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In temporomandibular disorder (TMD), the effects of standard interventions such as using an occlusal splint and its impact on pain relief and pain catastrophizing are poorly understood. Earlier work pointed to a crucial role of insula activation with changes in pain relief by occlusal splint treatment. We performed a functional imaging study using specially developed splint systems to allow for a placebo-controlled longitudinal design. Using functional MRI we examined 20 TMD patients during repetitive occlusal movements at baseline and over the course of splint therapy and also collected self-reported pain catastrophizing. For balancing performance between baseline and after intervention we used occlusion force measures in an individualized fMRI-splint system. Splint therapy lasted for approximately 7 weeks with one group selected by randomization wearing a palatine placebo splint over the first 3 weeks (delayed start; 11 individuals). As expected, fMRI activation in areas involved in pain processing (insula, primary and secondary somatosensory cortex) decreased with intervention. At baseline a positive correlation between activation of the left anterior insula and pain catastrophizing was present. Both parameters decreased over intervention while associations were primarily observable for patients with rather mild TMD., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Purpose: Definitive antiviral treatment is not available for COVID-19 infection, with the exception of remdesivir, which still evokes many doubts. Various monotherapy or combination therapies with antivirals or other agents have been tried. The present study aims to evaluate the therapeutic potential of hydroxychloroquine and lopinavir-ritonavir in combination with ribavirin in mild-severe COVID-19., Patients and Methods: A single-center, open-label, parallel-arm, stratified randomized controlled trial evaluated the therapeutic potential of combination antiviral therapies. Enrolled patients in the severe category were randomized into three groups: (A) standard treatment, (B) hydroxychloroquine+ribavirin+standard treatment, or (C) lopinavir+ritonavir+ribavirin+standard treatment; while the non-severe category comprised two groups: (A) standard treatment or (B) hydroxychloroquine+ribavirin. Combination antivirals were given for 10 days and followed for 28 days. The primary endpoints were safety, symptomatic and laboratory recovery of organ dysfunctions, and time to SARS-CoV-2 RT-PCR negative report., Results: In total, 111 patients were randomized: 24, 23, and 24 in severe categories A, B, and C, respectively, and 20 in each of the non-severe groups. Two patients receiving ribavirin experienced drug induced liver injury, and another developed QT prolongation after hydroxychloroquine. In the severe category, 47.6%, 55%, and 30.09% in A, B, and C groups, respectively, showed symptomatic recovery, compared to 93.3% and 86.7% in A and B groups, respectively, in the non-severe category at 72 hours ( P >0.05)., Conclusion: Though the results failed to show statistical superiority of the antiviral combination therapies to that of the standard therapy in both the severe and non-severe categories in symptomatic adult patients of COVID-19 due to very small sized trial, clinically hydroxychloroquine+ribavirin therapy is showing better recovery by 7.4% than standard therapy in the former category. However, results do indicate the benefit of standard therapy in the non-severe category by 6.6%. Furthermore, the dose of ribavirin needs to be reconsidered in the Indian population., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Panda et al.)

Background: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics., Methods: This study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias., Results: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60-200), and the median length of the trial periods was 179 d (IQR: 94-366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low., Conclusions: Intensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.

Preclinical data have shown that rilmenidine can regulate autophagy in models of Huntington's disease (HD), providing a potential route to alter the disease course in patients. Consequently, a 2-year open-label study examining the tolerability and feasibility of rilmenidine in mild-moderate HD was undertaken. 18 non-demented patients with mild to moderate HD took daily doses of 1 mg Rilmenidine for 6 months and 2 mg for a further 18 months followed by a 3-month washout period. The primary outcome was the number of withdrawals and serious adverse events. Secondary outcomes included safety parameters and changes in disease-specific variables, such as motor, cognitive and functional performance, structural MRI and serum metabolomic analysis. 12 patients completed the study; reasons for withdrawal included problems tolerating study procedures (MRI, and venepuncture), depression requiring hospital admission and logistical reasons. Three serious adverse events were recorded, including hospitalisation for depression, but none were thought to be drug-related. Changes in secondary outcomes were analysed as the annual rate of change in the study group. The overall change was comparable to changes seen in recent large observational studies in HD patients, though direct statistical comparisons to these studies were not made. Chronic oral administration of rilmenidine is feasible and well-tolerated and future, larger, placebo-controlled, studies in HD are warranted., Trial Registration: EudraCT number 2009-018119-14.

Objectives: We sought to systematically evaluate the external validity of a contemporary randomized controlled stent trial (BIOSCIENCE)., Methods: Baseline characteristics and clinical outcomes of patients enrolled into the BIOSCIENCE trial at Bern University Hospital (n = 1216) were compared to those of patients included in the CARDIOBASE Bern PCI Registry at the same institution (n = 1045). The primary study endpoint was the rate of target lesion failure (TLF), defined as a composite of cardiac death, target vessel-myocardial infarction (MI) or target lesion revascularization (TLR), at 1 year., Results: Women were underrepresented in the RCT compared to the registry (25 vs. 29.4 %, p = 0.020). Non-participants were older compared to study participants (69.2 ± 12.4 vs. 67.0 ± 11.6, p < 0.001), and had a higher prevalence of previous cerebrovascular events (10.8 vs. 5.2 %, p < 0.001), and chronic renal failure (35.5 vs. 15.6 %, p < 0.001). ST-segment elevation myocardial infarction (STEMI) and Killip class IV at presentation were more common among non-participants than participants (30.7 vs. 21.1 %, p < 0.001 and 7.8 vs. 0.4 %, p < 0.001, respectively). At 1 year, non-participants experienced a significantly higher rate of TLF, (15.0 vs. 6.5 %, p < 0.001), and patient-oriented composite endpoint (POCE), including death, MI or any repeat revascularization (21.6 vs. 11.2 %, p < 0.001). There was a significant interaction between POCE and presence or absence of an acute coronary syndrome in participants versus non-participants, respectively (p = 0.009)., Conclusions: Non-participants of this all-comers trial had a higher risk profile and adverse prognosis compared to study participants. Further efforts are needed to improve the external validity of contemporary RCTs.

Objective: Statin pleiotropy is still an evolving concept, and the lack of clarity on this subject is due at least in part to the lack of a definitive biomarker for statin pleiotropy. Using plasma mRNA analysis as a novel research tool for the non-invasive in vivo assessment of gene expression in vascular beds, we hypothesised that atorvastatin lowers the plasma mRNA level from statin pleiotropy-target genes, and the reduction is independent of the reduction of low-density lipoprotein cholesterol (LDL-C)., Design and Methods: Forty-four patients with stable angina received atorvastatin therapy (20 mg/day, 10 weeks). Plasma chemokine (C-C motif) ligand 2 (CCL2) and intercellular adhesion molecule-1 (ICAM1) mRNA levels and their protein concentrations (MCP-1, sICAM-1) were analysed before and after the treatment. Plasma vascular adhesion molecule-1 (sVCAM-1) concentrations were also analysed., Results: Atorvastatin lowered plasma mRNA levels (CCL2: -31.76%, p=0.037; ICAM1: -34.09%, p<0.001) and MCP-1 protein concentration (-18.88%, p=0.008) but did not lower sICAM-1 and sVCAM-1 protein concentrations, and the decreases appeared to be independent from the lowering of LDL-C. The plasma mRNA levels correlated with their protein concentrations following statin treatment only., Conclusion: Our results significantly strengthen the clinical evidence in support of statin pleiotropy. Furthermore, this unique simultaneous measurement of plasma mRNAs and their protein concentrations offers an advanced non-invasive in vivo assessment of the circulation pathology., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)