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Background : The number of papers published by an institution is acknowledged as an easy-to-understand research outcome. However, the quantity as well as the quality of research papers needs to be assessed. Methods: To determine the relation between the number of published papers and paper quality, a survey was conducted to assess publications focusing on interventional clinical trials reported by 11 core clinical research hospitals. A score was calculated for each paper using Système d'interrogation , de gestionet d'analyse des publications scientifiques scoring system, allowing for a clinical paper quality assessment independent of the field. Paper quality was defined as the relative Journal impact factor (IF) total score/number of papers. Results: We surveyed 580 clinical trial papers. For each of the 11 medical institutions (a–k), respectively, the following was found: number of published papers: a:66, b:64, c:61, d:56, e:54, f:51, g:46, h:46, i:46, j:45, k:45 (median: 51, maximum: 66, minimum: 45); total Journal IF: a:204, b:252, c:207, d:225, e:257, f:164, g:216, h:190, i:156, j:179, k:219 (median: 207, maximum: 257, minimum: 156); relative Journal IF total score: a:244, b:272, c:260, d:299, e:268, f:215, g:225, h:208, i:189, j:223, k:218 (median: 225, maximum: 299, minimum: 189); and paper quality (relative Journal IF total score/number of papers): a:3.70, b:4.25, c:4.26, d:5.34, e:4.96, f:4.22, g:4.89, h:4.52, i:4.11, j:4.96, k:4.84 (median: 4.52, maximum: 5.34, minimum: 3.70). Additionally, no significant relation was found between the number of published papers and paper quality (correlation coefficient, −0.33, P = 0.32). Conclusions: The number of published papers does not correspond to paper quality. When assessing an institution's ability to perform clinical research, an assessment of paper quality should be included along with the number of published papers. [ABSTRACT FROM AUTHOR]

Introduction: The World Health Organization identified Pharmaceutical and Therapeutics Committees (PTCs) at district and hospital levels as one of the pivotal models to promote rational use of medicines (RUM). This is endorsed by the Government in South Africa. Formulary development and management is one of the main functions of PTCs. This study aimed to describe the formulary management activities among PTCs in public hospitals in Gauteng Province, South Africa, following initiatives to promote RUM in South Africa. Methods: Qualitative, nonparticipatory, observational study, observing 26 PTC meetings. Data were coded and categorized using NVivo9® qualitative data analysis software. Themes and sub-themes were developed. The themes and sub-themes on formulary management are the principal focus of this paper. Results: More than half of the observed PTCs reviewed their formulary lists. There was variation in the review process among institutions providing different levels of care. Various aspects were considered for formulary management especially requests for medicines to be added. These included cost considerations (mainly focusing on acquisition costs), evidence-based evaluation of clinical trials, patient safety, clinical experience and changes in the National Essential Medicines List (NEML). The tertiary PTCs mostly dealt with applications for new non-EML medicines, while PTCs in the other hospitals mainly requested removal or addition of EML medicines to the list. Conclusion: This is the first study from Gauteng Province, South Africa, reporting on how decisions are actually taken to include or exclude medicines onto formularies within public sector hospitals providing different levels of care. Various approaches are adopted at different levels of care when adding to- or removing medicines from the formulary lists. Future programs should strengthen PTCs in specialized aspects of formulary management. A more structured approach to formulary review at the local PTC level should be encouraged in line with the national approach when reviewing possible additions to the NEML. [ABSTRACT FROM AUTHOR]

