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Journal of the International Society of... Dec 2024Cannabidiol (CBD) is a non-psychoactive phyto-cannabinoid derived from the plant. CBD exhibits various interactions at receptor sites, prompting the research of its... (Randomized Controlled Trial)
Randomized Controlled Trial
The effects of a brand-specific, hemp-derived cannabidiol product on physiological, biochemical, and psychometric outcomes in healthy adults: a double-blind, randomized clinical trial.
BACKGROUND
Cannabidiol (CBD) is a non-psychoactive phyto-cannabinoid derived from the plant. CBD exhibits various interactions at receptor sites, prompting the research of its potential anti-inflammatory, immunomodulatory, psychological, and pain-relieving effects. This study aimed to investigate the physiological, biochemical, and psychometric effects of a brand-specific, hemp-derived CBD product in healthy adults over a 12-week observation period.
METHODS
54 healthy males and females (age = 25 ± 7y; BMI = 24.82 ± 3.25 kg/m) recruited from a large Southeastern University completed the study. Participants arrived at the laboratory after > 8 h of fasting, and > 48 h without alcohol consumption and vigorous exercise. Following baseline measurements (height, weight, blood pressure, electrocardiogram (ECG), and blood work), participants were stratified by sex and randomized to either CBD or placebo groups. Products were administered double-blinded, with both given in liquid form containing medium-chain triglyceride oil, while the CBD product specifically contained 50 mg/mL of CBD. Participants were instructed to consume 1 mL of their product twice daily and were given enough product to last until their next laboratory visit. Data were collected at baseline and on days 30 ± 3, 60 ± 3, and 90 ± 3. Blood was drawn for analysis of immune and inflammatory biomarkers. Chronic pain among participants was calculated using urine samples according to the foundational pain index (FPI). Self-reported psychometric questionnaires were utilized (Cohen's Perceived Stress Scale, Pittsburgh Sleep Quality Index, Profile of Mood States,10-item Likert scale for perceived pain) to assess stress, sleep quality, mood state, and body discomfort. To determine overall wellbeing, participants completed a daily survey indicating if they missed work or school due to illness. Change from baseline was calculated for each measure, and mixed effects models were used to determine differences between groups over time while adjusting for baseline values (α = 0.05). Data are presented as mean ± standard deviation.
RESULTS
There were no Group-by-Time interactions or Group or Time main effects for immune or inflammatory biomarkers ( > 0.05). Analyses revealed no Group-by-Time interactions or main effects observed for perceived stress, sleep quality, overall mood disturbance, and all the profile of mood state subscales ( > 0.05), except "vigor-activity." A Time main effect was found for the sub-score for "vigor-activity" ( = 0.007; Pre CBD = 19.5 ± 5.2, Post CBD = 17.3 ± 5.3; Pre PL = 19.0 ± 5.7, Post PL = 17.9 ± 7.1), which decreased from Visit 3 to Visit 4 ( = 0.025) and from Visit 3 to Visit 5 ( = 0.014). There was a Group main effect for FPI ( = 0.028; Pre CBD = 11.9 ± 14.4, Post CBD = 8.8 ± 10.9; Pre PL = 9.0 ± 14.2, Post PL = 12.9 ± 11.5), indicating that the placebo group had greater increases in pain over the intervention compared to the CBD group. No significant differences were found between groups in the incidence and prevalence of "colds or flus" ( > 0.05).
DISCUSSION
CBD was safe and well tolerated in healthy adults. These findings show pain was lower in the CBD group, suggesting a potentially positive effect for consumption of CBD. "Vigor-activity" decreased across the intervention, which may be a confounding effect of the academic semester. While the dosage chosen was safe, more research may be warranted using higher doses as these may be needed to observe further therapeutic effects in healthy populations.
Topics: Humans; Cannabidiol; Male; Double-Blind Method; Female; Adult; Young Adult; Humulus; Psychometrics; Cannabis; Biomarkers
PubMed: 38904150
DOI: 10.1080/15502783.2024.2370430 -
Frontiers in Pharmacology 2024Targeted agents are widely utilized in the treatment of ulcerative colitis (UC). Hence, a comprehensive understanding of comparative drug efficacy in UC is of great...
