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Nevin Manimala Statistics

Validation of a secondary dose check tool against Monte Carlo and analytical clinical dose calculation algorithms in VMAT

J Appl Clin Med Phys. 2021 Mar 18. doi: 10.1002/acm2.13209. Online ahead of print.

ABSTRACT

PURPOSE: Patient-specific quality assurance (QA) is very important in radiotherapy, especially for patients with highly conformed treatment plans like VMAT plans. Traditional QA protocols for these plans are time-consuming reducing considerably the time available for patient treatments. In this work, a new MC-based secondary dose check software (SciMoCa) is evaluated and benchmarked against well-established TPS (Monaco and Pinnacle3 ) by means of treatment plans and dose measurements.

METHODS: Fifty VMAT plans have been computed using same calculation parameters with SciMoCa and the two primary TPSs. Plans were validated with measurements performed with a 3D diode detector (ArcCHECK) by translating patient plans to phantom geometry. Calculation accuracy was assessed by measuring point dose differences and gamma passing rates (GPR) from a 3D gamma analysis with 3%-2 mm criteria. Comparison between SciMoCa and primary TPS calculations was made using the same estimators and using both patient and phantom geometry plans.

RESULTS: TPS and SciMoCa calculations were found to be in very good agreement with validation measurements with average point dose differences of 0.7 ± 1.7% and -0.2 ± 1.6% for SciMoCa and two TPSs, respectively. Comparison between SciMoCa calculations and the two primary TPS plans did not show any statistically significant difference with average point dose differences compatible with zero within error for both patient and phantom geometry plans and GPR (98.0 ± 3.0% and 99.0 ± 3.0% respectively) well in excess of the typical 95% clinical tolerance threshold.

CONCLUSION: This work presents results obtained with a significantly larger sample than other similar analyses and, to the authors’ knowledge, compares SciMoCa with a MC-based TPS for the first time. Results show that a MC-based secondary patient-specific QA is a clinically viable, reliable, and promising technique, that potentially allows significant time saving that can be used for patient treatment and a per-plan basis QA that effectively complements traditional commissioning and calibration protocols.

PMID:33735491 | DOI:10.1002/acm2.13209

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Effectiveness of Biofeedback Relaxation and Audio Visual Distraction on Dental Anxiety among 7 – 12 year Old Children while Administering Local Anesthesia: A Randomized Clinical Trial

Int J Paediatr Dent. 2021 Mar 18. doi: 10.1111/ipd.12787. Online ahead of print.

ABSTRACT

BACKGROUND: Local anesthesia (LA) administration provokes maximum dental anxiety in children. BrightHearts is a biofeedback relaxation application designed to reduce anxiety in children during pain inflicting procedural interventions.

AIM: To compare the effectiveness of biofeedback relaxation (BR) and audio visual distraction (AV) on dental anxiety among 7 – 12 year old children while administering LA DESIGN: A total of 70 children requiring dental treatment under LA for three visits were recruited for this single blinded randomized control trial. They were randomly divided into two equal groups. Group A received BR and the Group B received AV distraction during LA delivery in the first two visits and both groups did not receive any intervention during LA in third visit. Outcomes were measured using heart rate and a cartoon based anxiety measuring scale (Chotta Bheem Chutki (CBC) scale).

RESULTS: AV group had statistically significant higher mean heart rates than BR group (p<0.001) during needle penetration and post-intervention respectively. CBC scales showed no statistical differences between the groups.

CONCLUSION: Both the interventions are effective in reducing dental anxiety during LA administration. Based on objective measures, BR is found to be better than AV distraction. However subjective scores show no differences between the two.

PMID:33735517 | DOI:10.1111/ipd.12787

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SULF2 monoclonal antibody 5D5 suppresses human cholangiocarcinoma xenograft growth via regulation of a SULF2-PDGFRβ-YAP signaling axis

Hepatology. 2021 Mar 18. doi: 10.1002/hep.31817. Online ahead of print.