Background: The CONSORT Extension for Chinese Herbal Medicine Formula 2017 (CONSORT-CHM Formula 2017) has established a reporting standard for randomized controlled trials (RCTs) of Chinese Herbal Medicine Formula (CHMF) interventions; however, its adherence and implications for the design and execution of study design remain ambiguous. It is necessary to evaluate the level of compliance with the CONSORT-CHM Formula 2017 in RCTs conducted over the past 5 years, and to determine the reporting quality of clinical trials in this field. Methods: First, a systematic search is conducted for RCTs on CHMF in EBM Reviews, Allied and Complementary Medicine (AMED), Embase, Ovid-MEDLINE(R), Wanfang data, China National Knowledge Infrastructure (CNKI), VIP Chinese Medical Journal Database (VIP) and Chinese Biomedical Literature (CBM) database, that encompassed CHMF interventional RCTs published from 1 January 2018 to 8 June 2022, with language restriction to English or Chinese. Second, a descriptive analysis will be performed regarding the study design and general characteristics of the included trials. Third, for the quality assessment, we have subdivided the CONSORT-CHM Formula 2017 checklist (consisting of 22 extended items) into a total of 42 sub-questions to facilitate scoring, with a specific focus on the description, quality control, and safety assessment of CHMF interventions. Professional training and a pilot test on 100 randomly selected articles will be provided for all reviewers. Throughout this process, a standard operating procedure (SOP) for quality assessment will be developed to ensure consistency. Each item will be assessed by two reviewers in a paired back-to-back manner, and the compliance rate will be calculated to assess interrater agreement. Discussion: This review will identify the current reporting characteristics and quality of CHMF interventional studies and further evaluate the impact of CONSORT-CHM Formula 2017. The results may provide suggestions for future application or promotion of the guideline. Registration: The study has been registered on Open Science Framework (https://osf.io/xpn7f). [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the overall reporting quality of randomized controlled trials (RCTs) in Chinese herbal medicine (CHM) formulas for patients with diabetes, and to identify factors associated with better reporting quality. Methods: Four databases including PubMed, Embase, Cochrane Library and Web of Science were systematically searched from their inception to December 2022. The reporting quality was assessed based on the Consolidated Standards of Reporting Trials (CONSORT) statement and its CHM formula extension. The overall CONSORT and its CHM formula extension scores were calculated and expressed as proportions separately. We also analyzed the pre-specified study characteristics and performed exploratory regressions to determine their associations with the reporting quality. Results: Seventy-two RCTs were included. Overall reporting quality (mean adherence) were 53.56% and 45.71% on the CONSORT statement and its CHM formula extension, respectively. The strongest associations with reporting quality based on the CONSORT statement were multiple centers and larger author numbers. Compliance with the CHM formula extension, particularly regarding the disclosure of the targeted traditional Chinese medicine (TCM) pattern (s), was generally insufficient. Conclusion: The reporting quality of RCTs in CHM formulas for diabetes remains unsatisfactory, and the adherence to the CHM formula extension is even poorer. In order to ensure transparent and standardized reporting of RCTs, it is essential to advocate for or even mandate adherence of the CONSORT statement and its CHM formula extension when reporting trials in CHM formulas for diabetes by both authors and editors. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trials are the gold standard for testing new therapies. Databases like ClinicalTrials.gov provide access to trial information, mainly covering the US and Europe. In 2006, WHO introduced the global ICTRP, aggregating data from ClinicalTrials.gov and 17 other national registers, making it the largest clinical trial platform by June 2019. This study conducts a comprehensive global analysis of the ICTRP database and provides framework for large-scale data analysis, data preparation, curation, and filtering. Materials and methods: The trends in 689,793 records from the ICTRP database (covering trials registered from 1990 to 2020) were analyzed. Records were adjusted for duplicates and mapping of agents to drug classes was performed. Several databases, including DrugBank, MESH, and the NIH Drug Information Portal were used to investigate trends in agent classes. Results: Our novel approach unveiled that 0.5% of the trials we identified were hidden duplicates, primarily originating from the EUCTR database, which accounted for 82.9% of these duplicates. However, the overall number of hidden duplicates within the ICTRP seems to be decreasing. In total, 689 793 trials (478 345 interventional) were registered in the ICTRP between 1990 and 2020, surpassing the count of trials in ClinicalTrials.gov (362 500 trials by the end of 2020). We identified 4 865 unique agents in trials with DrugBank, whereas 2 633 agents were identified with NIH Drug Information Portal data. After the ClinicalTrials.gov, EUCTR had the most trials in the ICTRP, followed by CTRI, IRCT, CHiCTR, and ISRCTN. CHiCTR displayed a significant surge in trial registration around 2015, while CTRI experienced rapid growth starting in 2016. Conclusion: This study highlights both the strengths and weaknesses of using the ICTRP as a data source for analyzing trends in clinical trials, and emphasizes the value of utilizing multiple registries for a comprehensive analysis. [ABSTRACT FROM AUTHOR]

Background: The impact of cigarette smoking on perianesthesia management is not clear elucidated. This paper studies the impact of long-term cigarette smoking on the dose-response of rocuronium and vecuronium used under general anesthesia and the type of antibiotics used after surgery. Methods: We enrolled 240 participants from a teaching hospital in China in which finally enrolled in 221 participants. 106 participants have a history of long-term cigarette use and 115 participants without a history of smoking. All participants received general anesthesia for various surgeries, and rocuronium was used as the muscular relaxant. The primary outcome was the effective onset time of rocuronium after adjusting for its dose. The secondary outcomes included a recovery index and the time of muscle recovery changing from 25 to 75%. Results: There was no measurable difference in the muscle relaxant onset time, duration of effectiveness, 75% recovery, recovery index, dose of opiates, anesthetics during surgery, or complication rate between smokers or non-smokers. However, the results showed a significant difference in antibiotic use between smokers and non-smokers (chi-squared = 13.695, p < 0.001), and a significant difference in the type of antibiotics used (chi-squared = 21.465, p = 0.003). Smokers had a significantly higher rate of cefathiamidine use. Conclusion: Smoking cigarettes had no effect on muscle relaxants used under general anesthesia, but patients who had a history of smoking were more likely to receive antibiotics after surgery. Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR-OIC-16009157. [ABSTRACT FROM AUTHOR]

Objectives: Traumatic brain injury (TBI) is one of the top causes of morbidity and mortality worldwide. The review aimed to discuss and summarize the current evidence on the effectiveness of adjuvant neuroprotective treatments in terms of their effect on brain injury biomarkers in TBI patients. Methods: To identify relevant studies, four scholarly databases, including PubMed, Cochrane, Scopus, and Google Scholar, were systematically searched using predefined search terms. English-language randomized controlled clinical trials reporting changes in brain injury biomarkers, namely, neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCHL1) and/or S100 beta (S100 ß), were included. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool. Results: A total of eleven studies with eight different therapeutic options were investigated; of them, tetracyclines, metformin, and memantine were discovered to be promising choices that could improve neurological outcomes in TBI patients. The most utilized serum biomarkers were NSE and S100 ß followed by GFAP, while none of the included studies quantified UCHL1. The heterogeneity in injury severity categories and measurement timing may affect the overall evaluation of the clinical efficacy of potential therapies. Therefore, unified measurement protocols are highly warranted to inform clinical decisions. Conclusion: Few therapeutic options showed promising results as an adjuvant to standard care in patients with TBI. Several considerations for future work must be directed towards standardizing monitoring biomarkers. Investigating the pharmacotherapy effectiveness using a multimodal biomarker panel is needed. Finally, employing stratified randomization in future clinical trials concerning potential confounders, including age, trauma severity levels, and type, is crucial to inform clinical decisions. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common type of dementia in the elderly. Several hypotheses emerged from AD pathophysiological mechanisms. However, no neuronal protective or regenerative drug is available nowadays. Researchers still work in drug development and are finding new molecular targets to treat AD. Therefore, this study aimed to summarize main advances in AD pharmacological therapy. Clinical trials registered in the National Library of Medicine database were selected and analyzed accordingly to molecular targets, therapeutic effects, and safety profile. The most common outcome was the lack of efficacy. Only seven trials concluded that tested drugs were safe and induced any kind of therapeutic improvement. Three works showed therapeutic effects followed by toxicity. In addition to aducanumab recent FDA approval, antibodies against amyloid-β (Aβ) showed no noteworthy results. 5-HT6 antagonists, tau inhibitors and nicotinic agonists' data were discouraging. However, anti-Aβ vaccine, BACE inhibitor and anti-neuroinflammation drugs showed promising results. [ABSTRACT FROM AUTHOR]