BACKGROUND
Targeted agents are widely utilized in the treatment of ulcerative colitis (UC). Hence, a comprehensive understanding of comparative drug efficacy in UC is of great importance for drug development and clinical practice. Our objective was the quantitative evaluation of the comparative efficacy of targeted agents for UC.
METHODS
Three mathematical models were developed based on data from randomized controlled trials in patients with moderate-to-severe UC to describe the time-course and dose-response of efficacy defined as clinical remission, clinical response, and endoscopic improvement, as well as the placebo effect. The covariate effects were further evaluated. Model simulation was performed in a hypothetical population to compare the efficacies across different drugs.
RESULTS
The analysis dataset was composed of data from 35 trials of 12 drugs in UC. Time-response relationships were evaluated that indicated a gradual onset of drug efficacy in adalimumab, ozanimod, and Janus kinase (JAK) inhibitors. The dose-response relationships were estimated for each drug respectively. Patient age, disease duration, baseline weight, prior tumor necrosis factor (TNF) inhibitor exposure, and current treatment with corticosteroid showed an impact on efficacy, suggesting that younger patients with shorter UC duration without prior anti-TNF treatment and current corticosteroids therapy tend to display greater treatment effects.
CONCLUSION
This study developed three longitudinal models for UC to quantitatively describe the efficacy of targeted agents, as well as the influencing factors of efficacy. Infliximab and upadacitinib were determined to be the most effective biological and small targeted molecules, respectively. These findings may provide valuable implications for guiding future decision-making in clinical practice and drug development for UC.
PubMed: 38903997
DOI: 10.3389/fphar.2024.1399963 -
Frontiers in Allergy 2024Birch pollen-related food allergy (BPFA) is the most common type of food allergy in birch-endemic areas such as Western and Central Europe. Currently, there is no... (Review)
Review
BACKGROUND
Birch pollen-related food allergy (BPFA) is the most common type of food allergy in birch-endemic areas such as Western and Central Europe. Currently, there is no treatment available for BPFA. Due to the cross-reactivity between birch pollen and a range of implicated plant foods, birch pollen allergen immunotherapy (AIT) may be effective in the treatment of BPFA. In this study, we systematically evaluate the effectiveness of birch pollen-specific subcutaneous or sublingual immunotherapy in treating BPFA.
METHODS
A search was performed in the PubMed, Embase, and Cochrane libraries. Studies were independently screened by two reviewers against predefined eligibility criteria. The outcomes of interest were changes in (1) severity of symptoms during food challenge, (2) eliciting dose (ED), and (3) food allergy quality of life (FA-QoL). The validity of the selected articles was assessed using the revised Cochrane risk of bias tool. We focused on studies with the lowest risk of bias and considered studies with a high risk of bias as supportive. Data were descriptively summarized.
RESULTS
Ten studies were selected that included 475 patients in total. Seven studies were categorized into "high risk of bias" and three into "moderate risk of bias." The three moderate risk of bias studies, with a total of 98 patients, reported on severity of symptoms during challenge and on the ED. All three studies had a control group. Compared to the control group, improvement in severity of symptoms was observed during challenge in two out of the three studies and on the eliciting dose in one out of three. Only one study investigated the effect of birch pollen AIT on FA-QoL, showing that there was no significant difference between patients receiving subcutaneous immunotherapy or a placebo. Of the seven supportive studies, four had a control group and of those, three showed improvement on both severity of symptoms and ED. None of the supportive studies investigated the effect of the therapy on FA-QoL.
CONCLUSION
This systematic review shows that there is not enough evidence to draw firm conclusions about the effect of AIT on BPFA. Future research is warranted that uses robust clinical studies that include long-term effects, QoL, and multiple BPFA-related foods.
PubMed: 38903704
DOI: 10.3389/falgy.2024.1360073 -
Therapeutic Advances in Gastroenterology 2024Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it... (Review)
Review
BACKGROUND
Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE.
OBJECTIVES
This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose.
DESIGN
A systematic review and network meta-analysis.
DATA SOURCES AND METHODS
Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted.
RESULTS
In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline.
CONCLUSION
This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients.
TRIAL REGISTRATION
The study protocol was registered with INPLASY (registration number INPLASY2023120053).