ABSTRACT

Existing therapeutic approaches to treat cholangiocarcinoma (CCA) have limited effectiveness, prompting further study to develop novel therapies for CCA. Here we report a novel mechanistic role for the heparan sulfate editing enzyme sulfatase 2 (SULF2) in CCA pathogenesis. In silico analysis revealed elevated SULF2 expression in human CCA samples, occurring partly through gain of SULF2 copy number. We examined the effects of knockdown or overexpression of SULF2 on tumor growth, chemoresistance, and signaling pathway activity in human CCA cell lines in vitro. Upregulation of SULF2 in CCA leads to increased PDGFRβ-YAP signaling activity, promoting tumor growth and chemotherapy resistance. To explore the utility of targeting SULF2 in the tumor microenvironment for CCA treatment, we tested an anti-SULF2 mouse monoclonal antibody 5D5 in a mouse CCA xenograft model. Targeting SULF2 by monoclonal antibody 5D5 inhibited PDGFRβ-YAP signaling and tumor growth in the mouse xenograft model. Conclusion: These results suggest that SULF2 monoclonal antibody 5D5 or related agents may be potentially promising new therapeutic agents in CCA.

PMID:33735525 | DOI:10.1002/hep.31817

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Suggested role of Silent Information Regulator 1 (SIRT1) Gene in Female Infertility: A Cross Sectional Study in Pakistan

Int J Clin Pract. 2021 Mar 18:e14132. doi: 10.1111/ijcp.14132. Online ahead of print.

ABSTRACT

AIM & OBJECTIVE: Silent Information Regulator 1 (SIRT1) gene stimulates the expression of antioxidants and repairs damaged cells. It affects the mitochondrial activity within the oocytes to overcome the oxidant stress. We aimed to assess an association of SIRT1 polymorphism (Tag SNPs rs10509291 and rs12778366) with fertility, and assess serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, manganese superoxide (MnSOD) and SIRT1.

MATERIAL AND METHODS: In this cross-sectional study, 207 fertile and 135 infertile subjects between the ages of 18-45 year were recruited. Polymerase chain reaction (PCR) was performed; products were electrophoresed in a 2% agarose gel. Descriptive analysis of continuous variables was expressed as mean ± standard deviation. Mann-Whitney test was performed for comparison of groups, p value <0.001 was considered significant. Single Nucleotide Polymorphism (SNP) data was analyzed by applying chi-squared statistics.

RESULTS: All subjects were age matched (p = 0.896). SIRT1 levels were significantly lower in infertile females when compared with fertile subjects (p<0.001). AA (rs10509291) and CC (rs12778366) variant frequency was higher in the infertile than fertile subjects (p<0.01). Similarly, the frequency of A allele (rs10509291) and C allele (rs12778366) was higher in infertile subjects (p<0.001). Infertile females (29%) showed existence of SNP rs10509291 while 49% demonstrated genetic variation of rs12778366. MnSOD and SIRT1 levels were found to be lower in these subjects.

CONCLUSION: Presence of SIRT1 genetic variants (rs10509291 and rs12778366) apparently disturbs the expression of SIRT1 deteriorating mitochondrial antioxidant function within the oocytes, instigating oxidative stress within. Their probable effect on modulating oocyte maturation may be the cause of infertility in females.

PMID:33735475 | DOI:10.1111/ijcp.14132

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Maintaining Changes in Physical Activity among Type 2 Diabetics – A Systematic Review of Rehabilitation Interventions

Scand J Med Sci Sports. 2021 Mar 18. doi: 10.1111/sms.13951. Online ahead of print.

ABSTRACT

The prevalence of Type 2 diabetes mellitus (T2DM) is increasing worldwide and physical activity (PA) is a suitable way of preventing and managing the disease. However, improving long-term levels of PA in people with T2DM is a challenge and the best approach to rehabilitation in this regard is unknown. With the aim of outlining the existing knowledge regarding the maintenance of active lifestyles among people with T2DM after rehabilitation programmes and gaining knowledge about options and challenges for their long-term engagement in PA, a systematic review of original research articles assessing PA after rehabilitation programmes was conducted. Two-thousand-two-hundred-and-fourty-one articles were identified through PubMed or secondary sources and subjected to various inclusion criteria. Only articles published between the 1st of January 2000 and the 30th of June 2020 were considered. Additionally, the minimum time frame from intervention start to last PA assessment was 6 months and only articles based on interventions performed in Europe were included. The review was based on eighteen randomised controlled trials, four randomised trials without control and four case studies. The 26 articles described 30 interventions that were categorized as personalized counselling, generalized teaching, supervised exercise or a combination of personalized and generalized interventions. Statistical and narrative syntheses revealed no clear pattern regarding the effectiveness in eliciting maintained changes in PA. However, across categories, individual involvement, goal setting, social support and the formation of habits are argued to be important components in sustaining PA and relieving challenges associated with the transition out of rehabilitation programmes.