Keywords: drug repurposing; oncology; clinical trials; bioinformatics; database EN drug repurposing oncology clinical trials bioinformatics database 1 6 6 11/12/21 20211110 NES 211110 Introduction Drug repurposing is a strategy that seeks new medical treatments from existing licensed medications rather than from I de novo i development of new molecules. The ReDO Trials DB is the first database of repurposing trials focused solely on interventional trials of non-cancer drugs as new cancer treatments. In terms of the patent status, the ReDO database shows 287 drugs (80.6%) are off-patent, which is similar to the ReDO trials database with 134 of the 164 (81.7%) trials investigating ReDO drugs being off-patent. [Extracted from the article]

Background: The combination of strengthening Qi and eliminating pathogens is an available therapeutic principle in traditional Chinese medicine (TCM) for primary liver cancer (PLC) at middle-advanced stage. However, there is a lack of reasonable evidence to support the proper application of this therapeutic principle. This meta-analysis aims to evaluate the efficacy and safety of Chinese medicinal formulas (CMFs), including two subgroup analyses of the principle of strengthening Qi and eliminating pathogens. Method: Clinical trials were obtained through searching of EMBASE, Web of Science, PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, and two clinical trial registries. The randomized controlled trials with the combination of CMFs and transcatheter arterial chemoembolization (TACE) in the experiment group were acceptable, in contrast to the TACE alone in the control group. The statistics analysis was performed on Review Manager 5.4. Results: A total of eligible 24 trials were accessed in this work. Overall, CMFs could improve the survival duration of 6 months, 1 year, and 2 years, Karnofsky Performance Status, tumor objective response rate (ORR), AFP, and symptom. In the subgroup analysis, trials complying with the principle of single strengthening Qi did not show any significant difference in increasing tumor ORR. Meanwhile, the principle of combined strengthening Qi and eliminating pathogens was uncertain in improving symptoms and 1-year and 2-year survival time. In addition, the outcome indexes of ALT and AST were heterogeneous. In last, the total occurrence of adverse events could not be reduced via using CMFs. Patients treated with CMFs exhibited liver injury, fever, and white blood cell decline, with mild events occurring more frequently and severe events occurring less. Conclusion: CMFs are an effective treatment method to cure PLC at the middle-advanced stage. Adopting the principle of single strengthening Qi presents better efficacy in the long term by prolonging the survival duration. Following the principle of combined strengthening Qi and eliminating pathogens could be more beneficial to patients in short term by lessening the tumor size. CMFs have the advantage of reducing certain serious adverse events. [ABSTRACT FROM AUTHOR]

Background: The prevention or early treatment of pathological scars is the most appropriate therapeutic approach. Gels and patches containing onion extract and allantoin are safe and effective in patients with scars of various origins and severity. However, no controlled studies have evaluated the effects of the patch formulation in women after Cesarean delivery. This study aimed to investigate the effects of a patch containing Allium cepa and allantoin on Cesarean section (C-section) scars. Methods: This is an observational study. Women were consecutively recruited at the University Hospital of Salerno and subdivided into two groups considering the number of C-section. Group A included subjects without and group B with a history of C-section. Scars assessment was made using digital photographs and the Patient and Observer Scar Assessment Scale (POSAS). After 4 weeks, the C-section of the women who had applied a patch containing Allium cepa and allantoin and those of women who had not used any products (controls) were re-evaluated as at baseline. The Observers independently performed the scars assessment at baseline and after 4 weeks. Data are expressed as the difference of the POSAS scores after 4 weeks minus the POSAS scores at baseline. The statistical significance was established at a p value <0.05. Results: Ninety-three subjects completed the study (47 in group A and 46 in group B). Women who had used a patch showed an improvement in total score by observer scale when compared with controls (p = 0.013). By the patient scale, no significant changes from baseline were found in group A and group B. Group B with patch showed changes in scars' pigmentation (p = 0.015), relief (p = 0.039), and pliability (p = 0.046) in comparison of controls. Digital photographs confirmed such improvements in women who had already undergone previous C-section, while no significant changes from baseline were found in women without a history of C-section. Conclusions: Intense treatment of just 4 weeks with a patch containing Alium Cepa extract and allantoin was able to improve pigmentation, relief, and pliability of C-section scars in women with a history of C-section. Clinical trial registration: ClinicalTrials.gov, identifier NCT04046783. [ABSTRACT FROM AUTHOR]