PubMed: 38903448
DOI: 10.1177/17562848241251567 -
International Breastfeeding Journal Jun 2024Many individuals who experience preterm birth struggle with early breast milk supply, which can translate into suboptimal longer-term breastfeeding outcomes. Further... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Many individuals who experience preterm birth struggle with early breast milk supply, which can translate into suboptimal longer-term breastfeeding outcomes. Further investigations into the potential role of early non-pharmacological and pharmacological interventions in improving breast milk production soon after birth is growing. While natural galactagogues, such as brewer's yeast, are widely perceived by women to be safer than pharmaceutical galactagogues and are taken by many women, evidence to support their efficacy is largely absent. The BLOOM study has been designed to determine the efficacy and safety of brewer's yeast and beta-glucans, derived from Saccharomyces cerevisiae, when administered soon after birth for increasing early breast milk supply in mothers who have delivered preterm.
METHODS
The BLOOM study is a multicentre, double-blinded, randomised controlled trial that will assess if brewer's yeast or beta-glucan can increase early breast milk production following preterm birth. Target population are mothers of preterm infants born at less than 34 weeks' gestation who intend to provide breast milk for their infant, are less than 72 h following birth and able to give informed consent. Participants will be randomly allocated into three parallel groups at 1:1:1 ratio (n = 33 per group) to receive either brewer's yeast, beta-glucan or placebo capsules for seven days. The primary outcome is total expressed breast milk volume over a 24-hour period on day 7 of intervention. Participants and their infants will be followed until the infant reaches term corrected age or is discharged home from the neonatal unit (whichever occurs first).
DISCUSSION
The use of brewer's yeast as a galactagogue to enhance milk production is extremely common amongst breastfeeding mothers, however, there are no trials evaluating its efficacy and safety. This will be the first randomised controlled trial to evaluate the efficacy and safety of two commonly used galactagogues, brewer's yeast and beta-glucan, compared with placebo in improving maternal breast milk supply following preterm birth. The trial will also evaluate whether early intervention with galactagogues soon after a preterm birth improves longer-term breastfeeding outcomes.
TRIAL REGISTRATION
Australian and New Zealand Clinical Trials Registry ACTRN12622000968774 (registered on 8 July 2022) and UTN U1111-1278-8827.
Topics: Humans; beta-Glucans; Female; Milk, Human; Infant, Newborn; Double-Blind Method; Premature Birth; Breast Feeding; Saccharomyces cerevisiae; Infant, Premature; Adult; Pregnancy; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38902831
DOI: 10.1186/s13006-024-00650-z -
Italian Journal of Pediatrics Jun 2024Researches have found that alteration of intestinal flora may be closely related to the development of autism spectrum disorder (ASD). However, whether probiotics... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Researches have found that alteration of intestinal flora may be closely related to the development of autism spectrum disorder (ASD). However, whether probiotics supplementation has a protective effect on ASD remains controversial. This meta-analysis aimed to analyze the outcome of probiotics in the treatment of ASD children.
METHODS
The Pubmed, Cochrane Library, Web of Science and Embase were searched until Sep 2022. Randomized controlled trials (RCTs) relevant to the probiotics and placebo treatment on ASD children were screened. Quality assessment of the included RCTs was evaluated by the Cochrane collaboration's tool. The primary outcomes were ASD assessment scales, including ABC (aberrant behavior checklist) and CBCL (child behavior checklist) for evaluating the behavior improvement, SRS (social responsiveness scale) for social assessment, DQ (developmental quotient) for physical and mental development and CGI-I (clinical global impression improvement) for overall improvement. The secondary outcome was total 6-GSI (gastrointestinal severity index).
RESULTS
In total, 6 RCTs from 6 studies with 302 children were included in the systemic review. Total 6-GSI (MD=-0.59, 95%CI [-1.02,-0.17], P < 0.05) decreased significantly after oral administration of probiotics. Whereas, there was no statistical difference in ABC, CBCL, SRS, DQ and CGI-I between probiotics and placebo groups in ASD children.
CONCLUSION
Probiotics treatment could improve gastrointestinal symptoms, but there was no significant improvement in ASD.
Topics: Humans; Probiotics; Autism Spectrum Disorder; Child; Randomized Controlled Trials as Topic; Treatment Outcome; Gastrointestinal Microbiome
PubMed: 38902804
DOI: 10.1186/s13052-024-01692-z -
Journal of Physiotherapy Jun 2024What is the effect of a 4-week regimen of Mulligan manual therapy (MMT) plus exercise compared with exercise alone for managing cervicogenic headache? Is MMT plus...