PMID:33735484 | DOI:10.1111/sms.13951

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Digital anatomic table in teaching-learning process of the temporomandibular joint anatomy

Eur J Dent Educ. 2021 Mar 18. doi: 10.1111/eje.12680. Online ahead of print.

ABSTRACT

INTRODUCTION: The use of teaching resources and digital objects has gradually been incorporated into dental schools. This study aimed to evaluate the digital anatomy table in teaching-learning process of the temporomandibular joint (TMJ) anatomy and the student’s perception regarding this resource.

METHODS: A cross-sectional study was conducted on 41 undergraduate dental students. knowledge assessment tests were applied at different time intervals: before and after the TMJ theoretical class, after the practical class on prosected specimens and after the use of digital anatomy table. The medians of the scores obtained in the three groups (theoretical class, practical class, and digital table) were descriptively analyzed and submitted to Wilcoxon, Kruskal-Wallis and Student-Newman-Keuls statistical tests. The perception survey was conducted at the end of the study.

RESULTS: When the teaching strategies were compared among each other, the medians of the scores with the digital anatomy table were significantly higher than after the theoretical and practical classes. At the end of the research, there were no differences among the three groups (theoretical class, practical class and digital table). Regarding the perception, the majority of the students reported that the digital anatomy table helped them to understand the content of the theoretical class.

CONCLUSION: It was concluded that learning with the use of the digital anatomy table did not increase the knowledge of dental students with respect to the TMJ anatomy. The students’ perceptions of the digital anatomy table were positive and that it could be used as an additional resource in the teaching-learning process.

PMID:33735486 | DOI:10.1111/eje.12680

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Diffuse Large B-cell Lymphoma Segmentation in PET-CT Images via Hybrid Learning for Feature Fusion

Med Phys. 2021 Mar 18. doi: 10.1002/mp.14847. Online ahead of print.

ABSTRACT

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of lymphoma with high mortality and poor prognosis that especially has a high incidence in Asia. Accurate segmentation of DLBCL lesions is crucial for clinical radiation therapy. However, manual delineation of DLBCL lesions is tedious and time-consuming. Automatic segmentation provides an alternative solution but is difficult for diffuse lesions without the sufficient utilization of multi-modality information. Our work is the first study focusing on positron emission tomography and computed tomography (PET-CT) feature fusion for the DLBCL segmentation issue. We aim to improve the fusion performance of complementary information contained in PET-CT imaging with a hybrid learning module in the supervised convolutional neural network.

METHODS: First, two encoder branches extract single-modality features, respectively. Next, the hybrid learning component utilizes them to generate spatial fusion maps which can quantify the contribution of complementary information. Such feature fusion maps are then concatenated with specific-modality (i.e. PET and CT) feature maps to obtain a representation of the final-fused feature maps in different scales. Finally, the reconstruction part of our network creates a prediction map of DLBCL lesions by integrating and up-sampling the final-fused feature maps from encoder blocks in different scales.

RESULTS: The ability of our method was evaluated to detect foreground and segment lesions in three independent body regions (nasopharynx, chest, and abdomen) of a set of 45 PET-CT scans. Extensive ablation experiments compared our method to four baseline techniques for multi-modality fusion (input-level (IL) fusion, multi-channel (MC) strategy, multi-branch (MB) strategy, and quantitative weighting (QW) fusion). The results showed that our method achieved a high detection accuracy (99.63% in the nasopharynx, 99.51% in the chest, and 99.21% in the abdomen) and had the superiority in segmentation performance with the mean dice similarity coefficient (DSC) of 73.03% and the modified Hausdorff Distance (MHD) of 4.39 mm, when compared with the baselines (DSC: IL: 53.08%, MC: 63.59%, MB: 69.98%, and QW: 72.19%; MHD: IL: 12.16 mm, MC: 6.46 mm, MB: 4.83 mm, and QW: 4.89 mm).

CONCLUSIONS: A promising segmentation method has been proposed for the challenging DLBCL lesions in PET-CT images, which improves the understanding of complementary information by feature fusion and may guide clinical radiotherapy. The statistically significant analysis based on p-value calculation has indicated a degree of significant difference between our proposed method and other baselines (almost metrics: p < 0.05). This is a preliminary research using a small sample size, and we will collect data continually to achieve the larger verification study.

PMID:33735451 | DOI:10.1002/mp.14847

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First-line antiepileptic drug treatment in glioma patients with epilepsy: Levetiracetam vs valproic acid

Epilepsia. 2021 Mar 18. doi: 10.1111/epi.16880. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed at estimating the cumulative incidence of antiepileptic drug (AED) treatment failure of first-line monotherapy levetiracetam vs valproic acid in glioma patients with epilepsy.

