title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
|---|---|---|---|---|
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 amendment), in cohort 1, objective responses were achieved in 18 (67%; 95% CI, 47.7–85.7) of 27 patients, and 22 patients had disease control (82% [65.8–97.1]) in the full analysis set. In cohort 2, objective responses were achieved in 40.0% (95% CI, 19.4–60.6) of 25 patients and 18 patients had disease control (72.0% [53.1–90.9]) in the full analysis set (Supplementary Table After the protocol amendment and inclusion of additional patients, the median time of follow-up at the time of data analysis (the data cutoff was 31 October 2022) was 23.3 months (IQR 22.4–24.2 months) for cohort 1 and 18.5 months (17.3–19.7 months) for cohort 2. In cohort 1, 3 (7.5%) of 40 patients had a confirmed complete response, 23 (57.5%) had a confirmed partial response, 6 (15.0%) had stable disease, and 4 (10.0%) had progressing disease in the full analysis set. In total, objective responses were achieved in 26 (65%; 95% CI, 49.6–80.4) of 40 patients, and 32 patients had disease control (80% [67.0–93.0]) in the full analysis set (Fig. | 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 that the patients with liver metastasis had a similar ORR compared with the patients without. Patients who had previously been treated with EGFR inhibitors had a higher ORR than those who had not been treated with EGFR inhibitors in both cohort 1 (72.7% vs 62.1%) and cohort 2 (57.1% vs 24.0%). A higher ORR was also observed in patients with EBV DNA titers <10,000 copies/ml than in patients with >10,000 copies/ml in both cohort (73.1% vs 50.0%)1 and cohort 2(42.9% vs 18.2%). But the difference was not statistically significant ( | 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 of camrelizumab in 15 (20.8%) patients. The most common reasons for interruptions of apatinib were hypertension (19 [38.8%]), hand and foot syndrome (15 [30.6%]), increased aspartate aminotransferase (nine [18.4%]), and increased alanine aminotransferase (eight [16.3%]); similarly, increased aspartate aminotransferase (nine [18.4%]) and increased alanine aminotransferase (eight [16.3%]) led to camrelizumab interruptions. Nine patients discontinued apatinib because of nasopharyngeal necrosis (seven [77.8%]), increased alkaline phosphatase (one [11.1%]), and thrombocytopenia (one [11.1%]). Three patients discontinued camrelizumab because of rash (two [66.7%]) and immune myocarditis (one [33.3%]).The most common grade 3–4 adverse events were hypertension (27.8%), hand-foot syndrome (12.5%), and the increase in AST (11.1%). Serious adverse events were reported in three patients, with two presenting with rash, and one with acute immune myocarditis, all of which were considered treatment-related. In nine (12.5%) of patients, receptive cutaneous slender endothelial multiplication (RCCEP), a common and self-limiting trAE of camrelizumab, was observed, with two individuals revealing grade 3 events. RCCEP occurred only on the skin, with pathology revealing hairlike endothelial hyperplasia and slender hyperplasia in the dermis. During the treatment period, we saw the occurrence of nasopharyngeal necrosis in 9 cases (12.5%) and the diagnosis for all cases of nasopharyngeal necrosis was confirmed through nasopharyngoscope and/or magnetic resonance imaging. All nine patients with nasopharyngeal necrosis were classified as grade 3 or higher (Supplementary Table | 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. These factors contribute to the variability in patient response observed in our study. In order to explore the mechanism of PD-1 inhibitor resistance in patients with advanced nasopharyngeal carcinoma, we analyzed the baseline sequencing data in two cohorts. Compared with the patient in cohort 1, differentially expressed genes such as | 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 treatmentThis study reported a similar safety profile of camrelizumab plus apatinib treatment that was consistent with previous studies for other solid tumors. The most common treatmentrelated adverse events of any grade were leukopenia, neutropenia, fatigue, proteinuria, hand and foot syndrome, increased ALT and AST level, and hypothyroidism. Notably, compared with camrelizumab monotherapyA key finding from cohort 1 of our study is that the immune microenvironment prior to treatment in baseline tumor tissues appears to drive the clinical activity of camrelizumab plus apatinib in RM-NPC. A consistent trend of increasing efficacy with increasing levels of PD-L1 and KDR expression both in cohort 1 and cohort 2. The positive and negative expression of PD-L1 and KDR and their associations with ORR in both cohorts suggest a strong interplay between the immune reaction and anti-angiogenesis in RM-NPC. Notably, our gene expression analysis found that the B cell-related gene signature further reinforced the clinical significance of B cells, indicating that B cell had a significant interaction with T cells in the tumor microenvironment (TME). More robust responses to the combination of camrelizumab and apatinib occur in patients whose tumors have higher levels of TLS, consistent with other malignancies treated with immune checkpoint inhibitor monotherapyLastly, intrinsic resistance and delayed resistance to anti-PD-1 and anti-VEGF combination therapy