Category: Statistics

J Gastrointest Oncol. 2023 Apr 29;14(2):676-691. doi: 10.21037/jgo-22-862. Epub 2023 Mar 27.

ABSTRACT

BACKGROUND: Little is known about the biweekly combined use of cetuximab and chemotherapy as second-line treatment of metastatic colorectal cancer (mCRC). Recently, DNA methylation status has been reported to be a new possible predictor of the efficacy from the anti-epidermal growth factor receptor (EGFR) antibody treatment. The purpose of this study was to examine the efficacy and safety of biweekly cetuximab plus mFOLFOX6 or mFOLFIRI as a second-line treatment for KRAS exon 2 wild-type mCRC. We also investigated the predictability of DNA methylation status on the efficacy of the EGFR antibody-containing treatment.

METHODS: Patients who were refractory or intolerant to the first-line chemotherapy were enrolled and received biweekly cetuximab plus mFOLFOX6 or mFOLFIRI. The primary endpoint was progression-free survival (PFS). Tumor evaluations were performed every 2 months using Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Adverse events (AEs) were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0. DNA methylation status of colorectal cancer cells was defined by a modified MethyLight assay.

RESULTS: Sixty-six cases were enrolled. The median PFS (mPFS) was 5.1 [95% confidence interval (CI), 3.8-7.6] months. The median overall survival (mOS) was 12.7 (95% CI, 7.5-15.3) months. Grade 3 or higher neutropenia occurred in 53.0% of patients, whereas skin disorders with a grade 3 or higher occurred in <15% of patients. In multivariate analysis, DNA methylation status could not be an independent predictor of PFS [hazard ratio (HR), 1.43; P=0.39] and OS (HR, 2.13; P=0.086). However, in RAS/BRAF wild-type patients, the mPFS and mOS in the low-methylated colorectal cancer (LMCC) group was numerically better than those in the highly-methylated colorectal cancer (HMCC) group, although the difference was not statistically significant [mPFS: 8.5 (95% CI, 6.1-10.9) vs. 3.3 (95% CI, 1.2-not reached) months, P=0.79; ΔmPFS, 5.2 months; mOS: 15.3 (95% CI, 11.9-23.5) vs. 6.5 (95% CI, 3.1-not reached) months, P=0.53; ΔmOS, 8.8 months].

CONCLUSIONS: Biweekly cetuximab plus mFOLFOX6 or mFOLFIRI is a useful second-line therapy for mCRC. DNA methylation status warrants further exploration as a predictive biomarker for anti-EGFR efficacy in mCRC.

PMID:37201044 | PMC:PMC10186538 | DOI:10.21037/jgo-22-862

Mol Biol Res Commun. 2023;12(1):1-16. doi: 10.22099/mbrc.2023.45131.1798.

ABSTRACT

Extracting high-yield, high-quality DNA from plant samples is challenging due to the presence of the cell wall, pigments, and some secondary metabolites. The main CTAB method, two of its modified protocols (beta-mercaptoethanol or ammonium acetate were eliminated), the modified Murray and Thompson method, and the Gene All kit were statistically compared based on the quantity and quality of the total DNA (tDNA) extracted from fresh and dried leaves of three medicinal herbs P. harmala, T. ramosissima, and P. reptans. The suitability of the tDNAs for molecular studies was evaluated by polymerase chain reaction (PCR) of the fragments of the internal transcribed spacer (ITS) in nuclear DNA and the trnL-F region in chloroplast DNA. Some significant differences were found between the tDNAs extracted by five extraction methods. With the exception of P. harmala, where the PCR of both the ITS fragments and the trnL-F region worked successfully in all DNA samples, but only the ITS fragments, not the chloroplast trnL-F region, were amplified in the DNA samples of T. ramosissima and P. reptans. The chloroplast trnL-F region was amplified only in DNA samples extracted from fresh and dried leaves of the three studied herbs using the commercial kit. Gene All kit, the main CTAB method, and its modified protocols were the less time-consuming protocols that yielded DNA suitable for downstream PCR vis-a-vis the modified Murray and Thompson method.

PMID:37201033 | PMC:PMC10186858 | DOI:10.22099/mbrc.2023.45131.1798

Mol Biol Res Commun. 2023;12(1):17-25. doi: 10.22099/mbrc.2023.45296.1802.

