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Modules
PMC10141827
Module 1
Body plethysmography measurements (MasterScreen Body®, Vyaire Medical GmbH, Höchberg, Germany) were performed as described previously
PMC10141827
Module 2
CPET (MasterScreen CPX®, Vyaire Medical GmbH, Höchberg, Germany) was performed using a standard silicone CPET mask (Hans Rudolph™ mask) on a bicycle ergometer according to current recommendationsBefore each examination (modules 1 and 2), the measuring device was calibrated with the specific mask adapter and the specifi...
PMC10141827
Module 3
LEAKAGE
Since the CPET examination does not reflect the normal wearing of a face mask (without leakage), due to the standard silicone CPET mask, ergometric exercise was repeated using the identical step protocol as in module 2 and the masks were worn under real-life conditions (including leakage).
PMC10141827
Module 4
LEAKAGE
For a 4-h workplace examination, masks were regularly worn (including leakage) during light/moderate work in the office or laboratory. For modules 3 and 4, the correct fit of the mask was checked by the investigator prior to each measurement and the subjects were instructed to do the same during the workplace measureme...
PMC10141827
Mask characteristics and mask adapter
®, CM
To compare breathing resistances and filter efficiencies, the three masks were tested on a “Sheffield head” according to the European Standard EN 149 (applied solely to CE certification of FFP masks)In all modules, participants wore in randomized order (1) NM, (2) SM (Typ II, MedicalCare & Serve industry®, Wilfried Ros...
PMC10141827
Physiological and physical parameters
nose and mouth
LUNG, APS
Lung volume associated parameters (e.g. forced vital capacity (FVC), forced expiratory volume in one second (FEVBlood gas analysis (BGA) from hyperaemic capillary earlobe blood was taken before and after CPET and ergometry and at the end of each load level (5th minute) as well as before and at the end (while wearing a ...
PMC10141827
Subjects’ perceived physical exertion
Perceived physical exertion was assessed in CPET and ergometry before, after, and within the last 20 s of each load as well as before and after the 4-h workplace examination using the BORG Scale
PMC10141827
Data and statistical analysis
Median values of cardiopulmonary parameters of CPET and ergometry were calculated during the last three minutes of each 6-min load after reaching the physiological steady state. Measurement values are presented as boxplots (box: median, 25th-75th percentile; whiskers: 3.5-fold interquartile range). In tables, data are ...
PMC10141827
Ethic approval
The study was conducted in accordance with the latest revision of the Declaration of Helsinki and the Ethics Committee of the medical faculty of the Ruhr-University Bochum provided ethical approval of the study (Reg. No.: 20-7024). All subjects gave written informed consent—both for study participation and for the publ...
PMC10141827
Results
PMC10141827
Performance characteristics of the face masks
inspiratory airflow, CM
LEAKAGE
Using the “Sheffield head” system according to EN 149, in- and expiratory breathing resistance of SM and CM was similar and lower compared to FFP2, probably due to the better filter efficiency of FFP2 (Table S1). For all types of masks breathing resistance increased with higher inspiratory airflow and decreased for SM ...
PMC10141827
Workplace (Module 4)
During the 4-h workplace measurement, a slightly increased COWorkplace measurement: Results of (
PMC10141827
Subjects’ perceived physical exertion
During CPET and ergometry, study subjects reported progressively higher BORG ratings during exercise when wearing a mask. For FFP2 these findings were statistically significant (Table
PMC10141827
Discussion
PMC10141827
Principal findings
CM
In this partially double-blinded randomized cross-over study wearing SM, CM, and FFP2 caused an increase in total airway resistance and specific airway resistance, which was most pronounced for FFP2. The increased breathing resistance led to an increase in work of breathing and respiratory power and thus to a slightly ...
PMC10141827
Strengths of the study
DISEASES
A special feature of our study is the complex study design which allowed to examine all 40 subjects in all four modules, partly even double-blinded, without and when wearing three different masks at different workloads and up to four hours continuously. Mask types were previously checked according to EN 149 and confirm...
PMC10141827
Limitations of the study
asthma
HEART DISEASES, ASTHMA, HIGH BLOOD PRESSURE
Due to the fact that exercise tests were carried out in air-conditioned laboratory rooms, effects of differing environmental conditions (e.g. temperature, humidity) on physiological parameters and the microclimate behind the mask could not be considered. Although some subjects with mild asthma and high blood pressure t...