showed different evolutionary patterns during relapse. The increase of fibroblasts was the main reason for relapse of patients with intrinsic resistance. However, for the delayed resistance patients, the B cell density in the tissues decreased, while the number of cytotoxic T cells and fibroblasts increased, indicating that the decrease of B cells is the decisive inducement for the relapse. Without B cells’ synergetic promotion, the increased cytotoxic T cells cannot perform the function of killing tumor cells. Exhaustion may also be the reason why cytotoxic T cells do not perform their functions; this requires more detailed evidence from subsequent studies. An increase of fibroblasts was also observed in delayed resistance when the tumor relapsed, which suggests that the induction of fibroblasts is common consequence of camrelizumab plus apatinib therapy.This study has several limitations. First, it had a small sample size given the rarity of the disease. Second, the trial design of this exploratory trial did not allow us to assess whether antitumor activity of apatinib occurred primarily through a direct effect or by reversal of primary PD1 antagonists’ resistance. We did not compare the efficacy of this apatinib-camrelizumab regimen with those of anti-PD-1/PD-L1 monotherapies or more recent combined chemoimmunotherapy in this study. Further phase III randomized controlled trials are needed to directly compare apatinib in combination with camrelizumab versus camrelizumab monotherapy or with chemotherapy in treating RM NPC patients as the second or later line treatment therapy. In addition, the reliability and interpretability of biomarker selection may be limited due to the small sample size of sequencing. Although we found that the tertiary lymph structure was related to therapeutic efficiency, we did not detect the detailed characteristics of the tertiary lymph structure, such as its maturity and heterogeneity, which need to be confirmed in future research. Finally, for this study, the number of front-line treatments included in the population was not completely consistent, and the treatment plans for front-line therapy varied. Aside from discrepancies in chemotherapy plans, some patients also received anti-EGFR drugs, resulting in significant heterogeneity among the populations studied. Future studies will require further refinement of the characteristics of the study population to conduct large-scale studies.In conclusion, camrelizumab plus apatinib showed promising anti-tumor activity with a manageable safety profile in platinum-resistant and in PD1 antagonist-resistant RM-NPC. Patients with high expression of PD-L1, KDR and B-cell-related gene signatures will be important to predict which subsets of patients are more likely to benefit from this combination treatment strategy. This combination could be a potential second-line treatment option for patients with RM NPC and warrants phase 3 trials to validate the potential benefits of this regimen. | 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 recurrent or metastatic disease; cohort 2 included patients with immune checkpoint inhibitors-resistant RM-NPC. The first and last patients were officially enrolled in cohort 1 on 8 September 2020, and 30 August 2021, respectively. In cohort 2, patients were enrolled beginning on 2 November 2020, and ending on 7 September 2021.Eligible patients were aged 18–75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, histologically or cytologically confirmed with RM-NPC, not suitable for local treatment, who progressed after receiving first-line platinum-based chemotherapy (cohort 1) or immune checkpoint inhibitor immunotherapy with or without platinum-based chemotherapy (cohort 2), and who presented with measurable tumor lesions assessed by the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Further inclusion criteria were adequate organ function as determined by: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelet count ≥75 × 109/L; Hemoglobin ≥9 g/dL; serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN) (for subjects with liver metastases, TBIL ≤ 3 × ULN; ALT and AST ≤ 5 × ULN); Creatinine ≤1.5 × ULN or creatinine clearance rate ≥ 50 ml/min (Cockcroft-Gault formula); serum albumin ≥28 g/L; Thyroid-stimulating hormone (TSH) levels ≤1 × ULN; INR, APTT ≤ 1.5 × ULN, and a life expectancy of at least 3 month. Eligible patients were required to provide tumor tissue samples for biomarker analysis. Patients with any active autoimmune disease or history of autoimmune disease, a history of severe bleeding or any bleeding events with a serious grade of 3 or more, MRI showed that the tumor may have invaded important blood vessels or nasopharyngeal necrosis, or those who were previously treated with VEGFR inhibitors (antiangiogenic smallmolecule tyrosine kinase inhibitors, or antiangiogenic monoclonal antibodies) were excluded. Full eligibility and exclusion criteria are included in the study protocol (available in the Supplementary Information file). The trial was approved by the Research Ethics Board of Sun Yat-sen University Cancer Center and was done in accordance with the Declaration of Helsinki. All patients provided written informed consent. | 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 the basis of previous published phase I studies in advanced cancersBaseline assessment was done