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Results | PMC10578185 | |||
General information | Cancer | CANCER | A total of 33 patients with ER+/HER2- MBC progressed on previous treatment of anastrozole or letrozole in the Guangxi Medical University Cancer Hospital were recruited between April 2017 and November 2019. Two cases who did not take apatinib and one who only underwent 3 days of treatment were excluded. Finally, 30 cases were included in the analysis (Flowchart of the participants through the trial (CONSORT diagram).Patient characteristics ( | PMC10578185 |
Toxic effects | ADVERSE EVENTS | The drug-related adverse events (AEs) are presented in | PMC10578185 | |
Discussion | tumor, breast cancer | ADVERSE EVENTS, TUMOR, METASTASIS, BREAST CANCER | Endocrine therapy is a standard of care for ER+/HER2- MBC, and chemotherapy is the second approach. Unfortunately, resistance eventually develops in MBC and becomes a major clinical challenge. There is a need to find new therapeutic strategies to improve treatment outcomes. Angiogenesis promotes tumor invasion and metastasis,The adverse events observed in this study were mainly due to apatinib. The safety profile of apatinib in our study was consistent with that reported in the other breast cancer study, | PMC10578185 |
Limitations | Besides, there were several limitations in this study. First, only 30 eligible patients were included in our study, and the subgroup analysis relied on a small number of subjects, which would affect the accuracy of results. Besides, it was of great urgency to explore and unveil alternative treatment option for highly pretreated patients with ER+/HER2- MBC. Hence, only a limited number of clinical cases were involved in this preliminary attempt. Second, this study was a single-arm, single-center, non-blind study with no control group, which could inevitably lead to some biases. Therefore, more clinical cases will be continuously accumulated to conduct larger sample size, multi-center, randomized and controlled clinical trials to provide definitive validation for the use of apatinib plus exemestane as a follow-up strategy against ER+/HER2- MBC. | PMC10578185 | ||
Author contribution | RECRUITMENT | Yongkui Lu conceived this study. Aihua Tan designed the study. Hongxue Wang, Li Nong, Yuxian Jia, Wuning Zhong, Fanghui Qin, Han Wang, Jing Tang were responsible for subject recruitment and data collection. Li Nong performed statistical analysis. Yan Liu oversaw the statistical analysis. Aihua Tan wrote the paper. Yongkui Lu and Yan Liu contributed to data interpretation and critical revision. All authors reviewed the final version of the manuscript. | PMC10578185 | |
Disclosure statement | No potential conflict of interest was reported by the authors. | PMC10578185 | ||
Data sharing statement | The data used and analyzed in the study is available from the corresponding author on reasonable request. | PMC10578185 | ||
Ethical statement | The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All of the enrolled patients or their family members signed the informed consent and could actively cooperate with the treatment. All procedures performed in this study involving human participants were in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Chinese Ethics Committee of Registering Clinical Trials (No. ChiCTR-OIC-17010440). | PMC10578185 | ||
Reporting checklist | The authors have completed the TREND reporting checklist. | PMC10578185 | ||
References | PMC10578185 | |||
Subject terms | ADVERSE REACTIONS, INFLUENZA B, INFLUENZA A, SECONDARY, INFLUENZA | Despite vaccine availability, influenza remains a substantial global public health concern. Here, we report interim findings on the primary and secondary objectives of the safety, reactogenicity, and humoral immunogenicity of a quadrivalent messenger RNA (mRNA) vaccine against seasonal influenza, mRNA-1010, from the first 2 parts of a 3-part, first-in-human, phase 1/2 clinical trial in healthy adults aged ≥18 years (NCT04956575). In the placebo-controlled Part 1, a single dose of mRNA-1010 (50 µg, 100 µg, or 200 µg) elicited hemagglutination inhibition (HAI) titers against vaccine-matched strains. In the active-comparator-controlled Part 2, mRNA-1010 (25 µg, 50 µg, or 100 µg) elicited higher HAI titers than a standard dose, inactivated seasonal influenza vaccine for influenza A strains and comparable HAI titers for influenza B strains. No safety concerns were identified; solicited adverse reactions were dose-dependent and more frequent after receipt of mRNA-1010 than the active comparator. These interim data support continued development of mRNA-1010.Here the authors report initial findings of a phase 1 clinical trial, showing that an investigational, mRNA-based vaccine for seasonal influenza (mRNA-1010) has no safety concerns and produces immune responses in adults that are similar or higher than a licensed comparator vaccine. | PMC10279702 | |
Introduction | human illness, death, infectious, A/H1N1 | INFLUENZA A, DISEASE, INFLUENZA | Vaccination remains an essential public health strategy for the prevention of influenzaFour types of influenza viruses exist: A, B, C, and D; however, only A and B are responsible for the majority of human illness, with influenza A the major cause of severe disease and death in older adultsGenerally, the overall effectiveness of currently available seasonal influenza vaccines, which utilize egg-, cell-, or recombinant protein-based platformsMessenger RNA (mRNA) technology has recently become a promising alternative to conventional vaccine approaches against infectious diseasesThe investigational mRNA-1010 vaccine is a quadrivalent seasonal influenza vaccine encoding membrane-bound HA surface glycoproteins of four influenza strains (A/H1N1, A/H3N2, B/Victoria, and B/Yamagata) recommended by the WHO for cell- or recombinant vaccines | PMC10279702 |
Results | PMC10279702 | |||
Participants | In Part 1 of the study, a total of 180 participants aged ≥18 years were randomly assigned to receive placebo or 1 dose of mRNA-1010 (50 µg, 100 µg, or 200 µg) between July 6, 2021, and August 18, 2021 (Fig. | PMC10279702 | ||
Participant disposition by study part. | infection | INFECTION, ADVERSE EVENT, CARDIAC ARREST, INFLUENZA | One participant in the mRNA-1010 100-µg group in Part 2 of the study died due to cardiac arrest. This adverse event was considered by the investigator as unrelated to the study vaccination. All randomly assigned participants who received study vaccination were included in the safety population; participants were included in the group based on the actual vaccine received. The immunogenicity per-protocol population included all randomly assigned participants who received vaccination and complied with immunogenicity blood sampling timing to have baseline and ≥1 post-vaccination time point assessment, did not have influenza infection at baseline through Day 29 (as documented by polymerase chain reaction), and had no major protocol deviation that impacted the immune response. mRNA messenger RNA. *There was 1 dosing error in Part 1 (In Part 2 of the trial, a total of 501 participants aged ≥18 years were randomly assigned to receive a single dose of Afluria ( | PMC10279702 |
Safety | In Part 1 of the trial, any solicited local ARs within 7 days of mRNA-1010 vaccination were reported by 82.6%, 85.7%, and 91.3% of participants aged 18–49 years in the 50-µg, 100-µg, and 200-µg groups, respectively, and by 63.6%, 92.0%, and 90.5% of participants aged ≥50 years, respectively (Fig. | PMC10279702 | ||
Immunogenicity | INFLUENZA | In Part 1 of the trial, all dose levels of mRNA-1010 (50 µg, 100 µg, and 200 µg) elicited immune responses in participants aged 18–49 years and ≥50 years against all vaccine-matched influenza strains at Day 29 (28 days after vaccination) as measured by HAI (Fig. | PMC10279702 | |