PMC10141827
Breathing physiology and cardiopulmonary data
PMC10141827
Body plethysmography and CPET (Modules 1–2)
CM
The increased breathing resistance due to the different filter materials of the face masks was confirmed by the testing on the Sheffield head according to EN 149. Body plethysmographic examinations showed increases in total airway resistance (Rtot), specific airway resistance, work of breathing and respiratory power, a...
PMC10141827
Ergometry (Module 3)
Presumably due to the physiological adaptation under CPET, a decrease of pODuring physical exertion (up to approx. 150 watts and comparable to the PWC
PMC10141827
Workplace (Module 4)
CM
The small partial rebreathing of CODue to reduced permeability of the masks, the warm and humid exhaled breath condenses behind the mask and leads to increases in humidity and temperature. In addition to the breathing resistance of the mask, the material (cotton vs. synthetic) needs to be considered. Although testing o...
PMC10141827
Conclusions
In conclusion, wearing face masks caused significant physiological strain, but did not represent a health risk. Study participants reported a higher perceived physical exertion due to enhanced breathing resistance together with increased humidity and temperature behind the mask. All effects were most pronounced when we...
PMC10141827
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-023-32180-9.
PMC10141827
Acknowledgements
The authors thank Christoph Thelen and the Institute for Occupational Safety and Health of the German Social Accident Insurance (IFA) for the mask testing according to EN 149. Additionally, we would like to thank Susann Widmer, Vanessa Thiele, Karla Bosse, Raphael Kollenberg and Philipp Zaghow, for their excellent tech...
PMC10141827
Author contributions
E.M.M.: project administration and organization (lead), project conceptualization (lead), investigation (lead), writing—original draft (lead); formal analysis (lead); visualization (lead); writing—review and editing (lead). V.v.K.: project conceptualization (equal); project organization (lead) investigation (equal); fo...
PMC10141827
Funding
Open Access funding enabled and organized by Projekt DEAL. This study was funded by the German Social Accident Insurance (Deutsche Gesetzliche Unfallversicherung, DGUV).
PMC10141827
Data availability
Additional data will be supplied on reasonable request. The request should be addressed to the corresponding author.
PMC10141827
Competing interests
All authors declare that they have no known competing financial interests. As staff of the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University (IPA), the authors are employed by the study’s main financing body, the German Social Accident Insurance...
PMC10141827
References
PMC10141827
Introduction
Mental contrasting with implementation intentions (MCII) has been successfully applied to improve health-related behaviors (e.g. exercise). We explored its effectiveness to improve sleep outcomes beyond effects of sleep hygiene (SH) information, and investigated associations with stress. Eighty university employees (me...
PMC10492430
Implementation intentions and sleep
The formulation of implementation intentions is a post-intentional behavior change technique fostering the translation of intention into behavior which has been applied in interventions based on the Theory of Planned Behavior (
PMC10492430
Mental contrasting
cognitive and motivational mechanisms
Mental contrasting is a pre-intentional self-regulation technique that uses cognitive and motivational mechanisms to facilitate strong goal commitments or goal intentions (
PMC10492430
Stress and poor sleep
SECONDARY
A secondary objective of our study was to investigate associations between daily stress and sleep outcomes, as well as possible additional intervention effects on subjective stress and the cortisol awakening response (CAR). Self-reported stress has been linked to both subjective and objective sleep quality. For example...
PMC10492430
Study aims and hypotheses
The present study aimed to expand the self-regulation technique of MCII to the context of sleep outcomes, namely sleep duration and sleep quality, in a non-clinical population. Our main objective was to compare the effects of sleep hygiene information only (SH) with the combined effects of MCII + SH regarding objective...
PMC10492430
Method
Data were analyzed using R version 4.2.1 for Windows. Multilevel models were estimated using the nlme package (
PMC10492430
Recruitment and sample
Early career researchers, that is, doctoral candidates and scientific staff, employed at Heidelberg University were invited via e-mail and newsletters to participate if they had the intention to improve their sleep. To approach the statistical power for the multilevel models, we approximated the effect size that can be...
PMC10492430
Procedure
The present study compared two intervention conditions (MCII + SH vs SH) and analyzed associations between stress and sleep outcomes and in a single-blinded, randomized controlled trial with daily/nightly assessments in a baseline-week and analog daily/nightly assessments in a post-intervention week (Procedure and flow...
