Nevin Manimala

BMJ Open. 2023 Jun 13;13(6):e069047. doi: 10.1136/bmjopen-2022-069047.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of combination immunochemotherapy regimens for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).

DESIGN: Meta-analysis and systematic review.

DATA SOURCES: PubMed, Embase, Web of Science and Cochrane library and the Clinicaltrials.gov clinical trials registry were searched up to 14 March 2022.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included randomised controlled trials that compared combination immunochemotherapy with conventional chemotherapy for R/M HNSCC. Primary outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse effects (AEs).

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data.

RESULTS: A total of 1214 relevant papers were obtained after the initial search, and five papers that met the inclusion criteria were included; these studies included a total of 1856 patients with R/M HNSCC. Meta-analysis showed that the OS and PFS of patients with R/M HNSCC in the combination immunochemotherapy group were significantly longer than those in the conventional chemotherapy group (HR=0.84; 95% CI 0.76, 0.94; p=0.002; HR=0.67; 95% CI 0.61, 0.75; p<0.0001), and the ORR was significantly higher (OR=1.90; 95% CI 1.54, 2.34; p<0.00001). The analysis of AEs showed that there was no significant difference in the overall incidence rate of AEs between two groups (OR=0.80; 95% CI 0.18, 3.58; p=0.77), but the rate of grade III and IV AEs was significantly higher in patients in the combination immunochemotherapy group (OR=1.39; 95% CI 1.12, 1.73; p=0.003).

CONCLUSIONS: Combination immunochemotherapy prolonged OS and PFS in patients with R/M HNSCC and improved the ORR; while this approach did not increase the overall incidence of AEs in patients, it increased the rate of grade III and IV AEs.

PROSPERO REGISTRATION NUMBER: CRD42022344166.

PMID:37311638 | DOI:10.1136/bmjopen-2022-069047

BMJ Open. 2023 Jun 13;13(6):e070277. doi: 10.1136/bmjopen-2022-070277.

ABSTRACT

OBJECTIVES: We assess different approaches to seeking consent in research in secondary schools.

DESIGN: We review evidence on seeking active versus passive parent/carer consent on participant response rates and profiles. We explore the legal and regulatory requirements governing student and parent/carer consent in the UK.

RESULTS: Evidence demonstrates that requiring parent/carer active consent reduces response rates and introduces selection biases, which impact the rigour of research and hence its usefulness for assessing young people’s needs. There is no evidence on the impacts of seeking active versus passive student consent but this is likely to be marginal when researchers are directly in communication with students in schools. There is no legal requirement to seek active parent/carer consent for children’s involvement in research on non-medicinal intervention or observational studies. Such research is instead covered by common law, which indicates that it is acceptable to seek students’ own active consent when they are judged competent. General data protection regulation legislation does not change this. It is generally accepted that most secondary school students age 11+ are competent to provide their own consent for interventions though this should be assessed individually.

CONCLUSION: Allowing parent/carer opt-out rights recognises their autonomy while giving primacy to student autonomy. In the case of intervention research, most interventions are delivered at the level of the school so consent can only practically be sought from head teachers. Where interventions are individually targeted, seeking student active consent for these should be considered where feasible.

PMID:37311635 | DOI:10.1136/bmjopen-2022-070277

BMJ Open. 2023 Jun 13;13(6):e064174. doi: 10.1136/bmjopen-2022-064174.

ABSTRACT

OBJECTIVES: The purpose of this study was to synthesise data on the prevalence of post-dialysis fatigue (PDF) among haemodialysis (HD) patients.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: China National Knowledge Infrastructure, Wanfang, Chinese Biological Medical Database, PubMed, EMBASE and Web of Science were searched from their inception to 1 April 2022.

ELIGIBILITY CRITERIA: We selected patients who must receive HD treatment for at least 3 months. Cross-sectional or cohort studies published in Chinese or English were eligible for inclusion. The main search terms used in the abstract were: “renal dialysis”, “hemodialysis” and “post-dialysis”, in combination with the word “fatigue”.

DATA EXTRACTION AND SYNTHESIS: Two investigators independently performed data extraction and quality assessment. Data were pooled to estimate the overall prevalence of PDF among HD patients using the random-effects model. Cochran’s Q and I² statistics were adopted to evaluate heterogeneity.

RESULT: A total of 12 studies were included, with 2152 HD patients, of which 1215 were defined as having PDF. The overall prevalence of PDF in HD patients was 61.0% (95% CI: 53.6% to 68.3%, p<0.001, I²=90.0%). Subgroup analysis failed to explain the source of heterogeneity, but univariable meta-regression showed that a mean age of ≥50 years might be the source of heterogeneity. Egger’s test revealed no publication bias among the studies (p=0.144).

CONCLUSIONS: PDF is highly prevalent among HD patients.

PMID:37311633 | DOI:10.1136/bmjopen-2022-064174

BMJ Open. 2023 Jun 13;13(6):e071080. doi: 10.1136/bmjopen-2022-071080.

