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Supplementary Information
The online version contains supplementary material available at 10.1186/s12885-023-10945-9.
PMC10183678
Keywords
PMC10183678
Background
cancer
CANCER, EVENT
Since the beginning of 2020, COVID-19 has spread worldwide - including in Germany [These strategies affect all patients but particularly vulnerable patients such as cancer patiens [Such an unpredictable event as the COVID-19 pandemic may affect study conditions. The present survey investigates the influence of the pand...
PMC10183678
Methods
PMC10183678
Setting – the background of the PIKKO study
cancer
CANCER
PIKKO is a care concept funded by the Innovation Fund of the Federal Joint Committee in Germany (Gemeinsamer Bundesausschuss, funding number 01NVF17011) which supplements oncological care with an additional counseling and information pathway [But it was not only the surveys that were affected by the pandemic, but also ...
PMC10183678
Participants and inclusion criteria
cancer disease
All participants of the supplementary survey met the inclusion criteria of the PIKKO study (age 18–90 years, diagnosis of any cancer disease, treatment by doctors from the Saarland, insured with one of the four statutory health insurance companies participating in this study) [
PMC10183678
Design
cancer
CANCER, GROUP B
In the present survey, we investigated two groups with a quasi experimental design. Group A was not affected (“affected” is related to participation in the PIKKO study) by the lockdown because the patients went through the PIKKO intervention as planned. The end of the PIKKO intervention or the voluntary exit from the P...
PMC10183678
Variables
cancer
CANCER, DISEASE
To assess the impact of pandemic containment strategies on our cancer patients, we asked them questions about four aspects: Restrictions (“Have you had any restrictions with regard to your disease since 16 Mar 2020?: Yes/No If yes, which?”), influence on disease (“Do you think that the limitations due to the COVID-19 p...
PMC10183678
Data sources
The four questions concerning COVID-19 were collected using a two-page questionnaire.From our regular patient survey [
PMC10183678
Bias
cancer
CANCER
Since the cancer patients interviewed were already part of the main PIKKO study, a selection bias can be assumed here.
PMC10183678
Study size
A full survey of all living PIKKO-IG participants was intended (n = 503).
PMC10183678
Statistical methods
cancer
REGRESSION, CANCER, DISEASE
First, selection effects were investigated by comparing participating and non-participating patients in the supplementary survey. To examine the selection bias, chi-square tests and F-tests were performed (independent variable: patient included versus excluded, depended variables: age, sex, etc.). Next, we compared the...
PMC10183678
Results
PMC10183678
Participants
GROUP B
A total of 503 (Group A = 241, Group B = 262) patients were contacted (the entire PIKKO intervention group). Of these, n = 356 returned a completed questionnaire of supplementary survey (n Flow chart of the supplementary surveyFor unknown reasons 147 patients did not respond and could not be interviewed again in the ma...
PMC10183678
Descriptive data
First, selection effects were investigated, to identify whether the sample of participating (n = 356) and non-participating patients (n = 147) differed. Corresponding statistics are listed in Table  Description of the sample and determination of the differences between the subgroups non-participants and participants as...
PMC10183678
Main results: comparison of “not affected” and “affected” by lockdown with regard to PIKKO
DISEASE
Comparisons of group A and group B in terms of socio-demographic data, disease data, and treatment (Table 
PMC10183678
Restrictions in relation to the disease
Out of all participants, 134 (37.6% of the sample) reported any restrictions. Group A and B differed significantly (χ²[
PMC10183678
Burdens due to the pandemic containment strategies
REGRESSION
The most perceived burdens of the entire sample were: „Restriction or ban on visits while I was on the ward” (m = 1.92, sd = 1.542); “Wear a protective mouth-nose mask” (m = 1.33, sd = 1.282) and “Restrictions on accompanying persons” (m = 1.19, sd = 1.355). As the analyses show, there were no group differences between...
