Long-term outcomes and late toxicity of adult medulloblastoma treated with combined modality therapy: a contemporary single-institution experience

alexandrossfakianakis shared this article with you from Inoreader Long-term outcomes and late toxicity of adult medulloblastoma treated with combined modality therapy: a contemporary single-institution experience via Neuro-Oncology Advance Access Abstract Background Medulloblastoma (MB) is a rare central nervous system malignancy of adults, with limited contemporary studies to define treatment guidelines and expected late toxicity. Methods A single-center, retrospective study was conducted of patients age ≥18-years from 1997-2019 with MB and who were treated with postoperative radiotherapy. Late toxicity was defined as a minimum of 18-months from diagnosis. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analyses. Results Fifty-nine patients met criteria, with median age of 25-years (range 18-62y) and median follow-up of 6.5-years (range 0.7-23.1y). At diagnosis, 68% were standard-risk, 88% Chang M0, and 22% with anaplastic histology. Gross total resection was achieved in 75%; median craniospinal irradiation dose was 30.6Gy(relative biological effectiveness [RBE]), median total dose was 54.0Gy(RBE), 80 % received proton radiotherapy; 81% received chemotherapy. 5-year PFS and OS were 86.5% and 95.8%, respectively; 10-year PFS and OS were 83.9% and 90.7%, respectively. Anaplastic histology was associated with worse PFS (p=0.04). Among eight recurrences, 25% presented after 5-years. Most common grade ≥2 late toxicities were anxiety/depressive symptoms (30%), motor dysfunction (25%), and ototoxicity (22%). Higher posterior fossa radiation dose was associated with increased risk of late toxicity, including worse cognitive dysfunction (p = 0.05). Conclusions Adults with MB have favorable survival outcomes, but late failures and toxicity are not uncommon. Better understanding of prognostic factors, possibly from molecular subtyping, may help to define more personalized treatments for patients with high risk of recurrence and long-term treatment sequelae. View on Web

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Cumulative erythemal ultraviolet radiation and risk of cancer in three large US prospective cohorts

alexandrossfakianakis shared this article with you from Inoreader Cumulative erythemal ultraviolet radiation and risk of cancer in three large US prospective cohorts via American Journal of Epidemiology - Advance Access Abstract Ultraviolet radiation (UVR) exposure is the major risk factor for melanoma. However, epidemiologic studies on UVR and non-cutaneous cancers have reported inconsistent results, with some suggesting an inverse relationship potentially mediated by vitamin D. To address this, we examined three U.S. prospective cohorts, the Health Professionals Follow-Up Study (HPFS) (1986) and Nurses' Health Study (NHS) I and II (1976 and 1989), for associations between cumulative erythemal UVR and incident cancer risk, excluding non-melanoma skin cancer. We used a validated spatiotemporal model to calculate erythemal UVR. Participants (47,714 males; 212,449 females) were stratified into quintiles by cumulative average erythemal UVR, using the first quintile as reference for Cox proportional hazards regression analysis. In the multivariable-adjusted meta-analysis of all cohorts, compared to the lowest quintile, risk of any cancer was slightly increased across all o ther quintiles [highest quintile Hazard Ratio (HR),1.04; 95% Confidence Interval (CI),1.01,1.07; P-heterogeneity (P-het)=0.41]. All UVR quintiles were associated with similarly increased risk of any cancer excluding melanoma. As expected, erythemal UVR was positively associated with risk of melanoma (highest quintile HR,1.17; 95% CI,1.04,1.31; P-het=0.83). These findings suggest that elevated UVR is associated with increased risk of both melanoma and non-cutaneous cancers. View on Web

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MicroRNA Signature and Cellular Characterization of Undifferentiated and Differentiated House Ear Institute-Organ of Corti 1 (HEI-OC1) Cells

alexandrossfakianakis shared this article with you from Inoreader MicroRNA Signature and Cellular Characterization of Undifferentiated and Differentiated House Ear Institute-Organ of Corti 1 (HEI-OC1) Cells via JARO - Journal of the Association for Research in Otolaryngology via MedWorm.com This study therefore aimed to compare the miRNA profiles and cellular characteristics of HEI-OC1 cells cultured under permissive (P-HEI-OC1) and non-permissive (NP-HEI-OC1) conditions. A significant increase in the level of expression of tubulin β1 class VI(Tubb1), e-cadherin(Cdh1), espin(Espn), and SRY (sex determining region Y)-box2(Sox2) mRNAs was identified in non-permissive cells compared with permissive cells (P <  0.05, Kruskal–Wallis H test, 2-sided). miR-200 family, miR-34b/c, and miR-449a/b functionally related cluster miRNAs, rodent-specific maternally imprinted geneSfmbt2 intron 10th cluster miRNAs (-466a/ -467a), and miR-17 family were significantly (P <  0.05, Welch'st-test, 2-tailed) differentially expressed in non-permissive cells when compared with permi... View on Web

