title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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Efficacy | DISEASE | After enrollment of 27 and 25 patients in cohort 1 and cohort 2, respectively, considering that the primary study endpoint had been met for both cohorts, (cohort 1 with 18 responders and cohort 2 with 10 responders). By intention-to-treat analysis, of the 52 patients in the original cohort (i.e., before the protocol am... | PMC10425437 | |
Survival | LIVER METASTASIS | In cohort 1, 34 (85.0%) of 40 patients had discontinued the treatment by the cutoff date, and 6 (15.0%) patients remained on treatment (Fig. In cohort 2, 31 (97%) of the 32 patients had dropped out, and 1 (3%) was still on treatment (Fig. Exploratory subgroup analysis of the full analysis set for cohorts 1 and 2 showed... | PMC10425437 | |
Safety | hyperplasia, thrombocytopenia, myocarditis, rash, nasopharyngeal necrosis, necrosis, hypertension, hand and foot syndrome | PATHOLOGY, HYPERPLASIA, ADVERSE EVENTS, THROMBOCYTOPENIA, MYOCARDITIS, HAND-FOOT SYNDROME, NECROSIS, EVENTS, HYPERTENSION | In the safety set, dose reductions occurred in 49 (68.1%) of 72 patients for apatinib, of whom 39 (79.6%) patients required only one level of dose reduction and 17 (34.7%) patients had two levels of dose reduction. Treatment-related adverse events led to dose interruptions of apatinib in 49 (68.1%) of 72 patients, and ... | PMC10425437 |
B cells and tertiary lymphatic structure found in the tumors of responders in cohort 1 | tumor | TUMOR | To gain insight into the mechanisms of therapeutic responses as well as biomarkers of response and resistance, longitudinal tumor samples, including baseline (before combination therapy) and relapse, were taken in the context of therapy, and molecular and immune profiling was performed (Supplementary Fig. | PMC10425437 |
Angiogenesis and blood vessel density are predictive of clinical response to camrelizumab plus apatinib in cohort 2 | NASOPHARYNGEAL CARCINOMA | Given that the response rate of camrelizumab plus apatinib in cohort 2 (PD-1 inhibitor-resistant) was much lower compared with cohort 1 (PD-1 inhibitor-naive), suggesting that there is significant heterogeneity among patients in these cohorts, possibly due to variances in immune microenvironments and vascular density. ... | PMC10425437 | |
Evolution of tumor immune contexture at relapse | SECONDARY | We interrogated the TME dynamic changes of camrelizumab plus apatinib in treated patients developing secondary treatment resistance. 11 paired samples were collected at baseline and after relapse (responder | PMC10425437 | |
Discussion | tumor, neutropenia, fatigue, leukopenia, proteinuria, tumors, hand and foot syndrome | TUMOR, NEUTROPENIA, LEUKOPENIA, ADVERSE EVENTS, DISEASE, SOLID TUMORS, MALIGNANCIES, HYPOTHYROIDISM, TUMORS | The combination of immune checkpoint inhibitors with anti-angiogenesis drugs has previously shown synergistic efficacy in patients with several types of solid tumorsDespite of a high proportion of patients with RM-NPC can achieve a response with GP plus toripalimab or camrelizumab regimens during first-line treatmentTh... | PMC10425437 |
Methods | PMC10425437 | |||
Study design and participants | tumor, bleeding, cancer, Tumors, necrosis, autoimmune disease, Cancer | TUMOR, BLEEDING, LIVER METASTASES, CANCER, METASTATIC DISEASE, TUMORS, NECROSIS, ONCOLOGY, EVENTS, AUTOIMMUNE DISEASE, CANCER | This singlearm, openlabel, phase 2 trial was done at a single cancer center in Guangzhou, China. The same inclusion criteria would be applied to both cohorts, but the patient selection criteria differed: cohort 1 included patients with platinum-resistant RM-NPC without received immune checkpoint inhibitors for recurr... | PMC10425437 |
Procedures | tumor, Tumor, Cancer | ADVERSE EVENT, TUMOR, TUMOR, ADVERSE EVENTS, ADVERSE EVENT, CANCER | Patients in cohort 1 received intravenous camrelizumab 200 mg every 3 weeks plus oral apatinib 250 mg daily, and patients in cohort 2 received apatinib monotherapy in the first two weeks to modify the immune-resistant microenvironment, and then they were administered camrelizumab plus apatinib. The doses were chosen on... | PMC10425437 |
Outcomes | death | DISEASE PROGRESSION, DISEASE, DISEASE | The primary endpoint was the proportion of patients achieving an objective response according to RECIST version 1.1, which included patients with measurable disease who had a complete or partial response. Secondary endpoints were progression-free survival, duration of response, proportion of disease control, and safety... | PMC10425437 |