ABSTRACT

Despite various treatment options available for colorectal cancer, the survival rates for patients remain low. This study investigated the effects of hyperthermia and Ibuprofen on human colorectal adenocarcinoma cells (HT-29) viability, proliferation, and gene expression related to tumor suppression, Wnt signaling pathways, proliferation, and apoptosis The cells were exposed to hyperthermia at 42 or 43°C for 3 hours or Ibuprofen at different concentrations (700-1500 μM), and the effects were analyzed through MTT assay, trypan blue staining, and quantitative Real-time PCR. The study used quantitative Real-time PCR (qRT-PCR) to evaluate the effect of hyperthermia and Ibuprofen on the expression of various genes associated with tumor suppression, proliferation, Wnt signaling pathway, and apoptosis. The results revealed that hyperthermia caused a minor reduction in the viability and proliferation of HT-29 cells, but the decrease was not statistically significant (P<0.05). On the other hand, Ibuprofen caused a concentration-dependent decrease in the viability and proliferation of HT-29 cells. Both hyperthermia and Ibuprofen reduced the expression of WNT1, CTNNB1, BCL2, and PCNA genes, and increased the expression of KLF4, P53, and BAX genes. However, the changes in gene expression were not statistically significant in cells treated with hyperthermia. The findings suggest that Ibuprofen is more effective in reducing cancer cell proliferation by promoting apoptosis and inhibiting the Wnt signaling pathway than hyperthermia, which had some impact but was not statistically significant. The study highlights the potential of Ibuprofen as a targeted therapy for colorectal cancer.

PMID:37201032 | PMC:PMC10186857 | DOI:10.22099/mbrc.2023.45296.1802

Turk J Phys Med Rehabil. 2022 Dec 14;69(1):89-96. doi: 10.5606/tftrd.2023.10470. eCollection 2023 Mar.

ABSTRACT

OBJECTIVES: The aim of this study was to investigate central sensitization and associated factors in knee osteoarthritis (OA) patients and compare them with rheumatoid arthritis (RA) patients and healthy controls.

PATIENTS AND METHODS: This cross-sectional study was conducted with 125 participants (7 males, 118 females; mean age: 57.2±8.2 years; range, 45 to 75 years) between January 2017 and December 2018. Sixty-two patients with symptomatic knee OA, 32 RA patients with knee pain, and 31 healthy controls constituted the participants. Central sensitization was investigated with the Central Sensitization Inventory (CSI) and pressure pain threshold (PPT) measurements. Pain, functional status, and psychosocial features were assessed with self-reported questionnaires.

RESULTS: The OA and RA groups had significantly lower PPT values at local, peripheral, and remote regions compared to the healthy controls. Pressure hyperalgesia was shown at the knee with a 43.5% prevalence, 27.4% at the leg, and 8.1% at the forearm of OA patients. Pressure hyperalgesia was present at the knee, leg, and forearm in 37.5%, 25%, and 9.4% of RA patients, respectively. Pressure pain threshold values, CSI scores, frequency of pressure hyperalgesia, and frequency of central sensitization according to the CSI were not statistically different between the OA and RA groups. Psychosocial features and structural damage were not correlated with PPT values in the OA group.

CONCLUSION: The severity of chronic pain and functional status may be the clinical clues to recognizing patients with central sensitization since local joint damage does not play a direct role in the etiopathogenesis of central sensitization in OA patients and severe pain persisting in the chronic process is associated with central sensitization regardless of the pathogenesis.

PMID:37201014 | PMC:PMC10186014 | DOI:10.5606/tftrd.2023.10470

Turk J Phys Med Rehabil. 2022 Oct 27;69(1):8-14. doi: 10.5606/tftrd.2023.9923. eCollection 2023 Mar.

ABSTRACT

OBJECTIVES: The purpose of the study was to compare low-level laser therapy (LLLT) and local corticosteroid injection in the treatment of plantar fasciitis.

PATIENTS AND METHODS: This retrospective study was performed with 56 patients (6 males, 50 females; mean age: 44.7±10.1 years; range, 18 to 65 years) between January 2015 and March 2016. The patients were equally divided into two groups: Group 1, comprising patients who underwent a one-time local corticosteroid injection into the heel by the same physician, and Group 2, including patients who had gallium arsenide laser therapy at a wavelength of 904 nm lasting 10 sessions. Evaluations were done at pre-treatment, post-treatment, and two weeks, one month, and three months after the post-treatment evaluation. The post-treatment evaluation was accepted as the 10^th day after the injection in Group 1 and as the time after the last session of the laser treatment in Group 2. Each visit was compared with the previous visit for within-group analysis. The Visual Analog Scale (VAS), Heel Tenderness Index (HTI), and Foot Function Index (FFI) were assessed.