PMC10183678
Assumption of an influence on the course of the disease
DISEASE, SAID
Although 39% (140/356) said they fear that the restrictions will have an influence on the course of their disease, in most cases a psychological influence (124/140, 88.6%). The two groups did not differ on this point (χ²[
PMC10183678
Using of parts of the PIKKO intervention during the lockdown
55.2% of the participants in group B (123/223) and 36.8% in group A (49/133) reported to the additional survey that they had used some PIKKO moduls during the lockdown. The two groups differed significantly on this point (χ²[
PMC10183678
Other analyses: general use of the PIKKO modules during the lockdown
Beyond the information from the supplementary survey, the data from the regular patient questionnaires (contacts to PNs), the SCS data and the logfile data from the knowledge database provide information about the use of the PIKKO modules during the lockdown.The contacts to the PNs are shown in Fig.  The utilization of...
PMC10183678
Discussion
cancer, life-threatening diseases, PIKKO cancer
REGRESSION, CANCER
It was the aim of this supplementary survey to identify the restrictions and burdens of the pandemic containment strategies on the PIKKO cancer patients and thus on the PIKKO study itself.To this aim, we surveyed participants and analyzed these data using frequency analyses and linear regression analyses to determine w...
PMC10183678
Strengths of the study
cancer
CANCER, DISEASE
We were able to provide insight into how an unforeseen disruption such as the COVID-19 crisis can impact an intervention study. This showed that a combination of flexibility (e.g., switching courses), diversity (e.g., face-to-face opportunities for patients), and location independence (e.g., web-based knowledge base) e...
PMC10183678
Limitations
cancer
CANCER
Data on contacts to the PN are based on patient self-reports, some of whom were undergoing cancer treatment. There is evidence that chemotherapy can impair memory and recall [The supplementary survey took place in the summer of 2020, a few weeks after the first lockdown. Memories of something that happened a few weeks ...
PMC10183678
Acknowlegdements
Cancer
CANCER
We would like to thank Anna Bäcker, Katja Brenk-Franz, Heide Wenzel and Clara Korn from IPMPP Jena for their valuable support in planning and conducting the PIKKO study.Furthermore, we thank Robert Terbach from the German Cancer Society for providing the transfer data for the knowledge database.We would also like to th...
PMC10183678
Authors’ contributions
RECRUITMENT
BS, UA and JH conceptualized the PIKKO study. NS and UA developed the design of this supplementary survey and data collection. CK, FB, NS, SR, and UA were involved in patient recruitment, study conduct, and data collection. NS and UA analyzed the data of this supplementary survey. CK, FB, NS, SR, and UA interpreted the...
PMC10183678
Funding
PIKKO was funded by the Innovation Fund of the Federal Joint Committee (Gemeinsamer Bundesausschuss) (01NVF17011) in the period from 31 to 2017 to 31 Dec 2020.Open Access funding enabled and organized by Projekt DEAL.
PMC10183678
Data Availability
The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.
PMC10183678
Declarations
PMC10183678
Competing interests
The authors declare no competing interests.
PMC10183678
Ethics approval and consent to participate
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the ethics committee of medical association of the Saarland (2 Nov 2017/No. 114/17). The informed consent by study participants was obtained in a written way.
PMC10183678
Consent for publication
Not applicable.
PMC10183678
Abbreviations
Cancer
CANCER
COVID-19 conditional burden scalecontrol groupintervention grouponline knowledge databasePatient information, communication and competence empowerment in oncologypatient navigator (PN)Saarland Cancer Society
PMC10183678
References
PMC10183678
Subject terms
COVID-19 PNEUMONIA
Chest computed tomography (CT) has played a valuable, distinct role in the screening, diagnosis, and follow-up of COVID-19 patients. The quantification of COVID-19 pneumonia on CT has proven to be an important predictor of the treatment course and outcome of the patient although it remains heavily reliant on the radiol...
PMC10039355
Introduction
CAD
CAD, PULMONARY INVOLVEMENT, SECONDARY
The COVID-19 pandemic has created new ways in which existing and developing technologies are used in radiology. Although definitive diagnosis relies on real-time reverse-transcriptase-polymerase chain reaction (RT–PCR), CT still plays an essential role in the screening and monitoring of COVID-19 evolution, setting pati...
