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Previous protocol
A description of the assay can be found in a previously published article [
PMC9927051
Cohort details of the earlier clinical trial
lung cancer, Lung cancer
LUNG CANCER, -11, LUNG CANCER
Subjects were enrolled between 2014-06-02 and 2017-11-16 in three medical centers. In all cases, the study received approval of Institutional Review Boards (IRB) in accordance with the Declaration of Helsinki, and subjects read and signed a dedicated consent form. Inclusion and exclusion criteria were applied as descri...
PMC9927051
Cohort details of the later clinical trial
lung cancer, Lung cancer
LUNG CANCER, LUNG CANCER
Subjects were enrolled between 2019-03-24 and 2021-03-09 in three medical centers. In all cases, the study received IRB approval in accordance with Declaration of Helsinki, and subjects read and signed a dedicated consent form. The same inclusion and exclusion criteria were applied as described in our previous publishe...
PMC9927051
Data analysis
cancer stage, cancer, malignancy, lung cancer, Machine Learning
CANCER, LUNG CANCER, REGRESSION, SEPARATION, PATHOLOGY
Each subject was assigned a datasheet containing raw fluorescent readings of the plate wells as a function of time. The fluorescent readings were transformed into values which correlate with the acidity of the sample. We modeled the biological progression of the immunological response and extracted a set of informative...
PMC9927051
Results
PMC9927051
Analytical sensitivity and specificity of the metabolic activity lung cancer test (MA-LC)
The Metabolic Activity test measures the change in acid concentration over time in reaction to exposure to a stimulant. We use 8-Hydroxypyrene-1,3,6-trisulfonic acid (HPTS)—a highly water-soluble, membrane-impermeant pH indicator (pH 6.6 to 8.0) that is added to each plate’s well. HPTS exhibits a pH-dependent adsorptio...
PMC9927051
Data analysis
lung cancer, cancer, malignancy, cancer stage
REGRESSION, CANCER, PATHOLOGY, LUNG CANCER
Each subject was assigned a datasheet containing raw fluorescent readings of the plate wells as a function of time. The fluorescent readings were transformed into values which correlate with the acidity of the sample. We modeled the biological progression of the immunological response and extracted a set of informative...
PMC9927051
Discussion
tumor, allergy, lung cancer, early-stage lung cancer, TAA
VIRUS, TUMOR, DISEASE, ALLERGY, SENSITIVITY, LUNG CANCER, DISEASES
We describe an improved immunometabolism blood test that measures the function of the immune cells in response to LC antigenic stimuli based on enhancement of the glycolysis metabolic pathway of immune cells. Glycolysis enhancement is a marker for the rapid activation of most immune cells [This research article compare...
PMC9927051
Conclusions
lung cancer, lung cancer stage, lung cancer stage II
LUNG CANCER
Data analysis of a clinical trial applying the improved protocol of the ImmunoBiopsy™ test shows test specificity and sensitivity of 94.0% and 97.3%, respectively in detecting lung cancer stage I, and test specificity and sensitivity of 94.0% and 100%, respectively in detecting lung cancer stage II. The sensitivity and...
PMC9927051
Acknowledgements
THORACIC
The authors are indebted to Dr. Ori Haberfeld, Dr. Yaron Saiet, Dr. Eran Gilad from Department of General Thoracic Surgery, Rambam Health Care Campus, Israel and to Dr. Yana Kogan, Dr. Einat Fireman Klain, Dr. Sonia Shneer and Dr. Raya Cohen from Pulmonary Division, Faculty of Medicine, Lady Davis Carmel Medical Center...
PMC9927051
Author contributions
ONCOLOGY, THORACIC
SS—Conceptualization, project administration, investigation, writing—original draft, review and editing. FP—Biochemistry expert, methodology. HD—Software, formal analysis, data curation, writing—original draft. ES—Resources, investigation, validation. ED—Formal analysis, funding acquisition, visualization. ST—Software,...
PMC9927051
Funding
This work was supported by Savicell Diagnostics Ltd.
PMC9927051
Availability of data and materials
Available from the corresponding author on reasonable request.
PMC9927051
Declarations
PMC9927051
Ethics approval and consent to participate
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committees and with the 1964 Helsinki declaration and its later amendments (subjects read and signed a dedicated consent form). Ethics committee approval numbers of the Institutio...