ABSTRACT

INTRODUCTION: Patient education is a critical component of healthcare delivery. However, medical information and knowledge are complex and can be difficult for patients and families to comprehend when delivered verbally. The use of virtual reality (VR) to convey medical information to patients may bridge this communication gap and lead to more effective patient education. It may be of increased value to those with low health literacy and levels of patient activation, in rural and regional settings. The objective of this randomised, single-centre pilot study is to examine the feasibility and preliminary effectiveness of VR as an education tool for people with cancer. The results will provide data to inform the feasibility of a future randomised controlled trial, including sample size calculations.

METHODS AND ANALYSIS: Patients with cancer undergoing immunotherapy will be recruited. A total of 36 patients will be recruited and randomised to one of three trial arms. Participants will be randomised 1:1:1 to receive VR, a two-dimensional video or standard care (ie, verbal communication and information leaflets). Feasibility will be assessed by recruitment rate, practicality, acceptability, usability and related adverse events. The potential impact of VR on patient-reported outcomes (ie, perceived information provision quality, knowledge about immunotherapy and patient activation) will be assessed and stratified by information coping style (ie, monitors vs blunters) whenever statistical analyses are significant. The patient-reported outcomes will be measured at baseline, post-intervention and 2 weeks post-intervention. In addition, semistructured interviews will be conducted with health professionals and participants randomised to the VR trial arm, to further explore acceptability and feasibility.

ETHICS AND DISSEMINATION: Ethics approval was obtained from the Greater Western Human Research Ethics Committee, New South Wales Local Health District (2022/ETH01760). Informed consent will be obtained from all participants. Findings will be disseminated via relevant conference presentations and publications in peer-reviewed journals.

TRIAL REGISTRATION NUMBER: ACTRN12622001473752.

PMID:37311632 | DOI:10.1136/bmjopen-2022-071080

Anal Chim Acta. 2023 Aug 22;1270:341304. doi: 10.1016/j.aca.2023.341304. Epub 2023 May 19.

ABSTRACT

This article contains a comprehensive tutorial on classification by means of Soft Independent Modelling of Class Analogy (SIMCA). Such a tutorial was conceived in an attempt to offer pragmatic guidelines for a sensible and correct utilisation of this tool as well as answers to three basic questions: “why employing SIMCA?”, “when employing SIMCA?” and “how employing/not employing SIMCA?”. With this purpose in mind, the following points are here addressed: i) the mathematical and statistical fundamentals of the SIMCA approach are presented; ii) distinct variants of the original SIMCA algorithm are thoroughly described and compared in two different case-studies; iii) a flowchart outlining how to fine-tune the parameters of a SIMCA model for achieving an optimal performance is provided; iv) figures of merit and graphical tools for SIMCA model assessment are illustrated and v) computational details and rational suggestions about SIMCA model validation are given. Moreover, a novel Matlab toolbox, which encompasses routines and functions for running and contrasting all the aforementioned SIMCA versions is also made available.

PMID:37311606 | DOI:10.1016/j.aca.2023.341304

BMJ Open Diabetes Res Care. 2023 Jun;11(3):e003167. doi: 10.1136/bmjdrc-2022-003167.

ABSTRACT

INTRODUCTION: It has been suggested that type 1 diabetes was associated with increased COVID-19 morbidity and mortality. However, their causal relationship is still unclear. Herein, we performed a two-sample Mendelian randomization (MR) to investigate the causal effect of type 1 diabetes on COVID-19 infection and prognosis.

RESEARCH DESIGN AND METHODS: The summary statistics of type 1 diabetes were obtained from two published genome-wide association studies of European population, one as a discovery sample including 15 573 cases and 158 408 controls, and the other data as a replication sample consisting of 5913 cases and 8828 controls. We first performed a two-sample MR analysis to evaluate the causal effect of type 1 diabetes on COVID-19 infection and prognosis. Then, reverse MR analysis was conducted to determine whether reverse causality exists.

RESULTS: MR analysis results showed that the genetically predicted type 1 diabetes was associated with higher risk of severe COVID-19 (OR=1.073, 95% CI: 1.034 to 1.114, p_FDR=1.15×10^-3) and COVID-19 death (OR=1.075, 95% CI: 1.033 to 1.119, p_FDR=1.15×10^-3). Analysis of replication dataset showed similar results, namely a positive association between type 1 diabetes and severe COVID-19 (OR=1.055, 95% CI: 1.029 to 1.081, p_FDR=1.59×10^-4), and a positively correlated association with COVID-19 death (OR=1.053, 95% CI: 1.026 to 1.081, p_FDR=3.50×10^-4). No causal association was observed between type 1 diabetes and COVID-19 positive, hospitalized COVID-19, the time to the end of COVID-19 symptoms in the colchicine treatment group and placebo treatment group. Reverse MR analysis showed no reverse causality.

CONCLUSIONS: Type 1 diabetes had a causal effect on severe COVID-19 and death after COVID-19 infection. Further mechanistic studies are needed to explore the relationship between type 1 diabetes and COVID-19 infection and prognosis.