In December 2019, a severe outbreak of a novel coronavirus (COVID-19) occurred in the whole world, posing a great threat to people's health. With the outbreak and development of the epidemic, how to improve the cure rate, find effective drugs against this virus, has been the most urgent problem. Chloroquine (CQ) was verified effective against COVID-19 in vitro. As CQ's analogue, hydroxychloroquine (HCQ) was also reminded as a potential candidate for treating COVID-19. This review summarizes the latest clinical trials of CQ and HCQ against COVID-19 and its therapeutic regimen in China aiming to share their current usage to the whole world and provide insight into its appropriate future use in the treatment of COVID-19. Through searching the CNKI and Wangfang databases in Chinese language and PubMed, EMBASE, and Ovid databases in English language to identify published reports with the keywords including "coronavirus/COVID, chloroquine, hyroxychloroquine" in alone or combined, we found out the potential preclinical or clinical evidence for using CQ and HCQ against COVID-19. Consequently, we also searched the website of Chinese Clinical Trial Registry (http://www.chictr.org.cn/) till the day on 27th, June, 2020. This review found that there are 23 programs aimed to treat the different phases under COVID-19 pipeline in clinic with CQ and HCQ, totally. The inclusion criteria, exclusion criteria and therapeutic regimen were all shared to consult. Among them, seven have been canceled due to lack of patients or other objective factors. There are two trials have completed, which the potential relationship between usage and adverse reactions was discussed emphatically. Through literature research, we suggested that paid close attention to retinal toxicity and ophthalmologic adverse symptom of CQ and HCQ. And the outcome of HCQ in clinic shows better than CQ especially in protective effect with low dosage. [ABSTRACT FROM AUTHOR]

Purpose: Carboprost may induce adverse reactions when used to treat postpartum hemorrhage. We aimed to explore the effects of intravenous infusion of low-dose remifentanil to prevent such reactions. Methods: We enrolled parturient patients scheduled for elective cesarean section. Anesthesiologist administered combined spinal epidurals at the L3/4 interspace, with 0.5% hyperbaric bupivacaine subarachnoid space injections (1.5–2.5 ml). We randomly divided parturient patients, administered carboprost during surgery, into the remifentanil group (group R) and the control group (group C). Patients in group R received an intravenous target-controlled infusion of remifentanil (target effect-site concentration, 1.5 ng/ml) simultaneously with a carboprost tromethamine injection (250 µg). Patients in group C received a normal saline infusion with carboprost. We recorded and analyzed the incidence of carboprost-related adverse reactions (vomiting, nausea, chest congestion, flushing, hypertension, tachycardia, cough, and shivering), and assessed patient comfort using a numerical rating scale ([NRS], on which 0 was very uncomfortable and 10 was very comfortable). Results: After applying inclusion and exclusion criteria, we conducted statistical analysis of the data from 70 women. The incidence of vomiting was significantly lower in group R than in group C (14.3 vs. 51.4%, p < 0.01); and the incidence of nausea, chest congestion, facial flushing, and hypertension were significantly lower in group R than in group C (all p < 0.01). Furthermore, the patients' comfort scores were significantly higher in group R than in group C (8.0 ± 1.8 vs. 3.6 ± 2.1, p < 0.01). Conclusion: Our results demonstrate that an intravenous low-dose remifentanil infusion can effectively prevent carboprost-related adverse reactions during cesarean delivery under combined spinal and epidural anesthesia. Clinical Trial Registration: We pre-registered this study at http://www.chictr.org.cn/showproj.aspx?proj=27707 (ChiCTR1800016292). [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS) is characterized by high morbidity and high mortality. The integration of Traditional Chinese medicine (TCM) and western medicine has shown promising benefits in relieving symptoms, promoting neurological recovery, and improving the quality of life of patients with IS. In TCM, Qi -deficiency along with blood-stasis (QDBS) syndrome is one of the common types of IS that is treated by invigorating Qi and activating blood circulation. In TCM theory, improving the corresponding degree of prescription–syndrome correlation (PSC) is helpful to improve clinical efficacy. In this study, we intend to use similar prescriptions that invigorate Qi and activate blood circulation: Buyang Huanwu granules (BHG), Naoxintong capsules (NXTC), and Yangyin Tongnao granules (YTG). The goal is to evaluate their level of PSC inpatients with IS with QDBS syndrome and find relevant biomarkers to provide an objective basis for precise treatment of TCM and improve the clinical therapeutic effects. A multicenter, randomized, double-blinded, and placebo-controlled intervention trial will be conducted in IS patients with QDBS syndrome, followed by an add-on of Chinese patent medicine. A total of 160 subjects will be randomly assigned to the BHG, NXTC, YTG, and placebo groups in a 1:2:1:1 allocation ratio. All subjects will undergo 28 days of treatment and then followed for another 180 days. The primary outcome is the changes in the National Institutes of Health Stroke Scale score after 28 days of medication. The secondary outcomes include the modified Rankin scale score, activity of daily living scale score, and TCM symptom score. Data will be analyzed in accordance with a predefined statistical analysis plan. Ethical approval of this trial has been granted by the Research Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (ID: 2017-Y-004-02). Written informed consent of patients will be required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR1800015189), and the results will be disseminated to the public through peer-reviewed journals and academic conferences. [ABSTRACT FROM AUTHOR]