PMC9927051
Consent for publication
Not applicable.
PMC9927051
Competing interests
Shafrira Shai, Hagai Drori, Eyal J. Scheinman, Eyal Davidovits, Giora Davidovits, Shoval Tirman, are employed by Savicell Diagnostics and own stock and/or options in Savicell Diagnostics’ parent company. Fernando Patolsky and Yochai Adir are consultants and own stock and/or options in Savicell Diagnostics’ parent compa...
PMC9927051
References
PMC9927051
Methods
cancers, cancer testis antigen-specific immune
CANCERS
Forty-nine patients with CCR4-negative solid cancers were enrolled in the phase Ia and Ib trials on KW-0761. An integral analysis of safety, clinical responses, prognosis, blood laboratory data, and cancer testis antigen-specific immune responses was performed.
PMC10511099
Results
lung cancer
ADVERSE EVENTS, DISEASE, LUNG CANCER
Grade 3–4 treatment-related adverse events were reported in 21 (42.9%) out of 49 patients, all of which were manageable. A partial response and stable disease were observed in 1 and 9 patients, respectively. A durable clinical response was noted in 2 esophageal and 2 lung cancer patients. eTreg depletion in peripheral ...
PMC10511099
Conclusions
A durable clinical response was noted in some patients, and high lymphocyte levels before treatment initiation may be a biomarker for the efficacy of KW-0761. The synergistic effect of KW-0761 for depleting Tregs and other immunotherapies is expected in the future.
PMC10511099
Data Availability
All relevant data are within the paper and its
PMC10511099
Introduction
Sezary Syndrome, various cancer, Cancer
MYCOSIS FUNGOIDES, SEZARY SYNDROME, CYTOTOXICITY, ADULT T-CELL LEUKEMIA-LYMPHOMA, CANCER
Cancer immunotherapy is now more frequently used in clinical practice and immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with various cancer types; however, their efficacy is still insufficient [KW-0761 (mogamulizumab) is a humanized anti-C-C chemokine receptor type 4 (CCR4) IgG1 monoclonal...
PMC10511099
Materials and methods
PMC10511099
Patients
cancer
CANCER
Patients were eligible if they had CCR4-negative advanced or recurrent solid cancer with target lesions. CCR4 expression was examined by immunohistochemistry (IHC) using an anti-CCR4 mAb (KM2160; Kyowa Kirin) and confirmed by a review committee with a central evaluation. The inclusion criteria were the same as those in...
PMC10511099
Study design
DISEASE PROGRESSION
The present study was designed as multi-institutional, open-label, investigator-initiated phase Ia and Ib clinical trials on KW-0761 (mogamulizumab). The investigational drug KW-0761 was provided by Kyowa Kirin. Patients received 8 intravenous infusions of KW-0761 weekly followed by monthly infusions until disease prog...
PMC10511099
CONSORT diagram for trial.
Phase Ia (a) and Phase Ib (b) studies.
PMC10511099
Toxicity evaluation
Tumor, Toxicity, Cancer
ADVERSE EVENT, TUMOR, CANCER
Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The independent data monitoring committee chaired by Professor Ryuzo Ueda, Department of Tumor Immunology, Aichi Medical University School of Medicine evaluated the safety data for each dose level.
PMC10511099
Clinical response evaluation
Responses were evaluated 12 weeks after the first KW-0761 treatment or at the point of study discontinuation based on computed tomography (CT) scans according to RECIST (ver. 1.1) and immune-related RECIST [
PMC10511099
Blood laboratory data
BLOOD
Peripheral blood sampling was performed at baseline and at every timepoint of KW-0761 infusions. Blood laboratory tests consisted of a blood count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), phosphate, albumin, γ-glutamyltransferase (GGT), ...
PMC10511099
Treg depletion effects on PBMCs
Treg depletion was assessed as previously described [
PMC10511099
IHC
tumor
TUMOR
Archived or newly obtained tumor samples from patients were screened for the expression of CCR4, NY-ESO-1, and XAGE1 (GAGED2a) by IHC as previously described [
PMC10511099
Enzyme-linked Immunosorbent Assay (ELISA) for NY-ESO-1 or XAGE1 antibodies
Serum samples were obtained at baseline, 4 and 8 weeks after the first KW-0761 treatment, and every 4 weeks during the continuous treatment until the point of study discontinuation. Recombinant NY-ESO-1 and the synthetic XAGE1 protein (1 μM) in ELISA Buffer kit (PeproTech, Rocky Hill, NJ) were adsorbed onto a 96-well E...