within 14 days before treatment, which included thoracic contrast-enhanced CT and abdominal-pelvic and head neck contrast-enhanced CT or MRI scans; electrocardiogram or echocardiography; biochemical, hematological, virological, endocrinological, and urine and feces examinations; and archival tumor tissue assessments. Tumor response was assessed by investigators, according to RECIST version 1.1, used CT and MRI scans every 6 weeks for the first 12 cycle, and every 12 weeks thereafter. Complete or partial response was confirmed by subsequent scans at least 28 days apart. Routine blood and hepatic, renal function examinations, hematological, biochemical, endocrinological, and urine and fecal examinations were done every cycle. Adverse events were monitored before each drug administration and at each examination throughout the treatment process, and at 30 days (30, 60, and 90 days for serious adverse events) after the last dose of the study drug. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. | 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. Progression-free survival was defined as the interval from the start of treatment to disease progression or death for any cause (whichever occurred first) or the last progression-free survival assessment for patients alive without progression. Duration of response was assessed in patients who achieved a response and was defined as the time from the date of the first documented response until the date of documented progression or death from any cause. Disease control was defined as the proportion of patients who achieved complete response, partial response or stable disease. The overall survival was defined as the time from treatment initiation to death for any reason. | 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 30%The statistical comparison between responder and non-responder groups for a given continuous variable was performed using two-sided Mann–Whitney | 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 staining and multiple immunofluorescence staining. | 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 the RNA sample preparations. Sequencing libraries were generated using NEBNext® UltraTM RNA Library Prep Kit for Illumina® (NEB, USA) following manufacturer’s recommendations and index codes were added to attribute sequences to each sample. Purified mRNA was randomly fragmented using divalent cations under elevated temperature in NEBNext First Strand Synthesis Reaction Buffer(5X). Using mRNA as template, double-stranded cDNA was synthesized by reverse transcription. cDNA fragments of around 200 bp were selected (AMPure XP beads) and purified (Agilent Bioanalyzer 2100 system) to ensure the quality of the library. The clustering of the index-coded samples was performed on a cBot Cluster Generation System using TruSeq PE Cluster Kit v3-cBot-HS (Illumia) according to the manufacturer’s instructions. After cluster generation, the library preparations were sequenced on an Illumina Novaseq platform and 150 bp paired-end reads were generated. | 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 website. Hisat2 v2.0.5 was used to build the index of the reference genome and to align paired-end clean reads to the reference genome. | 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 of sequencing depth and gene length for the reads count at the same time, and is currently the most commonly used method for estimating gene expression levels. | 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. The resulting | 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% neutralized formaldehyde. Then, antigen was retrieved using heated Tris- EDTA buffer (pH 8.0 or pH 9.0) for 2.5 min. Each section was subjected to four successive rounds of antibody staining after the initial establishment of staining conditions for each individual primary antibody and successive optimization. Each staining step consisted of blocking with 20% normal goat serum/fetal bovine serum in PBS and incubation with primary antibodies, followed by biotinylated anti-mouse/anti-rabbit secondary antibodies and streptavidin–horseradish peroxidase (HRP) substrate. Then, the immunoreactive stains were visualized using tyramide signal amplification (TSA) with fluorophores Opal 480, 520, 570, and 690 diluted in 1×Plus Amplification Diluent. Finally, the Ab–TSA complexes were stripped in heated Tris-EDTA buffer (pH 8.0 or pH 9.0) for 2.5 min. Nuclei were counterstained with 4′, 6- diamidino-2- phenylindole, dihydrochloride (DAPI) and sections were mounted using Perma Fluorfluorescence mounting medium (PANOVUE). The same procedure without primary antibodies was used as a negative control. The multiplex immunohistochemical staining results were scored based on the percentage of the number of cell subsets. Computer recognition software used indicated molecules to identify subsets of cells automatically and count them. Cell quantification was performed across whole tumor sections using Halo analysis software (PANOVU). The antibodies used for IHC staining are CD4 (ZM-0418, ZSbio, Clone: EP204); CD19 (ZM-0038, ZSbio, Clone: UMAB103); CD8 (ZA-0508, ZSbio, Clone: SP16); CD3 (ZM-0417 ZSbio Clone: LN10); Eomes (ab183991, Abcam, 1:200); α-SMA (ab7817, Abcam, 1μg/mL); KDR (ab2349, Abcam, 1:100); PD-L1 (ab205921, Abcam, 2μg/mL); CD31(ab28364, Abcam, 1:50); IL8 (94407 T, Cell Signaling Technology, 1:100); VEGFA (ab52917, Abacm, 1:100); c-KIT (ab32363, Abcam, 1:400); SRC (ab109381,Abacam, 1:400). | 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 funders had no role in study design, data collection and analysis, or manuscript writing. | 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.J., X.F.L., S.Y.X., S.S.G., D.F. L., Q.Y.C., L.Q.T., and H.Q.M. Manuscript writing: all authors. | 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 of respiratory parameters to indicate readiness for a spontaneous breathing trial prior to liberation from ventilation. 