Statistical analysis | We used Simon’s two-stage design. For cohort 1, the previously reported data indicated that the objective response of PD-1 monotherapy in platinum-resistant NPC was about 25%For cohort 2, although the previously reported data indicated that the response rate of apatinib monotherapy in platinum-resistant NPC was about 3... | PMC10425437 | ||
Tumor sample collection and preparation | tumor | TUMOR | Fresh tumor biopsies were retrieved from NPC patients and divided into two parts on the premise of informed consent. One part of tumor biopsies was immediately put into liquid nitrogen for rapid freezing for subsequent RNA sequencing; the other part was embedded in paraffin and sectioned for immunohistochemical stainin... | PMC10425437 |
RNA extraction and RNA sequence | tumor | TUMOR | Total RNA was extracted from snap-frozen tumor specimens. RNA purity was checked using the NanoPhotometer ® spectrophotometer (IMPLEN, CA, USA). RNA integrity was assessed using the RNA Nano 6000 Assay Kit of the Bioanalyzer 2100 system (Agilent Technologies, CA, USA). 1 µg RNA per sample was used as input material for... | PMC10425437 |
RNA-seq data processing and quality check | Raw data (raw reads) of fastq format were firstly processed through in-house perl scripts. At the same time, Q20, Q30, and GC content the clean data were calculated. All the downstream analyses were based on the clean data with high quality. Reference genome and gene model annotation files were downloaded from genome w... | PMC10425437 | ||
Gene expression quantification and normalization | featureCounts v1.5.0-p3 was used to count the reads numbers mapped to each gene. And then FPKM of each gene was calculated based on the length of the gene and reads count mapped to this gene. FPKM, expected number of Fragments Per Kilobase of transcript sequence per Millions base pairs sequenced, considers the effect o... | PMC10425437 | ||
Identification of DEGs | Differential expression analysis of two conditions/groups (two biological replicates per condition) was performed using the DESeq2 R package (1.16.1). DESeq2 provide statistical routines for determining differential expression in digital gene expression data using a model based on the negative binomial distribution. Th... | PMC10425437 | ||
Deconvolution of the cellular composition with MCP-counter | The R package software MCP-counter was applied to the normalized log | PMC10425437 | ||
Pathway enrichment analyses | The network-based pathway enrichment analysis was performed using DEGs across responder and non-responder groups in the bulk-tissue RNA-seq data. In the bulk-tissue, the differentially expressed genes that had a | PMC10425437 | ||
Immunohistochemistry and multiplex immunohistochemical staining | tumor | TUMOR, AMPLIFICATION, SECONDARY | A retrospective study was performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissues of NPC and metastatic liver, lung and lymph gland. Multiplex immunohistochemical staining was performed as follow steps, 4 μm sections from full FFPE blocks of tumor tissues were sectioned, dewaxed, and fixed with 10% neutrali... | PMC10425437 |
TLS quantification | tumor | TUMOR | TLSs were qualified and quantified using both H&E and CD19 + CD3+ IHC staining. Structures were identified as aggregates of lymphocytes having histological features with analogous structures to that appearing in the tumor area. For the current study, criteria used for the quantification of TLS is mean area. | PMC10425437 |
Reporting summary | Further information on research design is available in the | PMC10425437 | ||
Supplementary information |
Supplementary InformationPeer Review FileDescription of Additional Supplementary FilesSupplementary Data 1Supplementary Data 2Supplementary Data 3Supplementary Data 4Supplementary Data 5Supplementary Data 6Reporting Summary | PMC10425437 | ||
Supplementary information | The online version contains supplementary material available at 10.1038/s41467-023-40402-x. | PMC10425437 | ||
Acknowledgements | This study was funded by grants from the National Key Research and Development Program of China (2022YFC2505800, L.Q.T.; 2022YFC2705005, H.Q.M.), National Natural Science Foundation of China (82173287, H.Q.M. and 82073003, L.Q.T.), Guangdong Basic and Applied Basic Research Foundation (2021B1515230002, H.Q.M.). The fun... | PMC10425437 | ||