PMC10511099
Statistical analysis
Quantitative data without a normal distribution were analyzed using the 2-tailed non-parametric Mann-Whitney U test. The 2-tailed Fisher’s exact probability test was used for bivariate analyses. Cumulative survival was plotted using the Kaplan–Meier method, and differences were compared using the Log-rank test. Statist...
PMC10511099
Results
PMC10511099
Patient characteristics
cancer
CANCER
Between October 2013 and April 2016, 49 patients with CCR4-negative advanced solid cancer were assigned to receive the KW-0761 treatment at doses of 0.1 mg/kg (n = 23), 0.5 mg/kg (n = 3), and 1.0 mg/kg (n = 23) in the phase I study (
PMC10511099
Adverse events (AEs)
All grade and grade 3–4 treatment-related AEs occurred in 46 (93.9%) and 21 (42.9%), respectively, out of 49 patients (
PMC10511099
Reagent-related adverse events.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, Gamma-glutamyltransferase
PMC10511099
Clinical responses
PD, SD
DISEASE
Clinical responses were 1 partial response (PR), 9 stable disease (SD), and 39 PD (
PMC10511099
Characteristics of clinical responses.
esophageal cancer, tumor, Tumor
TUMOR, METASTASIS, TUMOR, OESOPHAGEAL CANCER, ADVERSE EVENTS, TUMOR GROWTH
(a) A Waterfall plot for the best percentage change from baseline. A positive change in the tumor burden indicates tumor growth, while a negative change reflects a tumor reduction. The tumor type, presence or absence of adverse events, and presence or absence of NY-ESO-1 and XAGE1 antibody responses are annotated for e...
PMC10511099
Representative CT imaging in patients with a durable clinical response.
esophageal cancer, Multiple liver metastases, cancer, Esophageal cancer, pleural tumor
METASTASIS, OESOPHAGEAL CANCER, CANCER, PLEURAL METASTASIS, LYMPH NODE METASTASIS, ESOPHAGEAL CANCER, DISEASE PROGRESSION
(a) Esophageal cancer patient B-09. Pleural metastasis (yellow arrow) was observed on CT and FDG-PET at baseline. The pleural tumor was decreased in size by the KW-0761 treatment, which was also confirmed by a reduction in standardized uptake value-max (SUV-max) on FDG-PET. Although pleural metastasis shrank, abdominal...
PMC10511099
FoxP3
eTreg depletion in peripheral blood by KW-0761 was examined at baseline and during the KW-0761 treatment by flow cytometry. The percentage of eTregs in CD4
PMC10511099
Blood laboratory data
The lymphocyte count, percent lymphocytes in leukocytes (% lymphocytes), NLR, MLR, and PLR were analyzed by blood laboratory tests at baseline and weekly after the initiation of KW-0761 until 8 infusions. The lymphocyte count and % lymphocytes markedly decreased immediately after the initiation of KW-0761, along with r...
PMC10511099
Changes in blood laboratory data and correlations for overall survival.
(a) The lymphocyte count (/μl), percent lymphocytes in leukocytes (% lymphocytes), NLR, MLR, and PLR were assessed by blood laboratory tests at baseline and weekly after the first KW-0761 treatment until 8 infusions. Kaplan-Meier curves of OS were analyzed between high and low groups divided by the median values of cal...
PMC10511099
Cancer-testis (CT) antigen-specific antibody responses
Serum NY-ESO-1 and XAGE1 antibodies at baseline and after the first 8 infusions or at the time of the discontinuation of treatment were analyzed by ELISA in patients with less than 8 infusions (
PMC10511099
Discussion
cancer, peripheral T-cell lymphoma
NON-SMALL CELL LUNG CANCER, PERIPHERAL T-CELL LYMPHOMA, HTLV-1-ASSOCIATED MYELOPATHY-TROPICAL SPASTIC PARAPARESIS, CANCER, SOLID TUMORS, ADULT T-CELL LEUKEMIA/LYMPHOMA
We conducted phase Ia and Ib clinical trials on KW-0761 to examine the selective depletion of Tregs in 49 patients with CCR4-negative solid cancer [Strategies targeting Tregs to increase anti-tumor immunity, including antibodies against CTLA-4, OX40, 4-1BB, and ICOS, have attracted attention [Treg reductions by KW-0761...