193 clinical staff were interviewed towards the end of the trial. Interview data were thematically analysed, and quantitative adherence data were analysed using descriptive statistics. | 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 greater intervention effect. | 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 Belfast, email: | 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 interacting components [Process evaluations provide important insights into how complex interventions do or do not produce change. This is achieved by studying the processes of intervention implementation, receipt and delivery [ | 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 the usual care period, and one ICU was sequentially randomised every four weeks to enter an eight week training period, before crossing over to the intervention period for the remainder of the trial ( | 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 staff trained in the interventionNumbers of children admitted requiring IMV and numbers screened for trial eligibilityTrained research nurses collected and recorded the daily adherence data onto case report forms (CRF). Staff training data were recorded on study training logs, and admission and recruitment data were collected from the study recruitment logs, and the paediatric intensive care national database. | 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, but provide the final mean adherence proportions for each ICU, ranked from highest to lowest. The trial’s primary outcome was the duration of IMV, measured from initiation of ventilation to the first successful extubation event. The estimate of the treatment effect was a time and cluster adjusted hazard ratio (HR) with 95% confidence intervals. The duration of IMV was analysed using a Cox proportional hazards model, with a frailty term for clustering by ICU. The time to event outcome was censored at the transition from usual care to the intervention training period, hospital discharge, 90-days, death, or if the child received a tracheostomy. We derived an absolute measure of effect by calculating the median of the model-based prediction of survival duration at all 22 periods in the stepped wedge trial and the difference between the intervention and usual care periods, and we summarised the extent of variability over the 22 periods using the interquartile range. | 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 comprising an introduction, with attached Participant Information Sheet (PIS). The email was distributed to all eligible staff ahead of site visits. From amongst the staff working on the days of site visits, a range of clinicians and grades were purposively selected for interview. Prior to the interview, participants were given an opportunity to read the PIS again and ask questions. Once satisfied that informed consent had been completed, participants were asked to sign a Consent Form.No prior relationship between JJ and participating staff existed, and all were made aware of her impartiality and need to gain candid insight into their experiences of trial delivery. Guided by a semi-structured interview schedule, discussions explored participant understanding and experience in relation to the five areas theorised as underpinning intervention effectiveness: training; flexibility; proactivity; consistent weaning and sedation care and management; and MDT working. The interview guide was developed by JJ and the Chief Investigator (BB). It was piloted with another author (LMcI), who is a paediatric intensive care nurse. Interviews were undertaken in a quiet location close to the paediatric ICU, lasting between 30–90 minutes. They were audio-recorded and fully transcribed, with anonymisation. Only JJ had access to information that could identify individual participants during and after data collection. | 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 children showed a significant reduction of 7.1 hours median difference (IQR -9.6 to -5.3, p = 0.01) between usual practice and the intervention in favour of the SANDWICH intervention. Further detailed results from the clinical trial are published elsewhere [ | 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]) and COMFORT assessment (83% [IQR 82, 91]); moderate for daily screening (74% [IQR 66, 83]) and lowest for undertaking a SBT when criteria were met (40% [IQR 31, 51]). The mean of all components was 75% (range 59–85%). The proportion of intervention adherence within each ICU is presented in | 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 health professionals (physiotherapists, pharmacists and nursing assistants); and 25 research team members. | 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 enjoyable and effective due to its practical nature and focus, including as