GMTs and GMFRs of anti-hemagglutinin antibodies for vaccine-matched seasonal influenza strains in adults in Part 1. | INFLUENZA A, INFLUENZA B | Hemagglutination inhibition GMTs with associated 95% CIs against seasonal influenza A strains (A/Wisconsin/588/2019[H1N1]pdm09 and A/Hong Kong/45/2019[H3N2]) or influenza B strains (B/Washington/02/2019 (B/Victoria lineage) and B/Phuket/3073/2013 (B/Yamagata lineage)) are shown at Day 1 (baseline) and Day 29 (28 days after vaccination) among participants At 28 days after vaccination (Day 29) in Part 2 of the trial, all dose levels of mRNA-1010 (25 µg, 50 µg, and 100 µg) elicited GMTs for influenza A (H1N1 and H3N2) strains across age groups that exceeded GMTs elicited by Afluria (Fig. | PMC10279702 | |
GMTs and GMFRs of anti-hemagglutinin antibodies for vaccine-matched seasonal influenza strains in adults in Part 2. | INFLUENZA A, INFLUENZA B | Hemagglutination inhibition GMTs with associated 95% CIs against seasonal influenza A strains (A/Wisconsin/588/2019[H1N1]pdm09 and A/Cambodia/e0826360/2020[H3N2]) or influenza B strains (B/Washington/02/2019 (B/Victoria lineage) and B/Phuket/3073/2013 (B/Yamagata lineage)) are shown at Day 1 (baseline) and Day 29 (28 days after vaccination) among participants | PMC10279702 | |
Ratios of GMTs of anti-hemagglutinin antibodies after vaccination with mRNA-1010 compared with Afluria in adults in Part 2. | INFLUENZA | Ratios of HAI GMTs with associated 95% CIs against vaccine-matched seasonal influenza strains (A/Wisconsin/588/2019[H1N1]pdm09, A/Cambodia/e0826360/2020[H3N2], B/Washington/02/2019 (B/Victoria lineage), and B/Phuket/3073/2013 (B/Yamagata lineage)) at 28 days after vaccination with mRNA-1010 compared with Afluria are shown for participants | PMC10279702 | |
Discussion | deaths | INFLUENZA A, EVENTS, INFLUENZA B, INFLUENZA | This manuscript presents interim analysis findings from 2 parts of a phase 1/2, first-in-human clinical trial on the safety and immunogenicity of an investigational mRNA-based quadrivalent vaccine against seasonal influenza (mRNA-1010) in healthy adults ≥18 years. The placebo-controlled Part 1 of this study showed that a single dose of mRNA-1010 (50 µg, 100 µg, or 200 µg) elicited HAI antibodies against vaccine-matched strains at 28 days after vaccination in both younger and older healthy adults. Based on the comparable immunogenicity across the mRNA-1010 dose levels in Part 1, a lower dose level range of mRNA-1010 (25 µg, 50 µg, or 100 µg) was evaluated in a larger number of participants in Part 2. Findings in Part 2 suggest that mRNA-1010 could elicit higher immunogenicity than a standard-dose influenza vaccine for influenza A strains and comparable immunogenicity for influenza B strains in medically stable adults. Higher responses for influenza A strains remain important, as the A/H3N2 strain in particular causes a larger burden of severe outcomes in older adultsIn both parts of the trial, no treatment-related SAEs were reported nor any safety concerns identified. In Part 1 of the trial, the frequency and severity of solicited ARs generally increased in a dose-dependent manner and was higher among younger (18–49 years) than older (≥50 years) adults. In Part 2, all three mRNA-1010 dose levels had an acceptable reactogenicity profile. For all age groups, solicited ARs were more common with mRNA-1010 than Afluria and were typically grade 1 or grade 2 in severity. No grade 4 solicited ARs were reported for any vaccine group and grade 3 events were less frequent for lower dose levels and for older adults (≥65 years). Overall, these safety data support the continued evaluation of mRNA-1010.A single dose of mRNA-1010 (50 µg, 100 µg, or 200 µg) in Part 1 of the trial elicited HAI antibodies against all vaccine-included strains at Day 29 in adults irrespective of participant age. Overall, the 50-µg dose level induced HAI titers that were comparable to those elicited by higher dose levels (100 µg and 200 µg). In both younger and older adults, the GMFRs from baseline exceeded 4-fold for influenza A strains, which is notable, as influenza A strains are the primary drivers of influenza-related hospitalizations and deaths, particularly in older adultsOverall, these first-in-human safety and immunogenicity findings in adults aged ≥18 years support the continued investigation of mRNA-1010 against seasonal influenza and highlight the potential of the mRNA platform to improve the effectiveness of influenza vaccines. Vaccines using mRNA technology are readily amenable to both antigenic drift and shift in influenza strains, allowing for rapid deployment of vaccines that are more closely matched to currently circulating strains and can avoid aberrant mutations in vaccine antigens caused by egg- or cell-culture approachesStudy strengths include the randomized, observer-blind, placebo-controlled (Part 1) and active comparator (Part 2) design. The study design did not specify any hypothesis testing; thus, the sample sizes of participants enrolled (Part 1, In conclusion, the interim analysis findings from the placebo-controlled Part 1 and active comparator controlled Part 2 of this phase 1/2 trial of mRNA-1010 in adults aged ≥18 years raised no safety concerns and showed that the vaccine was immunogenic against all tested influenza strains in both younger and older adults. Further, the investigational mRNA-1010 vaccine elicited either higher or comparable immune responses to a standard-dose, quadrivalent inactivated vaccine. These findings support the continued clinical development of mRNA-1010 to combat seasonal influenza. | PMC10279702 |
Methods | PMC10279702 | |||
Trial design and participants | chronic diseases | CHRONIC DISEASES, INFLUENZA | This is a first-in-human, phase 1/2, randomized, observer-blinded study at 20 sites in the United States to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1010 in adults ≥18 years of age (NCT04956575). The study comprises 3 parts, which assessed mRNA-1010 or placebo in healthy adults in Part 1, followed by additional dose-ranging assessments in Parts 2 and 3 to evaluate mRNA-1010 versus licensed comparator vaccines in medically stable adults. This report summarizes interim findings for Parts 1 and 2 of the study, with final results to be separately reported.Eligible participants in Part 1 of the study were healthy adults ≥18 years of age (Supplementary Fig. Part 2 of the study enrolled medically stable adults ≥18 years of age, excluding those adults with chronic diseases requiring ongoing medical intervention within the 3 months before enrollment and with immunocompromising conditions or medications. Approximately 500 participants were planned to be randomly assigned (3:3:3:1) to receive a single dose of mRNA-1010 (25 µg, 50 µg, or 100 µg) or a licensed quadrivalent seasonal influenza vaccine (Afluria®; Seqirus Pty Ltd, Parkville, Victoria, Australia; Supplementary Fig. In each part of the study, participants were followed for approximately 6 months, with a single dose of the vaccine administered on Day 1 and the final study visit on Day 181 (Month 6). Both parts of the study had a planned interim analysis to evaluate safety and immunogenicity data of all participants through Day 29. Participants in Part 1 were recommended to receive a licensed 2021–2022 NH seasonal influenza vaccine after Day 29 of the study.The study was conducted in accordance with the protocol, applicable laws, and regulatory requirements, as well as International Council for Harmonization Good Clinical Practice guidelines, and the consensus ethical principles derived from international guidelines, including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines. The protocol was approved by the central institutional review board (Advarra, Inc., Columbia, MD) prior to study initiation, and written informed consent was obtained from all participants before enrollment. | PMC10279702 |