PMC10511099
Supporting information
PMC10511099
Clinical courses of patients.
cancer, PD
CANCER, DISEASE
Kaplan–Meier curves of OS and PFS for 49 CCR4-negative solid cancer patients were analyzed with doses of KW-0761 (a, b) and clinical responses (c, d). PD, progressive disease; SD, stable disease; PR, partial response.(TIF)Click here for additional data file.
PMC10511099
Characteristics of clinical responses and survival in esophageal cancer patients.
esophageal cancer, tumor, cancer, Esophageal cancer, non-esophageal cancer
ESOPHAGEAL CANCER, TUMOR, OESOPHAGEAL CANCER, CANCER, ESOPHAGEAL CANCER
(a) A Spaghetti plot for the percentage change in the target lesion tumor burden from baseline over time in esophageal cancer patients (n = 14, left) and non-esophageal cancer patients (n = 35, right). (b-c) Kaplan-Meier curves of OS and PFS for 49 CCR4-negative solid cancer patients were analyzed with or without esoph...
PMC10511099
Effects of Treg depletion in peripheral blood.
Longitudinal changes in the percentage of eTregs in CD4(TIF)Click here for additional data file.
PMC10511099
Longitudinal changes in serological immune responses for NY-ESO-1 and XAGE-1.
Antibody responses in the phase Ib trial were analyzed for NY-ESO-1 (a) and XAGE-1 (b) in patients with positive antibody responses at baseline or during the KW-0761 treatment.(TIF)Click here for additional data file.
PMC10511099
Clinical courses of patients based on NY-ESO-1 and XAGE1 antibody responses.
tumor
TUMOR
Kaplan-Meier curves of OS and PFS were analyzed based on the presence or absence of tumor NY-ESO-1 or XAGE1 antigen expression (a, b), baseline serum NY-ESO-1 or XAGE1 antibody responses (c, d), and increased NY-ESO-1 or XAGE1 antibody responses after the KW-0761 treatment (e, f).(TIF)Click here for additional data fil...
PMC10511099
Patient characteristics and serological immune response.
(DOCX)Click here for additional data file.
PMC10511099
CONSORT 2010 checklist of information to include when reporting a randomised trial*.
(DOC)Click here for additional data file.
PMC10511099
References
PMC10511099
Summary
Both authors contributed equally.ICON study group members are listed in the
PMC10755111
Background
CHRONIC CLUSTER HEADACHE
We demonstrated in the randomised controlled ICON study that 48-week treatment of medically intractable chronic cluster headache (MICCH) with occipital nerve stimulation (ONS) is safe and effective. In L-ICON we prospectively evaluate its long-term effectiveness and safety.
PMC10755111
Methods
attack-frequency
ICON participants were enrolled in L-ICON immediately after completing ICON. Therefore, earlier ICON participants could be followed longer than later ones. L-ICON inclusion was stopped after the last ICON participant was enrolled in L-ICON and followed for ≥2 years by completing six-monthly questionnaires on attack fre...
PMC10755111
Findings
±
EVENTS
Of 103 eligible participants, 88 (85%) gave informed consent and 73 (83%) were followed for ≥2 year, 61 (69%) ≥ 3 year, 33 (38%) ≥ 5 years and 3 (3%) ≥ 8.5 years. Mean (±SD) follow-up was 4.2 ± 2.2 years for a total of 370 person years (84% of potentially 442 years). The pooled geometric mean (95% CI) weekly attack fre...
PMC10755111
Interpretation
ONS is a safe, well-tolerated and long-term effective treatment for MICCH.
PMC10755111
Funding
The
PMC10755111
Keywords
PMC10755111
Research in context
PMC10755111
Evidence before this study
cluster headache, headache
ADVERSE EVENTS, CHRONIC CLUSTER HEADACHE, CLUSTER HEADACHE
We searched PubMed on November 13th, 2023, with the keywords “chronic cluster headache”, “cluster headache”, and “occipital nerve stimulation” (ONS), without restrictions to language or publication year. Of the 171 items, we excluded reviews and publications that did not report attack frequency at least 24 months after...
