Tag: nevin manimala

Lancet Oncol. 2023 Mar;24(3):286-296. doi: 10.1016/S1470-2045(23)00016-5. Epub 2023 Feb 14.

ABSTRACT

BACKGROUND: Adding immunotherapy to first-line chemotherapy might improve outcomes for patients with advanced or recurrent endometrial cancer. We aimed to compare carboplatin and paclitaxel versus avelumab plus carboplatin and paclitaxel as first-line treatment with avelumab given concurrent to chemotherapy and as maintenance after the end of chemotherapy.

METHODS: MITO END-3 is an open-label, randomised, controlled, phase 2 trial conducted at 31 cancer institutes, hospitals, and universities in Italy. Eligible patients were aged 18 years or older with histologically confirmed advanced (FIGO stage III-IV) or recurrent endometrial cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no previous systemic anticancer therapy as primary treatment for advanced or metastatic disease. Participants were randomly assigned (1:1) using a computerised minimisation procedure stratified by centre, histology, and stage at study entry, to either receive carboplatin (area under the curve [AUC] 5 mg/mL × min) and paclitaxel (175 mg/m²; standard group) intravenously every 3 weeks for six to eight cycles or avelumab (10 mg/kg intravenously) added to carboplatin and paclitaxel (experimental group) every 3 weeks and then every 2 weeks as a single maintenance treatment after the end of chemotherapy until disease progression or unacceptable toxicity. Patients, treating clinicians, and those assessing radiological examinations were not masked to study treatment. The primary endpoint was investigator-assessed progression-free survival, measured in the intention-to-treat (ITT) population. Patients who received at least one dose of study drug were included in the safety analysis. Experimental group superiority was tested with 80% power and one-tailed α 0·20. This trial is registered with ClinicalTrials.gov (NCT03503786) and EudraCT (2016-004403-31).

FINDINGS: From April 9, 2018, to May 13, 2021, 166 women were assessed for eligibility and 39 were excluded. 125 eligible patients were randomly assigned to receive carboplatin and paclitaxel (n=62) or avelumab plus carboplatin and paclitaxel (n=63) and included in the ITT population. The median follow-up was 23·3 months (IQR 13·2-29·6) and was similar between the two groups. 91 progression-free survival events were reported, with 49 events in 62 patients in the standard group and 42 events in 63 patients in the experimental group. The median progression-free survival was 9·9 months (95% CI 6·7-12·1) in the standard group and 9·6 months (7·2-17·7) in the experimental group (HR of progression or death 0·78 [60% CI 0·65-0·93]; one-tailed p=0·085). Serious adverse events were reported more frequently in the experimental group (24 vs seven events in the standard group); neutrophil count decrease was the most frequent grade 3-4 adverse event (19 [31%] of 61 patients in the experimental group vs 26 [43%] of 61 patients in the standard group). Two deaths occurred in the experimental group during treatment (one respiratory failure following severe myositis [possibly related to treatment] and one cardiac arrest [not related to treatment]).

INTERPRETATION: Adding avelumab to first-line chemotherapy deserves further testing in patients with advanced or recurrent endometrial cancer, although consideration of mismatch repair status is warranted.

FUNDING: Pfizer.

PMID:37052965 | DOI:10.1016/S1470-2045(23)00016-5

Invest Ophthalmol Vis Sci. 2023 Apr 3;64(4):15. doi: 10.1167/iovs.64.4.15.

ABSTRACT

PURPOSE: To determine if macular reticular pseudodrusen (RPD) were associated with markers of impaired macular choroidal perfusion, we investigated measurements of macular choriocapillaris (CC) flow deficits (FDs), CC thickness, and mean choroidal thickness (MCT) in eyes with macular RPD compared with normal eyes and eyes with soft drusen.

METHODS: Eyes with intermediate age-related macular degeneration (iAMD) and normal eyes underwent 6 × 6 mm swept-source optical coherence tomography angiography (SS-OCTA) imaging to diagnose macular RPD, occupying over 25% of the fovea-centered 5 mm diameter circle, and measure outer retinal layer (ORL) thickness, CC FDs, CC thickness, MCT, and choroidal vascularity index (CVI) using previously published strategies within the same fovea-centered 5 mm circle.

RESULTS: Ninety eyes were included; 30 normal eyes, 30 eyes with soft drusen, and 30 eyes with macular RPD. The RPD eyes showed higher macular CC FDs than normal eyes (P < 0.001) and soft drusen eyes (P = 0.019). Macular CC thickness was decreased in RPD eyes compared with normal eyes (P < 0.001) and soft drusen eyes (P = 0.016). Macular MCT in RPD eyes was thinner than normal eyes (P = 0.005) and soft drusen eyes (P < 0.001). No statistically and clinically significant differences were found in the ORL thickness and CVI measurements between RPD eyes and the other two groups (all P > 0.05).

