treatment involving surgical intervention and long-term weight-bearing walking training in spinal cord injury(SCI) subjects clinically diagnosed as complete or American Spinal Injury Association Impairment Scale(AIS) Class A(AIS-A). A total of 320 clinically complete SCI subjects(271 male and 49 female), aged 16–60 years, received early(≤ 7 days, n = 201) or delayed(8–30 days, n = 119) surgical interventions to reduce intraspinal or intramedullary pressure. Fifteen days post-surgery, all subjects received a weight-bearing walking training with the "Kunming Locomotion Training Program(KLTP)" for a duration of 6 months. The neurological deficit and recovery were assessed using the AIS scale and a 10-point Kunming Locomotor Scale(KLS). We found that surgical intervention significantly improved AIS scores measured at 15 days post-surgery as compared to the pre-surgery baseline scores. Significant improvement of AIS scores was detected at 3 and 6 months and the KLS further showed significant improvements between all pair-wise comparisons of time points of 15 days, 3 or 6 months indicating continued improvement in walking scores during the 6-month period. In conclusion, combining surgical intervention within 1 month post-injury and weight-bearing locomotor training promoted continued and statistically significant neurological recoveries in subjects with clinically complete SCI, which generally shows little clinical recovery within the first year after injury and most are permanently disabled. This study was approved by the Science and Research Committee of Kunming General Hospital of PLA and Kunming Tongren Hospital, China and registered at Clinical Trials.gov(Identifier: NCT04034108) on July 26, 2019.     

Repetitive transcranial magnetic stimulation for lower extremity motor function in patients with stroke: a systematic review and network meta-analysis

Transcranial magnetic stimulation, a type of noninvasive brain stimulation, has become an ancillary therapy for motor function rehabilitation. Most previous studies have focused on the effects of repetitive transcranial magnetic stimulation(rTMS) on motor function in stroke patients. There have been relatively few studies on the effects of different modalities of rTMS on lower extremity motor function and corticospinal excitability in patients with stroke. The MEDLINE, Embase, Cochrane Library, ISI Science Citation Index, Physiotherapy Evidence Database, China National Knowledge Infrastructure Library, and ClinicalTrials.gov databases were searched. Parallel or crossover randomized controlled trials that addressed the effectiveness of rTMS in patients with stroke, published from inception to November 28, 2019, were included. Standard pairwise meta-analysis was conducted using R version 3.6.1 with the "meta" package. Bayesian network analysis using the Markov chain Monte Carlo algorithm was conducted to investigate the effectiveness of different rTMS protocol interventions. Network meta-analysis results of 18 randomized controlled trials regarding lower extremity motor function recovery revealed that low-frequency rTMS had better efficacy in promoting lower extremity motor function recovery than sham stimulation. Network meta-analysis results of five randomized controlled trials demonstrated that highfrequency rTMS led to higher amplitudes of motor evoked potentials than low-frequency r TMS or sham stimulation. These findings suggest that rTMS can improve motor function in patients with stroke, and that low-frequency rTMS mainly affects motor function, whereas high-frequency rTMS increases the amplitudes of motor evoked potentials. More highquality randomized controlled trials are needed to validate this conclusion. The work was registered in PROSPERO(registration No. CRD42020147055) on April 28, 2020.     

Stem cell transplantation for spinal cord injury:a meta-analysis of treatment effectiveness and safety

OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of stem cell transplantation for spinal cord injury(SCI).DATA SOURCES: PubM ed, EMBASE, Cochrane, China National Knowledge Infrastructure, China Science and Technology Journal, Wanfang, and Sino Med databases were systematically searched by computer to select clinical randomized controlled trials using stem cell transplantation to treat SCI, published between each database initiation and July 2016. DATA SELECTION: Randomized controlled trials comparing stem cell transplantation with rehabilitation treatment for patients with SCI. Inclusion criteria:(1) Patients with SCI diagnosed according to the American Spinal Injury Association(ASIA) International standards for neurological classification of SCI;(2) patients with SCI who received only stem cell transplantation therapy or stem cell transplantation combined with rehabilitation therapy;(3) one or more of the following outcomes reported: outcomes concerning neurological function including sensory function and locomotor function, activities of daily living, urination functions, and severity of SCI or adverse effects. Studies comprising patients with complications, without full-text, and preclinical animal models were excluded. Quality of the included studies was evaluated using the Cochrane risk of bias assessment tool and Rev Man V5.3 software, provided by the Cochrane Collaboration, was used to perform statistical analysis. OUTCOME MEASURES: ASIA motor score, ASIA light touch score, ASIA pinprick score, ASIA impairment scale grading improvement rate, activities of daily living score, residual urine volume, and adverse events.RESULTS: Ten studies comprising 377 patients were included in the analysis and the overall risk of bias was relatively low level. Four studies did not detail how random sequences were generated, two studies did not clearly state the blinding outcome assessment, two studies lacked blinding outcome assessment, one study lacked follow-up information, and four studies carried out selective reporting. Compared with rehabilitation therapy, stem cell transplantation significantly increased the lower limb light touch score(odds ratio(OR) = 3.43, 95% confidence interval(CI): 0.01 – 6.86, P = 0.05), lower limb pinprick score(OR = 3.93, 95%CI: 0.74 – 7.12, P = 0.02), ASI grading rate(relative risk(RR) = 2.95, 95%CI: 1.64 – 5.29, P = 0.0003), and notably reduced residual urine volume(OR = –8.10, 95%CI: –15.09 to –1.10, P = 0.02). However, stem cell transplantation did not significantly improve motor score(OR = 1.89, 95%CI: –0.25 to 4.03, P = 0.08) or activities of daily living score(OR = 1.12, 95%CI: –1.17 to 4.04, P = 0.45). Furthermore, stem cell transplantation caused a high rate of mild adverse effects(RR = 14.49, 95%CI: 5.34 – 34.08, P 0.00001); however, these were alleviated in a short time. CONCLUSION: Stem cell transplantation was determined to be an efficient and safe treatment for SCI and simultaneously improved sensory and bladder functions. Although associated minor and temporary adverse effects were observed with transplanted stem cells, spinal cord repair and axon remyelination were apparent. More randomized controlled trials with larger sample sizes and longer follow-up times are needed to further validate the effectiveness of stem cell transplantation in the treatment of SCI.     

Transparency of outcome reporting and trial registration of randomized controlled trials in top psychosomatic and behavioral health journals: A systematic review

Objective

The most reliable evidence for evaluating healthcare interventions comes from well-designed and conducted randomized controlled trials (RCTs). The extent to which published RCTs reflect the efficacy of interventions, however, depends on the completeness and accuracy of published results. The Consolidated Standards of Reporting Trials statement, initially developed in 1996, provides guidelines intended to improve the transparency of published RCT reports. A policy of the International Committee of Medical Journal Editors, initiated in 2005, requires clinical trials published in member journals to be registered in publicly accessible registries prior to patient enrollment. The objective of this study was to assess the clarity of outcome reporting, proportion of registered trials, and adequacy of outcome registration in RCTs published in top behavioral health journals.

Methods

Eligible studies were primary or secondary reports of RCTs published in Annals of Behavioral Medicine, Health Psychology, Journal of Psychosomatic Research, and Psychosomatic Medicine from January 2008 to September 2009. Data were extracted for each study on adequacy of outcome reporting and registration.

Results

Of 63 articles reviewed, only 25 (39.7%) had adequately declared primary or secondary outcomes, whereas 38 (60.3%) had multiple primary outcomes or did not define outcomes. Only 13 studies (20.6%) were registered. Only 1 study registered sufficiently precise outcome information to compare with published outcomes, and registered and published outcomes were discrepant in that study.

Conclusion

Greater attention to outcome reporting and trial registration by researchers, peer reviewers, and journal editors will increase the likelihood that effective behavioral health interventions are readily identified and made available to patients.     