Background: Malaria is a major public health concern in Togo. The Est-Mono district of Togo has a population of 150,000. Accordingly, the Guangzhou University of Chinese Medicine, China and the Ministry of Health and Social Security, Togo launched a nationwide Mass Drug Administration Project with artemisinin–piperaquine (AP) in Est-Mono. Before launching this project, the sensitivity test of AP was conducted in a general clinic in Elawagnon, Togo. With this background, we evaluated the efficacy and safety of AP for the treatment of uncomplicated falciparum malaria in children under the age of 5 years. Methods: Children aged 6–59 months with uncomplicated falciparum malaria were enrolled in this study. The selected patients were treated with a combination regime of artemisinin–piperaquine. The patients were followed up for 28 days, during which signs of the following were observed for: the duration for fever clearance, parasitemia density, gametophyte generation, cure rate, hemoglobin level, and merozoite surface protein-2 (msp-2) polymorphism. The primary end point was a 28-day cure rate and polymerase chain reaction (PCR)-corrected reinfection and recrudescence. This research followed the standardized World Health Organization (WHO) protocol for the assessment of the efficacy of antimalarial drugs. Results: A total of 91 children with uncomplicated falciparum malaria were enrolled in this study. Adequate clinical and parasitological responses (ACPRs) before and after PCR-correction were 66 (73%) and 90 (99%), respectively. The average hemoglobin level in the patient increased by 0.05 g/dl per day (p < 0.0001) after the treatment. The gametophyte generation did not decline at the beginning of the treatment; however, after 14 days, it declined (day 21: p < 0.05; day 28: p < 0.01). In the msp-2 polymorphism study of 24 children treated for parasite infection, one case of msp-2 with 3D7 haplotype and FC27 haplotype was noted, indicating its recrudescence, with a frequency of 4%. The remaining 23 cases could have been of reinfection, with a frequency of 96%. No serious adverse reactions occurred, and AP was well-tolerated by all patients. Conclusion: Artemisinin–piperaquine was found to be an effective combination for treating uncomplicated falciparum malaria in children aged <5 years in Togo, and the drugs were well-tolerated. In Togo, Plasmodium falciparum remains sensitive to artemisinin–piperaquine, necessitating its trial in this region. Clinical Trial Registration: Trial registration: ECGPHCM No. B2017-054-01; MHSST AVIS N° 0001/2016/CBRS du 07 janvier 2016. Registered 17 March 2014, http://www.chinadrugtrials.org.cn/eap/main. [ABSTRACT FROM AUTHOR]

Weight gain and metabolic disturbances, potentially influenced by increased appetite, are common effects of olanzapine treatment in patients with schizophrenia. In this study, we explored the association between olanzapine-induced weight gain and metabolic effects with increased appetite. Drug-naïve, first-episode schizophrenia patients were treated with olanzapine for 12 weeks. Assessments included time to increased appetite, body weight, body mass index, biochemical indicators of blood glucose and lipids, proportion of patients who gained more than 7% or 10% of their baseline weight upon treatment conclusion, patients who developed dyslipidemia, and Positive and Negative Syndrome Scale scores. In total, 33 patients with schizophrenia receiving olanzapine were enrolled and 31 completed the study. During the 12-week olanzapine treatment, 77.4% (24/31) patients had increased appetite with 58.1% (18/31) patients having increased appetite within the first 4 weeks. The mean time for increased appetite was 20.3 days. More patients in the increased appetite group increased their initial body weight by more than 7% after 12 weeks when compared to patients with unchanged appetite (22/24 [91.7%] vs. 3/7 [42.9%], p = 0.004). Earlier increased appetite led to more weight gain during the following month. Overall, 50% of patients in the increased appetite group had dyslipidemia after 12 weeks. Our results demonstrated that olanzapine induced significantly appetite increase in first-episode patients with schizophrenia and appetite increase played a key role in olanzapine-induced weight gain and dyslipidemia. Clinical Trial Registration: NCT03451734. Registered March 2, 2018 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Background: All current approved antipsychotic drugs against schizophrenia spectrum disorders share affinity for the dopamine receptor (D2R). However, up to one-third of these patients respond insufficiently, and in some cases, side-effects outweigh symptom reduction. Previous data have suggested that a subgroup of antipsychotic-naïve patients will respond to serotonin 2A receptor (2AR) blockade. Aims: This investigator-initiated, translational, proof-of-concept study has overall two aims; 1) To test the clinical effectiveness of monotherapy with the newly approved drug against Parkinson's disease psychosis, pimavanserin, in antipsychotic-free patients with first-episode schizophrenia spectrum disorders; 2) To characterize the neurobiological profile of responders to pimavaserin. Materials and Equipment: Forty patients will be enrolled in this 6-week open label, one-armed trial with the selective serotonin 2AR antagonist (pimavanserin 34 mg/day). At baseline, patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR using the radioligand [¹¹C]Cimbi-36; structural magnetic resonance imaging (MRI); MR spectroscopy of cerebral glutamate levels and diffusion tensor imaging; cognitive and psychopathological examinations; electrocardiogram, and blood sampling for genetic- and metabolic analyses. Outcome Measures: The primary clinical endpoint will be reduction in the Positive and Negative Syndrome Scale (PANSS) positive score. Secondary clinical endpoints comprise multiple clinical ratings (positive and negative symptoms, depressive-, obsessive-compulsive symptoms, quality of life, social functioning, sexual functioning, and side-effects). PET, MRI, and cognitive parameters will be used for in-depth neuropsychiatric characterization of pimavanserin response. Anticipated Results: Clinically, we expect pimavanserin to reduce psychotic symptoms with similar effect as observed with conventional antipsychotics, for which we have comparable historical data. We expect pimavanserin to induce minimal side-effects. Neurobiologically, we expect psychotic symptom reduction to be most prominent in patients with low frontal serotonin 2AR binding potential at baseline. Potential pro-cognitive and brain structural effects of pimavanserin will be explored. Perspectives: Sub-Sero will provide unique information about the role serotonin 2AR in antipsychotic-free, first-episode psychosis. If successful, Sub-Sero will aid identification of a "serotonergic subtype" of schizophrenia spectrum patients, thereby promoting development of precision medicine in clinical psychiatry. Clinical Trial Registration: ClinicalTrials, identifier NCT03994965. [ABSTRACT FROM AUTHOR]