RESULTS: Pain scores in Group 1 and Group 2 were not associated with statistically significant differences (p>0.05). Within-groups analysis demonstrated statistically significant differences concerning VAS subgroups (p <0.05), except for Group 2’s resting VAS values (p=0.159). No statistically significant differences were found between groups in the means of FFI scores (p>0.05). Statistically significant differences were observed regarding within-group analyses for all subscores (p <0.001). No statistically significant differences were observed between the two groups for all visits regarding HTI scores (p>0.05). Statistically significant differences were found between baseline and the first after-treatment visit in all groups (p <0.05). Statistically significant differences were found in the first (p=0.020) and third (p=0.010) months compared to the one-week follow-up in Group 2 regarding HTI scores.

CONCLUSION: Both LLLT and local corticosteroid injection for plantar fasciitis have positive effects for three months after treatment. However, LLLT is more effective than local corticosteroid injection at the end of the third month in local tenderness.

PMID:37201000 | PMC:PMC10186012 | DOI:10.5606/tftrd.2023.9923

Front Cardiovasc Med. 2023 May 2;10:1091983. doi: 10.3389/fcvm.2023.1091983. eCollection 2023.

ABSTRACT

BACKGROUND: In pure aortic regurgitation, transcatheter aortic valve replacement (TAVR) is not yet used on a regular base. Due to constant development of TAVR, it is necessary to analyze current data.

METHODS: By use of health records, we analyzed all isolated TAVR or surgical aortic valve replacements (SAVR) for pure aortic regurgitation between 2018 and 2020 in Germany.

RESULTS: 4,861 procedures-4,025 SAVR and 836 TAVR-for aortic regurgitation were identified. Patients treated with TAVR were older, showed a higher logistic EuroSCORE, and had more pre-existing diseases. While results indicate a slightly higher unadjusted in-hospital mortality for transapical TAVR (6.00%) vs. SAVR (5.71%), transfemoral TAVR showed better outcomes, with self-expanding compared to balloon-expandable transfemoral TAVR having significantly lower in-hospital mortality (2.41% vs. 5.17%; p = 0.039). After risk adjustment, balloon-expandable as well as self-expanding transfemoral TAVR were associated with a significantly lower mortality vs. SAVR (balloon-expandable: risk adjusted OR = 0.50 [95% CI 0.27; 0.94], p = 0.031; self-expanding: OR = 0.20 [0.10; 0.41], p < 0.001). Furthermore, the observed in-hospital outcomes of stroke, major bleeding, delirium, and mechanical ventilation >48 h were significantly in favor of TAVR. In addition, TAVR showed a significantly shorter length of hospital stay compared to SAVR (transapical: risk adjusted Coefficient = -4.75d [-7.05d; -2.46d], p < 0.001; balloon-expandable: Coefficient = -6.88d [-9.06d; -4.69d], p < 0.001; self-expanding: Coefficient = -7.22 [-8.95; -5.49], p < 0.001).

CONCLUSIONS: TAVR is a viable alternative to SAVR in the treatment of pure aortic regurgitation for selected patients, showing overall low in-hospital mortality and complication rates, especially with regard to self-expanding transfemoral TAVR.

PMID:37200971 | PMC:PMC10187752 | DOI:10.3389/fcvm.2023.1091983

Front Hum Neurosci. 2023 May 2;17:1115699. doi: 10.3389/fnhum.2023.1115699. eCollection 2023.

ABSTRACT

INTRODUCTION: Women are vulnerable during pregnancy as they experience multiple physical and psychological problems which can lead to stress and poor quality of life ultimately affecting the development of the fetus and their health during and after pregnancy. Prior evidence suggests that prenatal yoga can improve maternal health and well-being and can have a beneficial effect on immune system functioning. To date, no study has been conducted in a rural, low-resource setting in India to assess the feasibility, acceptability, and preliminary efficacy of a yoga-based intervention on perceived stress, quality of life, pro-inflammatory biomarkers, and symptoms of upper respiratory tract infections.