PMC10492430
Intervention
Participants in the SH-group (After this, participants were asked to formulate three implementation intentions, by specifying how, where and when they could act to (a) prevent their obstacle from occurring, (b) overcome their obstacle in case it occurred, and (c) specify another goal-directed behavior to improve their ...
PMC10492430
Assessment of the CAR
Salicaps
PMC10492430
Laboratory analysis and preprocessing of CAR data
Saliva samples were stored at −80°C. The concentration of sCort (ng/mL) was analyzed using an enzyme-linked immunosorbent assay at the Institute of Medical Psychology in Heidelberg, Germany. The inter-assay coefficient of variation (CV) was 5.46% and the intra-assay CV was 2.91%. Following
PMC10492430
Data analysis
Data were analyzed using multilevel modeling to account for the nested data structure with repeated measurements (Level 1) nested within individuals (Level 2). For our hypotheses targeting intervention effects, individual Formal model description:Level 1: (within participants) Level 2: (between participants) For the ...
PMC10492430
Results
Three observations were set to missing, since time stamps indicated that morning assessments were filled in prior to the evening assessments of the previous day.Descriptive statistics separated by study group.Table depicts descriptive statistics on the between-person level.Estimates in the upper diagonal depict estimat...
PMC10492430
Intervention effects
PMC10492430
Exploratory analyses
To account for the possibility of gradual improvement of the sleep parameters after the intervention, we conducted piecewise growth models. Specifically, two variables were created to code the number of the study days. The first variable (time to intervention) counted the number of days to the first night after the int...
PMC10492430
Association of stress with sleep parameters
We examined if daily stress was associated with the three sleep parameters on the within-person level (e.g. “Is sleep quality lower on nights following days with higher than usual stress?”) and the between person level (e.g. “Do participants with higher average stress levels report worse sleep quality on average?”). To...
PMC10492430
Discussion
sleep behavior, Health behaviors
DETACHMENT
Our randomized-controlled study did not support the effectiveness of an MCII intervention component over sleep hygiene information in a sample of early career researchers. Across all participants, results indicated an increase in sleep quality and subjective (but not objective) sleep duration from baseline to post-inte...
PMC10492430
Research Data
PMC10492430
sj-csv-12-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-csv-12-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of...
PMC10492430
sj-csv-13-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-csv-13-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of...
PMC10492430
sj-csv-14-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-csv-14-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of...
PMC10492430
sj-DOCX-16-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.Supplemental material, sj-DOCX-16-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika ...
PMC10492430
sj-inp-10-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-inp-10-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of...
PMC10492430
sj-inp-11-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-inp-11-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of...
PMC10492430
sj-inp-9-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-inp-9-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of ...
PMC10492430
sj-pdf-15-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-pdf-15-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of...
PMC10492430
sj-R-1-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-R-1-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of He...
PMC10492430
sj-R-2-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-R-2-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of He...
PMC10492430
sj-R-3-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-R-3-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of He...
PMC10492430
sj-R-4-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-R-4-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of He...
PMC10492430
sj-txt-5-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-txt-5-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of ...
PMC10492430
sj-txt-6-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-txt-6-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of ...
PMC10492430
sj-txt-7-hpq-10.1177_13591053231159168 – Supplemental material for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial
SCHMIDT
Click here for additional data file.sj-txt-7-hpq-10.1177_13591053231159168 for Effects of mental contrasting on sleep and associations with stress: A randomized controlled trial by Laura I Schmidt, Andreas B Neubauer, Martin Stoffel, Beate Ditzen, Jana Schirmaier, Claudia Farrenkopf and Monika Sieverding in Journal of ...
PMC10492430
References
PMC10492430
Rationale
antipsychotic-induced weight gain, Weight gain
SIDE EFFECT
Weight gain is a frequent side effect of treatment with SGAs (second-generation antipsychotics) and a leading cause for nonadherence. Several candidate genes have been identified that could influence the amount of AIWG (antipsychotic-induced weight gain). The polymorphism rs17782313 near the
PMC10006246
Objective
weight gain
We therefore examined the influence of the rs17782313 polymorphism on SGA-related weight gain.
PMC10006246
Methods
Weight gain, schizophrenia or schizoaffective disorder
REGRESSION
Participants of a multicenter randomized, controlled, double-blind study comparing two treatment strategies in individuals with schizophrenia or schizoaffective disorder were genotyped using a rapid-cycle polymerase chain reaction. Up to 252 individuals completed the first 2 weeks (phase I), 212 the entire 8 weeks (hen...