Background: Dose requirements of vitamin K antagonists are associated with CYP2C9 and VKORC1 , but, compared to warfarin, less data is available about phenprocoumon. Furthermore, the effects on dose stability and anticoagulation quality are still unclear. Methods: Aim was to scrutinize phenprocoumon dose requirements, dose stability and anticoagulation quality in association to CYP2C9 and VKORC1 in a natural cohort of elderly primary care patients. As a subgroup within the IDrug study, phenprocoumon treated patients with at least two INR values within three months before enrollment (n = 209) were analyzed concerning average weekly dose, standard deviation of weekly dose (intra-subject variability), constant dose (yes/no), average INR and TTR grouped by CYP2C9 and VKORC1 (and combinations). Results: Average weekly dose per patient was 14.4 ± 5.3 mg, 11.9 ± 4.0 mg and 11.2 ± 4.3 mg in CYP2C9 wildtypes, *2 and *3 carriers (p <.0001) and 16.0 ± 4.2 mg, 13.3 ± 5.1 mg and 8.0 ± 2.7 mg per week in VKORC1 CC, CT and TT genotypes, respectively (p <.0001). Significant differences concerning intra-subject variability were detected among all groups (p <.0001) with the smallest variability in CYP2C9*3 carriers. TTR medians were 75.4%, 79.4% and 100% in wildtypes, *2 and *3 carriers, respectively (p = 0.0464). The proportion of patients with perfect control was highest among *3 carriers, but this result was not significant (p = 0.0713). Discussion: Our analyses support the results of previous investigations regarding genotype-associated dose requirements and raise the hypothesis that dose stability and anticoagulation quality may be increased in CYP2C9*3 carriers. However, our data should be treated cautiously due to the small sample size. Clinical Trial Registration: German Clinical Trials Register, identifier DRKS00006256. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine possesses sedative, sympatholytic, and opioid-sparing properties, but its impact on postoperative gastrointestinal function is controversial. Methods: This single-center, prospective, randomized study compared low-dose dexmedetomidine and placebo on gastrointestinal function recovery and inflammation after posterior lumbar spinal fusion. Sixty-six patients were randomized into two groups and received normal saline (control group) or dexmedetomidine (DEX group) during posterior lumbar fusion. Blood was taken at five timepoints to measure lipopolysaccharides, tumor necrosis factor-α, and C-reactive protein. The primary outcome was duration to first flatus. The secondary outcomes were inflammatory mediators and determination of correlations between perioperative factors and duration to first flatus. Results: Patients in DEX group showed significantly lower duration to first flatus (15.37 [13.35–17.38] vs 19.58 [17.31–21.86] h; p = 0.006) and overall sufentanil consumption (67.19 [63.78–70.62] vs 74.67 [69.96–79.30] μg; p = 0.011) than controls. Lipopolysaccharides, tumor necrosis factor-α, and C-reactive protein did not differ between the groups at any timepoint (all p > 0.05). Multiple linear regression modeling assessed the ability of independent variables to predict variance in duration to first flatus (adjusted R2 = 0.379, p = 0.000). In the model, age (β = 0.243, p = 0.003), gender (β = −3.718, p = 0.011), BMI (β = −0.913, p = 0.001), operative segments (β = −4.079, p = 0.028), and overall sufentanil consumption (β = 0.426, p = 0.000) contributed significantly. Conclusions: Thus, low-dose dexmedetomidine accelerates gastrointestinal function recovery after lumbar spinal fusion. The effect may be partially produced by opioid-sparing effects rather than inhibition of inflammation. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR1800018127. [ABSTRACT FROM AUTHOR]

Introduction: The Mediterranean Diet (MD) is useful in the prevention of overweight, obesity and metabolic disease. High Quality-Extra Virgin Olive Oil (HQ-EVOO), an essential component of this diet, exerts protective effects against chronic diseases. Gut Microbiota (GM), recognized as a key factor in driving metabolic activities, is involved in the regulation of host immunity. Lactic Acid Bacteria (LAB) and their probio-active cellular substances produce beneficial effects in the gastrointestinal tract. Materials and Methods: Eighteen overweight/obese subjects (cases, BMI ≥25 kg/m2) and 18 normal weight controls (BMI 18.5–24.9 kg/m2) were fed with MD enriched with 40 g/die HQ-EVOO for three months. Feces and blood samples were collected at time 0 (T0) and after three months (T1) for LAB composition, oxidative stress, metabolic and inflammation parameter determinations. Results: Myeloperoxidase and 8-hydroxy-2-deoxyguanosine, markers of inflammation and oxidative stress, were significantly decreased after MD rich in HQ-EVOO both in controls and in cases. Proinflammatory cytokines levels were significantly decreased in cases in comparison to controls, while IL-10 and adiponectin were significantly increased in cases. LAB's rpo B copies/ng of DNA increased 55.6 folds in cases compared to their baseline after MD rich in HQ-EVOO. MD rich in HQ-EVOO increased adiponectin and IL-10 concentration in overweight/obese subjects and decreased oxidative stress and inflammation parameters and at the same time, increased LAB number in GM. Discussion: Our results indicate that MD rich in HQ-EVOO induces an increase of LAB in GM and could have a potential role in the prevention of inflammation. Clinical Trial Registration: www.ClinicalTrials.gov , identifier NCT03441802. [ABSTRACT FROM AUTHOR]