METHODS: To address this gap and assess whether a yoga-based intervention could improve maternal mental health and immunity during the COVID-19 crisis (Yoga-M2 trial), a single-blind individual randomized parallel group-controlled pilot trial with a 1:1 allocation ratio was implemented. We randomly allocated 51 adult pregnant women, with gestational age between 12-24 weeks in the Yoga-M2 arm (n = 25) or the enhanced usual care arm (EUC) (n = 26). Feasibility and acceptability were assessed using the process data and In-Depth Interviews (IDIs) with the trial participants and yoga instructors. Multiple linear regression was used to compare follow-up scores for quantitative outcomes.

RESULTS: A three-month follow-up assessment was completed for 48 out of 51 participants (94.12%). We did not find any statistically significant difference between both arms in total Perceived Stress Scale scores, quality of life (Eq-5D-5L index), and serum C Reactive Protein levels at the three-month follow-up assessment. The critical barriers to practicing yoga were lack of knowledge about the benefits of yoga, lack of ‘felt need’ to practice yoga, lack of time to practice, lack of space, lack of transport, and lack of peer group to practice yoga. Despite this, women who regularly practiced yoga described the benefits and factors which motivated them to practice regularly.

DISCUSSION: The learnings from this trial will help design the explanatory trial in the future and the study findings can also be used by the primary health care system to deliver yoga-based interventions in the newly created health and wellness centers.

TRIAL REGISTRATION: This trial was prospectively registered with the Clinical Trials Registry of India on 25 January 2022. https://www.ctri.nic.in/Clinicaltrials/showallp.php?mid1=65173&EncHid=&userName=CTRI/2022/01/039701. Trial registration number: CTRI/2022/01/039701.

PMID:37200951 | PMC:PMC10185826 | DOI:10.3389/fnhum.2023.1115699

Front Nutr. 2023 May 2;10:1182445. doi: 10.3389/fnut.2023.1182445. eCollection 2023.

ABSTRACT

INTRODUCTION: Patient compliance with oral nutritional supplements (ONS) is not optimal for meeting energy and nutritional requirements in a high proportion of patients with disease-related malnutrition (DRM). Energy density or prescribed volume of ONS may impact compliance.

METHODS: A randomized, open-label crossover trial was conducted in outpatients with DRM to compare compliance with a high energy-dense ONS (edONS, 2.4 kcal/mL) and a reference ONS (heONS, 2.0 kcal/mL; NCT05609006). Patients were randomly assigned to two 8-week treatment sequences of four-weeks periods: edONS + heONS (sequence A) or heONS + edONS (sequence B). Patients daily reported the amount of product left over gastrointestinal tolerance and satisfaction with ONS. A non-inferiority analysis was performed to compare the compliance rate (percentage of consumed energy over the prescribed) for each period and sequence.

RESULTS: Fifty-three patients were assigned to sequence A and 50 to sequence B (55.7 ± 13.9 years, 37.0% female, 67.1% oncology patients). In sequence A, the compliance rates were 88.6% ± 14.3% vs. 84.1 ± 21.8% (p = 0.183), while in sequence B, they were 78.9% ± 23.8% vs. 84.4% ± 21.4% (p < 0.01). In both sequences, the lower range of the confidence interval for compliance with edONS was greater than the non-inferiority threshold (for sequence A Δ_Comp^A was 4.5% [95% CI, -2.0% to 10.0%], and for sequence, B Δ_Comp^B was 5.6% [95% CI, -3.0% to 14.0%]). The total discarded cost for each ONS was higher for heONS than edONS, being the difference statistically significant in sequence B. BMI increased slightly and not significantly in both sequences, and the percentage of patients with severe malnutrition was reduced. The frequency of gastrointestinal symptoms was low for both sequences, and satisfaction with ONS was slightly higher for edONS.

CONCLUSION: Our findings highlight that edONS was non-inferior to heONS in terms of consumed energy over the prescribed, with a lower amount of edONS discarded, which suggests a higher efficiency of edONS.

PMID:37200944 | PMC:PMC10186345 | DOI:10.3389/fnut.2023.1182445

J Med Internet Res. 2023 May 18;25:e41048. doi: 10.2196/41048.

ABSTRACT

BACKGROUND: European national disparities in the integration of data linkage (ie, being able to match patient data between databases) into routine public health activities were recently highlighted. In France, the claims database covers almost the whole population from birth to death, offering a great research potential for data linkage. As the use of a common unique identifier to directly link personal data is often limited, linkage with a set of indirect key identifiers has been developed, which is associated with the linkage quality challenge to minimize errors in linked data.

OBJECTIVE: The aim of this systematic review is to analyze the type and quality of research publications on indirect data linkage on health product use and care trajectories in France.

