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BMC Complementary Medicine and Therapies Jul 2023Knee osteoarthritis (KOA) is a common public health problem and a leading cause of long-term pain, decreased muscle strength, and even disability. Tai Chi has been...
BACKGROUND
Knee osteoarthritis (KOA) is a common public health problem and a leading cause of long-term pain, decreased muscle strength, and even disability. Tai Chi has been proved effective and highly recommended for KOA management worldwide. However, little is known about its benefits on quadriceps strength which is closely associated with relieving knee pain. This trial is designed to evaluate the efficacy and safety of Tai Chi on knee pain and muscle strength in middle-aged and older adults with KOA.
METHODS
A total of 100 participants will be randomly divided into a Tai Chi group (TC group) (1x/week for 12 weeks) and a control group with a health education and stretching program (1x/week for 12 weeks) with a follow-up period of 6 weeks. The primary outcome is the change of Western Ontario and McMaster Universities (WOMAC) pain subscale at week 12 compared with baseline. Secondary outcomes include WOMAC stiffness and function subscales, data from isokinetic dynamometry, gait analysis with electromyography (EMG), and a 36-item short form health survey (SF-36). The daily dose of pain-relieving medication will also be recorded. All adverse effects will be assessed by the Treatment Emergent Symptom Scale (TESS).
DISCUSSION
We expect this randomized trial to evaluate the effectiveness of Tai Chi on relieving pain and increasing quadriceps strength in KOA patients. This protocol, if proven effective, will contribute to providing a promising alternative intervention for middle-aged and older adults with KOA.
TRIALS REGISTRATION NUMBER
This trial has been registered in the China Clinical Trials Registry (registration number: ChiCTR2300069339).
Topics: Middle Aged; Humans; Aged; Osteoarthritis, Knee; Tai Ji; Treatment Outcome; Pain; Muscle Strength; Randomized Controlled Trials as Topic
PubMed: 37474949
DOI: 10.1186/s12906-023-04070-0 -
BMC Psychiatry Oct 2023The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years....
BACKGROUND
The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture.
METHODS
A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research.
DISCUSSION
This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma.
TRIAL REGISTRATION
NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14 of October 2022.
Topics: Adult; Humans; Autoimmune Diseases; Double-Blind Method; Inflammation; Psychotic Disorders; Randomized Controlled Trials as Topic; Rituximab; Treatment Outcome
PubMed: 37872497
DOI: 10.1186/s12888-023-05250-5 -
Japanese Journal of Radiology Oct 2023Glioblastoma is the most common of malignant primary brain tumors and one of the tumors with the poorest prognosis for which the overall survival rate has not... (Review)
Review
Glioblastoma is the most common of malignant primary brain tumors and one of the tumors with the poorest prognosis for which the overall survival rate has not significantly improved despite recent advances in treatment techniques and therapeutic drugs. Since the emergence of immune checkpoint inhibitors, the immune response to tumors has attracted increasing attention. Treatments affecting the immune system have been attempted for various tumors, including glioblastomas, but little has been shown to be effective. It has been found that the reason for this is that glioblastomas have a high ability to evade attacks from the immune system, and that the lymphocyte depletion associated with treatment can reduce its immune function. Currently, research to elucidate the resistance of glioblastomas to the immune system and development of new immunotherapies are being vigorously carried out. Targeting of radiation therapy for glioblastomas varies among guidelines and clinical trials. Based on early reports, target definitions with wide margins are common, but there are also reports that narrowing the margins does not make a significant difference in treatment outcome. It has also been suggested that a large number of lymphocytes in the blood are irradiated by the irradiation treatment to a wide area in a large number of fractionations, which may reduce the immune function, and the blood is being recognized as an organ at risk. Recently, a randomized phase II trial comparing two types of target definition in radiotherapy for glioblastomas was conducted, and it was reported that the overall survival and progression-free survival were significantly better in a small irradiation field group. We review recent findings on the immune response and the immunotherapy to glioblastomas and the novel role of radiotherapy and propose the need to develop an optimal radiotherapy that takes radiation effects on the immune function into account.
Topics: Humans; Glioblastoma; Brain Neoplasms; Immunotherapy; Progression-Free Survival; Immunity; Clinical Trials, Phase II as Topic; Randomized Controlled Trials as Topic
PubMed: 37071249
DOI: 10.1007/s11604-023-01434-x -
The Journal of Clinical Psychiatry Oct 2023To determine if there are differences in the number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH) between lemborexant...
Lemborexant and Daridorexant for the Treatment of Insomnia: An Indirect Comparison Using Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed.
To determine if there are differences in the number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH) between lemborexant and daridorexant and to compare lemborexant with daridorexant indirectly. Dichotomous efficacy and tolerability outcomes reported for Phase 3 daridorexant trials (conducted May 29, 2018-May 14, 2020) for months 1 and 3 were identified from published literature and regulatory documents. Analogous data were extracted for lemborexant from Phase 3 studies (conducted May 31, 2016-January 8, 2019). NNT, NNH, and LHH were then calculated. Lemborexant 5 mg and 10 mg had clinically relevant therapeutic effect sizes, evidenced by most NNT values versus placebo < 10 for Insomnia Severity Index [ISI], subjective total sleep time [sTST], and polysomnography outcomes. NNH values for adverse events (AEs) were > 10, suggesting relative tolerability. Somnolence was the most common AE. Discontinuation rates of lemborexant because of an AE were low, including for somnolence. Efficacy outcomes for daridorexant 25-mg and 50-mg doses pooled resulted in most NNT values versus placebo ≥ 10, with more robust NNT estimates for the 50-mg dose than for the 25-mg dose. Discontinuation rate because of an AE at month 3 was higher for placebo than for daridorexant, rendering favorable LHH calculations. Daridorexant evidenced low rates of somnolence or fatigue. In Phase 3 trials, the benefit-risk ratios for both lemborexant and daridorexant were favorable as measured by NNT, NNH, and LHH. Indirect comparisons of lemborexant with daridorexant suggest an efficacy advantage for lemborexant and a tolerability advantage for daridorexant. NCT02783729, NCT02952820, NCT03545191, NCT03575104.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Sleepiness; Treatment Outcome; Clinical Trials, Phase III as Topic
PubMed: 37796657
DOI: 10.4088/JCP.23m14851 -
Biostatistics (Oxford, England) Dec 2023Trial-level surrogates are useful tools for improving the speed and cost effectiveness of trials but surrogates that have not been properly evaluated can cause...
Trial-level surrogates are useful tools for improving the speed and cost effectiveness of trials but surrogates that have not been properly evaluated can cause misleading results. The evaluation procedure is often contextual and depends on the type of trial setting. There have been many proposed methods for trial-level surrogate evaluation, but none, to our knowledge, for the specific setting of platform studies. As platform studies are becoming more popular, methods for surrogate evaluation using them are needed. These studies also offer a rich data resource for surrogate evaluation that would not normally be possible. However, they also offer a set of statistical issues including heterogeneity of the study population, treatments, implementation, and even potentially the quality of the surrogate. We propose the use of a hierarchical Bayesian semiparametric model for the evaluation of potential surrogates using nonparametric priors for the distribution of true effects based on Dirichlet process mixtures. The motivation for this approach is to flexibly model relationships between the treatment effect on the surrogate and the treatment effect on the outcome and also to identify potential clusters with differential surrogate value in a data-driven manner so that treatment effects on the surrogate can be used to reliably predict treatment effects on the clinical outcome. In simulations, we find that our proposed method is superior to a simple, but fairly standard, hierarchical Bayesian method. We demonstrate how our method can be used in a simulated illustrative example (based on the ProBio trial), in which we are able to identify clusters where the surrogate is, and is not useful. We plan to apply our method to the ProBio trial, once it is completed.
Topics: Humans; Bayes Theorem; Treatment Outcome; Clinical Trials as Topic
PubMed: 36610075
DOI: 10.1093/biostatistics/kxac053 -
Current Hypertension Reports Oct 2023PURPOSE OF REVIEW: Resistant hypertension (RH) defined as uncontrolled blood pressure despite the use of a combination of a renin-angiotensin system blocker, a calcium... (Review)
Review
PURPOSE OF REVIEW: Resistant hypertension (RH) defined as uncontrolled blood pressure despite the use of a combination of a renin-angiotensin system blocker, a calcium channel blocker, and a diuretic at maximally tolerated doses is associated with a substantially increased risk of cardiovascular and renal events. Despite targeting relevant pathophysiological pathways contributing to elevated blood pressure, approximately 10-15% of hypertensive patients remain above recommended blood pressure targets. Further optimization of blood pressure control is particularly challenging in patient populations who frequently present with RH such as elderly and patients with chronic kidney disease, due to the unfavorable safety profile of the recommended fourth-line therapy with mineralocorticoid receptor antagonists. This review explores the potential role of endothelin antagonists as an alternative fourth-line therapy. RECENT FINDINGS: Despite the well-described role of the endothelin pathway in the pathogenesis of hypertension, it is currently not targeted therapeutically. Recently however, main outcome data from the PRECISION study, a randomized placebo-controlled phase 3 trial, in patients with RH on guideline-recommended standardized single-pill background therapy convincingly demonstrated the safety and blood pressure-lowering efficacy of the dual endothelin antagonist Aprocitentan. Findings from the phase 3 PRECISION study could signify a turning point in the utilization of endothelin receptor antagonists as a standard treatment for patients with RH.
Topics: Humans; Aged; Hypertension; Endothelin Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Endothelins; Randomized Controlled Trials as Topic; Clinical Trials, Phase III as Topic
PubMed: 37566184
DOI: 10.1007/s11906-023-01259-z -
Translational Neurodegeneration May 2024The use of biomarker-led clinical trial designs has been transformative for investigating amyloid-targeting therapies for Alzheimer's disease (AD). The designs have... (Review)
Review
The use of biomarker-led clinical trial designs has been transformative for investigating amyloid-targeting therapies for Alzheimer's disease (AD). The designs have ensured the correct selection of patients on these trials, supported target engagement and have been used to support claims of disease modification and clinical efficacy. Ultimately, this has recently led to approval of disease-modifying, amyloid-targeting therapies for AD; something that should be noted for clinical trials investigating tau-targeting therapies for AD. There is a clear overlap of the purpose of biomarker use at each stage of clinical development between amyloid-targeting and tau-targeting clinical trials. However, there are differences within the potential context of use and interpretation for some biomarkers in particular measurements of amyloid and utility of soluble, phosphorylated tau biomarkers. Given the complexities of tau in health and disease, it is paramount that therapies target disease-relevant tau and, in parallel, appropriate assays of target engagement are developed. Tau positron emission tomography, fluid biomarkers reflecting tau pathology and downstream measures of neurodegeneration will be important both for participant recruitment and for monitoring disease-modification in tau-targeting clinical trials. Bespoke design of biomarker strategies and interpretations for different modalities and tau-based targets should also be considered.
Topics: Alzheimer Disease; Humans; tau Proteins; Biomarkers; Clinical Trials as Topic
PubMed: 38773569
DOI: 10.1186/s40035-024-00417-w -
Journal of Clinical Epidemiology Dec 2023To inform clinical practice guidelines, randomized controlled trials (RCTs) of the management of pneumonia need to address the outcomes that are most important to...
OBJECTIVES
To inform clinical practice guidelines, randomized controlled trials (RCTs) of the management of pneumonia need to address the outcomes that are most important to patients and health professionals using consistent instruments, to enable results to be compared, contrasted, and combined as appropriate. This systematic review describes the outcomes reported in clinical trials of pneumonia management and the instruments used to measure these outcomes.
STUDY DESIGN AND SETTING
Based on a prospective protocol, we searched MEDLINE/PubMed, Cochrane CENTRAL and clinical trial registries for ongoing or completed clinical trials evaluating pneumonia management in adults in any clinical setting. We grouped reported outcomes thematically and classified them following the COMET Initiative's taxonomy. We describe instruments used for assessing each outcome.
RESULTS
We found 280 eligible RCTs of which 115 (41.1%) enrolled critically ill patients and 165 (58.9%) predominantly noncritically ill patients. We identified 43 distinct outcomes and 108 measurement instruments, excluding nonvalidated scores and questionnaires. Almost all trials reported clinical/physiological outcomes (97.5%). Safety (63.2%), mortality (56.4%), resource use (48.6%) and life impact (11.8%) outcomes were less frequently addressed. The most frequently reported outcomes were treatment success (60.7%), mortality (56.4%) and adverse events (41.1%). There was significant variation in the selection of measurement instruments, with approximately two-thirds used in less than 10 of the 280 RCTs. None of the patient-reported outcomes were used in 10 or more RCTs.
CONCLUSION
This review reveals significant variation in outcomes and measurement instruments reported in clinical trials of pneumonia management. Outcomes that are important to patients and health professionals are often omitted. Our findings support the need for a rigorous core outcome set, such as that being developed by the European Respiratory Society.
Topics: Adult; Humans; Pneumonia; Treatment Outcome; Clinical Trials as Topic
PubMed: 37898460
DOI: 10.1016/j.jclinepi.2023.10.011 -
PloS One 2023Some patients have insufficient treatment response to conventional disease-modifying antirheumatic drugs (cDMARD); although biologics have proven to be an effective... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Some patients have insufficient treatment response to conventional disease-modifying antirheumatic drugs (cDMARD); although biologics have proven to be an effective treatment for RA, the effects that bDMARDs have on integumentary, cardiac, and immune systems and the high costs associated with these treatments, make that mesenchymal stem cell-based therapies (MSCs) for RA are being considered potential treatment methods. This work analyses the performance in safety and efficacy terms of MSCs techniques.
METHODS AND FINDING
A literature search was performed in PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey databases from inception to October 28, 2022. Three randomized controlled trials (RCTs) and one non-randomized controlled trial (non-RCTs), including 358 patients met our inclusion criteria and were included in qualitative synthesis; only RCTs were eligible for quantitative synthesis (meta-analysis). Meta-analysis of adverse events (AE) in RCTs showed no significant differences in the incidence of AE in the MSCs group compared to the control group (Risk ratio: 2.35; 95% CI, 0.58 to 9.58; I2 = 58.80%). The pooled Risk ratio for non-serious and serious adverse events showed no statistical difference between intervention and control groups concerning the incidence of non-serious and serious adverse events (Risk ratio: 2.35; 95% CI, 0.58 to 9.51; I2 = 58.62%) and (Risk ratio: 1.10; 95% CI, 0.15 to 7.97; I2 = 0.0%) respectively. The Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS28) decreased in agreement with the decreasing values of C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR). Additionally, a trend toward clinical efficacy was observed; however, this improvement was not shown in the studies after 12 months of follow-up without continuous treatment administration.
CONCLUSION
This Systematic review and meta-analysis showed a favorable safety profile, without life-threatening events in subjects with RA, and a trend toward clinical efficacy that must be confirmed through high-quality RCTs, considerable sample size, and extended follow-up in subjects with RA.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Methotrexate; Treatment Outcome; Controlled Clinical Trials as Topic
PubMed: 37498842
DOI: 10.1371/journal.pone.0284828 -
Trials Dec 2023Since birth, during the exploration of the environment to interact with objects, we exploit both the motor and sensory components of the upper limb (UL). This ability to...
BACKGROUND
Since birth, during the exploration of the environment to interact with objects, we exploit both the motor and sensory components of the upper limb (UL). This ability to integrate sensory and motor information is often compromised following a stroke. However, to date, rehabilitation protocols are focused primarily on recovery of motor function through physical therapies. Therefore, we have planned a clinical trial to investigate the effect on functionality of UL after a sensorimotor transcranial stimulation (real vs sham) in add-on to robot-assisted therapy in the stroke population.
METHODS
A randomised double-blind controlled trial design involving 32 patients with a single chronic stroke (onset > 180 days) was planned. Each patient will undergo 15 consecutive sessions (5 days for 3 weeks) of paired associative stimulation (PAS) coupled with UL robot-assisted therapy. PAS stimulation will be administered using a bifocal transcranial magnetic stimulator (TMS) on the posterior-parietal cortex and the primary motor area (real or sham) of the lesioned hemisphere. Clinical, kinematics and neurophysiological changes will be evaluated at the end of protocol and at 1-month follow-up and compared with baseline. The Fugl-Meyer assessment scale will be the primary outcome. Secondly, kinematic variables will be recorded during the box-and-block test and reaching tasks using video analysis and inertial sensors. Single pulse TMS and electroencephalography will be used to investigate the changes in local cortical reactivity and in the interconnected areas.
DISCUSSION
The presented trial shall evaluate with a multimodal approach the effects of sensorimotor network stimulation applied before a robot-assisted therapy training on functional recovery of the upper extremity after stroke. The combination of neuromodulation and robot-assisted therapy can promote an increase of cortical plasticity of sensorimotor areas followed by a clinical benefit in the motor function of the upper limb.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05478434. Registered on 28 Jul 2022.
Topics: Humans; Stroke Rehabilitation; Robotics; Treatment Outcome; Stroke; Upper Extremity; Recovery of Function; Randomized Controlled Trials as Topic
PubMed: 38129910
DOI: 10.1186/s13063-023-07849-1