PMC10039355
Results
PMC10039355
Bias validation in the synthetic experiment
The first experiment involved 40 radiologists who answered a survey regarding 18, nine intuitive and nine unintuitive, synthetically generated images (Fig. Synthetically crafted lung CT slices. The same starting slice was predelineated differently to simulate real involvement rates (18 slices and 9 involvement rates in...
PMC10039355
Overestimation in retrospective analysis
Next, the bias was further studied in a retrospective analysis of the CT studies of 109 patients with RT–PCR-confirmed COVID-19 from HOSP-TM and EXMED. As part of the standard clinical practice, all radiological reports mentioned the total percentage of COVID-19 lung involvement.Similar to the previous experiment, a vi...
PMC10039355
CAD effectiveness in the clinical trial
CAD, fibrosis
PULMONARY INVOLVEMENT, PNEUMOTHORAX, FIBROSIS, CAD
To study the effect of CAD on the involvement assessment problem, we used the AI-PROBE protocol with A total of 85 enrolled patients were randomised between the control arm (AI intervention off) and the experimental arm (access to AI results). An additional analysis exclusion criterion eliminated 9 studies that failed ...
PMC10039355
Discussion
CAD, AI-induced
LUNG, CAD
This study analysed the CT quantification of lung involvement in COVID-19 in three ways. The first synthetic experiment validated the translation of a theoretical model from psychophysical science to radiology, demonstrating that radiologists are susceptible to a cognitive bias that leads to overestimating the level of...
PMC10039355
Methods and materials
EMERGENCY
All procedures were conducted in conformity with the Declaration of Helsinki and International Conference on Harmonisation Good Clinical Practice guidelines. The clinical trial received approval from the Ethical Committee for Scientific Research of Pius Brinzeu County Emergency Hospital (no. 282/01/02/2022). The inform...
PMC10039355
Preliminary analysis
pulmonary deterioration
To test H1 and facilitate power calculation before conducting a full prospective clinical trial, two preliminary experiments were carried out.The first experiment involved 40 voluntary diagnostic radiologists. A call for volunteers reached physicians from eleven Romanian medical institutions. The eligibility criteria c...
PMC10039355
Clinical trial design
CAD, lung volume deterioration
CAD
To test H2, we used the AI-PROBE-2 protocol with The clinical trial took place at HOSP-TM, between 21 February 2022 and 15 March 2022., where physicians were already using Rayscape, a commercial CAD system for COVID-19 volumetric quantification. The Rayscape CAD system is an existing medical device that complies with t...
PMC10039355
Data collection
The enrolment inclusion criteria included an age of 16 or older (as per the Rayscape technical requirements), a non-contrast CT examination and positive RT-PCR results confirming COVID-19. The entire enrolment flow is illustrated in Fig. Chest CT investigations were performed using NeuViz 16 Essence (Neusoft Medical Sy...
PMC10039355
Statistical analysis
REGRESSION
Based on the two preliminary experiments, we calculated that a sample size of 32 CT studies for each arm would be sufficient to detect a mean difference of 5% (alpha = 0.05, beta = 0.8) with regard to H2. To account for the risk of post-analysis exclusions, 20 extra patients were planned to be enrolled. We did not assu...
PMC10039355
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-023-31910-3.
PMC10039355
Author contributions
B.A.B. and A.B. designed the study concept and planned the study. A.B. originally observed and informally validated the cognitive bias presence in practice. B.A.B. wrote the first draft of the study. B.A.B. and A.B. had full access to the data in the trial and auxiliary experiments and take responsibility for the integ...
PMC10039355
Data availability
The raw data (CT studies, radiological reports, patient characteristics) are not publicly available, as consented by the ERBs and patients for research use only by the investigators of this study. If other authors are interested in additional experiments on the collected data, a request can be made to the corresponding...
PMC10039355
Code availability
The Rayscape AI system is a publicly available medical device, available as a commercial software product and it’s also offered upon request for scientific enquiries. The code that generates the samples used in the first experiment (Fig. 
PMC10039355
Competing interests
This study was organised and coordinated by Rayscape, a start-up company developing AI algorithms for medical images and producer of the mentioned AI system. B.A.B., A.B., P.G.A., I.B., M.M.B., C.A., A.T., and S.I. are employees of Rayscape that own stock in the company. The rest of the authors declare no competing int...