CONCLUSIONS: Eyes with macular RPD had decreased macular CC perfusion, decreased CC thickness, and decreased MCT measurements compared with normal and soft drusen eyes, suggesting that RPD may result from impaired choroidal perfusion.

PMID:37052925 | DOI:10.1167/iovs.64.4.15

J Autism Dev Disord. 2023 Apr 13. doi: 10.1007/s10803-023-05977-w. Online ahead of print.

ABSTRACT

The Repetitive Behaviours Questionnaire for Adults (RBQ-2A) measures two factors of restricted and repetitive behaviours (RRBs) associated with autism. However, the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) provides four criteria for RRBs: repetitive motor behaviours, insistence on sameness, restricted interests, and interest in sensory aspects of the environment (or atypical sensitivity). The current paper aimed to examine whether the RBQ-2A is a psychometrically sound measure of these four factors. Study 1 had university students (N = 368) complete the RBQ-2A and other related measures online and revealed that the RBQ-2A can assess the factors highlighted in the DSM-5 and that these four factors comprise a general RRB construct. Study 2 had individuals disclosing a diagnosis of autism (N = 283) complete the RBQ-2A and other related measures online and supported that this four-factor structure provided good psychometric properties. While the current paper provides findings for an online autistic population, further research is needed to generalize these findings to autistic individuals less likely to partake in online studies (e.g., those with intellectual or language disabilities). Overall, the results suggest that the RBQ-2A reliably and validly assesses RRBs.

PMID:37052863 | DOI:10.1007/s10803-023-05977-w

J Magn Reson Imaging. 2023 Apr 13. doi: 10.1002/jmri.28734. Online ahead of print.

ABSTRACT

BACKGROUND: Papilledema is thought to be the hallmark sign of increased intracranial pressure (ICP). Distension of the subarachnoid space within the optic nerve sheath is also commonly reported in MR studies as an indirect sign of increased ICP.

HYPOTHESIS: General anesthesia and positive pressure ventilation might result in changes in optic sheath diameter (OSD) observed on clinical brain MRI.

STUDY TYPE: Retrospective.

POPULATION: One hundred forty-five patients (154 MRI scans, 7.3 years ± 5.1); 97 studies in the anesthesia group (4.4 years ± 3.4) of which 22 had papilledema, and 57 in the non-anesthesia group (12.3 years ± 3.2), of which 28 had papilledema.

FIELD STRENGTH/SEQUENCE: 1.5T or 3.0T volumetric T2 images. T2 images were obtained from different vendors.

ASSESSMENT: OSD, optic nerve diameter (OND), and peri-optic cerebrospinal fluid (CSF) were measured manually on T2-weighted MR images for various population subgroups (with and without anesthesia; with or without papilledema). The correlation between these measurements and the clinical diagnosis of papilledema was evaluated via receiver operating characteristic (ROC) analysis.

STATISTICAL TESTS: Chi-square test; Mann-Whitney Test; Spearman’s test and ROCs; Interclass correlation coefficient, P = 0.05.

RESULTS: General anesthesia resulted in significantly larger mean OSD in patients with or without papilledema (7.3 ± 1.0 mm vs. 6.1 ± 1.1 mm and 6.7 ± 1.0 mm vs. 5.4 ± 0.9 mm, respectively). In the non-anesthesia group, the average OSD values (6.1 ± 1.1 mm) were significantly higher in papilledema patients compared to non-papilledema patients (5.4 ± 0.9 mm), with larger peri-optic CSF rim (1.6 ± 0.4 mm vs. 1.3 ± 0.3 mm). In the anesthesia group, OND was significantly larger in papilledema patients (3.4 ± 0.4 mm vs. 3.1 ± 0.5 mm), though the average peri-optic CSF rim did not reach a significance in papilledema compared with non-papilledema patients (2.0 ± 0.3 mm vs. 1.8 ± 0.4 mm, P = 0.06). In patients with general anesthesia, peri-optic CSF rim had a limited correlation with increased ICP.

DATA CONCLUSION: In the pediatric population, imaging findings of increased OSD on brain MRI might be related to general anesthesia rather than increased ICP. The interpretation of optic nerve sheath distention should be reported cautiously in conjunction with anesthesia status, especially in the pediatric population.

EVIDENCE LEVEL: 4 Technical Efficacy: 5.