Vaccines | STERILE, VIRUS, INFLUENZA | In Part 1, participants received mRNA-1010 or placebo (normal saline), while in Part 2, participants received mRNA-1010 or a licensed standard dose quadrivalent influenza vaccine (Afluria). mRNA-1010 includes mRNAs encoding for the surface glycoprotein HA of four influenza virus strains formulated in lipid nanoparticles. In Part 1, mRNA-1010 encoded influenza strains recommended by the WHO for 2020-2021 SH cell- or recombinant-based vaccines (see Supplementary Methods for details). In Part 2, mRNA-1010 encoded strains recommended by the WHO for 2021–2022 NH cell- or recombinant-based vaccines (see Supplementary Methods for details). mRNA-1010 was provided as a sterile liquid for injection and diluted to different dose levels with normal saline. All vaccines were administered intramuscularly as a single 0.5-mL injection. | PMC10279702 | |
Objectives | INFLUENZA A, SECONDARY | The primary objectives of Part 1 were to evaluate the safety and reactogenicity of a single dose of mRNA-1010 (50 µg, 100 µg, and 200 µg) versus placebo and to evaluate the humoral immunogenicity of a single dose of mRNA-1010 against vaccine-matched influenza A and B strains at Day 29. The objectives of Part 2 were to evaluate the safety and reactogenicity of mRNA-1010 (25 µg, 50 µg, and 100 µg; primary) and to evaluate the humoral immunogenicity of mRNA-1010 and active comparator against vaccine-matched influenza A and B strains at Day 29 (primary and secondary). | PMC10279702 | |
Safety assessments | swelling/tenderness, myalgia, fatigue, fever, pain, headache, chills, arthralgia | ADVERSE REACTIONS, ADVERSE EVENTS | Safety endpoints included solicited local and systemic adverse reactions (ARs) for 7 days after vaccination, safety laboratory abnormalities (Part 1 only), unsolicited adverse events (AEs) for 28 days after vaccination, as well as serious AEs (SAEs), AEs of special interest (AESIs), and medically attended AEs (MAAEs) through the end of the study (Day 181). Interim safety data through Day 29 are included in this report. Participants used an electronic diary to record local ARs (ie, injection site pain, injection site redness, injection site hardness, or axillary swelling/tenderness ipsilateral to the side of injection), or systemic ARs (ie, headache, fatigue, myalgia, arthralgia, nausea/vomiting, chills, and fever). Safety laboratory assessments in Part 1 (at baseline and Day 8) included white blood cell count, hemoglobin, platelets, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, and creatinine. | PMC10279702 |
Immunogenicity assessments | BLOOD, INFLUENZA A | Blood samples for immunogenicity assessments were collected on Days 1 (baseline), 8 (Part 1 only), 29, and 181 (end of study). This report summarizes immunogenicity assessments at baseline and Day 29. Immunogenicity endpoints included geometric mean titers (GMTs) at Day 1 and 29, geometric mean fold rises (GMFRs) at Day 29 over Day 1 (baseline), and percentage of participants with seroconversion at Day 29 of serum anti-HA antibodies against vaccine-matched influenza A and B strains as measured by hemagglutination inhibition (HAI) assay using red blood cells from guinea pig and cell-grown viruses as described in the Supplementary Methods. | PMC10279702 | |
Statistical analyses | infection | EVENTS, INFECTION, INFLUENZA | This phase 1/2 study did not test any formal statistical hypotheses. Sample size (described in the Supplementary Methods) was considered sufficient to provide a descriptive summary of the safety and immunogenicity of different dose levels of mRNA-1010. All safety assessments except for solicited local and systemic ARs were assessed in the safety population, which included all randomized participants who received vaccination. Solicited ARs were assessed in all participants in the safety population who contributed any solicited AR data (solicited safety population). The number of events of unsolicited AEs, SAEs, AESIs, and MAAEs were summarized, while descriptive summary statistics were provided for all other safety analyses.Immunogenicity analyses were performed in the per-protocol population, which included all randomly assigned participants who received vaccination and complied with immunogenicity blood sampling timing to have baseline and ≥1 post-vaccination time point assessment, did not have influenza infection at baseline through Day 29 (as documented by polymerase chain reaction), and had no major protocol deviation that impacted the immune response. The geometric mean of specific antibody titers with corresponding 95% confidence intervals (CIs) at Day 29 and GMFRs of specific antibody titers with corresponding 95% CI at Day 29 over Day 1 (baseline) were calculated for each vaccination group; 95% CIs were calculated based on the | PMC10279702 |
Reporting summary | Further information on research design is available in the | PMC10279702 | ||
Supplementary information | The online version contains supplementary material available at 10.1038/s41467-023-39376-7. | PMC10279702 | ||
Acknowledgements | We thank the participants for their dedication and contributions to the study, the Study Investigators, and our clinical team colleagues at PPD for their collaboration. Medical writing and editorial assistance were provided by Emily Stackpole, PhD, and Jared MacKenzie, PhD, of MEDiSTRAVA in accordance with Good Publication Practice (GPP3) guidelines, funded by Moderna, Inc., and under the direction of the authors. Moderna, Inc., was involved in the study design, data collection and analysis, and the writing of this manuscript. This study was funded by Moderna, Inc. | PMC10279702 | ||
Author contributions | C.H. | I.L., R.N., L.C., K.S., D.S., C.H., W.H., D.R.S., J.A., and R.P. contributed to the study concept and design. Data were collected by DE and HS, then analyzed and interpreted by I.L., R.N., D.E., H.S., A.A., R.C., W.H., D.R.S., J.A., and R.P. All authors contributed to the drafting and critical review of this manuscript and approved the final draft. | PMC10279702 | |
Peer review | PMC10279702 | |||
Data availability | Access to patient-level data presented in this article (antibody assays, safety, and reactogenicity) and supporting clinical documents with external researchers who provide methodologically sound scientific proposals will be available upon reasonable request and subject to review from 2 years after study completion. Such requests can be made to Moderna Inc., 200 Technology Square, Cambridge, MA 02139. A materials transfer and/or data access agreement with the sponsor will be required for accessing shared data. All other relevant data are presented in the paper. The protocol is available as online supplementary material to this article. ClinicalTrials.gov: NCT04956575. | PMC10279702 | ||
Competing interests | C.H. | I.L., R.N., L.C., K.S., A.A., D.S., C.H., R.C., W.H., D.R.S., J.A., and R.P. are employees of and shareholders in Moderna, Inc. D.E. and H.S. declare no competing interests. | PMC10279702 | |
References | PMC10279702 | |||
Background | stress-related disorders | DISORDER, DISEASE, DISORDERS | Stress-related mental health disorders have steadily increased and contributed to a worldwide disease burden with up to 50% experiencing a stress-related mental health disorder worldwide. Data suggest that only approximately 20%-65% of individuals receive treatment. This gap in receiving treatment may be attributed to barriers such as limited treatment access, negative stigma surrounding mental health treatment, approachability (ie, not having a usual treatment plan or provider), affordability (ie, lack of insurance coverage and high treatment cost), and availability (ie, long waits for appointments) leaving those who need treatment without necessary care. To mitigate the limited access mental health treatment, there has been a rise in the application and study of digital mental health interventions. As such, there is an urgent need and opportunity for effective digital mental health interventions to alleviate stress symptoms, potentially reducing adverse outcomes of stress-related disorders. | PMC10612013 |