METHODS: In this retrospective observational study, a competing risks model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as a competing event. Patients were matched on baseline covariates potentially related to treatment assignment and outcomes of interest according to the nearest neighbor propensity score matching technique. Maximum duration of follow-up was 36 months.

RESULTS: In total, 776 patients using levetiracetam and 659 using valproic acid were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure for any reason was significantly lower for levetiracetam compared to valproic acid (12 months: 33% [95% confidence interval (CI) 29%-38%] vs 50% [95% CI 45%-55%]; P < .001). When looking at specific reasons of treatment failure, treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95% CI 12%-19%] vs 28% [95% CI 23%-32%]; P < 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95% CI 11%-18%] vs 15% [95% CI 11%-18%]; P = .636).

SIGNIFICANCE: Our results suggest that levetiracetam may have favorable efficacy compared to valproic acid, whereas level of toxicity seems similar. Therefore, levetiracetam seems to be the preferred choice for first-line AED treatment in patients with glioma.

PMID:33735464 | DOI:10.1111/epi.16880

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Chondrodermatitis nodularis helicis in the 21st century: demographic trends from a gender and age perspective. A single University hospital retrospective histopathological register study of 215 patients in Asturias, North Spain (2000-2017)

J Eur Acad Dermatol Venereol. 2021 Mar 18. doi: 10.1111/jdv.17234. Online ahead of print.

ABSTRACT

Chondrodermatitis nodularis helicis (CNH) is an exceptionally investigated disease1 . Male sex and old age characterize its demographic profile1-3 but this has not been recently investigated. With this aim, we performed this descriptive, retrospective, observational investigation including 215 patients histopathologically diagnosed of CNH at Central University Hospital of Asturias, northern Spain, (years 2000 to 2017). It was approved by the Hospital’s ethics committee. Univariate analyses were conducted by chi square test and Fisher Test. A 2-sided P value of 0.05 was considered statistically significant (R program; R Development Core Team, version 3.6.0).

PMID:33735466 | DOI:10.1111/jdv.17234

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Clinical predictors of discordance between screening tests and psychiatric assessment for depressive and anxiety disorders among patients being evaluated for seizure disorders

Epilepsia. 2021 Mar 18. doi: 10.1111/epi.16871. Online ahead of print.

ABSTRACT

OBJECTIVE: This study was undertaken to identify factors that predict discordance between the screening instruments Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and Generalized Anxiety Disorder scale (GAD-7), and diagnoses made by qualified psychiatrists among patients with seizure disorders. Importantly, this is not a validation study; rather, it investigates clinicodemographic predictors of discordance between screening tests and psychiatric assessment.

METHODS: Adult patients admitted for inpatient video-electroencephalographic monitoring completed eight psychometric instruments, including the NDDI-E and GAD-7, and psychiatric assessment. Patients were grouped according to agreement between the screening instrument and psychiatrists’ diagnoses. Screening was “discordant” if the outcome differed from the psychiatrist’s diagnosis, including both false positive and false negative results. Bayesian statistical analyses were used to identify factors associated with discordance.

RESULTS: A total of 411 patients met inclusion criteria; mean age was 39.6 years, and 55.5% (n = 228) were female. Depression screening was discordant in 33% of cases (n = 136/411), driven by false positives (n = 76/136, 56%) rather than false negatives (n = 60/136, 44%). Likewise, anxiety screening was discordant in one third of cases (n = 121/411, 29%) due to false positives (n = 60/121, 50%) and false negatives (n = 61/121, 50%). Seven clinical factors were predictive of discordant screening for both depression and anxiety: greater dissociative symptoms, greater patient-reported adverse events, subjective cognitive impairment, negative affect, detachment, disinhibition, and psychoticism. When the analyses were restricted to only patients with psychogenic nonepileptic seizures (PNES) or epilepsy, the rate of discordant depression screening was higher in the PNES group (n = 29, 47%) compared to the epilepsy group (n = 70, 30%, Bayes factor for the alternative hypothesis = 4.65).

SIGNIFICANCE: Patients with seizure disorders who self-report a variety of psychiatric and other symptoms should be evaluated more thoroughly for depression and anxiety, regardless of screening test results, especially if they have PNES and not epilepsy. Clinical assessment by a qualified psychiatrist remains essential in diagnosing depressive and anxiety disorders among such patients.

PMID:33735445 | DOI:10.1111/epi.16871