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Conclusions
SARCOMA
Overall, MASCT-I plus camrelizumab and apatinib was safe and showed encouraging efficacy in advanced bone and soft-tissue sarcoma, and schedule-II administration method was recommended.
PMC10687909
Trial registration
ClinicalTrials.gov, NCT04074564.
PMC10687909
Supplementary Information
The online version contains supplementary material available at 10.1186/s12916-023-03132-x.
PMC10687909
Keywords
PMC10687909
Background
cancers, tumor, bone sarcomas, chemotherapy-refractory, undifferentiated pleomorphic sarcoma, cancer, cancers of bone and soft tissue, soft-tissue sarcoma, Sarcomas, soft-tissue sarcomas
CANCERS, TUMOR, BONE SARCOMAS, CANCER, SOLID TUMORS, UNDIFFERENTIATED PLEOMORPHIC SARCOMA, SARCOMAS, DEDIFFERENTIATED LIPOSARCOMA
Sarcomas are a rare and heterogeneous group of cancers of bone and soft tissue that originate from mesenchymal cells [Immune checkpoint inhibitors (ICIs) have demonstrated remarkable clinical outcomes in many chemotherapy-refractory solid cancers. But ICI monotherapy only showed promising anti-tumor activity in certain...
PMC10687909
Methods
PMC10687909
Study design and patients
hepatitis B, death, Tumors, clear cell sarcoma, human immunodeficiency virus, 14–70, autoimmune diseases or syndrome, ASPS
DISORDER, ACTIVE TUBERCULOSIS, ALVEOLAR SOFT PART SARCOMA, HEPATITIS B, HUMAN IMMUNODEFICIENCY VIRUS, SARCOMAS, BRAIN METASTASES, RECRUITMENT, TUMORS, SARCOMA, CLEAR CELL SARCOMA, HEPATITIS C, ONCOLOGY, SOFT TISSUE AND BONE TUMOR, SYPHILIS INFECTION, METASTASES, BONE METASTASES
MASCT-I-1005 was a single-center, open-label, 2-part, phase 1 trial (clinicaltrials.gov, NCT04074564). Part A assessed the safety and efficacy of two administration schedules for MASCT-I when combined with camrelizumab and apatinib at fixed doses in patients with advanced bone and soft-tissue sarcomas, and part B furth...
PMC10687909
Preparation for MASCT-I
tumor
TUMOR
MASCT-I cells were manufactured by HRYZ Biotech Co. in a Good Manufacturing Practice grade facility according to the manufacturing protocol as previously described with some modifications [For dendritic cell preparation, PBMCs were thawed and incubated in a culture flask (Corning) at 37 °C, 5% COTo prepare tumor antige...
PMC10687909
Treatments
toxicity, death
DISEASE PROGRESSION
Eligible patients were randomly assigned (1:1) to 2 groups based on different administration schedules of MASCT-I in the first course, by the randomization specialist of Shanghai Canming Medical Technology Co., Ltd, using a central block randomization method. One MASCT-I course consisted of 3 DC subcutaneous injections...
PMC10687909
Outcomes and assessments
tumor, soft-tissue sarcoma, death, Cancer
ADVERSE EVENT, TUMOR, ADVERSE EVENTS, SECONDARY, CANCER
The primary endpoint was safety of MASCT-I in combination with camrelizumab plus apatinib in patients with advanced bone and soft-tissue sarcoma. The secondary endpoints included ORR, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and immune response.Safety assessments, including mo...
PMC10687909
Statistical analysis
Due to the exploratory nature of this phase 1 study, sample sizes of the 2 parts were not determined on the basis of statistical hypotheses. For part A reported here, a total of 20 patients were planned.Safety analyses were done in patients who received study treatment and had at least one record of safety assessment. ...