PMC10755111
Added value of this study
±
ADVERSE EVENTS
This study provides a prospective detailed follow-up (range 2–8.5 years) of the long-term efficacy and safety of ONS in patients with MICCH who had participated in the only randomized, dose-controlled study of the effects of ONS in MICCH to date (ICON trial). Both participants who had improved at the end of the randomi...
PMC10755111
Implications of all the available evidence
ONS offers long-term and well-tolerated improvement in MICCH and may also be considered for patients with CCH who respond only sub-optimally to standard medical treatment but do not yet meet the strict criteria of MICCH. Improved ONS devices and stimulation protocols currently under development may confer even better e...
PMC10755111
Introduction
CHRONIC CLUSTER HEADACHE, CLUSTER HEADACHE
Medically intractable chronic cluster headache (MICCH) is the most extreme and disabling form of cluster headache, in which patients continue to have frequent, often daily, attacks despite a variety of standard prophylactic medication.We showed in the randomized double-blind ICON study that both 100% and 30% electrical...
PMC10755111
Methods
PMC10755111
Ethics
Written informed consent was obtained from all participants and the study protocol was approved by the ethical committee of the LUMC (METC-LDD; Protocol number P10.016).
PMC10755111
ICON trial
paresthesia
PARESTHESIA
The parent study (ICON trial) was an investigator-initiated, international, multicentre, randomised, double-blind, phase 3, electrical dose-controlled clinical trial. After 12 weeks of baseline observation, participants were randomised to 24 weeks of occipital nerve stimulation at either 100% or 30% of the individually...
PMC10755111
Patients and questionnaires
MOS, COMPLICATIONS
For logistic reasons, only Dutch patients who had completed the full 48-week ICON study were invited for prospective structured follow-up every 6 months for at least two years but if possible longer.ICON study participants were asked to participate and enrolled in the L-ICON follow-up study immediately after completion...
PMC10755111
Statistics
REGRESSION, ADVERSE EVENT, EVENT, ADVERSE EVENTS
Because participants in the LICON follow-up study were each enrolled immediately after completion of the ICON study (i.e. 48 weeks after ONS implantation), while the ICON study was still recruiting new patients until December 3rd 2017, the initial LICON participants (who started the ICON study already in 2013) had a mu...
PMC10755111
Outcomes
ADVERSE EVENTS
The primary outcome was the change in mean weekly attack frequency 2 years after completion of the ICON study (i.e. 3 years after ONS implantation) compared to baseline (i.e. the three months before ONS implantation). Secondary outcomes were (i) Change in mean attack frequency from baseline after 1, 2 and 5 years (ii) ...
PMC10755111
Role of the funding source
The funders had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
PMC10755111
Results
PMC10755111
Subjective response and satisfaction
Most participants (69/88; 78% [68%–86%]) reported a subjective improvement from baseline at their last follow-up; 9/88 (10% [5%–19%]) reported no change and 4/88 (5%) a worsening. The remaining 6 (7%) could not answer the question since they had a broken stimulator (n = 2) or the stimulator was turned off for varying r...
PMC10755111
Predictive factors for efficacy at 2 years
DISEASE
Sex, age, number of autonomic symptoms, disease duration, restlessness and attack frequency at baseline are presented in
PMC10755111
Adverse events
ADVERSE EVENTS
From the end of the ICON trial to the last follow-up visit, N = 202 serious adverse events (SAE) occurred in 63/88 (72%) participants (
PMC10755111
Discussion
headache, attack-frequency, fracture, dislocation
ADVERSE EVENTS, THIGH DISEASE, CLUSTER HEADACHE, STAGGERED, EVENTS
In this study, we prospectively and structurally assessed the long-term effectiveness, safety and tolerability of ONS in 88 patients with MICCH who had initially completed the 48-week randomised, double-blind, electrically dose-controlled ICON trial. Both ICON responders and non-responders were followed for at least tw...