Author contributions | Conception and design: H.Q.M., L.Q.T., L.Y., and Q.Y.C. designed the study. Provision of study materials or patients: L.Y., G.D.J., X.F.L., S.Y.X., S.S.G., D.F. L., L.T.L., D.H.L., Y.F.L, S.W.D., L.G., M.S.Z., X.Y.C., S.L.L., X.S.S., X.Y.L., S.C.L., Q.Y.C., L.Q.T., and H.Q.M. Data analysis and interpretation: L.Y., G.D... | PMC10425437 | ||
Peer review | PMC10425437 | |||
Data availability | The trial protocol is available as Supplementary Note The raw sequencing data can be accessed through GSA under the accession code Source data are provided with this paper. The remaining data are available within the Article, Supplementary Information, and Source Data. | PMC10425437 | ||
Code availability | No novel code/algorithm were used in this study. All code used in this study for different expression genes, GO and KEGG enrichment, MCP–counter, and gene set variation analysis (GSVA) is available from the corresponding author upon request. | PMC10425437 | ||
Competing interests | The authors declare no competing interests. | PMC10425437 | ||
References | PMC10425437 | |||
Methods | 10,495 children admitted to 18 paediatric intensive care units (ICUs) in the United Kingdom participated in a stepped-wedge, cluster randomised controlled trial, with 1955 clinical staff trained to deliver the intervention. The intervention comprised assessment and optimisation of sedation levels, and bedside screening... | PMC10681213 | ||
Results | The intervention led to a reduced duration of IMV (adjusted median difference– 7.1 hours, 95% CI -9.6 to -5.3, | PMC10681213 | ||
Conclusions | The SANDWICH trial showed a significant, although small, reduction in duration of IMV. Findings suggest that greater direction in decision-making pathways, robust embedment of new practice in unit routine, and capitalising on the skills of Advanced Nurse Practitioners and physiotherapists would have contributed to grea... | PMC10681213 | ||
Trial registration | isrctn.org Identifier: | PMC10681213 | ||
Data Availability | Owing to the data being sensitive, the minimal dataset is available via restricted access. Data is embargoed until 1 November 2025. Thereafter, it is available via restricted access conditions. To request access after the embargo period, please contact the Research Data Management (RDM) Team at Queen’s University Belfa... | PMC10681213 | ||
Introduction | critically ill | CRITICALLY ILL | This paper reports the findings of a process evaluation conducted alongside a pragmatic clinical trial that evaluated a behaviour-change intervention designed to expedite liberation from mechanical ventilation for critically ill children in the intensive care unit (ICU). The intervention was complex including several i... | PMC10681213 |
The sedation and weaning in children (SANDWICH) trial | The | PMC10681213 | ||
SANDWICH and usual care. | COMFORT is the name of the tool used to assess sedation and comfort of infants and children in paediatric intensive care. A full description of the intervention using the TIDieR checklist is available [The stepped wedge trial had 22 time periods; each period duration was four weeks. All participating ICUs started in th... | PMC10681213 | ||
The SANDWICH trial schematic. | The process evaluation was conducted to aid understanding of delivery of the intervention. The Medical Research Council (MRC) guidance on process evaluations [ | PMC10681213 | ||
Methods | PMC10681213 | |||
Aim and objectives | The aim of the study was to determine how the processes involved in intervention delivery affected the outcome of the trial. The objectives were to determine the fidelity, dose and reach of the intervention, and the factors and processes involved in delivery of the intervention. | PMC10681213 | ||
Design | This was a process evaluation using mixed methods. We developed a logic model for the SANDWICH intervention, based on our earlier Cochrane review [ | PMC10681213 | ||
SANDWICH logic model. | Adapted from Blackwood et al., 2022 [ | PMC10681213 | ||
Data collection and analysis | PMC10681213 | |||
Quantitative data collection | CRF | RECRUITMENT, CRF | Data collected to determine the fidelity, dose and reach of the intervention included:Daily adherence to conducting the intervention components (multidisciplinary ward round; COMFORT assessment; screening for readiness for a spontaneous breathing trial; undertaking an SBT when screening criteria were met)Numbers of sta... | PMC10681213 |
Quantitative data analysis | death | EVENT, RECRUITMENT | Adherence was measured by the proportion of each intervention component performed and captured daily; the number of staff trained; and intervention reach (admissions screened divided by IMV admissions during the trial period). Due to sequential recruitment of clusters over time, we did not measure adherence over time, ... | PMC10681213 |