PMC10687909
Results
PMC10687909
Clinical efficacy
Tumor, soft-tissue sarcomas
TUMOR
In the intention-to-treat population, 6 of 19 patients achieved confirmed partial responses with MASCT-I plus camrelizumab and apatinib, resulting an ORR of 31.6% (95% CI, 12.6–56.6). The DCR was 68.4% (95% CI, 43.5–87.4). In total, 13 of 19 (68.4%) patients showed a decrease from baseline in the size of target lesions...
PMC10687909
Immune response
Of the 19 patients, 14 (73.7%) had an immune response, while the other 5 (26.3%) did not during the treated courses (Additional file Fig. S
PMC10687909
Discussion
diarrhea, soft-tissue sarcomas, sarcomas, proteinuria, anemia, rash, sarcoma, lung vein embolism, deaths, hypertension, TRAEs
HYPERCHOLESTEROLEMIA, PNEUMOTHORAX, INTERSTITIAL PNEUMONIA, SARCOMAS, DISEASE, EVENTS, ANEMIA, SARCOMA, HYPERTRIGLYCERIDEMIA, HYPOTHYROIDISM, HYPERTENSION, PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME
Patients with unresectable recurrent or metastatic bone and soft-tissue sarcoma have limited treatment options after failure of chemotherapy. Although monotherapy with angiogenesis-targeted TKI or ICI has been developed, the outcomes are far from satisfactory. In this study, we adopted intensive immunotherapy-antiangio...
PMC10687909
Conclusions
Overall, MASCT-I plus camrelizumab and apatinib had acceptable safety profile and promising efficacy in patients with unresectable recurrent or metastatic bone and soft-tissue sarcoma. After comprehensive consideration of efficacy and safety, schedule-II administration method was recommended. Our study displayed more f...
PMC10687909
Acknowledgements
The study was sponsored by HRYZ Biotech Co. We are grateful to the patients and their families as well as the investigators and personnel for their contribution in this study. We also thank Shanghai Canming Medical Technology Co., Ltd, for statistical analyses.
PMC10687909
Authors’ contributions
YZ: conceptualization, data curation, supervision, funding acquisition, investigation, methodology, writing—original draft, project administration, writing—review and editing. ML: conceptualization, data curation, investigation, writing—original draft, writing—review and editing. BZ, CY, YW1, SZ, LT, CZ, GQ, YH, WY, HL...
PMC10687909
Funding
The study was sponsored by HRYZ Biotech Co and supported by the National Natural Science Foundation of China (grant number: 82072967, 82102866), Shanghai Pujiang Program (NO. 21PJD051), and Science Foundation of Shanghai Sixth People’s Hospital (NO. ynqn202114).
PMC10687909
Availability of data and materials
The data generated in this study are available within the article and its Supplementary Data Files or from the corresponding author 24 months after study completion upon reasonable request.
PMC10687909
Declarations
PMC10687909
Ethics approval and consent to participate
The study was done in accordance with the Declaration of Helsinki and the Good Clinical Practice guidelines. The protocol and all amendments were approved by the Ethics Committee of Shanghai Sixth People’s Hospital (approval number: 2019–086-(5)), and all patients provided written informed consent.
PMC10687909
Consent for publication
Not applicable.
PMC10687909
Competing interests
XL is an employee of HRYZ Biotech Co. All other co-authors declare no competing interests.
PMC10687909
References
PMC10687909
Key Points
PMC10018327
Question
Does losing sleep affect health-related quality of life in children?
PMC10018327
Findings
SECONDARY
In this secondary analysis of a randomized crossover trial involving 100 healthy children aged 8 to 12 years, receiving 39 minutes less sleep per night resulted in significantly lower physical and overall well-being, ability to cope well at school, and total health-related quality of life, especially in children with a...
PMC10018327
Meaning
SECONDARY
Findings of this secondary analysis of a randomized clinical trial indicate that ensuring children receive sufficient good-quality sleep is an important child health issue.
PMC10018327
Importance
LITTLE
Little is known regarding the effect of poor sleep on health-related quality of life (HRQOL) in healthy children.