PMID:37052820 | DOI:10.1002/jmri.28734

3D Print Med. 2023 Apr 13;9(1):10. doi: 10.1186/s41205-023-00176-w.

ABSTRACT

BACKGROUND: 3D (three-dimensional) printing has been adopted by the medical community in several ways, procedure planning being one example. This application of technology has been adopted by several subspecialties including interventional radiology, however the planning of transjugular intrahepatic portosystemic shunt (TIPS) placement has not yet been described. The impact of a 3D printed model on procedural measures such as procedure time, radiation exposure, intravascular contrast dosage, fluoroscopy time, and provider confidence has also not been reported.

METHODS: This pilot study utilized a quasi-experimental design including patients who underwent TIPS. For the control group, retrospective data was collected on patients who received a TIPS prior to Oct 1, 2020. For the experimental group, patient-specific 3D printed models were integrated in the care of patients that received TIPS between Oct 1, 2020 and April 15, 2021. Data was collected on patient demographics and procedural measures. The interventionalists were surveyed on their confidence level and model usage following each procedure in the experimental group.

RESULTS: 3D printed models were created for six TIPS. Procedure time (p = 0.93), fluoroscopy time (p = 0.26), and intravascular contrast dosage (p = 0.75) did not have significant difference between groups. Mean radiation exposure was 808.8 mGy in the group with a model compared to 1731.7 mGy without, however this was also not statistically significant (p = 0.09). Out of 11 survey responses from interventionists, 10 reported “increased” or “significantly increased” confidence after reviewing the 3D printed model and all responded that the models were a valuable tool for trainees.

CONCLUSIONS: 3D printed models of patient anatomy can consistently be made using consumer-level, desktop 3D printing technology. This study was not adequately powered to measure the impact that including 3D printed models in the planning of TIPS procedures may have on procedural measures. The majority of interventionists reported that patient-specific models were valuable tools for teaching trainees and that confidence levels increased as a result of model inclusion in procedure planning.

PMID:37052816 | DOI:10.1186/s41205-023-00176-w

Curr Treat Options Oncol. 2023 Apr 13. doi: 10.1007/s11864-023-01071-6. Online ahead of print.

ABSTRACT

The need for evidence-based data in the rapidly growing group of older patients is vast and more elderly-specific studies are desperately needed, for which there is clear demand from both patients and providers. Notably, many of the studies discussed in this review included unplanned subset analyses based on age and/or were not originally stratified by age; therefore, these data, particularly overall survival data, need to be interpreted with some caution as they may not be statistically valid based on the initial trial design and statistical plan. As we await data from ongoing elderly-specific trials, our recommendation for managing older patients with CRC should include geriatric screening tools (e.g., CSGA, VES-13, G8, CARG, CRASH) to help guide treatment adjustments for improved tolerability without sacrificing efficacy. For patients with a positive screen for significant geriatric concerns, a full geriatric assessment is recommended to guide treatment approach and supportive care. Prior data support the use of all approved medications for CRC in older adults who are fit; however, treatment breaks and dose attenuation with potential escalation are reasonable options for these patients. Ultimately, management decisions in the care of older adults with mCRC must be made through shared decision-making with the patient with consideration for the patient’s functional status, comorbidities, goals of care, social support, as well as potential toxicities and possible effect on QoL.

PMID:37052812 | DOI:10.1007/s11864-023-01071-6

Environ Monit Assess. 2023 Apr 13;195(5):562. doi: 10.1007/s10661-023-11192-y.

ABSTRACT

The main objective of this research is to assess the impacts land use and land cover changes (LULC) on hydrological components using novel spatial models at sub-basin scales. The Soil and Water Assessment Tool (SWAT) was employed to analyze the long-term effect of LULC on hydrological components. The results of the calibrated and validated SWAT model demonstrated that run-off and actual evapotranspiration (ET) are expected to experience the largest increase, more than 130% and 90% in autumn, whereas the largest decrease is anticipated to occur in the summer and winter for potential evapotranspiration (PET) (-59%) and ET (-80%) by the projected time. The impacts of hydrological components, elevation, LULC, and an indicator of urbanization and land-use intensity (La) on water yield (WYLD) at sub-basin levels were then considered by four novel spatial models due to the problem of multicollinearity which is prevalent in traditional models. In particular, the Moran eigenvector spatially varying coefficients (MESVC) showed that the soil class out of LULC categories and lateral flow among hydrological properties are expected to have a statistically significant effect on spatial fluctuation of WYLD at the sub-basin scale. The results of spatially filtered unconditional quantile regression (SF-UQR) confirm the findings of the MESVC model and further implied that the lateral flow remains as a statistically significant contributor to WYLD only in lower quantiles (e.g., for quantiles lower than 0.25). The impacts of LULCs on WYLD were statistically lower than the effects caused by the hydrological components.