Objective | This study examined if app-based guided mindfulness could improve subjective levels of stress and influence physiological markers of stress reactivity in a population with elevated symptoms of stress. | PMC10612013 | ||
Methods | PHYSIOLOGICAL STRESS, COLD, HEART | The study included 163 participants who had moderate to high perceived stress as assessed by the Perceived Stress Scale (PSS-10). Participants were randomly allocated to 1 of 5 groups: a digital guided program designed to alleviate stress (Managing Stress), a digital mindfulness fundamentals course (Basics), digitally delivered breathing exercises, an active control intervention (Audiobook), and a Waitlist Control group. The 3 formats of mindfulness interventions (Managing Stress, Basics, and Breathing) all had a total duration of 300 minutes spanning 20-30 days. Primary outcome measures were perceived stress using the PSS-10, self-reported sleep quality using the Pittsburgh Sleep Quality Index, and trait mindfulness using the Mindful Attention Awareness Scale. To probe the effects of physiological stress, an acute stress manipulation task was included, specifically the cold pressor task (CPT). Heart rate variability was collected before, during, and after exposure to the CPT and used as a measure of physiological stress. | PMC10612013 | |
Results | The results showed that PSS-10 and Pittsburgh Sleep Quality Index scores for the Managing Stress (all | PMC10612013 | ||
Conclusions | These results demonstrate efficacy of app-based mindfulness in a population with moderate to high stress on improving self-reported stress, sleep quality, and physiological measures of stress during an acute stress manipulation task. | PMC10612013 | ||
Trial Registration | ClinicalTrials.gov NCT05832632; https://www.clinicaltrials.gov/ct2/show/NCT05832632 | PMC10612013 | ||
Introduction | PMC10612013 | |||
Background | cognitive functioning | Elevated stress is a state in which an individual experiences excessive or prolonged psychological and physiological strain [Mindfulness is defined as a state of being attentive to and bringing awareness to sensations that are taking place in the present moment without judgment [However, the MBSR program is time consuming and costly. In recent years digital mental health interventions have been developed using self-guided mindfulness-based interventions [Research has also found that mindfulness may improve cognitive functioning in healthy participants, which refers to the mental activities involved in maintaining and acquiring and using information. Specifically, studies using the Headspace mindfulness app have shown that 4 weeks of app-based mindfulness practice reduces behavioral indicators of mind wandering [ | PMC10612013 | |
Effects of Mindfulness on Physiological Stress Reactivity | DYSFUNCTION | In addition to its psychological and cognitive effects, mindfulness has been found to have physiological effects that reduce stress. Regular mindfulness practice has been associated with decreased blood pressure, increased heart rate variability (HRV), and reduced cortisol levels [Elevated stress is widely regarded as healthy and functional when confronted with acute stressful situations, however permanent exposure to elevated stress—and in particular the failure to recover from stress—may lead to dysfunction of the underlying neurobiology [Research studies have found that engaging in mindfulness can increase HRV [ | PMC10612013 | |
Effects of Mindfulness on Acute Stress | PHYSIOLOGICAL STRESS, COLD | The cold pressor task (CPT) is a laboratory test commonly used to induce a physiological stress response in participants. The CPT involves immersing the participant's hand in an ice-cold water bath for 3 minutes, which causes vasoconstriction in the submerged hand. This triggers a physiological response, which activates the SNS, leading to an increase in heart rate, blood pressure, and peripheral vasoconstriction [ | PMC10612013 | |
Aims of the Study | PHYSIOLOGICAL STRESS | This study examined if 3 different formats of digital mindfulness interventions demonstrated efficacy in terms of reducing self-reported levels of stress, sleep quality, and influencing physiological markers of stress reactivity in a population with elevated levels of stress.To accomplish the experimental aim, participants with moderate and high stress according to the Perceived Stress Scale (PSS-10) [The 3 types of mindfulness interventions were identical in total training dosage but varied in content and intervention length. That is, 2 of the 3 mindfulness interventions (Basics and Breathing) consisted of 30 sessions, whereas the third intervention (Managing Stress) consisted of 20 sessions. The type of content also varied whereby 2 interventions (Basics and Managing Stress) were programmatic that progressed from session to session, whereas the third interventions (Breathing) consisted of single succinct exercises. Furthermore, 1 intervention was designed specifically to reduce stress in people with elevated stress using mindfulness-based content (Managing Stress). This interventional setup allowed us to investigate if the unique characteristic of each intervention would result in differential efficacy in a population with moderate to high stress, while keeping the total training duration of each intervention identical. In other words, the rationale for employing 3 formats of mindfulness interventions was to explore if there were any differential effects between these distinct formats of mindfulness.To probe psychological (self-reported) effects of stress, the study examined if changes in stress (PSS-10), sleep quality (PSQI), and mindfulness (MAAS) showed differences between the preintervention and postintervention periods.We hypothesized (H1) that the app-based mindfulness interventions would yield significant improvements in self-reported stress (PSS-10) as compared to the active and Waitlist Control groups. We also hypothesized that trait mindfulness (MAAS) and sleep quality (PSQI) would improve in the mindfulness groups compared to control groups.To probe physiological effects of stress, the study employed an acute stress manipulation task (ie, the CPT) at the preintervention and postintervention stage while measuring physiological activity (HRV) before, during, and after exposure to the acute stressor, and in addition self-reported stress perception immediately after stress exposure.We hypothesized (H2) that the app-based mindfulness interventions would result in reduced physiological stress reactivity during exposure to the CPT, expressed as increased HRV activity compared to the active and Waitlist Control groups. | PMC10612013 | |
Methods | PMC10612013 | |||
Ethical Considerations | The participants were recruited through flyers and advertisements at a local university (University of Southern Denmark) and the Region of Southern Denmark. All procedures were conducted in accordance with the local ethical committee ( | PMC10612013 | ||