PMC10018327
Objective
To determine the effect of induced mild sleep deprivation on HRQOL in children without major sleep issues.
PMC10018327
Design, Setting, and Participants
SECONDARY, -11
This prespecified secondary analysis focused on HRQOL, a secondary outcome of the Daily Rest, Eating, and Activity Monitoring (DREAM) randomized crossover trial of children who underwent alternating weeks of sleep restriction and sleep extension and a 1-week washout in between. The DREAM trial intervention was administ...
PMC10018327
Interventions
Bedtimes were manipulated to be 1 hour later (sleep restriction) and 1 hour earlier (sleep extension) than usual for 1 week each. Wake times were unchanged.
PMC10018327
Main Outcomes and Measures
Sleep Disturbance
All outcome measures were assessed during both intervention weeks. Sleep timing and duration were assessed using 7-night actigraphy. Children and parents rated the child’s sleep disturbances (night) and impairment (day) using the 8-item Pediatric Sleep Disturbance and 8-item Sleep-Related Impairment scales of the Patie...
PMC10018327
Results
sleep disturbance, −0.21
The final sample comprised 100 children (52 girls [52%]; mean [SD] age, 10.3 [1.4] years). During the sleep restriction week, children went to sleep 64 (95% CI, 58-70) minutes later, and sleep offset (wake time) was 18 (95% CI, 13-24) minutes later, meaning that children received 39 (95% CI, 32-46) minutes less of tota...
PMC10018327
Conclusions and Relevance
SECONDARY
Results of this secondary analysis of the DREAM trial indicated that even 39 minutes less of sleep per night for 1 week significantly reduced several facets of HRQOL in children. This finding shows that ensuring children receive sufficient good-quality sleep is an important child health issue.
PMC10018327
Trial Registration
Australian New Zealand Clinical Trials Registry:
PMC10018327
Introduction
OBSTRUCTIVE SLEEP APNEA
While inadequate or poor-quality sleep has been associated with a wide range of adverse physical and psychological health outcomes in infants, children, and adolescents,To date, most research has examined the association of more medically related sleep issues, such as obstructive sleep apnea,To our knowledge, no experi...
PMC10018327
Methods
PMC10018327
Study Design
eating behaviors
The DREAM randomized crossover trial investigated how mild sleep deprivation influenced eating behaviors and activity patterns in children aged 8 to 12 years in the naturalistic home environment. Detailed information on this trial is provided in the protocol
PMC10018327
Participants
Healthy children were recruited by advertisement between October 2018 and March 2020 and were eligible to participate if they were aged 8 to 12 years; lived in the wider Dunedin area in New Zealand; had no underlying medical conditions or medications that could affect sleep; and scored 39 or lower, which indicated no m...
PMC10018327
Randomization and Masking
Children were randomized to the order in which they underwent sleep restriction and sleep extension weeks and were stratified by age group (8-10 years or 11-12 years) and sex (male or female). Randomization to order was generated by one of us (J.J.H., the study biostatistician) using random block lengths in Stata, vers...
PMC10018327
Procedures
To achieve mild sleep deprivation, children were asked to go to bed 1 hour earlier than usual for 1 week (sleep extension) and 1 hour later than usual for 1 week (sleep restriction), separated by a 1-week washout to allow sufficient time for children to return to their usual sleeping habits before the next intervention...
PMC10018327
Measures Collected at Baseline
Demographic data were obtained from the parent, including age, sex, and race and ethnicity of the child; presence of any siblings; and maternal educational level (the index used in New Zealand; and all participating parents or guardians identified as mothers). Area-level deprivation for a family was measured with the 2...
PMC10018327
Measures Collected During Each Intervention Week
Actigraphy data were collected for each child for the duration of each intervention week, as occurred at baseline. Questionnaire data were collected at the end of each intervention week (day 8) during an assessment session.Children also completed the 27-item KIDSCREEN questionnaire, which assessed HRQOL over the past w...