Qualitative data collection | JJ, PIS | RECRUITMENT | A senior ethnographer (JJ), who was not involved in the clinical trial, visited participating sites to undertake face-to-face individual and focus group interviews. All clinical staff involved in delivering the intervention were eligible for interviews. Recruitment entailed an initial email from the researcher comprisi... | PMC10681213 |
Qualitative data analysis | Data were analysed deductively and inductively. Deductively, the four components of the intervention and associated processes were used as a ‘point of entry’ into data. Inductively, Braun and Clarke’s thematic content analysis framework [ | PMC10681213 | ||
Findings | RECRUITMENT | The patient recruitment period in the clinical trial was from February 2018 to October 2019 and last patient follow up was November 2019. The recruitment period for the process evaluation was from February 2018 to March 2020.In total, 10,495 admissions to 18 paediatric ICUs were analysed. Findings for all ventilated ch... | PMC10681213 | |
Fidelity, dose and reach of the SANDWICH intervention | Across the paediatric ICUs, the intervention reached a high proportion of patients (median 82%, IQR 77%, 89%). The median (IQR) of percentage adherence to the intervention components across the paediatric ICUs was highest for setting targets on the ward round (ventilation, 90% [QR 81, 96]; sedation, 85% [IQR 63, 89]) a... | PMC10681213 | ||
Interview participants | In total, 1,955 staff from 18 paediatric ICUs were trained in the intervention and 193 of these staff participated in end of trial interviews. They included 112 nurses (bedside, senior clinical management, and advanced nurse practitioners); 42 medical staff (medical trainees and consultant intensivists); 14 allied heal... | PMC10681213 | ||
Factors and processes involved in delivery of the intervention | Supporting quotes for the following analysis are presented in | PMC10681213 | ||
Training promotes understanding and skill set | Overall, the training was considered integral to staff understanding of the purpose and content of the intervention and the effective discharge of their respective roles and responsibilities. Training was regularly discussed as time-consuming, particularly the online component. Face-to-face training was considered more... | PMC10681213 | ||
Ease and flexibility of use | PMC10681213 | |||
Intervention acceptability | The intervention was consistently validated as technically straightforward to use and accommodate within routines of care. Although bedside nurses were aware of increased documentation, overall, they endorsed the ease and flexibility with which COMFORT scoring and SBT readiness screening could be undertaken. That the i... | PMC10681213 | ||
Stasis in the absence of explicit direction | Although the intervention’s strategic flexibility was widely endorsed, it was also discussed as inadvertently working against optimal intervention delivery. Three main issues were identified. First, the flexibility inherent in the COMFORT assessment, which was categorised into a range of scores indicating sedation ‘sta... | PMC10681213 | ||
Discussion | PMC10681213 | |||
Summary of findings | The trial met its primary outcome, achieving a significant (if small) reduction in time to successful ventilator liberation. Although the intervention reached a high proportion of patients, delivery did not always encompass all components that were deemed necessary in progression towards extubation. This may explain th... | PMC10681213 | ||
Implications of the evidence for trial theory | An extensive body of research demonstrates the benefits of staff training in promoting effective delivery of novel ICU interventions [Our theory prioritised intervention ease and flexibility of use, an approach consistent with the ICU literature showing the benefits of ready integration within unit routines [Developmen... | PMC10681213 | ||
Study strengths and limitations | We followed recommended guidance and tailored the process evaluation to the trial, the intervention and the outcomes studied [The MRC Guidance on the conduct of process evaluations recommends the use of theory as a means of testing and refinement [ | PMC10681213 | ||
Implications for future research | Future research should examine sustainability of the intervention in participating sites. This may shed light on the active components that were deemed by clinicians to be the most effective. | PMC10681213 | ||