Experimental Procedures | RECRUITMENT, COLD | The study included 5 experimental groups using a pre-post design.Overall, 48 hours prior to the laboratory visit, eligible participants were emailed instructions to refrain from alcohol and nicotine before coming to the laboratory to avoid known influences of these factors on autonomic activity [Upon arrival for the first laboratory visit (ie, preintervention or T1), the participants initially signed the consent form. Participants were subsequently instructed on how to complete the experimental procedures (Outline of the study procedures. CPT: cold pressor task; HRV: heart rate variability; MAAS: Mindful Attention Awareness Scale; PSQI: Pittsburgh Sleep Quality Index; PSS-10: Perceived Stress Scale.The randomization procedure was determined after study recruitment, but before study launch. Specifically, participants were randomly allocated to 1 of 5 groups (Managing Stress, Basics, Breathing, Audiobook, or Waitlist Control) using sequence generation by the research team, who were not formally blinded to group allocation. Participants were not informed about group allocation until after completion of the preintervention experimental procedures. HRV was collected continuously during the CPT procedure. That is, the CPT procedure was broken up into 3 parts: | PMC10612013 | |
Psychological Measures and Physiological Measures | The experimental methods and outcome measures are described in detail in the | PMC10612013 | ||
Interventions | The interventions were completed using a custom-built research smartphone app. Participants were given access to a smartphone app that was built for the purpose of conducting scientific research at the University of Southern Denmark that contained the training content for each specific intervention. The app has been applied in previous scientific research studies [Participants did not receive an introductory session to the active intervention conditions but were provided with oral and written instructions about the app usage for the intervention period. Participants were instructed to follow the program in full. | PMC10612013 | ||
Managing Stress (Mindfulness) Intervention | The content of the training was provided by Headspace [ | PMC10612013 | ||
Basics (Mindfulness) Intervention | The content of the training was provided by Headspace [ | PMC10612013 | ||
Breathing (Mindfulness) Intervention | The content of the training was provided by Headspace [ | PMC10612013 | ||
Audiobook Intervention | Mindfulness has been hypothesized to train attention and affect through interoceptive nonjudgmental awareness [ | PMC10612013 | ||
Waitlist Control | The Waitlist Control group required that participants did not follow an intervention. However, the Waitlist Control group was given the option to obtain access to 1 of the 3 active interventions after completion of the study. | PMC10612013 | ||
Statistical Analysis | SD, η²p | All data are presented as mean ± 1 SD unless otherwise stated. Assumptions of statistical tests for normal distribution and sphericity of data were checked. A series of mixed groups (Managing Stress, Basics, Breathing, Audiobook, Waitlist control) × time (pretest, posttest) ANOVAs were performed on PSS-10, PSQI, MAAS, and CPT self-reported stress. A series of mixed groups (Managing Stress, Basics, Breathing, Audiobook, Waitlist control) × time (pre, post) × task period (rest, during task, and recovery) ANOVAs were performed on HRV. Significant 3-way interactions were followed-up by Group by Time ANOVAs at each time point, and 2-way interactions were followed-up with relevant corrected pairwise comparisons using the Bonferroni method (post hoc analysis) for simple main effects within each group. Where no significant interactions were found, main effects of time, group, and task period were reported. Significance level was set at 0.05 (2-tailed) for all analyses. The effect sizes for the ANOVAs were calculated as partial eta squared (η²p), with 0.02, 0.13, and 0.26 indicating small, medium, and large effects, respectively. Data analysis was conducted using SPSS (version 27; IBM Corp). | PMC10612013 | |
Results | PMC10612013 | |||
Psychological Measures: PSS-10, PSQI, MAAS, and CPT Self-Reported Stress | There was an interaction for PSS-10 across the 5 groups and time (PSS-10 results pre and post across the 5 groups. $: interaction effect; #: simple main effects of time (follow-ups). PSS-10: Perceived Stress Scale.There was an interaction for PSQI across the 5 groups and time (There was no significant interaction (No interaction (PSQI results pre (A) and post (B) across the 5 groups. $: interaction effect; #: simple main effects of time (follow-ups). PSQI: Pittsburgh Sleep Quality Index. | PMC10612013 | ||
Discussion | PMC10612013 | |||
Principal Findings | depression, Stress, anxiety | PHYSIOLOGICAL STRESS, DISORDERS | This study sought to investigate if 3 formats of digital mindfulness interventions would show efficacy in reducing subjective and physiological levels of stress in a population with elevated symptoms of stress. The study found that self-reported stress as measured by PSS-10 was significantly reduced in the Managing Stress and Basics groups from the preintervention to the postintervention period compared to the other groups. Furthermore, the study found significant improvement in self-reported sleep quality as measured by the PSQI in the Managing Stress and Basics groups from the preintervention to the postintervention period compared to the other groups. Trait mindfulness, as measured by MAAS, did not yield significant differences across any of the groups. Finally, the results showed that only the Basics and Managing Stress groups displayed significantly reduced levels of physiological stress (ie, expressed as increased HRV activity) during exposure to the acute stress manipulation task (ie, CPT).To our knowledge this study is the first study to demonstrate stress-reducing effects of a digital mindfulness app in a population with elevated baseline stress levels. Stress is prevalent in modern society and is accepted as a contributing factor to the onset of a range of mental health disorders, including depression and anxiety [ | PMC10612013 |
Self-Reported Effects of Stress and Sleep Quality | insomnia | The magnitude of change for the PSS-10 was larger in the Managing Stress group and the Basics groups compared to the Breathing and control groups, thus finding partial support for hypothesis 1 (H1). Our findings expand upon the results of previous studies that found digital mindfulness interventions improved stress among the general population [This study found that the PSQI indexing subjective sleep quality improved in the Managing Stress and Basics groups from the preintervention to the postintervention period. It is noteworthy that the participant’s subjective sleep quality on the PSQI did not show statistical differences from the preintervention to the postintervention period for the Breathing group. However, the HRV results support this finding in that there was not a significant difference in HRV for the Breathing intervention. A recent meta-analysis reported a significant positive effect of mindfulness on sleep quality based on the results of 6 randomized controlled trials on people with insomnia [In contrast, we found no effects of the MAAS for any of the interventions. This finding is surprising in that previous findings have revealed that web- or app-based mindfulness has a significant impact on mindfulness, albeit with small effect sizes [ | PMC10612013 | |
Physiological Effects of Stress | pain | We did not find significant group differences in subjective levels of stress after administration of the CPT from the preintervention to the postintervention period. However, we did observe significant differences in HRV activity both in the expectation phase before the CPT, during the CPT, and in the recovery period after the CPT in both the Managing Stress group and the Basics group in support of hypothesis 2 (H2).A recent study employed the CPT in the context of a 30-day app-based mindfulness intervention and showed that mindfulness training was less affected by acute stress on their cognitive performance compared to the control group suggesting that mindfulness may mitigate the negative impact of acute stress [The results in this study found differential efficacy whereby only 2 of the 3 mindfulness groups, that is the Managing Stress and Basics group, but not the Breathing group, showed physiological and self-reported stress-buffering effects. This could be due to the relationship between the different ingredients of the mindfulness content across the different interventions. The content of the Breathing intervention was to engage in deep breathing and diaphragmatic breathing exercises for 10 min daily, which does not seem to translate into behavioral changes that could influence physiological reactivity as opposed to the Managing Stress and Basics interventions. This finding of differential effects between the 3 types of mindfulness is interesting. Reasons for such a difference might be found in the literature demonstrating mixed results in terms of the effect of deep breathing and diaphragmatic breathing interventions across various outcome measures. Further, 1 study found that breathing exercises did not yield pain reduction in a clinical population [ | PMC10612013 | |