METHODS: A comprehensive search for all papers published in PubMed/Medline and Embase databases up to December 31, 2022, involving linked French database focusing on health products use or care trajectories was realized. Only studies based on the use of indirect identifiers were included (ie, without a unique personal identifier available to easily link the databases). A descriptive analysis of data linkage with quality indicators and adherence to the Bohensky framework for evaluating data linkage studies was also realized.

RESULTS: In total, 16 papers were selected. Data linkage was performed at the national level in 7 (43.8%) cases or at the local level in 9 (56.2%) studies. The number of patients included in the different databases and resulting from data linkage varied greatly, respectively, from 713 to 75,000 patients and from 210 to 31,000 linked patients. The diseases studied were mainly chronic diseases and infections. The objectives of the data linkage were multiple: to estimate the risk of adverse drug reactions (ADRs; n=6, 37.5%), to reconstruct the patient’s care trajectory (n=5, 31.3%), to describe therapeutic uses (n=2, 12.5%), to evaluate the benefits of treatments (n=2, 12.5%), and to evaluate treatment adherence (n=1, 6.3%). Registries are the most frequently linked databases with French claims data. No studies have looked at linking with a hospital data warehouse, a clinical trial database, or patient self-reported databases. The linkage approach was deterministic in 7 (43.8%) studies, probabilistic in 4 (25.0%) studies, and not specified in 5 (31.3%) studies. The linkage rate was mainly from 80% to 90% (reported in 11/15, 73.3%, studies). Adherence to the Bohensky framework for evaluating data linkage studies showed that the description of the source databases for the linkage was always performed but that the completion rate and accuracy of the variables to be linked were not systematically described.

CONCLUSIONS: This review highlights the growing interest in health data linkage in France. Nevertheless, regulatory, technical, and human constraints remain major obstacles to their deployment. The volume, variety, and validity of the data represent a real challenge, and advanced expertise and skills in statistical analysis and artificial intelligence are required to treat these big data.

PMID:37200084 | DOI:10.2196/41048

Interact J Med Res. 2023 May 18;12:e42060. doi: 10.2196/42060.

ABSTRACT

BACKGROUND: Learning in the operating room (OR) for residents in anesthesiology is difficult but essential for successful resident education. Numerous approaches have been attempted in the past to varying degrees of success, with efficacy often judged afterward using surveys distributed to participants. The OR presents a particularly complex set of challenges for academic faculty due to the pressures required by concurrent patient care, production pressures, and a noisy environment. Often, educational reviews in ORs are personnel specific, and instruction may or may not take place in this setting, as it is left to the discretion of the parties without regular direction.

OBJECTIVE: This study aims to determine if a structured intraoperative keyword training program could be used to implement a curriculum to improve teaching in the OR and to facilitate impactful discussion between residents and faculty. A structured curriculum was chosen to allow for the standardization of the educational material to be studied and reviewed by faculty and trainees. Given the reality that educational reviews in the OR tend to be personnel specific and are often focused on the clinical cases of the day, this initiative sought to increase both the time and efficiency of learning interactions between learners and teachers in the stressful environment of the OR.

METHODS: The American Board of Anesthesiology keywords from the Open Anesthesia website were used to construct a weekly intraoperative didactic curriculum, which was distributed by email to all residents and faculty. A weekly worksheet from this curriculum included 5 keywords with associated questions for discussion. The residents and faculty were instructed to complete these questions on a weekly basis. After 2 years, an electronic survey was distributed to the residents to evaluate the efficacy of the keyword program.

RESULTS: A total of 19 teaching descriptors were polled for participants prior to and following the use of the intraoperative keyword program to assess the efficacy of the structured curriculum. The survey results showed no improvement in intraoperative teaching based on respondent perception, despite a slight improvement in teaching time, though this was statistically insignificant. The respondents reported some favorable aspects of the program, including the use of a set curriculum, suggesting that greater structure may be beneficial to facilitate more effective intraoperative teaching in anesthesiology.

CONCLUSIONS: Although learning is difficult in the OR for residents, the use of a formalized didactic curriculum, centered on daily keywords, does not appear to be a useful solution for residents and faculty. Further efforts are required to improve intraoperative teaching, which is well known to be a difficult endeavor for both teachers and trainees. A structured curriculum may be used to augment other educational modalities to improve the overall intraoperative teaching for anesthesia residents.

PMID:37200082 | DOI:10.2196/42060