PMC10039355
References
PMC10039355
Summary
Contributed equally to this work.
PMC10025757
Background
PWH, HIV infection, CVD, Inflammation, HIV (PWH
CARDIOVASCULAR DISEASE, CVD, INFLAMMATION, HIV INFECTION, INFLAMMATION
Persons with HIV (PWH) have an increased risk of cardiovascular disease (CVD) compared to HIV-seronegative individuals (SN). Inflammation contributes to this risk but the role of lipid mediators, with central roles in inflammation, in HIV infection remain to be established; further aspirin reduces CVD risk in the gener...
PMC10025757
Methods
PWH
We evaluated the relationship between plasma lipid mediators (i.e. 50 lipid mediators including classic eicosanoids and specialized pro-resolving mediators (SPMs)) and HIV status; and the impact of aspirin in PWH on regulating these autacoids. Plasma samples were obtained from 110 PWH receiving antiretroviral therapy (...
PMC10025757
Findings
PWH
PWH had lower levels of arachidonic acid-derived pro-inflammatory prostaglandins (PGs: PGE
PMC10025757
Interpretation
inflammation, PWH, CVD
CVD, INFLAMMATION
Together these observations demonstrate that plasma lipid mediators profiles, some with links to systemic inflammation and CVD risk, become altered in PWH. Furthermore, aspirin intervention did not increase levels of aspirin-triggered pro-resolving lipid mediators, consistent with other reports of an impaired aspirin r...
PMC10025757
Keywords
PMC10025757
Research in context
PMC10025757
Evidence before this study
inflammation, PWH, CVD, HIV (PWH
CVD, INFLAMMATION, CARDIOVASCULAR DISEASE
Aspirin can reduce cardiovascular disease (CVD) risk in the general population, in part through its anti-inflammatory properties. For example, aspirin is known to reduce levels of pro-resolving (i.e. anti-inflammatory) lipid mediators of inflammation. Persons with HIV (PWH) have higher risk of CVD and aspirin administr...
PMC10025757
Added value of this study
inflammation, PWH
INFLAMMATION
In a randomized trial of aspirin intervention in 110 PWH, we comprehensively assessed the levels of pro-inflammatory and pro-resolving lipid mediators before and after aspirin intervention. Our results show that, in the interval tested, 12 weeks of aspirin administration did not increase levels of pro-resolving lipid m...
PMC10025757
Implications of all the available evidence
inflammation, PWH
CVD, INFLAMMATION
Our findings suggest that the lipid mediator of inflammation profile, some with important functions in CVD risk, is distinct by HIV status. Importantly, our data also suggest aspirin does not increase the production of aspirin triggered specialized pro-resolving mediators (AT-SPM) in PWH. These results are in line with...
PMC10025757
Introduction
inflammation, PWH, CVD, HIV (PWH
CVD, INFLAMMATION, CARDIOVASCULAR DISEASE
Persons with HIV (PWH) have an increased risk of cardiovascular disease (CVD) compared to HIV-seronegative individuals (SN).Despite the critical role that inflammation plays in HIV outcomes such as CVD, the role of lipid mediators of inflammation (Bioactive lipid families. Illustration summarizing the bioactive mediato...
PMC10025757
Methods
PMC10025757
Study population
AIDS, inflammation, PWH
INFLAMMATION, AIDS
For this study, we assessed lipid mediators of inflammation from adult PWH on suppressive ART and from adult SN.All PWH with available baseline plasma samples (N = 110) from the AIDS Clinical Trials Group (ACTG) A5331 study (NCT02155985) were included in this analysis. The A5331 study, conducted in the United States fr...
PMC10025757
Ethics approval
Study participants provided written informed consent and the study was approved by relevant ethics committees (
PMC10025757
Laboratory assessment
PMC10025757
Targeted lipid mediator profiling
EDTA plasma samples were collected from participants as part of each study (details in
PMC10025757
Soluble and cellular markers of inflammation
Plasma levels of soluble CD14 (sCD14) was measured at baseline as part of the parent A5331 study using enzyme-linked immunosorbent assays (R&D Systems, Minneapolis, MN).