Mulligan manual therapy added to exercise improves headache frequency, intensity and disability more than exercise alone in people with cervicogenic headache: a randomised trial.
QUESTION
What is the effect of a 4-week regimen of Mulligan manual therapy (MMT) plus exercise compared with exercise alone for managing cervicogenic headache? Is MMT plus exercise more effective than sham MMT plus exercise? Are any benefits maintained at 26 weeks of follow-up?
DESIGN
A three-armed, parallel-group, randomised clinical trial with concealed allocation, blinded assessment of some outcomes and intention-to-treat analysis.
PARTICIPANTS
Ninety-nine people with cervicogenic headache as per International Classification of Headache Disorders (ICHD-3).
INTERVENTIONS
Participants were randomly allocated to 4 weeks of: MMT with exercise, sham MMT with exercise or exercise alone.
OUTCOME MEASURES
The primary outcome was headache frequency. Secondary outcomes were headache intensity, headache duration, medication intake, headache-related disability, upper cervical rotation range of motion, pressure pain thresholds and patient satisfaction. Outcome measures were collected at baseline and at 4, 13 and 26 weeks.
RESULTS
MMT plus exercise reduced headache frequency more than exercise alone immediately after the intervention (MD between groups in change from baseline: 2 days/month, 95% CI 2 to 3) and this effect was still evident at 26 weeks (MD 4 days, 95% CI 3 to 4). There were also benefits across all time points in several secondary outcomes: headache intensity, headache duration, headache-related disability, upper cervical rotation and patient satisfaction. Pressure pain thresholds showed benefits at all time points at the zygapophyseal joint and suboccipital areas but not at the upper trapezius. The outcomes in the sham MMT with exercise group were very similar to those of the exercise alone group.
CONCLUSIONS
In people with cervicogenic headache, adding MMT to exercise improved: headache frequency, intensity and duration; headache-related disability; upper cervical rotation; and patient satisfaction. These benefits were not due to placebo effects.
TRIAL REGISTRATION
CTRI/2019/06/019506.
PubMed: 38902195
DOI: 10.1016/j.jphys.2024.06.002 -
Diabetes & Metabolic Syndrome Jun 2024With the prevalence of diabetes reaching an epidemic level, there is a growing interest in the investigation of its remission. Proglucagon-derived peptides (PGDP) have...
BACKGROUND
With the prevalence of diabetes reaching an epidemic level, there is a growing interest in the investigation of its remission. Proglucagon-derived peptides (PGDP) have been shown to have a glucose-regulating effect. However, whether they play a role in diabetes remission remains poorly understood.
AIM
To investigate changes in plasma levels of PGDP in glycaemic responders versus non-responders.
METHODS
The study was a randomised placebo-controlled trial comprising 18 adults with prediabetes (registered at www.
CLINICALTRIALS
gov as NCT03889210). Following an overnight fast, participants consumed ketone β-hydroxybutyrate (KEβHB)-supplemented beverage and placebo beverage in crossover manner. Serial blood samples were collected from baseline to 150 min at 30-min intervals. The endpoints were changes in glucagon-like peptide-1 (GLP-1), glicentin, oxyntomodulin, glucagon, and major proglucagon fragment (MPGF). Participants were stratified into the 'responders' and 'non-responders' subgroups based on their glycaemic changes following the ingestion of KEβHB. The area under the curve (AUC) was calculated to estimate the accumulated changes in the studied PGDP and compared using paired-t test between the KEβHB and placebo beverages.
RESULTS
Responders had a significantly greater reduction in plasma glucose compared with non-responders following acute ketosis (p < 0.001). The AUC for oxyntomodulin was significantly lower following the KEβHB beverage compared with the placebo (p = 0.045) in responders, but not in non-responders (p = 0.512). No significant differences in AUCs were found for GLP-1, glicentin, glucagon, and MPGF in either responders or non-responders.
CONCLUSION
Oxyntomodulin is involved in lowering plasma glucose and may play an important role in diabetes remission.
PubMed: 38901179
DOI: 10.1016/j.dsx.2024.103052 -
Clinical Nutrition ESPEN Jun 2024Among the side effects of chemotherapy, there is dysgeusia, which is an alteration or damage to the taste perception that negatively impacts the biopsychosocial sphere...