Strengths and Limitations | Although the results of this study are promising regarding the efficacy in 2 of the 3 app-based mindfulness interventions, several limitations must be noted. First, the sample primarily comprised young university students in their twenties, thus the generalizability of our findings may be limited. Second, this study did not investigate the efficacy of the app-based interventions beyond 30 days, nor whether any of the findings were maintained (regardless of app usage) beyond this period. Future studies should consider including follow-up measurements to evaluate sustained outcomes. Third, the study did not collect endocrine measures such as cortisol to assess the acute stress response during the CPT, although the HRV-data supported, it would have been interesting to also inspect correlations between endocrine measures and HRV to be completely certain that the CPT elicited reliable stress reactivity in participants. Fourth, participants were instructed to follow the program in full, however training adherence was not checked during the intervention, and participants were not reminded by the researchers to complete the daily training in the intervention period, which might have increased adherence.Notably, a strength of this study was its relatively diverse population in terms of race, whereby 5 different ethnicities were represented in the study. In future interventions, it is important to explore the efficacy of diverse populations both in terms of race or ethnicity, age, socioeconomic status, and education level in order to generalize the findings to a broader population. A second strength of this study is that we employed multiple mindfulness interventions and were thus able to investigate if the unique characteristic of each intervention would result in differential efficacy. A third strength of this study was that both subjective and objective measures were employed which increased the inferences made in terms of reductions in both self-reported stress and objective measures of stress in the Managing Stress and Basics interventions. | PMC10612013 | ||
Conclusions | WS | In summary, our findings extend previous studies suggesting the efficacy of Headspace’s app-based mindfulness interventions, specifically the Managing Stress and Basics content, to reduce stress in populations with elevated stress levels. Specifically, we found stress-buffering effects in a relatively diverse sample of participants afflicted with elevated stress. More research in this area is needed to establish efficacy and explore the degree to which effects are sustained in the long-term. The findings presented here provide important data that may be applied to the design of future studies or mental health interventions in people who experience elevated levels of stress.UK and WS contributed equally to this study. This study was funded by Headspace.Conflicts of Interest: The following authors are current or former employees of Headspace: EH, CN, SK, ES, AC, CP, and LL.Managing Stress (mindfulness) guided program.Basics (mindfulness) course.CONSORT eHealth Checklist (V 1.6.2). | PMC10612013 | |
Abbreviations | autonomic nervous systemcold pressor taskheart rate variabilityMindful Attention Awareness Scalemindfulness-based stress reductionparasympathetic nervous systemPittsburgh Sleep Quality IndexPerceived Stress Scalesympathetic nervous system | PMC10612013 | ||
Data Availability | The data sets generated or analyzed during the study are available from the corresponding author upon request. | PMC10612013 | ||
Background | RECURRENCE | Although complete mesocolic excision (CME) is supposed to be associated with a higher lymph node (LN) yield, decreased local recurrence, and survival improvement, its implementation currently is debated because the evidence level of these data is rather low and still not supported by randomized controlled trials. | PMC10838239 | |
Method | SECONDARY, PERIOPERATIVE COMPLICATION | This is a multicenter, randomized, superiority trial (NCT04871399). The 3-year disease-free survival (DFS) was the primary end point of the study. The secondary end points were safety (duration of operation, perioperative complications, hospital length of stay), oncologic outcomes (number of LNs retrieved, 3- and 5-year overall survival, 5-year DFS), and surgery quality (specimen length, area and integrity rate of mesentery, length of ileocolic and middle-colic vessels). The trial design required the LN yield to be higher in the CME group at interim analysis. | PMC10838239 | |
Results | Interim data analysis is presented in this report. The study enrolled 258 patients in nine referral centers. The number of LNs retrieved was significantly higher after CME (25 vs. 20; | PMC10838239 | ||
Supplementary Information | The online version contains supplementary material available at 10.1245/s10434-023-14664-0. | PMC10838239 | ||
Keywords | tumor | DISEASE, TUMOR, COLORECTAL CANCER, POSTOPERATIVE COMPLICATIONS | Open access funding provided by Università degli Studi di Torino within the CRUI-CARE Agreement.Colorectal cancer (CC) is the third most common tumor worldwide and ranks second in terms of death-related cancer/year. Actually, the standard of care is surgery, with 5-year survival rates of 80% or higher for all stages together, excluding stage IV disease.In 1907 HalstedSeveral authors have reported main differences between right- and left-sided CC in terms of molecular alterations, treatment responsiveness, and survival rates.In 2009, Hohenberger et al.This new technique suddenly raised a great interest among surgeons, who attempted to demonstrate its superiority over the standard right colectomy. Nevertheless, to date there aren’t enough data supporting its routine adoption for RSCC treatment, in terms of both the number of LNs yielded and the survival rates.Very recently two randomized controlled trials (RCT) comparing CME with standard right colectomy have been published. The RELARC study is a multicenter, high-volume, phase 3 superiority trial from China, whereas the Agrusa study is a single-center low-volume trial from Italy.Our multicenter trial with a large Western population aims to investigate the three main outcomes of a controlled CME: the quality of surgery (number of nodes retrieved, integrity and area of resected mesocolon, length of IC and MC vessels, and Benz classification), its safety (intra- and postoperative complications), and its efficacy (early oncologic items and survival rates). | PMC10838239 |
Methods | PMC10838239 | |||
Study Design | tumors | ONCOLOGY, METASTASIS, TUMORS | The current study is a randomized, superiority, two-arm, interventional trial involving nine Italian referral centers from the Italian Society of Surgical Oncology (SICO). All consecutive patients with RSCC located between the cecum and proximal third of the transverse colon without distant metastasis were eligible for enrollment in the trial. Patients needed to meet the following inclusion criteria: age 18–85 years, tumors clinically staged as cT2-4aN0 or cT1-4aN+ according to preoperative staging, American Society of Anesthesiologists (ASA) physical status score lower than 4, body mass index (BMI) of 30 kg/mThis study was conducted in accordance with CONSORT guidelines | PMC10838239 |