PMC10025757
Statistical analysis
inflammation, PWH, A5331
REGRESSION, HEAT, INFLAMMATION
A total of 50 unique lipid mediators were measured in plasma samples, with 42 SPMs and 8 pro-inflammatory lipid mediators (The first objective of this study was to compare plasma levels of i) lipid mediators and ii) metabolomes between PWH (pre-intervention) and SN individuals. To visually examine how mediators/metabol...
PMC10025757
Role of the funding source
The study sponsors did have a 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.
PMC10025757
Results
PMC10025757
Study population characteristics
PWH
Our study population (N = 217) included 110 PWH on suppressive ART and 107 SN. As expected with the matching of PWH and SN cohorts, study population characteristics including age, sex, race/ethnicity and body max index were similar by HIV status (Study population baseline characteristics by cohort.BMI: body mass index....
PMC10025757
Lipid mediator profile in PWH and SN individuals
PWH
HEAT
To understand the profile of pro-inflammatory and pro-resolving lipid mediators in PWH (i.e. baseline: pre-aspirin intervention) and SN individuals, we measured plasma levels of 50 lipid mediators belonging to 12 lipid mediator families derived from four major fatty acids namely docosahexaenoic acid (DHA), n−3 docosape...
PMC10025757
Relationship of lipid mediators with protein mediators among PWH
inflammation, PWH
INFLAMMATION
As PWH with higher levels of the monocyte activation marker soluble CD14 (sCD14) have an increased risk of morbidity and mortality, another objective of this study was to determine the relationship of lipid mediators and sCD14 among PWH.At the family level, no statistically significant associations with ‘high sCD14’ (d...
PMC10025757
Effect of aspirin treatment on lipid mediators among PWH
PWH
PWH were randomized to 12 weeks of either daily aspirin 300 mg, aspirin 100 mg or placebo and self-reported adherence to the intervention was high.Effect of aspirin on lipid mediator metabolomes among PWH.The mean fold-change and mean fold-change percent from baseline is shown for the three study arms for each lipid me...
PMC10025757
Discussion
inflammation, PWH
CVD, INFLAMMATION
In this study, we assessed the relationship between circulating lipid mediators of inflammation and resolution with HIV status, monocyte activation and aspirin treatment. When compared with SN, PWH on suppressive ART had lower levels of Tx and various PGs, and higher MaRIn our comparison between PWH on ART and SN, we o...
PMC10025757
Data sharing statement
The authors confirm that all data are available upon request (
PMC10025757
Declaration of interests
RS, PWH, TTB
PCT
PCT: Merck has provided her institution with funding for her research; Gilead and Lilly have also provided her institution with funding for her to conduct industry-sponsored clinical trials. PWH: Gilead has provided funding to his institution, and Merck has provided donation of study drug for NIH-sponsored trial. He ha...
PMC10025757
References
PMC10025757
Supplementary data
PMC10025757
Supplement_Combined
PMC10025757
Acknowledgements
RS
The authors thank the study participants for their time and contributions in the A5331 and MWCCS sites. We thank E Turner Overton for help with the study design. We also thank Jonathan Kerman, Jennifer Cohen, Eryka Wentz, Gayle Springer and MWCCS Data Analysis and Coordinating Center for all their help with participant...
PMC10025757
Subject terms
human behavior, Pain, pain
Colors are an important factor that influences different aspects of people's lives. However, little is known about the effects of colors on pain. This preregistered study aimed to investigate whether the type of pain affects the impact of colors on pain intensity. 74 participants were randomly divided into 2 groups acc...
PMC10115883
Introduction
Color affects cognitive functions, hyperalgesia, pain
Colors have been proven to influence many aspects of life. Color affects cognitive functions such as attentionWhat is more, colors have been proven to affect pain. Red has been found to increase pain intensity more than green and blue when electrical pain stimuli are used; however, of all colors examined (red, blue, gr...