PMC10018327
Statistical Analysis
REGRESSION
All analyses were undertaken in Stata, version 17.0 (StataCorp LLC). Effects of mild sleep deprivation were estimated by mixed-effects regression models, with the child as a random effect. Mean differences and 95% CIs were determined for sleep restriction compared with sleep extension. Standardized mean differences (SM...
PMC10018327
Results
The
PMC10018327
CONSORT Flow Diagram
Sleep Disturbance
HRQOL indicates health-related quality of life; SDSC, Sleep Disturbance Scale for Children.
PMC10018327
Effect of Restricting and Extending Sleep on Health-Related Quality of Life (N = 100)
Calculated as sleep restriction compared with sleep extension.Effect sizes were standardized using a pooled SD.Scale ranged from 1 (never) to 5 (always) or 1 (not at all) to 5 (extremely), as appropriate.
PMC10018327
Discussion
SECONDARY
Results of this secondary analysis of the DREAM trial demonstrated that even relatively small reductions in nightly sleep duration can have a considerable effect on HRQOL in children. These children received 39 minutes less sleep per night between sleep conditions over only 1 week. This loss of sleep resulted in signif...
PMC10018327
Strengths and Limitations
SECONDARY
This study has several strengths. These strengths primarily centered on the randomized crossover trial design, wherein each child participant was able to act as their own control, with the sleep extension week providing the conditions for more sleep opportunity compared with the sleep restriction week that provided les...
PMC10018327
Conclusions
SECONDARY
In this secondary analysis of the DREAM randomized crossover trial of sleep manipulation, we showed that after only 1 week of receiving 39 minutes less sleep per night between sleep conditions, children reported significantly lower HRQOL in terms of their physical and overall well-being and ability to cope well at scho...
PMC10018327
References
Protocol Click here for additional data file. Data Sharing Statement Click here for additional data file.
PMC10018327
Objectives
To investigate rates of mpox beliefs, knowledge and intended behaviours in the general population and in gay, bisexual or other men who have sex with men (GBMSM), and factors associated with intended behaviours. To test the impact of motivational messages (vs a factual control) on intended behaviours.
PMC10583036
Design
Cross-sectional online survey including a nested randomised controlled trial.
PMC10583036
Setting
Data collected from 5 September 2022 to 6 October 2022.
PMC10583036
Participants
Participants were aged 18 years or over and lived in the UK (general population). In addition, GBMSM were male, and gay, bisexual or had sex with men. The general population sample was recruited through a market research company. GBMSM were recruited through a market research company, the dating app Grindr and targeted...
PMC10583036
Main outcome measures
Intention to self-isolate, seek medical help, stop all sexual contact, share details of recent sexual contacts and accept vaccination.
PMC10583036
Results
Sociodemographic characteristics differed by sample. There was no effect of very brief motivational messaging on behavioural intentions. Respondents from Grindr and Meta were more likely to intend to seek help immediately, completely stop sexual behaviour and be vaccinated or intend to be vaccinated, but being less lik...
PMC10583036
Conclusions
GBMSM were more likely to intend to enact protective behaviours, except for self-isolation. This may reflect targeted public health efforts and engagement with this group. Associations with socioeconomic factors suggest that providing financial support may encourage people to engage with protective behaviours.
PMC10583036
STRENGTHS AND LIMITATIONS OF THIS STUDY
A strength of this study is that it collected data from four large samples, including the general population and men who are gay, bisexual or have sex with men.Data collection occurred over a short period (5 September 2022 to 6 October 2022) during the mpox outbreak.Limitations include that responses may have been affe...
PMC10583036
Introduction
fever, rash, headache, blisters, aches
MONKEYPOX, PMT, VIRUS, MPOX
Mpox (also known as monkeypox) is an orthopox virus that causes fever, headache, exhaustion, swollen glands and aches (joint, muscle, back), followed by a rash with blisters.In the UK, people who thought they might have mpox were asked to call a sexual health clinic, to stay at home (self-isolate) and avoid close conta...