PMC10755111
Contributors
Study design (conceptualization and methodology): LAW, JH, WM, FJPMH, EWZ, MDF, ICON study group; Data collection and curation: RBB, LAW, IFC; Data analysis and formal analysis: RBB, EWZ; Writing—original draft: RBB, MDF, RF; Writing—review and editing: RBB, LAW, IFC, JH, WM, FJPMH, EWZ, MDF, RF; Supervision: MDF, RF.R...
PMC10755111
Data sharing statement
The data sets used and/or analysed during the present study are available from the corresponding author on reasonable request.
PMC10755111
Declaration of interests
BRAIN
WM reports honoraria from Novartis, Teva, AbbVie, Lundbeck and Lilly, and consultancy and lecture fees from Lilly; RF reports consultancy and lecture fees from Novartis, Lundbeck, AbbVie, Lilly and TEVA, and independent support from the Dutch Brain Foundation, Leiden University Fund and Innovation Fund Dutch Healthcare...
PMC10755111
References
PMC10755111
Supplementary data
PMC10755111
Supplementary Figures and Tables
PMC10755111
Study protocol
PMC10755111
PubMed table
PMC10755111
ICON group
PMC10755111
Acknowledgements
This study was funded by the Supplementary data related to this article can be found at
PMC10755111
Background
PD, anorexia nervosa, purging disorder, bulimia nervosa
DISORDER, PATHOPHYSIOLOGY, DELAYED GASTRIC EMPTYING
Prior work supports delayed gastric emptying in anorexia nervosa and bulimia nervosa (BN) but not binge-eating disorder, suggesting that neither low body weight nor binge eating fully accounts for slowed gastric motility. Specifying a link between delayed gastric emptying and self-induced vomiting could offer new insig...
PMC10106287
Methods
Women (
PMC10106287
Results
gastrointestinal distress, Delayed gastric emptying
DELAYED GASTRIC EMPTYING, PURGING
Delayed gastric emptying was associated with purging with no main or moderating effects of binge eating in the placebo condition. Medication eliminated group differences in gastric emptying but did not alter group differences in reported gastrointestinal distress. Exploratory analyses revealed that medication caused in...
PMC10106287
Conclusions
Delayed gastric emptying, purging behaviors
DELAYED GASTRIC EMPTYING, PURGING
Delayed gastric emptying demonstrates a specific association with purging behaviors. However, correcting disruptions in gastric emptying may exacerbate disruptions in gut peptide responses specifically linked to the presence of purging after normal amounts of food.
PMC10106287
Key words
gastrointestinal diseases, nausea, nonpurging, postprandial gastrointestinal distress, postprandial fullness, non-eating disorder, Delayed gastric emptying, vomiting, PD, increases gastric motility
GASTROINTESTINAL DISEASES, DELAYED GASTRIC EMPTYING, PURGING
Delayed gastric emptying has been observed in numerous gastrointestinal diseases marked by increased postprandial fullness, nausea, and stomach discomfort (Hajishafiee, Bitarafan, & Feinle-Bisset, The current study examined gastric emptying in women with PD and BN who used vomiting as their primary purging method, wome...
PMC10106287
Methods
PMC10106287
Participants
Women (The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. This study was approved by the Human Subjects Committee of the IRB at bo...
PMC10106287
Procedure
Axis I Disorders, Depression
SCID, MENDELSON
During their first visit, participants completed a medical exam, including pregnancy tests and tests of liver function, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) (First, Spitzer, Gibbon, & Williams, Descriptive statistics for clinical measures and gastric emptying by groupBDI, Beck Depression...
PMC10106287
Gastric emptying assessment
Plasma acetaminophen concentrations were measured using a validated Liquid Chromatography-Mass Spectrometry (LCMS) method (Baliga & Kallury,
PMC10106287
Gut peptide assessment
Plasma samples for PYY were collected, stored, and assayed following instructions for a commercially available radioimmunoassay (RIA) kit (Millipore, St. Charles, MO, USA; PYYT-66HK), with a sensitivity of 10 pg/ml, and intra-assay and interassay CVs of 5.3% and 7.0%.
PMC10106287
Data analyses
gastrointestinal distress
Multi-level models captured within-subject levels and changes in acetaminophen concentrations, gastrointestinal distress, and postprandial PYY (Level 1) and whether group (Level 2) differed in these levels or changes, with random effects for intercept and slope (time) (Keel et al.,
PMC10106287