participants could ask questions and resolve emerging issues. In contrast, the online component could be described as lacking an immediate “real-world” relevance. | 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 intervention explicitly accommodated independent clinical decision-making was considered particularly important for buy-in from unit consultants, who expressed no sense of being constrained in their decision-making regarding either the conduct of SBTs or patient extubation. The same independence was highlighted by nursing staff, primarily in relation to the management of patient sedation. | 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 ‘status’ for weaning. The categorisation could be problematic due to an overlap in ranges (10–12 consider weaning sedation; 12–17 comfortable and can be safely extubated). A child who scored in the range 12, or just above, could fail a SBT screen and remain longer on the ventilator. Second, the option of running a SBT for up to two hours. This period of time could allow attention to move away from a patient’s weaning progress as other priorities of patient care took precedence. It could also diminish the perceived importance of the need to extubate, as staff were aware a patient could remain on SBT settings for two hours. On the occasions when a patient remained on a SBT for longer than two hours, the end goal of extubation could be undermined in that the patient could tire and need to be returned to higher levels of support. Third, the intervention did not stipulate that extubation should follow within a set time after a successful SBT, in recognition that this might not be practically possible. However, the lack of such a requirement was linked to an indefinite postponement of extubation in some cases as other unit pressures took priority and/or relevant staff were unavailable. | 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 the lack of effect between adherence rates and the primary outcome. The setting of sedation and ventilator support targets, as well as COMFORT assessment, achieved high adherence, and were important foundational work for intervention effectiveness. However, sedation targets could be inadequately explicit and/or focused, so that assessment did not always result in optimal patient sedation. Furthermore, setting sedation and ventilator targets did not guarantee that these targets were acted on. The same was apparent in respect of daily SBT screening. Although this component achieved relatively high adherence and successfully moved patients along the weaning pathway, some drop-off was clear and, again, the passing of a SBT screen did not always ensure the subsequent performance of an SBT. Completion of SBTs achieved the lowest adherence; non-performance represented a detrimental ‘stop’ in patients’ pathway through the intervention and, by extension, progress towards extubation. Nevertheless, despite variable component adherence rates, the intervention was delivered as a coherent bundle.The process evaluation enabled a nuanced understanding of multiple, overlapping processes, operating at the individual, unit and wider institutional level, involved in the delivery of the intervention. Importantly, the evidence provides insight into these processes in respect of each of the intervention components. It also highlights the countervailing nature of their collective working to moderate intervention delivery as theorised in our logic model. | 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 [Development of the theory underpinning our intervention was based on an ICU specific evidence base [The evidence largely supports our theoretical assumptions concerning how the intervention would work to encourage proactivity in weaning. Even where intervention deviations occurred, still the units were operating with a bundle of components, meaning that, even incrementally, an overall imperative towards weaning was sustained. Our evidence aligns with other work on the effectiveness of multifaceted ICU interventions [As anticipated, the intervention worked to promote inter-disciplinary collaboration. Although the challenges inherent in inter-professional working in ICU have been documented [In terms of consistency of weaning related care (both sedation and weaning management), the evidence concerning our theoretical assumptions is more ambivalent. The protocol did work to improve consistency of care. Two examples are bedside nurses’ use of lighter patient sedation, and doctors’ uptake of a more dynamic approach to lowering ventilator settings. However, the impetus to adhere to established practice also meant that bedside nurses continued to over-sedate, and doctors continued to wean ‘down’ to lower support. The challenges inherent in changing established practice within ICUs are well documented [ | 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-making collectively worked to expedite extubation. To further enhance this momentum, findings suggest the benefits of more explicit direction in decision-making pathways, robustly embedding new practice as part of a collective endeavour within unit routines, and capitalising on the skills of ANPs and physiotherapists to include a greater role in patient extubation. | 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 app) use and face-to-face training on the clinical and laboratory parameters