PMC10006246
Results
weight gain
Within 212 ‘completers’, carriers of the C allele had a higher absolute weight gain than those homozygous for the T allele (2.6 kg vs. 1.2 kg), though this observation was not significant (
PMC10006246
Conclusion
weight gain, antipsychotic-induced
Our results indicate that the rs17782313 polymorphism might influence antipsychotic-induced weight gain and therefore confirm some of the earlier conclusions.
PMC10006246
Supplementary Information
The online version contains supplementary material available at 10.1007/s00213-023-06331-9.
PMC10006246
Keywords
Open Access funding enabled and organized by Projekt DEAL.
PMC10006246
Introduction
obesity, antipsychotic-induced weight gain, weight gain, schizoaffective disorder, Schizophrenia, schizophrenia, psychotic mental disease
OBESITY
Schizophrenia is a chronic, psychotic mental disease that affects approximately one percent of people. The time of onset is typically in late adolescence or early adulthood and regularly continues through the whole life (Freedman Pharmacological treatment was introduced more than half a century ago with the discovery o...
PMC10006246
Materials and methods
PMC10006246
Study design
schizophreniform disorder, schizophrenia, schizoaffective disorder
Patients aged between 18 and 65 who suffered from schizophrenia, schizoaffective disorder, or schizophreniform disorder were recruited as part of a multi-center study (Heres et al.
PMC10006246
Genotyping
We genotyped the rs17782313 polymorphism, a T to C transition located 188 kb downstream from the
PMC10006246
Statistics
weight gain
We analyzed weight gain and BMI increase occurring both during the first 2 weeks (phase I) and weight gain during the entire 8 weeks. This was due to the design of the study (the ‘switch’ in some patients’ medication after 2 weeks) and, as expected, discontinuations of some individuals. For both time periods, we at fir...
PMC10006246
Results
PMC10006246
Baseline characteristics
The average baseline BMI ± SD (standard deviation) of all 252 individuals participating in phase I was 25.8±5.4 kg/mAnalysis of variance for the rs17782313 polymorphism for phase i and the entire trial*mThose individuals completing the entire 8 weeks of the trial (‘completers’) numbered 212 and were on average 41.7 yea...
PMC10006246
Weight gain in phase I
Weight gain
After 2 weeks of treatment, Weight gain in kg observed within 8 weeks of treatment depending on medication in each genotype. Data are presented as mean+SD. Statistical tests compare TT with C carriers
PMC10006246
Weight gain in ‘completers’
After 8 weeks of treatment, the
PMC10006246
Multiple comparisons
Twenty-five variables were corrected for multiple comparisons by Holm’s method. The two lowest
PMC10006246
Discussion
amisulpride-induced weight gain, weight gain
REGRESSION, MINOR, REGRESSIONS
We observed a statistically significant association between the rs17782313 polymorphism and absolute weight gain and absolute BMI gain after 8 weeks of antipsychotic treatment in the amisulpride subpopulation when comparing carriers of the C allele with TT carriers. The same direction of effect could be seen in the ent...
PMC10006246
Supplementary information
Variables and Normal Distribution. Supplementary Table 2 Holm’s Test for Multiple Comparisons. Supplementary Table 3 Baseline Characteristics of Patients With a First Episode. Supplementary Table 4 Analysis of Variance for the rs17782313 Polymorphism for Phase I and the Entire Trial in Patients With a First Episode (P...
PMC10006246
Funding
Open Access funding enabled and organized by Projekt DEAL. The study conduct was supported by a grant from the “Bundesministerium fuer Bildung und Forschung” (BMBF), a German government agency (grant code 01KG0910). Eli Lilly provided the olanzapine medication for the trial, but had no influence on the protocol, data a...
PMC10006246
Declarations
PMC10006246
Conflict of interest
Johnson & Johnson, Pfizer, Bristol-Myers Squibb, Johnson & Johnson, Bristol-Myers Squibb, Johnson & Johnson.
WERNER
Korbinian Felix Schreyer declares no conflict of interest. In the past 3 years, Stefan Leucht has received honoraria as a consultant and/or advisor and/or for lectures from Alkermes, Angelini, Eisai, Gedeon Richter, Janssen, Lundbeck, Lundbeck Institute, Merck Sharp and Dohme, Otsuka, Recordati, Rovi, Sanofi Aventis, T...