Randomization and Blinding | Patients were enrolled in the trial by each participating surgeon after signing the informed consent agreement. The study was a single-blind trial, with only the patients blinded to the surgical procedure.The coordinating center was responsible for patient allocation (CME or non-CME). The randomization list was managed through a central computerized module. A permuted block randomization of size 30 stratified by the center was centrally implemented. The random assignment sequence was concealed until the procedure was allocated to the patients.No blinding was applied after group assignment. The assigned arm of the study was communicated to the surgeon only a few minutes before surgery. | PMC10838239 | ||
Interventions and Quality Control | METASTASES | The types of surgical interventions are detailed in the previously published study protocol.Furthermore, every surgical specimen was carefully measured according to promotor center indications to assess its quality according with Benz classification.Two types of protocol deviation were recognized: “contamination” for non-CME and “noncompliance” for CME. Contamination was the deviation with specimen picture proof of non-CME quality according to Benz classification (Benz <1), and noncompliance was the absence of complete dissection in the CME group according to Benz classification (Benz >0).The reasons for patient dropout were identification of distant metastases during surgery, a final histopathologic characterization not consistent with the inclusion criteria, and types of surgery performed differently from right hemicolectomy. The follow-up care schedule was reported in the study protocol. | PMC10838239 | |
Statistical Analysis | The descriptive statistics are reported by the intervention arm summarizing the continuous data as a median with the interquartile range (IQR). Categorical data are reported as absolute frequencies and percentages. Wilcoxon-type tests were performed for continuous variables and the Pearson chi-square test or Fisher’s exact test, whatever was appropriate, for the categorical variables. | PMC10838239 | ||
Interim Analysis | The interim analysis for the interim futility assessment was reported 12 months after the beginning of the study. Based on the results of this interim assessment, the study was stopped if no significant interim increase in LN yield was documented in the experimental arm. | PMC10838239 | ||
Secondary Outcomes | REGRESSION | Univariable logistic regression model estimates for the binary end points and linear regression model estimates for continuous ones were performed by considering the intervention as a covariate. Gamma regression models were considered for positive-skew end points. The model results are reported as odds ratios (ORs) with | PMC10838239 | |
Sample Size Calculation | Details of sample size calculation are available in the study protocol. | PMC10838239 | ||
Role of the Funding Source | The funding source for this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. | PMC10838239 | ||
Discussion | vascular injuries, tumor, early-stage disease | SYSTEMIC DISEASE, RECURRENCE, TUMOR, METASTASIS, POSTOPERATIVE COMPLICATIONS, POSTOPERATIVE COMPLICATION, MINOR, POSTOPERATIVE COMPLICATION, WEST, RECTAL CANCER | As a new technique, CME remains under investigation. Although renewed attention to meticulous surgical technique certainly has its merits, routine implementation of CME seems currently unfounded for several reasons. First, in contrast to rectal cancer, local recurrence originating from an incomplete or non-optimal removal of colonic mesentery is rare in CC and usually is a manifestation of a systemic disease. Second, although CME may increase nodal counts and therefore staging accuracy, this is unlikely to affect survival because the observed relationship between nodal counts and outcome in CC is most probably not causal but confounded by a range of different clinical variables. Third, several lines of evidence suggest that metastasis to locoregional nodes occurs early and is a stochastic rather than a stepwise phenomenon in CC, reflecting the tumor host-metastasis relationship.Available data document that CME with central vascular ligation (CVL) often is a more demanding procedure than standard right hemicolectomy, almost always has a longer duration (10–90 min or longer depending on the completeness of the learning curve), can carry a higher morbidity (longer time to first flatus and major vascular injuries above all), and also is more challenging based on the high variability of vascular anatomy. These issues support the actual debate on the reasons to implement the CME for the treatment of RSCC at least in referral centers.Above all, three main items currently remain under investigation: the efficacy of CME in increasing the LN yield, the risk of intra- and postoperative complications particularly concerning major vessels injuries, and mostly the relationship between CME and the improvement of survival outcomes.During the past decade, several systematic reviews and meta-analysis have effectively evaluated these items with the aim to crown CME as the standard of care for RSCC or definitively to reject it.Unfortunately, these studies had many limitations. First, most of the studies were case series of a prospective or retrospective nature, and no level 1 evidence from RCTs is available. Second, these studies were not homogeneous concerning the outcomes of interest (safety, quality, oncologic outcomes) because most of them had important missing outcomes. Third, most of the included patients had early-stage disease (60.6% stage 0, I, or II). These limitations represent confounding factors for the final analysis. In the end, most of these studies concluded that well-designed RCTs are necessary to strengthen the evidence base and eventually to justify the implementation of routine use of CME.Actually, only two RCTs comparing CME and non-CME in RSCC are available in the literature.The current study not only is the third RCT conducted in the world, but also is the first Western multicenter nationwide high-volume phase 3 superiority trial comparing CME with non-CME for RSCC. In this trial, the quality of surgery provided in the CME arm was assessed with the previously reported four indicators. The length of the specimen was similar between the two groups. However, the length of resected ICA and MCA, the area of resected mesentery, and its integrity rate were significantly superior in the CME arm. This observation was documented in all the participating centers, confirming the high quality of surgery performed. The quality of CME provided to the enrolled patients also was evaluated with Benz classification.Despite strict quality control, noncompliance (see definitions in the Methods section) was identified in 21.5 of the CME procedures and contamination in 20.7% of the non-CME procedures. The only significant correlation was between the magnitude of noncompliance per patient and the type of approach (Table These protocol violations may potentially have been responsible, in the intention-to-treat analysis, for an underestimation of the difference in number of LNs harvested between the two arms. However, significant underestimation appears unlikely because although the patients undergoing CME had a moderate grade of noncompliance, the number of nodes yielded was significantly higher in this group than in the non-CME group.Nevertheless, we should accept the continued occurrence of minor deviations considering the complexity of this trial. Consistent