PMC10583036
Method
PMC10583036
Design
Online cross-sectional survey conducted by Savanta, a Market Research Society Company Partner. Data were collected between 5 September 2022 and 6 October 2022.
PMC10583036
Participants
RECRUITMENT
Eligibility criteria for the general population sample were living in the UK and being aged 18 years or over. For the GBMSM samples, additional criteria were being a man and identifying as being gay, bisexual or having sex with men.Recruitment for the general population sample used quota sampling, a standard opinion po...
PMC10583036
Study materials
Full study materials are in
PMC10583036
Outcome measures
blisters, rash
EMERGENCY, SMALLPOX
Self-isolation intention was measured using two items, asking participants to imagine that they were contacted by public health officials and told that they needed to self-isolate for 21 days because they had mpox, and because they had come into high-risk contact with a case. Responses were given on a five-point scale ...
PMC10583036
Motivational messaging
PMT
Very brief motivational messages were constructed based on components of the PMT.
PMC10583036
Psychological factors
We asked participants how much they had seen or heard about mpox, how worried they were about mpox, and how much risk they thought mpox posed to people in the UK and themselves personally. For these items, answers of ‘don’t know’ were coded as missing.Participants were also asked about their perceived susceptibility to...
PMC10583036
Sociodemographic characteristics
hepatitis A
CHRONIC ILLNESS, HEPATITIS A, SMALLPOX
Participants were asked to report their age, gender,We asked participants if they or a household member had a chronic illness, whether they were pregnant, had ever taken pre-exposure prophylaxis (PrEP) for HIV, and for their vaccination status for smallpox (in 2022 and before 2022), hepatitis A and COVID-19 (two doses ...
PMC10583036
Patient and public involvement
To ensure the research aims and study information were appropriate, members of the public were involved in the development of the funding application and survey materials. For the funding application, six people gave feedback on the initial proposal resulting in changes to aims of the study and terminology used. For th...
PMC10583036
Power
REGRESSION
A sample size of 3000 allows a 95% CI of plus or minus 1.8% for the prevalence estimate for a survey item with a prevalence of around 50% (sample size of 250 gives a 95% CI of plus or minus 6.2%; sample size of 1000 gives a 95% CI of plus or minus 3.1%).For multiple linear regression analyses, a sample of 830 allowed o...
PMC10583036
Analysis
chronic illness
SMALLPOX, CHRONIC ILLNESS, RECRUITMENT, REGRESSIONS, REGRESSION
Information about data preparation is reported in We tested whether sociodemographic characteristics of GBMSM samples were different depending on the recruitment method (Savanta, Grindr, Meta). Due to significant differences, further analyses were conducted in each sample separately.First, we tested the influence of m...
PMC10583036
Results
REGRESSION
Top-line results for all survey materials, by sample, are shown in For regression analyses, we report imputed values. Results using imputed values were compared with non-imputed data. There were no substantial differences in results with and without imputed values.
PMC10583036
Participant characteristics
RECRUITMENT
There were significant differences in participant characteristics by sampling method. Most notably, participants recruited from Grindr and Meta were more likely to be working, need to leave home for work, more highly educated, higher socioeconomic grade and have less financial hardship (Participant characteristics, by ...
PMC10583036
Motivational messaging
There was no effect of motivational messaging on outcomes, except for in the sample recruited from Meta (see
PMC10583036
Self-isolation
sampleA
REGRESSION
Rates of intended self-isolation were higher when imagining you were a case than a high-risk contact. Three-quarters of the general population sample intended to self-isolate for 21 days if they were to develop mpox (75.2%, 95% CI 73.7% to 76.7%, n=2294; Main behavioural outcomes, by sample*p≤0.001.†Answers of ‘don’t k...
PMC10583036
Help seeking
Approximately half of participants in the general population, Savanta GBMSM and Grindr samples indicated that they would seek help immediately (95% CI 49.2% to 53.3%; In the general population, intention to seek help immediately was associated with being older (aOR (adjusted Odds Ratio) 1.012, 95% CI 1.006 to 1.019, p<...