Conclusion | The SANDWICH trial showed a significant, albeit small, reduction in duration of IMV for children. The process evaluation showed that the intervention’s ease of use and flexibility facilitated its adoption. Provision of a common language, designated bedside nursing involvement, and clear pathways for clinical decision-m... | PMC10681213 | ||
Supporting information | PMC10681213 | |||
SANDWICH implementation. | (DOCX)Click here for additional data file. | PMC10681213 | ||
Standards for Reporting Qualitative Research (SRQR) checklist. | (DOCX)Click here for additional data file. | PMC10681213 | ||
Process of theme development (following Braun & Clarke, 2006). | (DOCX)Click here for additional data file. | PMC10681213 | ||
Supporting quotes. | (DOCX)Click here for additional data file. | PMC10681213 | ||
References | (DOCX)Click here for additional data file.We thank the SANDWICH ICU staff champions who organised and supported the process evaluation site visits and the staff who gave of their time to participate in the interviews. We thank Ms. Margaret McKillen for transcribing the interviews. | PMC10681213 | ||
Background | COMPLICATIONS | Numerous factors are likely to result in poor treatment adherence, which is one of the important factors contributing to increased complications and the low efficacy of hemodialysis (HD), particularly inadequate knowledge of patients. This study aimed to compare the effects of a mobile health (mHealth) app (the Di Care... | PMC10308810 | |
Methods | HD, TG, weight gain | This single-blinded, two-stage/two-group randomized clinical trial was fulfilled in 2021-22 in Iran. Seventy HD patients were recruited, using the convenience sampling method, and were then randomized into two groups: mHealth (n = 35) and face-to-face training (n = 35). The patients in both groups received the same e... | PMC10308810 | |
Results | TG | Prior to the intervention, the mean IDWG and the K, P, TC, TG, AL, and FER levels, were not significantly different in both groups ( | PMC10308810 | |
Conclusions | The Di Care app use and the face-to-face training could improve dietary and fluid intake adherence in patients. However, mHealth could have more effect on the laboratory parameters than face-to-face training, largely reducing the IDWG. | PMC10308810 | ||
Trial registration | This study was registered in the Iranian Registry of Clinical Trials (No. ID IRCT20171216037895N5). | PMC10308810 | ||
Keywords | PMC10308810 | |||
Background | death, ESKD, kidney disease, CRF, ESRD | KIDNEY DISEASE, CRF, CHRONIC RENAL FAILURE, ESRD, COMPLICATIONS | Chronic renal failure (CRF) has been declared the 12th leading cause of death worldwide [When CRF progresses and patients reach the end stage of kidney disease (ESKD), renal replacement therapy (RRT), including hemodialysis (HD) as the most common treatment modality [However, adequate healthcare services are rarely del... | PMC10308810 |
Methods | PMC10308810 | |||
Design | This study was part of a single-blind, two-stage/two-group randomized clinical trial fulfilled in 2021-22 in one of the main HD centers in Isfahan, Iran, and registered in the Iranian Registry of Clinical Trials (No. ID IRCT20171216037895N5, Date: 28/04/2021). Before designing this study, a structural search was done a... | PMC10308810 | ||
Participants and sample size | HD | HEART FAILURE, CHRONIC DISEASES, DISORDERS | The sample size was calculated with 95% confidence interval and 80% test power, based on the standard deviation (SD) of treatment adherence to 4.9, obtained from the previous similar study [Then, considering the 10% sample loss in each group, 35 individuals were calculated. The inclusion criteria were the patients’ wil... | PMC10308810 |
Data collection | HD, TG, ® | To evaluate the effects of the interventions on treatment adherence among HD patients, the mean IDWG and the laboratory parameters were measured. One week before the intervention, the mean IDWG was recorded using the Seca 676 medical scale. To evaluate the reliability of the scale before recording the patients’ weight,... | PMC10308810 | |
Intervention | TG | In the mHealth group, the patients utilized a researcher-made mobile-based app on the Android platform. This app is being registered under the Di Care trademark in the Intellectual Property Center of the Islamic Republic of Iran, whose main language was Persian. Before designing the app, patients’ needs and other simil... | PMC10308810 | |
Data analysis | The data were analyzed using the SPSS Statistics software (ver. 16) via Kolmogorov-Smirnov test to checking normality, descriptive statistics (i.e., mean, SD, frequency, and percentage), and analytical tests (that is, independent-samples | PMC10308810 | ||
Results | PMC10308810 | |||
Secondary outcomes | And | According to the criteria for poor treatment adherence based on the laboratory values and IDWG mentioned in Table Of note, only 5.71% of the patients in the mHealth group had high serum K levels before the intervention, which reached zero after it (The serum TC level before the intervention in 54.28% of the patients ... | PMC10308810 | |
Discussion | HD, TG | This study aimed to compare the effects of the mHealth app use and face-to-face training on the clinical and laboratory parameters of dietary and fluid intake adherence in HD patients. This study showed that the mean IDWG in 48.57% of the patients was higher than 5.7% of their dry weight. The rate of fluid intake non-a... | PMC10308810 | |
Limitation | TG | The minimum version of the Android operating system was not considered as inclusion criteria and it caused some problems in sampling. Moreover, the performance of the app was different in a few smartphone brands, models, and versions of the operating system. Therefore, some features of the app, especially medication re... | PMC10308810 | |
Authors’ contributions | MTK: The study conception and design, study execution, data extraction and interpretation, and preparation of the initial draft of manuscript; ZF: study conception and design, study search, data analysis and interpretation, and critical revision of the manuscript; SAS: study search, data interpretation, and critical re... | PMC10308810 | ||
Funding | This study is funded by Aja University of Medical Sciences. Funding will be allocated after the article is published (Funding ID is 1400.006). | PMC10308810 | ||
Data Availability | The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request. | PMC10308810 | ||
Declarations | PMC10308810 | |||
Ethics approval and consent to participate | This study was approved by the Research Ethics Committee of Aja University of Medical Sciences, Tehran, Iran (ID: IR.AJAUMS.REC.1400.006). Written informed consent was obtained from all subjects after receiving an explanation of the study. All the ethical provisions of the Declaration of Helsinki for human samples were... | PMC10308810 | ||
Consent for publication | Not applicable. | PMC10308810 | ||
Competing interests | The authors declare that they have no competing interests. | PMC10308810 | ||
Abbreviations | kidney diseaserenal | RENAL DISEASE | hemodialysismobile healthinterdialytic weight gainpotassiumphosphorustotal cholesteroltriglyceridealbuminferritinchronic renal failureglomerular filtration rateend stage of kidney diseaserenal replacement therapyshort message servicetelephone follow-upIranian Registry of Clinical Trialsstandard deviationend stage renal... | PMC10308810 |
References | PMC10308810 | |||
1. Introduction | trunk muscle fatigue, LBP, thoracolumbar, fatigue, pain, muscle fatigue, Deep trunk muscles | CONTRACTION, CREST | Natural rubber is considered an economic plant in Thailand and is used to manufacture many products. Foam back pillows have proven to have various benefits for the lower back. However, no study has compared the effects of foam and rubber pillows. Therefore, the current study aimed to compare the efficacy of foam and ru... | PMC9964691 |
2. Materials and Methods | PMC9964691 | |||
2.1. Ethics Statement | Pain | This randomized crossover study was conducted at the Research Center in the Back, Neck, Other Joint Pain, and Human Performance (BNOJPH) laboratory at Khon Kaen University. The Khon Kaen University Ethics Committee (HE 632261, Khon Kaen, Thailand, 17 December 2020) approved the current study. | PMC9964691 | |
2.2. Study Population Recruitment | low LBP | Between January 2021 and April 2021, 30 healthy participants were recruited via social media advertisements. The inclusion criteria were as follows: (i) without low LBP for at least the previous six months [ | PMC9964691 | |
2.3. Procedure | trunk muscle fatigue | A screening process was used to determine participants’ eligibility for the study, and demographic data were recorded through direct interviews. Thirty healthy participants were asked to sign informed consent forms before participating. Participants who met the inclusion criteria were then asked to visit the research l... | PMC9964691 |
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