PMID:37311601 | DOI:10.1136/bmjdrc-2022-003167

J Aging Health. 2023 Jun 13:8982643231184098. doi: 10.1177/08982643231184098. Online ahead of print.

ABSTRACT

Objectives: The purpose of this study was to evaluate the psychometric properties of the modified 25-item Resilience Scale (RS-25) in older adults post-hip fracture using Rasch analysis. Methods: This was a descriptive study using baseline data from the Seventh Baltimore Hip Studies (BHS-7). There were 339 hip fracture patients included in this analysis. Results: Findings suggest there was support for reliability of the measure based on person and item separation index. The INFIT and OUTFIT statistics for testing validity were all in the acceptable range indicating that each item on the modified RS-25 fits the appropriate concept. There was no evidence of Differential Item Functioning (DIF) between genders. Conclusions: This study demonstrated evidence that the modified RS-25 is a reliable and valid measure to evaluate resilience among older adults post-hip fracture and therefore can be used in this population in clinical practice and research.

PMID:37311566 | DOI:10.1177/08982643231184098

Stat Med. 2023 Jun 13. doi: 10.1002/sim.9817. Online ahead of print.

ABSTRACT

External validation of the discriminative ability of prediction models is of key importance. However, the interpretation of such evaluations is challenging, as the ability to discriminate depends on both the sample characteristics (ie, case-mix) and the generalizability of predictor coefficients, but most discrimination indices do not provide any insight into their respective contributions. To disentangle differences in discriminative ability across external validation samples due to a lack of model generalizability from differences in sample characteristics, we propose propensity-weighted measures of discrimination. These weighted metrics, which are derived from propensity scores for sample membership, are standardized for case-mix differences between the model development and validation samples, allowing for a fair comparison of discriminative ability in terms of model characteristics in a target population of interest. We illustrate our methods with the validation of eight prediction models for deep vein thrombosis in 12 external validation data sets and assess our methods in a simulation study. In the illustrative example, propensity score standardization reduced between-study heterogeneity of discrimination, indicating that between-study variability was partially attributable to case-mix. The simulation study showed that only flexible propensity-score methods (allowing for non-linear effects) produced unbiased estimates of model discrimination in the target population, and only when the positivity assumption was met. Propensity score-based standardization may facilitate the interpretation of (heterogeneity in) discriminative ability of a prediction model as observed across multiple studies, and may guide model updating strategies for a particular target population. Careful propensity score modeling with attention for non-linear relations is recommended.

PMID:37311563 | DOI:10.1002/sim.9817

Stat Med. 2023 Jun 13. doi: 10.1002/sim.9823. Online ahead of print.

ABSTRACT

The receiver operating characteristic (ROC) curve is a powerful statistical tool and has been widely applied in medical research. In the ROC curve estimation, a commonly used assumption is that larger the biomarker value, greater severity the disease. In this article, we mathematically interpret “greater severity of the disease” as “larger probability of being diseased.” This in turn is equivalent to assume the likelihood ratio ordering of the biomarker between the diseased and healthy individuals. With this assumption, we first propose a Bernstein polynomial method to model the distributions of both samples; we then estimate the distributions by the maximum empirical likelihood principle. The ROC curve estimate and the associated summary statistics are obtained subsequently. Theoretically, we establish the asymptotic consistency of our estimators. Via extensive numerical studies, we compare the performance of our method with competitive methods. The application of our method is illustrated by a real-data example.

PMID:37311560 | DOI:10.1002/sim.9823

Eur J Dent. 2023 Jun 13. doi: 10.1055/s-0043-1768468. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to preliminarily evaluate the expression of two putative tumor suppressor proteins, including chronic lymphocytic leukemia deletion gene 7 (CLLD7) and chromosome condensation 1-like (CHC1L) proteins in oral squamous cell carcinoma (OSCC).

MATERIALS AND METHODS: Expression of CLLD7 and CHC1L proteins was analyzed in 19 OSCC and 12 normal oral mucosa (NOM) using immunohistochemistry. The percentage of positive cells and intensity of staining were semiquantitatively assessed and expressed with an immunoreactive score. The number of positive cells at various subcellular localizations was evaluated and presented in percentages. The immunoreactivity scores and percentages of positive cells at various localizations were compared between the normal and OSCC groups with statistical significance at p-value less than 0.05.

RESULTS: According to immunohistochemical analysis, the immunoreactivity scores for both CLLD7 and CHC1L were higher in NOM than those of OSCC. Analysis of CLLD7 localization revealed predominant nuclear staining at basal and parabasal areas in NOM, whereas more cytoplasmic staining was observed in OSCC. For CHC1L, nuclear staining was prominent in NOM. In contrast, significantly increased plasma membrane staining was detected in OSCC.

CONCLUSION: The expression of CLLD7 and CHC1L proteins was reduced in OSCC. Alterations in the subcellular localization of these two proteins in OSCC were also demonstrated. These preliminary results suggest that CLLD7 and CHC1L are aberrantly expressed in OSCC. The precise mechanisms of these putative tumor suppressor proteins in OSCC require future studies.

PMID:37311552 | DOI:10.1055/s-0043-1768468