BACKGROUND/OBJECTIVE
Among the side effects of chemotherapy, there is dysgeusia, which is an alteration or damage to the taste perception that negatively impacts the biopsychosocial sphere of the patient. Therefore, it is important to recognize and manage it appropriately. The objective of this study is to identify clinical pharmacological strategies to reduce dysgeusia in chemotherapy patients.
METHODS
A systematic literature review was conducted following the PRISMA guidelines between February and May 2023, utilizing PubMed, Embase, Cochrane Library, CINAHL, and the British Nursing Database. Methodological quality and bias risk assessment were performed using the JBI framework, while evidence certainty was evaluated using the Oxford OCEBM methodology.
RESULTS
Out of 1225 consulted records, 12 articles were included. The results underscore the efficacy of diverse pharmacological interventions in mitigating dysgeusia among chemotherapy patients. These include zinc supplementation with a daily dosage ranging between 50 and 220 mg (p ≤ 0.005), lactoferrin at 250 mg thrice daily (p < 0.001), delta-9-tetrahydrocannabinol at 2 mg per day (p < 0.05), and cannabidiol at 150 mg per day (p = 0.04). All studies analysed showed a low risk of bias. The zinc and Delta-9-Tetrahydrocannabinoid treatment proved particularly promising, compared to the other treatments considered, where sample sizes were smaller and the placebo effect was not always clear.
CONCLUSION
Among the various pharmacological strategies identified, those that appear most promising concern the integration of zinc and Delta-9-Tetrahydrocannabinoid. Future studies should further explore the treatments identified in this review to expand the evidence base in this relatively underexplored field.
PubMed: 38900642
DOI: 10.1016/j.clnesp.2024.05.026 -
Kidney International Reports Jun 2024Beta-carotene (BC) protects the body against free radicals that may damage the kidney and lead to the development of acute kidney injury and chronic kidney disease...
INTRODUCTION
Beta-carotene (BC) protects the body against free radicals that may damage the kidney and lead to the development of acute kidney injury and chronic kidney disease (CKD). Previous studies in animal models have demonstrated a potential protective effect of 30 mg/kg BC supplementation on renal ischemia or reperfusion injury and subsequently improved kidney function. The extension of these findings to humans, however, remains unclear.
METHODS
Our study leverages previously collected data from the Physicians' Health Study I (PHS I), a large-scale, long-term, randomized trial of middle-aged and older US male physicians testing 50 mg BC every other day for primary prevention of cardiovascular disease and cancer. We examined the impact of randomized BC supplementation on self-reported incident CKD identified by self-reports stating "yes" to kidney disease from annual follow-up questionnaires from randomization in 1982 through the end of the randomized BC intervention at the end of 1995, and on CKD defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m at the end of 1995. Analyses compared incident CKD between BC supplementation and placebo using Cox proportional hazards regression models and logistic regression. We also examined whether smoking status (current vs. former or never smoker) or other factors modified the effect of randomized BC supplementation on CKD.
RESULTS
A total of 10,966 participants were randomized to BC, and 10,952 participants were randomized to a placebo group. Baseline characteristics between randomized BC groups were similar. There was no significant benefit between BC supplementation and self-reported incident CKD after adjusting for age and randomized aspirin treatment (hazard ratio [HR] = 0.97, 95% confidence interval [CI]: 0.86-1.08, -value = 0.56). Stratified by smoking status, there was no significant benefit of BC supplementation and self-reported incident CKD either among former or never smokers (HR = 0.95, 95% CI: 0.84-1.07, -value = 0.41) or current smokers (HR = 1.08, 95% CI: 0.78-1.50, -value = 0.64). Smoking status did not modify the association between BC supplementation and incident CKD (-interaction = 0.47). In subgroup analysis among those with available serum creatinine at the study end (5480 with BC and 5496 with placebo), there was no significant benefit between BC supplementation and CKD based on eGFR < 60 ml/min per 1.73 m (odds ratio [OR] = 0.96, 95% CI: 0.85-1.08, -value = 0.49).
CONCLUSION
Long-term randomized BC supplementation did not affect the risk of incident CKD in middle-aged and older male physicians.
PubMed: 38899218
DOI: 10.1016/j.ekir.2024.04.001