of dietary and fluid intake adherence in patients undergoing HD. | 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 educational materials via the Di Care app and face-to-face training for one month. Before and 12 weeks after the intervention, the mean interdialytic weight gain (IDWG), potassium (K), phosphorus (P), total cholesterol (TC), triglyceride (TG), albumin (AL), and ferritin (FER) levels were measured and compared. The data were analyzed using the SPSS via descriptive statistics (mean, SD, frequency, and percentage) and analytical tests (independent-samples | 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 delivered to ESRD patients in low- and middle-income countries, including Iran. For instance, in Asia, 17–34% of people need to take advantage of RRT [Treatment non-adherence is one of the significant factors contributing to increased complications and the low efficacy of HD [Numerous factors are likely to result in poor treatment adherence, particularly inadequate knowledge [ | 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 and after investigating related published articles, the present method was designed. Studies from 2010 to 2022, which were published in PubMed, Science Direct, Google Scholar, Magiran, and SID, were included and education, patient education, face-to-face, mobile applications, mobile Health (mHealth), adherence, and adherence to treatment were used as keywords in the mentioned search. | 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’ willingness to participate in the study, aged over 18, the ability to read and write, access to a smartphone with an Android operating system, undergoing HD within the study setting permanently, experiencing three HD sessions per week, receiving HD for at least six months, using no other mHealth apps along with HD during the study, no mental illnesses or other chronic diseases, such as heart failure, and no disability causing disorders in the training process. In addition, unwillingness to continue cooperation with the study, being transferred to other centers, undergoing a kidney transplant during the study, not using the Di Care app for more than one week, not attending the face-to-face training sessions for over three sessions, and facing inadequate functioning of the Di Care app on smartphones were the exclusion criteria.The HD patients were recruited in this study using convenience sampling method by one of the researchers. All patients, who were in the center, enrolled in the study. Then, among those who were eager to participate, other criteria were checked to reach the calculated sample size. The study objectives were then explained to them, and informed consent was obtained. Afterward, the patients were randomized into two groups: mHealth (n = 35) and face-to-face training (n = 35) via tossing a coin, so the coin was tossed for each eligible patient and if the patients were on the coin head, they entered into the face-to-face training group, and if they were on the coin tail, they were included in the mHealth app use one. This procedure continued until the desired sample size was reached. To prevent the exchange of information between the patients in both groups, besides asking the patients not to exchange information until the end of the study, the app server was controlled daily during the intervention for the registration of patients in the face-to-face training group. | 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, the weight of five people in the same gown was measured twice at one-minute intervals, whose correlation coefficient was equal to 0.9. Weight measurement was also performed before undergoing HD and in hospital gowns. To prevent bias, it was practiced and supervised by a researcher and two trained nurse assistants unaware of patient groups. In the first training session, immediately after the patients were connected to the HD machines, 5 ml blood samples were taken from an arterial catheter to measure the serum K, P, total cholesterol (TC), triglyceride (TG), AL, and ferritin (FER) levels. In order to check K, Easy Electrolyte® kit and device were used. TG, AL, FER, and P level was measured by enzymatic method and Pars Azmoon® kit, bromocresol green test and Pars Azmoon® kit, ELISA method and Pishtaz Teb® kit, and UV test and Pars Azmoon® kit respectively. All biochemistry test was done by Hitachi® model 902. All the experiments were performed with laboratory devices and kits, and the same measurement methods in the study setting. All the tests were completed by a laboratory technician unaware of patient groups. | 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 similar applications and studies were investigated and checked by the researchers, and the final version was published after a long-term revision, which was held by the researchers and application developers. In the first training session, the Di Care app was installed on the patients’ smartphones in the mHealth group and its correct operation was ensured. For example, a reminder was set for one of the patient’s medications. To confirm the correct operation of the software, one of the researchers, with a master’s degree in nursing and two years of experience in the HD center, met the patients in the group trained with the app weekly and answered their possible questions.The Di Care app consisted of different features. Its educational materials were prepared in three-minute videos on seven topics for the patients. In these videos, some images, texts, and audios were used simultaneously (Fig.
Different parts of Di Care app. In the face-to-face training group, the educational materials prepared for the Di Care app were taught to the patients in person by the same researcher who evaluated the correct functioning of the software. The patients were thus consulted about the timing of the training during HD. The training was completed in 12 sessions (for four weeks and three sessions per week) and lasted for at least 10 min. The training sequence was the same as that provided by the app. At the end of each training session, the patients could also raise their questions about the issues related to the topics taught. In addition, at the end of each session per week, the educational materials taught in the previous week were delivered in writing to the patients.Twelve weeks after the onset of the intervention program (viz. eight weeks after the last training session), the mean IDWG in the patients was measured and recorded in the three training sessions of the twelfth week, the blood samples were taken to measure the serum K, P, TC, TG, AL, and FER levels, and sent to the hospital laboratory, where the study was being performed. The criteria for dietary and fluid intake non-adherence were as following: the IDWG of more than 5.7% of dry weight, the serum K level of more than 6 mmol/l, P of more than 7.5 mg/dl, TC of more than 200 mg/dl, TG of more than 150 mg/dl, AL less than 3.5 g/dl, and FER less than 30 and more than 300 µg/l [
The study process | 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 in the mHealth group and 60% of those in the face-to-face training one were not similar in the normal range. As the intervention was completed, this value decreased to 14.28% in the mHealth group (The serum TG level before the intervention in 65.71% of patients in the mHealth group and 62.85% of those in the face-to-face training one was not within the normal range, declining by 40% (And the serum AL level in 22.85% of the patients in both groups was not in the normal range. After the intervention, the serum AL level in the group trained with the Di Care app reached 2.85% (The serum FER level in the patients in the mHealth group (65.71%) and those in the face-to-face training group (54.28%) before the intervention were not within the normal range, decreasing to 42.84% after the intervention in the mHealth group ( | 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-adherence was differ from 33.6 to 68.8% in different studies [This study also indicated that the patients’ dietary adherence was appropriate in terms of the serum P level before the intervention. Considering K, only 2.85% of the patients had poor dietary adherence. In the previous studies, the mean serum K and P levels in the patients before the intervention had been in the normal range [In the present study, the serum TC and TG levels respectively in 57.14% and 64.28% of the HD patients were higher than normal, and they had poor dietary adherence. Saini et al. found that the mean baseline serum TC and TG levels in the patients undergoing HD had been out of the normal range [In this study, the serum AL and FER levels were out of the normal range in 22.85% and 59.99% of patients, respectively, and they showed poor dietary adherence in this line. Significantly, the HD patients had self-administered ferritin-boosting medications. It seems that the main reason for the decrease in the mean serum FER level after the intervention in this study was the training provided regarding the side effects of taking such medications with no consultation. Similar results had been further reported, wherein the serum FER level in the patients had dropped after the administration of oral vitamin C supplements, and their need for erythropoietin-stimulating agents (ESAs) had dwindled [Both training methods did not significantly reduce the mean IDWG and the serum K, P, and TC levels in the patients. Clinically, the changes were more significant in the group trained with the Di Care app. Unlike face-to-face training, the Di Care app use reduced the serum TG level, increased AL, and modulated the serum FER level in the patients. Both methods promoted dietary and fluid intake adherence in the patients, which could significantly improve dietary and fluid intake adherence in the mHealth group.In the present study, the mean IDWG and the serum TC and TG levels subsided in a significant manner in the patients trained with the Di Care app. The serum AL level also significantly dropped, but FER was adjusted. Despite the descending trend in the mean values of K and P, this decrease was not significant. Training HD patients by sending text messages in a study revealed that the mean serum P and K levels had diminished after the intervention but the IDWG had not significantly decreased [This study showed a decrease in the mean serum K and P levels in the HD patients receiving face-to-face training, which was not statistically significant. These results agreed with the reports in Jahanpeyma et al. [ | 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 reminders, did not work properly all the time while videos were playing without any problem. Furthermore, in order to watch videos, connecting to the internet was essential to download them from the server. Some of the patients couldn’t connect to the internet and some of them refused to participate since they did not want to use their smartphone data for this reason. Besides, despite of willingness of some patients to take part in the study, their families or other patients, who did not accept to participate in the study themselves, were prevented to enroll. Furthermore, it was hard for some patients to use the app, despite having all inclusion criteria, because of being old, not having the ability to work with their phone properly, etc. Furthermore, in the Di Care app, it was impossible for the patients to ask questions and receive answers, which was one limitation facing this study. During the face-to-face training, however, the patients could be in direct contact with the trainer. Due to their easy access to the Internet, many patients were likely to compare this training and the information found in cyberspace, so the information retrieved from unreliable sources sometimes contraindicated the training provided and could largely confuse the patients. Very limited studies have beenconducted on the effects of training methods, particularly mobile apps, on the blood parameters of HD patients, using questionnaires to evaluate the impact of interventions on various aspects of treatment adherence. In addition, the highest focus in the literature has been on the serum K, P, urea (UR), creatinine (CR), and Kt/v levels, but the effect of training methods on other values, such as the serum AL, FER, TC, and TG levels has not been examined, which can minimize the possibility of comparing the study results. Therefore, it was suggested to shed light on such issues in future studies. Moreover, owing to the limitation of budget and time, it was preferred to give up measuring other variables like hemoglobin, sodium, and so on. Finally, due to the regulation of the center and other conditions, it was impossible to control ultrafiltration volume and sodium concentration. Almost all dialysis machines were of the same brand and model. However, there were some different ones and it was not possible to use the same machine for all patients. Regarding dialyzers, there was approximately no choice even for the center to provide different types of filters, especially high-flux dialyzers, due to a shortage of material in Iran and difficulties to provide them because of sanctions. As a result, the majority of them were PS 16 LF and PS 180 HF. | 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 revision of the manuscript. All authors read and approved the final manuscript. | 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 observed. The patients received all health care services provided to other counterparts and were not charged any fees for their participation in the study. They further entered the study voluntary and could withdraw. The patients were even assured that all the data would be kept confidential, and they will be protected from any harm, loss, and bribery during the study. | 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 disease adherence questionnaireerythropoietin-stimulating agentsureacreatinine | 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 rubber pillows on transversus abdominis and internal oblique muscle fatigue, patient satisfaction, and discomfort scores during 60 min of prolonged sitting. Thirty healthy participants were invited to the study and randomized into three sitting conditions over three consecutive days. The three groups were as follows: control, foam pillow, and rubber pillow. Our results revealed that the discomfort score increased with the sitting time in all three groups (Sedentary workers experience increased levels of inactivity, with a high proportion of prolonged sitting (≥30 min) [Deep trunk muscles contribute to spinal stability [The TrA muscle initially arises from the iliac crest, the lower six ribs, and the middle and lateral raphe of the thoracolumbar fascia, and it passes medially to insert at the linea alba [Previous studies have reported that the continuous contraction of trunk muscles in prolonged seated postures could cause deep trunk muscle fatigue, and this is particularly true for the TrA and IO muscles [According to McKenzie’s concept, LBP may stem from hypo-lordosis of the lumbar spine [Many studies have focused on supporting lumbar lordotic curves during prolonged sitting to relieve pain and maintain mobility in the lumbar spine region [To our knowledge, no studies have compared the immediate effects that back pillow supports made from foam and rubber materials have on the TrA and IO muscles during prolonged sitting. Therefore, the current study aimed to investigate the immediate effects of back pillow support (foam and rubber materials) on fatigue in the TrA and IO muscles, discomfort scores, and participant satisfaction during prolonged sitting. | 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 laboratory on three consecutive days and were randomly selected to sit in three positions, as shown in One researcher informed the participants throughout the study. Another researcher measured the outcomes, including trunk muscle fatigue, participant satisfaction, and discomfort scores. The assessment times for each outcome are shown in | PMC9964691 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.