The causes, consequences and detection of publication bias in psychiatry

OBJECTIVE: Publication bias threatens the validity of published research, although this topic has received little attention in psychiatry. The purpose of this article is to produce a systematic overview of the causes and consequences of publication bias and to summarize the available methods with which it is detected and corrected. METHOD: Empirical evidence for the existence of publication bias is reviewed and the following methods are applied to an illustrative case example from psychiatry: funnel plot analysis; the 'file drawer method'; linear regression techniques; rank correlation; 'trim and fill'. RESULTS: Small studies are particularly susceptible to publication and related bias. All methods to detect publication bias depend upon the availability of a number of individual studies with a range of sample sizes. Unfortunately, large numbers of studies of varying sample size are not always available in many areas of psychiatric research. CONCLUSION: Where possible researchers should always test for the presence of publication bias. The problem of publication bias will not be solved by anything other than a prospective trials register.     

Olfactory ensheathing cell transplantation for spinal cord injury An 18-year bibliometric analysis based on the Web of Science

OBJECTIVE:Olfactory ensheathing cell (OEC) transplantation is a promising new approach for the treatment of spinal cord injury (SCI),and an increasing number of scientific publications are devoted to this treatment strategy.This bibliometric analysis was conducted to assess global research trends in OEC transplantation for SCI.DATA SOURCE:All of the data in this study originate from the Web of Science maintained by the Institute for Scientific Information,USA,and includes SCI-EXPANDED,SSCI,A&HCI,CPCI-S,CPCI-SSH,BKCI-S,BKCI-SSH,CCR-EXPANDED and IC.The Institute for Scientific Information’s Web of Science was searched using the keywords "olfactory ensheathing cells" or "OECs" or "olfactory ensheathing glia" or "OEG" or "olfactory ensheathing glial cells" or "OEGs" and "spinal cord injury" or "SCI" or "spinal injury" or "spinal transection" for literature published from January 1898 to May 2012.DATA SELECTION:Original articles,reviews,proceedings papers and meeting abstracts,book chapters and editorial materials on OEC transplantation for SCI were included.Simultaneously,unpublished literature and literature for which manual information retrieval was required were excluded.MAIN OUTCOME MEASURES:All selected literatures addressing OEC transplantation for SCI were evaluated in the following aspects:publication year,document type,language,author,institution,times cited,Web of Science category,core source title,countries/territories and funding agency.RESULTS:In the Web of Science published by the Institute for Scientific Information,the earliest literature record was in April,1995.Four hundred and fourteen publications addressing OEC transplantation for SCI were added to the data library in the past 18 years,with an annually increasing trend.Of 415 records,405 publications were in English.Two hundred and fifty-nine articles ranked first in the distribution of document type,followed by 141 reviews.Thirty articles and 20 reviews,cited more than 55 times by the date the publication data were downloaded by us,can be regarded as the most classical references.The journal Experimental Neurology published the most literature (32 records),followed by Glia.The United States had the most literature,followed by China.In addition,Yale University was the most productive institution in the world,while The Second Military Medical University contributed the most in China.The journal Experimental Neurology published the most OEC transplantation literature in the United States,while Neural Regeneration Research published the most in China.CONCLUSION:This analysis provides insight into the current state and trends in OEC transplantation for SCI research.Furthermore,we anticipate that this analysis will help encourage international cooperation and teamwork on OEC transplantation for SCI to facilitate the development of more effective treatments for SCI.     

Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial

BACKGROUND: Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3-6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). METHODS: We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3-6 h after onset of ischaemic stroke. PWI and DWI were done before and 3-5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537. FINDINGS: We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71.6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1.24 with alteplase and 1.78 with placebo (ratio 0.69, 95% CI 0.38-1.28; Student's t test p=0.239); the median relative infarct growth was 1.18 with alteplase and 1.79 with placebo (ratio 0.66, 0.36-0.92; Wilcoxon's test p=0.054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0.001), better neurological outcome (p<0.0001), and better functional outcome (p=0.010) than was no reperfusion. INTERPRETATION: Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted.