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British Journal of Pharmacology Jul 2024Pulmonary hypertension (PH) results from pulmonary vasculopathy, initially leading to a compensatory right ventricular (RV) hypertrophy, and eventually to RV failure....
BACKGROUND AND PURPOSE
Pulmonary hypertension (PH) results from pulmonary vasculopathy, initially leading to a compensatory right ventricular (RV) hypertrophy, and eventually to RV failure. Hypoxia can trigger both pulmonary vasculopathy and RV failure. Therefore, we tested if myo-inositol trispyrophosphate (ITPP), which facilitates oxygen dissociation from haemoglobin, can relieve pulmonary vasculopathy and RV hypoxia, and eventually prevent RV failure and mortality in the rat model of monocrotaline-induced PH.
EXPERIMENTAL APPROACH
Rats were injected with monocrotaline (PH) or saline (control) and received ITPP or placebo for 5 weeks. Serial echocardiograms were obtained to monitor the disease, pressure-volume loops were recorded and evaluated, myocardial pO was measured using a fluorescent probe, and histological and molecular analyses were conducted at the conclusion of the experiment.
KEY RESULTS AND CONCLUSIONS
ITPP reduced PH-related mortality. It had no effect on progressive increase in pulmonary vascular resistance, yet significantly relieved intramyocardial RV hypoxia, which was associated with improvement of RV function and reduction of RV wall stress. ITPP also tended to prevent increased hypoxia inducible factor-1α expression in RV cardiac myocytes but did not affect RV capillary density.
IMPLICATIONS
Our study suggests that strategies aimed at increasing oxygen delivery to hypoxic RV in PH could potentially be used as adjuncts to other therapies that target pulmonary vessels, thus increasing the ability of the RV to withstand increased afterload and reducing mortality. ITPP may be one such potential therapy.
PubMed: 38952183
DOI: 10.1111/bph.16482 -
Gerontology Jul 2024It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA...
Cognitive benefits of folic acid, docosahexaenoic acid and a combination of both nutrients in mild cognitive impairment; possible alterations though mitochondrial function and DNA damage.
INTRODUCTION
It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA and DHA supplementation, in combination or alone, on cognitive function, DNA oxidative damage, and mitochondrial function in participants with mild cognitive impairment (MCI).
METHODS
This randomized, double-blind, placebo-controlled trial recruited MCI participants aged 60 years and older. Two hundred and eighty participants were randomly divided in equal proportion into four groups: FA+DHA (FA 800μg/d + DHA 800mg/d), FA (800μg/d), DHA (800mg/d), and placebo groups daily orally for 12 months. The primary outcome was cognitive function evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-RC). Cognitive tests and blood mechanism-related biomarkers were determined at baseline and 12 months.
RESULTS
During the 12-month follow, scores of full intelligence quotient (FIQ) (βDHA: 1.302, 95%CI: 0.615, 1.990, p < 0.001; βFA: 1.992, 95%CI: 1.304, 2.679, p < 0.001; βFA+DHA: 2.777, 95%CI: 2.090, 3.465, p < 0.001), verbal intelligence quotient, and some subtests of the WAIS-RC were significantly improved in FA+DHA and single intervention groups compared to the placebo group. Moreover, the FA and DHA intervention combination was superior to either intervention alone (p < 0.001). Meanwhile, FA, DHA and their combined use significantly decreased 8-OHdG level and increased mitochondrial DNA copy number compared to the placebo (p < 0.05).
CONCLUSIONS
Supplementation of FA and DHA, alone or combined, for 12 months can improve cognitive function in MCI participants, possibly through mitigating DNA oxidative damage and enhancing mitochondrial function. Combined supplementation may provide more cognitive benefit than supplementation alone.
TRIAL REGISTRATION
Chinese Clinical Trial Registry, ChiCTR2000034351. Registered 3 July 2020 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=53345.
PubMed: 38952108
DOI: 10.1159/000540021 -
BMC Complementary Medicine and Therapies Jun 2024Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to medications, with many providing minimal relief or having adverse side effects that preclude use. Cannabidiol (CBD) has emerged as a potential treatment for chronic pain, yet research in this area remains limited, with few studies examining CBD's analgesic potential. Because Veterans have a high need for improved pain care, we designed a clinical trial to investigate CBD's effectiveness in managing chronic pain symptoms among Veterans. We aim to determine whether CBD oral solution compared to placebo study medication is associated with greater improvement in the Patient Global Impression of Change (PGIC).
METHODS
We designed a randomized, double-blind, placebo-controlled, pragmatic clinical trial with 468 participants. Participants will be randomly assigned in a 1:1 ratio to receive either placebo or a CBD oral solution over a 4-week period. The trial is remote via a smartphone app and by shipping study materials, including study medication, to participants. We will compare the difference in PGIC between the CBD and placebo group after four weeks and impacts on secondary outcomes (e.g., pain severity, pain interference, anxiety, suicide ideation, and sleep disturbance).
DISCUSSION
Once complete, this trial will be among the largest to date investigating the efficacy of CBD for chronic pain. Findings from this clinical trial will contribute to a greater knowledge of CBD's analgesic potential and guide further research. Given the relative availability of CBD, our findings will help elucidate the potential of an accessible option for helping to manage chronic pain among Veterans.
TRIAL REGISTRATION
This protocol is registered at clinicaltrials.gov under study number NCT06213233.
Topics: Humans; Cannabidiol; Chronic Pain; Veterans; Double-Blind Method; United States; Analgesics; Male; Pragmatic Clinical Trials as Topic; Female; Adult; Middle Aged
PubMed: 38951902
DOI: 10.1186/s12906-024-04558-3 -
BMC Urology Jul 2024The ARASENS trial recruited 1306 men with metastatic hormone sensitive prostate cancer. It investigated the effect of androgen deprivation therapy (ADT) and systemic...
The ARASENS trial recruited 1306 men with metastatic hormone sensitive prostate cancer. It investigated the effect of androgen deprivation therapy (ADT) and systemic therapy docetaxel in combination with a third novel drug - daralutamide, compared with placebo on overall survival. Triple therapy with ADT, docetaxel and darolutamide resulted in improved overall survival rates as compared with ADT, docetaxel and placebo (HR 0.68; 95% CI, 0.57-0.80; p < 0.001). The side effect profile for both treatments was similar. This randomised, double blinded, placebo controlled study, was assessed to have a low risk of bias using the Cochrane Risk of Bias 2 tool.
Topics: Male; Humans; Prostatic Neoplasms; Benzamides; Randomized Controlled Trials as Topic; Survival Rate; Androgen Antagonists; Docetaxel; Pyrazoles
PubMed: 38951868
DOI: 10.1186/s12894-024-01507-7 -
BMC Medical Education Jul 2024The effects of many treatments in healthcare are determined by factors other than the treatment itself. Patients' expectations and the relationship with their healthcare...
BACKGROUND
The effects of many treatments in healthcare are determined by factors other than the treatment itself. Patients' expectations and the relationship with their healthcare provider can significantly affect treatment outcomes and thereby play a major role in eliciting placebo and nocebo effects. We aim to develop and evaluate an innovative communication training, consisting of an e-learning and virtual reality (VR) training, for healthcare providers across all disciplines, to optimize placebo and minimize nocebo effects through healthcare provider-patient communication. The current paper describes the development, mid-term evaluation, optimization, and final evaluation of the communication training, conducted in The Netherlands.
METHODS
The development of both the e-learning and the VR training consisted of four phases: 1) content and technical development, 2) mid-term evaluation by healthcare providers and placebo/communication researchers, 3) optimization of the training, and 4) final evaluation by healthcare providers. To ensure the success, applicability, authenticity, and user-friendliness of the communication training, there was ongoing structural collaboration with healthcare providers as future end users, experts in the field of placebo/communication research, and educational experts in all phases.
RESULTS
Placebo/communication researchers and healthcare providers evaluated the e-learning positively (overall 7.9 on 0-10 scale) and the content was perceived as useful, accessible, and interesting. The VR training was assessed with an overall 6.9 (0-10 scale) and was evaluated as user-friendly and a safe method for practicing communication skills. Although there were some concerns regarding the authenticity of the VR training (i.e. to what extent the virtual patient reacts like a real patient), placebo and communication researchers, as well as healthcare providers, recognized the significant potential of the VR training for the future.
CONCLUSIONS
We have developed an innovative and user-friendly communication training, consisting of an e-learning and VR training (2D and 3D), that can be used to teach healthcare providers how to optimize placebo effects and minimize nocebo effects through healthcare provider-patient communication. Future studies can work on improved authenticity, translate the training into other languages and cultures, expand with additional VR cases, and measure the expected effects on providers communication skills and subsequently patient outcomes.
Topics: Humans; Virtual Reality; Placebo Effect; Nocebo Effect; Communication; Netherlands; Health Personnel; Physician-Patient Relations; Computer-Assisted Instruction; Female
PubMed: 38951784
DOI: 10.1186/s12909-024-05671-0 -
Pharmacological Reports : PR Jul 2024Asthma is a lifelong condition with varying degrees of severity and susceptibility to symptom control. Recent studies have examined the effects of individual genus,... (Review)
Review
Asthma is a lifelong condition with varying degrees of severity and susceptibility to symptom control. Recent studies have examined the effects of individual genus, species, and strains of probiotic microorganisms on the course of asthma. The present review aims to provide an overview of current knowledge on the use of probiotic microorganisms, mainly bacteria of the genus Lactobacillus and Bifidobacterium, in asthma prevention and treatment. Recent data from clinical trials and mouse models of allergic asthma indicate that probiotics have therapeutic potential in this condition. Animal studies indicate that probiotic microorganisms demonstrate anti-inflammatory activity, attenuate airway hyperresponsiveness (AHR), and reduce airway mucus secretion. A randomized, double-blind, placebo-controlled human trials found that combining multi-strain probiotics with prebiotics yielded promising outcomes in the treatment of clinical manifestations of asthma. It appears that probiotic supplementation is safe and significantly reduces the frequency of asthma exacerbations, as well as improved forced expiratory volume and peak expiratory flow parameters, and greater attenuation of inflammation. Due to the small number of available clinical trials, and the use of a wide range of probiotic microorganisms and assessment methods, it is not possible to draw clear conclusions regarding the use of probiotics as asthma treatments.
PubMed: 38951480
DOI: 10.1007/s43440-024-00618-0 -
Journal of Patient-reported Outcomes Jun 2024The Insomnia Severity Index (ISI) is a widely used measure of insomnia severity. Various ISI research findings suggest different factor solutions and meaningful... (Randomized Controlled Trial)
Randomized Controlled Trial
Re-examining the factor structure of the Insomnia Severity Index (ISI) and defining the meaningful within-individual change (MWIC) for subjects with insomnia disorder in two phase III clinical trials of the efficacy of lemborexant.
BACKGROUND
The Insomnia Severity Index (ISI) is a widely used measure of insomnia severity. Various ISI research findings suggest different factor solutions and meaningful within-individual change (MWIC) to detect treatment response in patients with insomnia. This study examined an ISI factor solution and psychometric indices to define MWIC in a robust patient sample from clinical trial settings.
METHODS
We endeavored to improve upon previous validation of ISI by examining structural components of confirmatory factor analysis (CFA) models using two large, placebo-controlled clinical trials of lemborexant for insomnia. Using the best-fitting two-factor solution, we evaluated anchor-based, distribution-based and receiver operating characteristic (ROC) curve methods to derive an estimate of the MWIC.
RESULTS
The model structure for the 7-item scale proposed in other research did not fit the observed data from our two lemborexant clinical trials (N = 1956) as well as a two-factor solution based on 6 items did. Using triangulation of anchor-based, distribution-based, and ROC methods, we determined that a 5-point reduction using 6 items best represented a clinically meaningful improvement in individuals with insomnia in our patient sample.
CONCLUSIONS
A 6-item two-factor scale had better psychometric properties than the 7-item scale in this patient sample. On the 6-item scale, a reduction of 5 points in the ISI total score represented the MWIC. Generalizability of the proposed MWIC may be limited to patient populations with similar demographic and clinical characteristics.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Male; Female; Severity of Illness Index; Middle Aged; Psychometrics; Adult; Factor Analysis, Statistical; Treatment Outcome; ROC Curve; Pyridines; Pyrimidines
PubMed: 38951287
DOI: 10.1186/s41687-024-00744-6 -
Mikrochimica Acta Jun 2024A cancer-targeted glutathione (GSH)-gated theranostic probe (CGT probe) for intracellular miRNA imaging and combined treatment of self-sufficient starvation therapy...
A cancer-targeted glutathione (GSH)-gated theranostic probe (CGT probe) for intracellular miRNA imaging and combined treatment of self-sufficient starvation therapy (ST) and chemodynamic therapy (CDT) was developed. The CGT probe is constructed using MnO nanosheet (MS) as carrier material to adsorb the elaborately designed functional DNAs. It can be internalized by cancer cells via specific recognition between the AS1411 aptamer and nucleolin. After CGT probe entering the cancer cells, the overexpressed GSH, as gate-control, can degrade MS to Mn which can be used for CDT by Fenton-like reaction. Simultaneously, Mn-mediated CDT can further cascade with the enzyme-like activities (catalase-like activity and glucose oxidase-like activity) of CGT probe, achieving self-sufficient ST/CDT synergistic therapy. Meanwhile, the anchored DNAs are released, achieving in situ signal amplification via disubstituted-catalytic hairpin assembly (DCHA) and FRET (fluorescence resonance energy transfer) imaging of miR-21. The in vitro and in vivo experiments demonstrated that accurate and sensitive miRNA detection can be achieved using the CGT probe. Overall, the ingenious CGT probe opens a new avenue for the development of early clinical diagnosis and cancer therapy.
Topics: MicroRNAs; Humans; Glutathione; Fluorescence Resonance Energy Transfer; Animals; Manganese Compounds; Oxides; Aptamers, Nucleotide; Mice; Mice, Nude; Theranostic Nanomedicine; Nucleolin; Neoplasms; Nanostructures; Oligodeoxyribonucleotides; Mice, Inbred BALB C; Fluorescent Dyes
PubMed: 38951214
DOI: 10.1007/s00604-024-06503-0 -
European Journal of Applied Physiology Jun 2024This study examined the effect of acute acetaminophen (ACTP) ingestion on physical performance during the 5 m shuttle run test (5mSRT), attention, mood states, and the...
Acute ingestion of acetaminophen improves cognitive and repeated high intensity short-term maximal performance in well-trained female athletes: a randomized placebo-controlled trial.
This study examined the effect of acute acetaminophen (ACTP) ingestion on physical performance during the 5 m shuttle run test (5mSRT), attention, mood states, and the perception of perceived exertion (RPE), pain (PP), recovery (PRS), and delayed onset of muscle soreness (DOMS) in well-trained female athletes. In a randomized, placebo-controlled, double-blind, crossover trial, fifteen well-trained female athletes (age 21 ± 2 years, height 165 ± 6 cm, body mass 62 ± 5 kg) swallowed either 1.5 g of ACTP or 1.5 g of placebo. The profile of mood states (POMS) and digit cancellation (DCT) were assessed 45 min postingestion, and 5mSRT was performed 60 min postingestion. The RPE and PP were determined immediately after each 30-s repetition of the 5mSRT, and the PRS and DOMS were recorded at 5 min and 24 h post-5mSRT. For the 5mSRT, ACTP ingestion improved the greatest distance (+ 10.88%, p < 0.001), total distance (+ 11.33%, p = 0.0007) and fatigue index (+ 21.43%, p = 0.0003) compared to PLA. Likewise, the DCT score was better on the ACTP (p = 0.0007) than on the PLA. RPE, PP, PRS, and DOMS scores were improved after ACTP ingestion (p < 0.01 for all comparisons) compared to PLA. POMS scores were enhanced with ACTP ingestion compared to PLA (p < 0.01). In conclusion, this study indicates that acute acetaminophen ingestion can improve repeated high intensity short-term maximal performance, attention, mood states, and perceptions of exertion, pain, recovery, and muscle soreness in well-trained female athletes, suggesting potential benefits for their overall athletic performance and mood state.
PubMed: 38951182
DOI: 10.1007/s00421-024-05534-y -
BMJ Open Jul 2024Obesity has become a worldwide public health problem and is directly linked to loss of quality of life, complications and comorbidities. One of them is chronic pain,...
Photobiomodulation therapy for chronic knee pain in obese patients in pre-rehabilitation for bariatric surgery: randomised, placebo-controlled, double-blinded, clinical trial protocol.
INTRODUCTION
Obesity has become a worldwide public health problem and is directly linked to loss of quality of life, complications and comorbidities. One of them is chronic pain, especially in the knees, which increases significantly and proportionally with weight gain. In patients with severe obesity, with indication for bariatric surgery, the presence of chronic pain disables and often prevents their participation in a pre-surgical rehabilitation programme. As an analgesic therapy, photobiomodulation (PBM) has been studied with safety, efficacy, well-tolerated used and low costs. Thus, this study aims to evaluate the use of PBM for the treatment of chronic knee pain in obese patients undergoing a pre-surgical rehabilitation programme for bariatric surgery.
METHODS AND ANALYSES
This is a double-blinded, randomised, placebo-controlled clinical, superiority, trial protocol. The PBM will be applied in bilateral knees and lumbar paraspinal points levels referring to the roots of innervation of the knee. The outcomes evaluated will be pain intensity, functionality, quality of life and clinical signs of neurological sensitization of chronic knee pain pathways.
ETHICS AND DISSEMINATION
This protocol has already been approved by the Comitê de Ética em Pesquisa do Hospital das Clínicas da Universidade Federal de Goiás/EBSERH-Ethics Committee and it is following SPIRIT guidelines. The results will be statistically analysed and subsequently published in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
Clinical Trials Platform (https://clinicaltrials.gov/) with the number NCT05816798.
Topics: Humans; Double-Blind Method; Bariatric Surgery; Chronic Pain; Low-Level Light Therapy; Randomized Controlled Trials as Topic; Obesity; Quality of Life; Knee Joint; Pain Measurement; Adult; Arthralgia
PubMed: 38951012
DOI: 10.1136/bmjopen-2023-079864