PMID:37052794 | DOI:10.1007/s10661-023-11192-y

Eur J Epidemiol. 2023 Apr 13. doi: 10.1007/s10654-023-01000-9. Online ahead of print.

ABSTRACT

Despite increasing therapeutic options to treat rheumatoid arthritis (RA), many patients fail to reach treatment targets. The use of antidiabetic drugs like thiazolidinediones has been associated with lower RA risk. We aimed to explore the repurposing potential of antidiabetic drugs in RA prevention by assessing associations between genetic variation in antidiabetic drug target genes and RA using Mendelian randomization (MR). A two-sample MR design was used to estimate the association between the antidiabetic drug and RA risk using summary statistics from genome-wide association studies (GWAS). We selected independent genetic variants from the gene(s) that encode the target protein(s) of the investigated antidiabetic drug as instruments. We extracted the associations of instruments with blood glucose concentration and RA from the UK Biobank and a GWAS meta-analysis of clinically diagnosed RA, respectively. The effect of genetic variation in the drug target(s) on RA risk was estimated by the Wald ratio test or inverse-variance weighted method. Insulin and its analogues, thiazolidinediones, and sulfonylureas had valid genetic instruments (n = 1, 1, and 2, respectively). Genetic variation in thiazolidinedione target (gene: PPARG) was inversely associated with RA risk (odds ratio [OR] 0.38 per 0.1mmol/L glucose lowering, 95% confidence interval [CI] 0.20-0.73). Corresponding ORs (95%CIs) were 0.83 (0.44-1.55) for genetic variation in the targets of insulin and its analogues (gene: INSR), and 1.12 (0.83, 1.49) 1.25 (0.78-2.00) for genetic variation in the sulfonylurea targets (gene: ABCC8 and KCNJ11). In conclusion, genetic variation in the thiazolidinedione target is associated with a lower RA risk. The underlying mechanisms warrant further exploration.

PMID:37052755 | DOI:10.1007/s10654-023-01000-9

Adv Health Sci Educ Theory Pract. 2023 Apr 13. doi: 10.1007/s10459-023-10219-w. Online ahead of print.

ABSTRACT

As one of the indicators reflecting student well-being in medical education practice, student satisfaction is no doubt an important topic. Instead of exploring student satisfaction from the perspectives of education quality and organizational factors, this study focused on student engagement to explore the impact of it on student satisfaction with medical education in China. Student engagement refers to students’ actions, efforts and persistence, indicating both time and energy students invested in educationally purposeful activities, especially academic activities. The data used in this study came from the first national survey of clinical undergraduates-the China Medical Student Survey-in which 10,062 clinical medical undergraduates in 33 medical schools participated. We developed a model of medical student engagement and satisfaction and utilized descriptive statistics, ordered logit regression, and path analysis to describe the relationship between medical student engagement and satisfaction. In this study, student engagement was categorized into behavioral, emotional and cognitive dimensions. The findings showed that medical student satisfaction was relatively low and was significantly affected by student satisfaction, especially the behavioral engagement in clinical rotations and professional identity of emotional engagement. These findings could put a supplementary perspective on improving student satisfaction through student engagement, and offer notable implications for future research and practice.

PMID:37052739 | DOI:10.1007/s10459-023-10219-w

Bull Environ Contam Toxicol. 2023 Apr 13;110(4):81. doi: 10.1007/s00128-023-03716-6.

ABSTRACT

This study was performed to evaluate the impact of microplastics and heavy metals (Pb, Cd, Cr, Cu, Zn, Ni) on sediments, water, aquatic plants (Pistia stratiotes, Alternanthera philoxeroides, and Ipomoea carnea), and fish (Labeo rohita) samples collected from five different sites in the Bajwat wetlands in Sialkot, Pakistan. The concentrations of Pb, Cd, and Cr were above the permissible limits devised by WHO in all the ecosystem components (i.e. sediments, water, plants, and fish) at all sites. The maximum amount of microplastic particles (2317 microplastic particles per kg of sediments) was recorded at Site 1. The filaments were the most commonly found type of microplastics. Plants and fish samples also showed considerable concentration of metals. The multivariate statistical analysis revealed anthropogenic sources of elevated concentrations of metal elements which could cause adverse biological effects in the ecosystem.

PMID:37052723 | DOI:10.1007/s00128-023-03716-6