PMC10006246
References
PMC10006246
Background
melanoma
MELANOMA
Recurrence-free survival (RFS) and overall survival (OS) data for adjuvant nivolumab versus placebo (proxy for routine surveillance) in patients with high-risk, resected melanoma are lacking. This post hoc, indirect treatment comparison (ITC) used pooled data from the phase 3 EORTC 18,071 (ipilimumab vs. placebo) and C...
PMC10025222
Methods
resected stage IIIB-C, cutaneous melanoma, Cancer
CUTANEOUS MELANOMA, CANCER
Patients with resected stage IIIB-C cutaneous melanoma (American Joint Committee on Cancer seventh edition) were included. Inverse probability treatment weighting (IPTW) was used to balance baseline characteristics. RFS NNTs were calculated for nivolumab versus ipilimumab and placebo. OS NNTs were calculated for nivolu...
PMC10025222
Results
This ITC included 278, 643, and 365 patients treated with nivolumab, ipilimumab, and placebo, respectively. Following IPTW, nivolumab was associated with improved RFS versus placebo (hazard ratio [HR]: 0.49; 95% confidence interval [CI] 0.39–0.61) and ipilimumab (HR: 0.69; 95% CI 0.56–0.85). RFS NNT was 4.2 for nivolum...
PMC10025222
Conclusions
resected stage IIIB-C, cutaneous melanoma
CUTANEOUS MELANOMA
In patients with resected stage IIIB-C cutaneous melanoma in this ITC, nivolumab improved RFS versus placebo and ipilimumab, and OS versus placebo after post-recurrence survival adjustment.
PMC10025222
Supplementary Information
The online version contains supplementary material available at 10.1007/s00262-022-03302-5.
PMC10025222
Keywords
PMC10025222
Introduction
resected stage IIIB-C, Melanoma, melanoma
DISEASE, MELANOMA, MELANOMA, OF SKIN CANCER
Melanoma is the deadliest form of skin cancer [Given that the prognosis among patients with melanoma is worse with advanced disease stage [Although the efficacy and safety of ipilimumab, pembrolizumab, and dabrafenib plus trametinib have been compared against placebo as adjuvant melanoma treatment in randomized clinica...
PMC10025222
Methods
PMC10025222
Data source
melanoma
STAGE IV MELANOMA, SECONDARY, MELANOMA, STAGE III MELANOMA
Individual patient data were pooled from EORTC 18,071 (NCT00636168) and CheckMate 238 (NCT02388906), both of which were multicenter, double-blind, randomized, phase 3 trials that evaluated RFS as the primary endpoint and OS as a secondary endpoint in patients with high-risk resected melanoma [In EORTC 18,071, patients ...
PMC10025222
Study population
tumor, cutaneous melanoma
REGRESSION, TUMOR, DISEASE, CUTANEOUS MELANOMA, ULCERATION, ONCOLOGY
To perform an ITC, patients with stage IIIB-C cutaneous melanoma who were enrolled in EORTC 18,071 and CheckMate 238 were included in this analysis, as they were the common population of the two trials (EORTC 18,071 and CheckMate 238 excluded patients with stage IV and stage IIIA disease, respectively). Inverse probabi...
PMC10025222
Study outcomes
death, primary melanoma
RECURRENCE, METASTASIS
In this study, RFS was separately compared between nivolumab versus placebo and nivolumab versus ipilimumab, and OS was compared between nivolumab versus placebo. The OS comparison between nivolumab versus ipilimumab was not included in the pooled population due to the differences in post-recurrence treatments availabl...
PMC10025222
RFS rate and NNT per additional recurrence-free survivor
Using the pooled patient data, the weighted RFS curves for nivolumab, placebo, and ipilimumab, were estimated using the Nelson-Aalen estimator [NNT represents the number of patients who needed to be treated with a treatment compared with another treatment to obtain one additional beneficial outcome [
PMC10025222
OS rate and NNT per additional overall survivor
tumor, melanoma
TUMOR, MELANOMA, ULCERATION
Due to the rapidly evolving treatment landscape, patients included in the two trials likely had access to different therapeutic options post-recurrence. To account for higher post-recurrence survival due to improved subsequent treatments for advanced melanoma in CheckMate 238 compared with EORTC 18,071, the analysis of...
PMC10025222