PMC10583036
Sexual contact behaviour when symptomatic
blisters, rash
REGRESSION
In the general population and Savanta GBMSM, 77.2% (95% CI 75.6% to 78.9%, n=1923) and 79.2% (73.7% to 84.6%, n=171) intended to completely stop sexual contact if they were to develop an unexplained rash with blisters and learn that they had come into contact with a mpox case (In the general population, intending to co...
PMC10583036
Sharing details of contacts
sampleA
REGRESSION
There was no difference in intention to share details of all sexual partners in the last 7 days between samples (In the general population sample, intention to share details of every sexual contact in the last 7 days was associated with being female, older, less financial hardship, higher perceived susceptibility to an...
PMC10583036
Vaccination
SMALLPOX
Few people had been vaccinated for smallpox in 2022 in the general population sample (5.3%, 95% CI 4.5% to 6.1%, n=162; In the general population, being vaccinated for smallpox in 2022 or intending to be vaccinated if offered a vaccine was associated with being older (aOR 1.015, 95% CI 1.007 to 1.023, p<0.001), more wo...
PMC10583036
Discussion
gonorrhoea reinfection
SMALLPOX, RECRUITMENT, INFLUENZA A H1N1, STIS, REINFECTED
We investigated mpox attitudes, beliefs and intended behaviours in a general population sample and three GBMSM samples. Samples differed by sociodemographic characteristics. This was reflected in intended behaviours, with GBMSM recruited from Grindr or Meta being more likely to intend to seek help immediately for mpox ...
PMC10583036
Supplementary Material
PMC10583036
Reviewer comments
PMC10583036
Data availability statement
Data are available in a public, open access repository. Anonymised data are available online.
PMC10583036
Ethics statements
PMC10583036
Patient consent for publication
Not applicable.
PMC10583036
Ethics approval
Ethical approval for this study was given by the King’s College London Psychiatry, Nursing and Midwifery Research Ethics Panel (reference number: LRS/DP-21/22-32287). Participants gave informed written consent before beginning survey materials.
PMC10583036
References
PMC10583036
Supplementary Information
COVID-19-related stress, familial COVID-19-related stress, AD, affective dysregulation
Analyzing COVID-19-related stress in children with affective dysregulation (AD) seems especially interesting, as these children typically show heightened reactivity to potential stressors and an increased use of maladaptive emotion regulation strategies. Children in out-of-home care often show similar characteristics t...
PMC9668221
Keywords
Open Access funding enabled and organized by Projekt DEAL.
PMC9668221
Introduction
COVID-19-related stress, AD, affective dysregulation
VIRUS
Following the first reported cases of COVID-19 in China in December 2019, the virus spread rapidly across the world (As a result of these measures, families were faced with persistent changes to their daily life. In accordance with these changes, empirical data suggest a negative effect of the COVID-19 crisis on the me...
PMC9668221
Methods
PMC9668221
Participants
AD [
The present sample comprised subsamples of the research consortium ADOPT (Affective Dysregulation—Optimizing Prevention and Treatment), which analyzes the effects of stepped care interventions in children with AD [
PMC9668221
Pre-pandemic recruitment
AD
Before the pandemic, three samples with AD (AD group,
PMC9668221
Pre-pandemic data collection
Data on potential risk and protective factors including sociodemographic characteristics, child characteristics, and caregiver characteristics were taken from the first in-depth assessment following the screening questionnaire, in which clinical, caregiver, and child report were used. In the No AD
PMC9668221
COVID-19 data collection
COVID-19-related stress
All families who participated in the intensive assessment following the screening questionnaire were asked to participate in the present study on COVID-19-related stress (
PMC9668221
Measures
PMC9668221
COVID-19-related stress
The
PMC9668221
Predictors of COVID-19-related stress
PMC9668221