with the design of the study, this interim analysis documented that the median number of LNs harvested in the CME group was significantly higher than in the non-CME group (25 vs. 20). Although a significant relationship between the number of nodes removed and patients’ survival has not been documented with sufficient evidence to date, providing a higher number of nodes with a demanding procedure that includes a super-extended LN dissection is essential to demonstrate any oncologic benefits and to continue enrollment of patients.Postoperative complications were described as comparable in the CME and non-CME arms of both previous RCTs. However, the RELARC trialAlthough both the AgrusaTo our best knowledge this trial is the first multicenter high-volume RCT from the West comparing the safety and feasibility of CME with standard right hemicolectomy for patients with RSCC. In this interim analysis, only the short-term outcomes are reported, whereas survival outcomes have not matured to date and are expected in January 2027.The current trial had some limitations. First, it involved only Italian referral centers for colorectal surgery with experienced surgeons and does not represent the reality of primary care facilities in which surgeons have less expertise. Second, only patients with a BMI of 30 kg/mIn conclusion, data available from this interim analysis document that the quality of surgery measured by the length of the specimen, the area and integrity rate of the resected mesentery, and the length of IC and MC vessels was higher in CME arm, confirming that CME is an extended procedure compared with non-CME. In addition, the interim data show that CME significantly increases the number of LNs harvested without increasing vascular injuries, postoperative complication rates, postoperative mortality, or length of hospital stay. Hence CME is a safe and feasible technique, particularly when performed by experienced surgeons in referral centers. | PMC10838239 |
Acknowledgment | This study was supported by the University of Turin Local Research funding SOLM_RILO_18_01. | PMC10838239 | ||
Funding | Open access funding provided by Università degli Studi di Torino within the CRUI-CARE Agreement. | PMC10838239 | ||
Data Availability | The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. | PMC10838239 | ||
DISCLOSURE | There are no conflicts of interest. | PMC10838239 | ||
References | PMC10838239 | |||
Key words | ± | SECONDARY | The objective of the present study was to evaluate the efficacy of oral administration of vitamin D supplementation in reducing BMI and lipid profile in adolescents and young adults from a cohort in Bucaramanga, Colombia. One hundred and one young adults were randomly assigned to one of two doses of vitamin D [1000 international units (IU) or 200 IU] administered daily for 15 weeks. The primary outcomes were serum 25(OH)D levels, BMI and lipid profile. The secondary outcomes were waist-hip ratio, skinfolds and fasting blood glucose. We found a mean ± Trial registration: NCT04377386 | PMC9947753 |
Introduction | diabetesVitamin D deficiency, stroke, obesity | OBESITY, CARDIOVASCULAR DISEASE, STROKE, CHRONIC DISEASES, VITAMIN D DEFICIENCY, VITAMIN D DEFICIENCY, DYSLIPIDEMIA | Vitamin D deficiency constitutes a worldwide public health problem. It is highly prevalent even in countries such as Colombia with a hot tropical climateSerum vitamin D deficiency has been associated with several chronic diseases, including cardiovascular disease, stroke and diabetesVitamin D deficiency has also been associated with dyslipidemia, although the evidence is conflictedThe exact mechanisms by which low vitamin D levels occur in people with obesity and influence the lipid profile have not been fully elucidatedThese associations are of clinical relevance and its study carries important public health implications related to the possible benefit from vitamin D supplementation in cardiovascular and metabolic health conditions | PMC9947753 |
Materials and methods | PMC9947753 | |||
Design | NCT04377386 | A triple-blind parallel two-arm randomised controlled clinical trial. The study participants were young adults from the SIMBA cohort, which began in 2006 with 1282 children between 6 and 10 years of age in the city of Bucaramanga, Colombia (latitude: 7⋅12539)Follow-up of the participants throughout the intervention.The protocol was registered in Clinicaltrials.gov with the NCT04377386 registry, and all methodological aspects related to the study have been previously publishedRepresentation of the main finding of this study. | PMC9947753 | |
Intervention | ’ adverse | DEFICIENCY | The intervention group received 1000 IU of vitamin D and the control group 200 IU of vitamin D daily for 15 weeks. All participants were given 105 doses of vitamin D in white containers identical in terms of organoleptic characteristics to ensure that both participants and researchers were blinded to treatment. The supplementation was provided by the Farma de Colombia laboratory, commercially known as Farma D, whose presentation is in soft gelatin capsules of vitamin D3. To maximise adherence to the intervention, the participants crossed off the daily intake of the supplement on a calendar with the period of the study, which they returned at the end of it. On the other hand, all participants were followed up by phone call at weeks 1, 2, 5, 7, 12 and 14; in these calls, they were inquired about any ‘potential’ adverse effect related to the intervention and adherence to taking vitamin D was evaluated through a self-report instrumentThe cut-off points to establish vitamin D levels were: Deficiency (≤20 ng/ml); Insufficiency (21–29 ng/ml) and Sufficiency (≥30 ng/ml) | PMC9947753 |
Sample size | overweight, obesity | It was calculated taking into account an expected difference in the results of the study (overweight, obesity and altered lipid profile) of 20 % | PMC9947753 | |
Outcomes | SECONDARY | The primary outcomes were serum 25(OH)D levels, BMI and lipid profile. The secondary were waist-hip ratio, skinfolds and fasting blood glucose. | PMC9947753 | |
Statistical methods | An intention-to-treat analysis was performed. The description of the categorical variables was made using absolute and relative values; of the quantitative variables that presented a normal distribution in the Shapiro–Wilk test the mean and standard deviation were reported, otherwise, the median and interquartile range [IQR] were presented. The baseline characteristics of the study groups (intervention and control) were compared using the proportions comparison test (χThe outcome variables were analysed quantitatively and contrasted through paired | PMC9947753 | ||
Ethical considerations | This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving human subjects/patients were approved by the Research Ethics Committee of the Fundación Cardiovascular de Colombia (Record No. 480 of July 16, 2019). Written informed consent was obtained from all subjects. | PMC9947753 | ||
Results | The potentially eligible population sample was 494 adolescents and young adults ( | PMC9947753 | ||
Baseline characteristics of study participants | The average age of the participants was 22⋅6 [±1⋅5] years, 56⋅44 % were women, with a median BMI of 23⋅3 [Q1: 20⋅8; Q3: 26⋅8]. Median baseline serum vitamin D [25(OH)D] levels for the 1000 IU group were 23⋅3 ng/ml [Q1: 20⋅2; Q3: 31⋅3], and for the 200 IU of 24⋅7 ng/ml [Q1: 21⋅6; Q3: 31⋅6]. No differences were found between groups concerning baseline characteristics, except for total energy intake and serum triacylglycerol levels. The baseline characteristics of the participants according to the treatment group are shown in Baseline characteristic of participants by vitamin D intervention group (Q, quartile; p values with statistical significance. | PMC9947753 |
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