Coronary heart disease (CHD) is one of the leading causes of morbidity and mortality worldwide, and more efforts should be made to reduce the risk of cardiovascular events. This study aimed to investigate the impact of clinical pharmacist intervention on the prognosis of acute coronary syndrome (ACS) in Chinese patients with CHD. Two hundred and forty patients who had ACS were recruited. Participants were randomly assigned to the intervention group (n = 120) or the control group (n = 120). The intervention group received a medication assessment and education by the clinical pharmacist at discharge and telephone follow-ups at 1 week and 1 and 3 months after discharge. The control group received usual care. The primary outcomes of this study were the proportion of patients who had major adverse cardiovascular events (MACEs), including mortality, nonfatal myocardial infarction (MI), stroke, and unplanned cardiac-related rehospitalizations within 6 and 12 months after hospital discharge. Secondary outcome was self-reported medication adherence to evidence-based medications for CHD (antiplatelets, statins, β-blockers, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers). Of 240 enrolled patients, 238 (98.3%) completed 6-month follow-up, and 235 (97.9%) completed 12-month follow-up. There were no significant differences between intervention and control groups in the percentages of patients who incurred MACEs within the 6-month follow-up (3.3% vs 7.6%, respectively, P = 0.145) or 12-month follow-up (10.9% vs 12.1%, respectively, P = 0.783). Significant improvements were found in the prescribing rates of β-blockers and all four classes of medications at discharge in the intervention group compared with the control group (P = 0.001 and P = 0.009, respectively). There was no significant difference between the intervention and control groups in the use of all four classes of medications at the 6-month follow-up (48.3% vs 45.8%, respectively, P = 0.691) and 12-month follow-up (47.9% vs 46.6%, respectively, P = 0.836). The use of β-blockers was nonsignificantly higher in the intervention group than in the control group at the 6-month follow-up (74.2% vs. 64.4%, P = 0.103) and 12-month follow-up (74.8% vs 63.8%, P = 0.068). Clinical pharmacist intervention had no significant effects on reduction in cardiovascular events among patients with CHD. Further studies with larger sample sizes and longer time frames for both intervention and follow-up are needed to validate the role of the clinical pharmacist in the morbidity and mortality of CHD. Clinical Trial Registration: chictr.org.cn , identifier ChiCTR-IOR-16007716. [ABSTRACT FROM AUTHOR]

High-risk neuroblastoma (NB) remains a significant therapeutic challenge facing current pediatric oncology patients. Structural variants such as gene fusions have shown an initial promise in enhancing mechanistic understanding of NB and improving survival rates. In this study, we performed a comprehensive in silico investigation on the translational ability of gene fusions for patient stratification and treatment development for high-risk NB patients. Specifically, three state-of-the-art gene fusion detection algorithms, including ChimeraScan, SOAPfuse, and TopHat-Fusion, were employed to identify the fusion transcripts in a RNA-seq data set of 498 neuroblastoma patients. Then, the 176 high-risk patients were further stratified into four different subgroups based on gene fusion profiles. Furthermore, Kaplan-Meier survival analysis was performed, and differentially expressed genes (DEGs) for the redefined high-risk group were extracted and functionally analyzed. Finally, repositioning candidates were enriched in each patient subgroup with drug transcriptomic profiles from the LINCS L1000 Connectivity Map. We found the number of identified gene fusions was increased from clinical the low-risk stage to the high-risk stage. Although the technical concordance of fusion detection algorithms was suboptimal, they have a similar biological relevance concerning perturbed pathways and regulated DEGs. The gene fusion profiles could be utilized to redefine high-risk patient subgroups with significant onset age of NB, which yielded the improved survival curves (Log-rank p value ≤ 0.05). Out of 48 enriched repositioning candidates, 45 (93.8%) have antitumor potency, and 24 (50%) were confirmed with either on-going clinical trials or literature reports. The gene fusion profiles have a discrimination power for redefining patient subgroups in high-risk NB and facilitate precision medicine-based drug repositioning implementation. [ABSTRACT FROM AUTHOR]

Background: Functional dyspepsia (FD) is a highly complex pathophysiologic disease, which shows low recovery and high relapse rates. Therefore, a growing number of clinicians and patients are looking for alternative herbal medicine. Banha-Sasim-Tang (BST) is an herbal prescription for treating a wide range of dyspepsia in traditional Korean medicine (TKM). Aim of the study: This study aimed to evaluate the efficacy of BST on FD in patients with psychological stress-related symptoms and to investigate the involvement of ghrelin. This study is registered at https://cris.nih.go.kr/with the identification number KCT 0002811. Materials and methods: A total of 31 participants with FD who met the Rome IV criteria and the psychological stress-related pattern were enrolled in a double-blind, randomized, and controlled study. Participants were randomly assigned to the BST group (10 g twice daily for 4 weeks) or placebo group. The primary endpoint was a change in the Nepean Dyspepsia Index–Korean (NDI-K) score. The secondary endpoints were changes in the Visual Analog Scale (VAS) scores and plasma ghrelin level. Results: All participants completed the study (n = 15 for BST, n = 16 for placebo). BST decreased NDI-K scores compared with placebo, but the difference was not statistically significant (37.40 ± 27.40 vs 22.50 ± 23.85, p = 0.12). VAS scores and plasma total ghrelin levels were significantly improved in patients who were treated with BST (3.19 ± 1.60 vs 1.38 ± 2.85, p = 0.03 for VAS and 105.69 ± 287.89 vs -142.31 ± 314.32, p = 0.03 for total ghrelin). No BST-related adverse effects were observed during the trial. Conclusion: Our results indicate the clinical potential of BST for FD patients and are the first study to show the modulation of plasma ghrelin as one of its corresponding mechanisms. Clinical Trial Registration: https://cris.nih.go.kr/, identifier KCT 0002811. [ABSTRACT FROM AUTHOR]

Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF (n = 283) or losartan (n = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: −2.25 ml/min/1.73 m2/year, 95% confidence interval [CI]: −4.03,−0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to explore the bioequivalence of a proposed biosimilar BAT1806 to its reference products marketed in the EU and US (RoActemra-EU and Actemra-US) among healthy Chinese men. The tolerance, immunogenicity, and pharmacokinetics (PK) of the three drugs were also investigated. Methods: In this randomized, double-blind, single-dose, three-arm, parallel study, a single-dose of 4 mg/kg of the reference products, or the biosimilar was administered to the participants. The participants were followed up for 57 days, and PK, immunogenicity, and tolerance evaluations were completed during this period. Results: The PK parameters were similar in all three groups: BAT1806 (n = 45), RoActemra-EU (n = 42), and Actemra-US (n = 42). The 90% confidence intervals (CIs) for the ratios of C max , AUC0– t and AUC0–∞ were 86.90–104.41% for BAT1806 vs. RoActemra-EU, 91.70–106.15% for BAT1806 vs Actemra-US, and 90.04–105.53% for Actemra-US vs RoActemra-EU. For all comparisons, the 90% CIs for the C max , AUC0– t , and AUC0–∞ were within the predefined bioequivalence limit of 80.00–125.00%. The intersubject variability ranged from 14.5% to 21.5%, which was considerably low. Among the participants, 19 (42.2%), 10 (23.8%), and 12 (28.6%) from the BAT1806, RoActemra-EU, and Actemra-US groups were, respectively, found to be positive for anti-drug antibodies, while 14 (31.1%), nine (21.4%), and 12 (28.6%) were positive for neutralizing antibodies. Nevertheless, these antibodies did not affect the drug concentrations, and the outcomes in the bioequivalence tests were similar after sensitivity analysis. Treatment-related and treatment-emergent adverse events (TEAEs) were recorded in 27, 34, and 32 participants in the BAT1806, RoActemra-EU, and Actemra-US groups, respectively. The most common treatment-related adverse events observed were a decrease in neutrophil, and white blood cell counts. Conclusion: The PK characteristics of BAT1806 were similar to those of the reference products, RoActemra-EU and Actemra-US. Both BAT1806 and the reference products exhibited low intersubject variability and similar safety profiles. Clinical trial registration number: http://www.chinadrugtrials.org.cn/index.html, CTR20180039; https://clinicaltrials.gov/NCT03606876 [ABSTRACT FROM AUTHOR]

Ultrasound-guided perineural dextrose injection (PDI) has been reported effective for carpal tunnel syndrome (CTS). Higher volume of injectate may reduce adhesion of median nerve from other tissues, but volume-dependent effects of PDI in CTS remain unknown. We aimed to investigate whether PDI with different injectate volumes had different effects for CTS participants. In this randomized, double-blinded, three-arm trial, 63 wrists diagnosed with CTS were randomized into three groups that received ultrasound-guided PDI with either 1, 2 or 4 ml of 5% dextrose water. All participants finished this study. Primary outcome as visual analog scale (VAS) and secondary outcomes including Boston Carpal Tunnel Questionnaire (BCTQ), Disability of the Arm, Shoulder and Hand score (QuickDASH), electrophysiological studies and cross-sectional area (CSA) of the median nerve at carpal tunnel inlet were assessed before and after PDI at the 1st, 4th, 12th and 24th weeks. For within-group analysis, all three groups (21 participants, each) revealed significant improvement from baseline in VAS, BCTQ and QuickDASH at the 1st, 4th, 12th and 24th weeks. For between-group analysis, 4 ml-group yielded better VAS reduction at the 4th and 12th weeks as well as improvement of BCTQ and QuickDASH at the 1st, 4th, and 12th weeks, compared to other groups. No significant between-group differences were observed in electrophysiological studies or median nerve CSA at any follow-up time points. There were no severe complications in this trial, and transient minor adverse effects occurred equally in the three groups. In conclusion, ultrasound-guided PDI with 4 ml of 5% dextrose provided better efficacy than with 1 and 2 ml based on symptom relief and functional improvement for CTS at the 1st, 4th, and 12th week post-injection, with no reports of severe adverse effects. There was no significant difference between the three groups at the 24th-week post-injection follow-up. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03598322. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) pandemic has affected an estimated 16 million persons and caused 0.6 million deaths worldwide by September 2020. The pandemic has led to a rush to repurpose existing drugs, although the underlying evidence base is of variable quality. The improving knowledge of the virology and clinical presentation of COVID-19 is leading to a broadening pool of potential pharmacological targets. The aim of this review is to describe regulatory and pharmacological aspects of drug repurposing and to identify drugs proposed for repurposing in COVID-19 based on registered clinical trials, discussing the evidence to support their use in the treatment of this disease. The challenges of the correct interpretation of existing pre-clinical/clinical evidence as well as the generation of new evidence concerning drug repurposing in COVID-19 will also be discussed. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04321174, NCT04342663, NCT04280705, NCT04244591, NCT04359329, NCT04348695, NCT04304313, NCT043505931 [ABSTRACT FROM AUTHOR]