PMC10115883
Results
±, pain
There were no differences between groups (electrical and thermal) in terms of participants' age (Basic descriptive statistics of the study participants, expressed as the mean (± standard deviation) or percentage (number) and p-values of between group analyses.Means and standard errors of differences between pain rating...
PMC10115883
Pain analyses
’, pain
The two-way mixed-design ANOVA performed on the pain ratings revealed a statistically significant main effect for ‘color’ (The post-hoc tests were carried out without the modality division as there was a significant main effect for ‘color’ but not for the ‘color’ x ‘modality’ interaction. The results showed that all co...
PMC10115883
Expectation analyses
The three-way mixed-design ANOVA that was performed on the expectation ratings showed a significant main effect for ‘color’ (As only the main effect of ‘color’ and the ‘color’ x ‘block’ interaction effect were significant, the post-hoc tests were carried out without the modality division. The results for the first expe...
PMC10115883
Secondary analyses
pain, ’
REGRESSION
Due to the non-significant ‘color’ x ‘modality’ interaction, the correlation and regression analyses were carried out without the division into modalities. Correlation analyses revealed that expectation ratings from the first expectation block were correlated with pain ratings for the following colors: blue (The post-s...
PMC10115883
Discussion
chronic pain, white reduced pain, pain
CHRONIC PAIN
This study aimed to examine the influence of pain modality, either thermal or electrical, on the effect of colors on pain perception. Consistent with previous researchPain intensity and pain expectations were highest for red, despite the pain modality. Furthermore, our data revealed that white reduced pain the most com...
PMC10115883
Material and methods
POLAND
The study protocol was approved by the ethics committee at the Institute of Psychology, Jagiellonian University, Cracow, Poland (KE/25_2021) and was preregistered in the Open Science Framework [osf.io/xrznm]. All methods were carried out in accordance with the Declaration of Helsinki.
PMC10115883
Participants
alcohol abuse, abnormal color vision, pain
DISORDERS
A total of 124 healthy participants aged 18 to 35 years were initially recruited through advertisements on social media and job portals, and by word of mouth. The exclusion criteria were previous participation in pain experiments; being a student (3 years or more) or graduate of psychology, cognitive science, or a medi...
PMC10115883
Sample size
The sample size calculation was conducted using G*Power 3.1 software
PMC10115883
Stimuli and measures
NRS, Pain, pain
When carrying out an experiment focused on color, significant elements are the participants’ color perception and the screen which displays the colors. The former was assessed via the Ishihara test during the screening phaseTo measure the effect of colors on pain perception, we used 6 different color hues: red (RGB (25...
PMC10115883
Experimental design
The experiment was based on a between-subject, repeated-measures design with between-factor modality (electrical, thermal) and within-factor color (black, blue, green, grey, orange, pink, red, white, yellow). Eligible participants were invited to an experimental session and randomly assigned to either the electrical or...
PMC10115883
Calibration
pain
Tactile threshold, pain threshold, and pain intensity were assessed during calibration. Participants in the electrical group received stimuli in steps of 1 mA per 5 s, starting from 0 mA. In the thermal group, stimuli were delivered in steps of 0.5 °C per 5 s, the baseline temperature was set at 32 °C and the first app...
PMC10115883
Main task
pain
The main task consisted of ten blocks: two pain baseline blocks, two expectation color blocks, and six pain color blocks (see the flow of the task in Fig. Study design. The study involved two groups that differed in the modality of pain applied: thermal or electrical. Part (After finishing the main task, participants w...
PMC10115883
Statistical analysis
’, handedness, pain
REGRESSION
First, descriptive statistics were calculated for age and body mass index (BMI), as well as the distribution of sex, education, job situation, and handedness. This was followed by analyses of the differences between the groups (electrical and thermal), calculated using the Student’s Then, the variables of interest were...
PMC10115883
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-023-33313-w.
PMC10115883
Author contributions
All authors discussed the results and commented on the manuscript. K.W.K. conceptualized and designed the study, collected and analyzed the data, and wrote the manuscript; J.B. designed the study, analyzed the data and wrote the manuscript; H.B. designed the study and wrote the manuscript; P.B. designed the study, supe...
PMC10115883