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Causal Effect of Chronic Pain on Mortality Through Opioid Prescriptions: Application of the Front-Door Formula

alexandrossfakianakis shared this article with you from Inoreader Causal Effect of Chronic Pain on Mortality Through Opioid Prescriptions: Application of the Front-Door Formula via Epidemiology - Current Issue Background: Chronic pain is the leading cause of disability worldwide and is strongly associated with the epidemic of opioid overdosing events. However, the causal links between chronic pain, opioid prescriptions, and mortality remain unclear. Methods: This study included 13,884 US adults aged ≥20 years who provided data on chronic pain in the National Health and Nutrition Examination Survey 1999–2004 with linkage to mortality databases through 2015. We employed the generalized form of the front-door formula within the structural causal model framework to investigate the causal effect of chronic pain on all-cause mortality mediated by opioid prescriptions. Results: We identified a total of 718 participants at 3 years of follow-up and 1260 participants at 5 years as having died from all causes. Opioid prescriptions increased the risk of all-cause mortality with an estimated odds ratio (OR) (95% confidence interval) = 1.5 (1.1, 1.9) at 3 years and 1.3 (1.1, 1.6) at 5 years. The front-door formula revealed that chronic pain increased the risk of all-cause mortality through opioid prescriptions; OR = 1.06 (1.01, 1.11) at 3 years and 1.03 (1.01, 1.06) at 5 years. Our bias analysis showed that our findings based on the front-door formula were likely robust to plausible sources of bias from uncontrolled exposure–mediator or mediator–outcome confounding. Conclusions: Chronic pain increased the risk of all-cause mortality through opioid prescriptions. Our findings highlight the importance of careful guideline-based chronic pain management to prevent death from possibly inappropriate opioid prescriptions driven by chronic pain. View on Web

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Prenatal Antidepressant Exposure and the Risk of Attention-deficit/Hyperactivity Disorder in Childhood: A Cohort Study With Triangulation

alexandrossfakianakis shared this article with you from Inoreader Prenatal Antidepressant Exposure and the Risk of Attention-deficit/Hyperactivity Disorder in Childhood: A Cohort Study With Triangulation via Epidemiology - Current Issue Background: Uncontrolled confounding from maternal depression and genetic and environmental factors is expected in studies investigating the effect of prenatal antidepressant exposure on the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood and may explain inconsistencies in the existing evidence. We aimed to assess this effect using triangulation. Methods: Using population-based health registries, we conducted a nationwide cohort study of all children born in Denmark between 1997 and 2017 and followed through 2018 for ADHD. We assessed the effect of prenatal antidepressant exposure on the risk of ADHD in childhood by comparing children with and without prenatal antidepressant exposure in terms of adjusted incidence rate ratios (IRRs), adjusted incidence rate differences (IRDs), and adjusted risk differences (RDs) and the associated 95% confidence intervals (CIs). We triangulated results from four different analytic approaches: an overall analysis, a negative control analysis, a sibling analysis, and a former-user analysis. Results: The overall study cohort consisted of 1,253,362 children, among whom 28,910 (2.3%) had prenatal antidepressant exposure. ADHD during follow-up was diagnosed among 1,411 (4.9%) of the exposed and in 37,196 (3.0%) of the unexposed children. Triangulation suggested an IRR of 1.09–1.15; an IRD less than 1 case/1,000 person-years, and an RD of 0.9%–2.2% over an up to 18-year period. Conclusions: Based on triangulation, we estimated a modest effect of prenatal antidepressant exposure on the risk of ADHD in childhood. However, considering the limitations of our approaches, this observed association may be partially due to residual biases. See video abstract at, http://links.lww.com/EDE/B935. View on Web

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Use of Recently Vaccinated Individuals to Detect Bias in Test-Negative Case–Control Studies of COVID-19 Vaccine Effectiveness

alexandrossfakianakis shared this article with you from Inoreader Use of Recently Vaccinated Individuals to Detect Bias in Test-Negative Case–Control Studies of COVID-19 Vaccine Effectiveness via Epidemiology - Current Issue Postauthorization observational studies play a key role in understanding COVID-19 vaccine effectiveness following the demonstration of efficacy in clinical trials. Although bias due to confounding, selection bias, and misclassification can be mitigated through careful study design, unmeasured confounding is likely to remain in these observational studies. Phase III trials of COVID-19 vaccines have shown that protection from vaccination does not occur immediately, meaning that COVID-19 risk should be similar in recently vaccinated and unvaccinated individuals, in the absence of confounding or other bias. Several studies have used the estimated effectiveness among recently vaccinated individuals as a negative control exposure to detect bias in vaccine effectiveness estimates. In this paper, we introduce a theoretical framework to describe the interpretation of such a bias indicator in test-negative studies, and outline strong assumptions that would allow vaccine effectiveness among recently vaccinated individuals to serve as a negative control exposure. View on Web

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Gestational hypertensive disorders and maternal breast cancer risk in a nationwide cohort of 40,720 parous women

alexandrossfakianakis shared this article with you from Inoreader Gestational hypertensive disorders and maternal breast cancer risk in a nationwide cohort of 40,720 parous women via Epidemiology - Published Ahead-of-Print Background: Pre-eclampsia and gestational hypertension are hypothesized to be associated with reduced maternal breast cancer risk, but the epidemiologic evidence is inconclusive. Our objective was to examine associations between gestational hypertensive disorders and breast cancer in a nationwide cohort of women with a family history of breast cancer. Methods: Women ages 35-74 years who had a sister previously diagnosed with breast cancer, but had never had breast cancer themselves, were enrolled in the Sister Study from 2003-2009 (N=50,884). At enrollment, participants reported diagnoses of eclampsia, pre-eclampsia, or gestational hypertension in each pregnancy. We used Cox proportional hazards models to estimate HRs and 95% CIs for the association between history of a gestational hypertensive disorder and incident invasive breast cancer or ductal carcinoma in situ among 40,720 parous women. We used age as the time scale and adjusted for birth cohort, race–ethnicity, and reproductive, socioeconomic, and behavioral factors. We examined effect measure modification by risk factors for gestational hypertensive disease and breast cancer and assessed possible etiologic heterogeneity across tumor characteristics. Results: The prevalence of gestational hypertensive disease was 12%. During follow-up (mean=10.9 years), 3198 eligible women self-reported a breast cancer diagnosis. History of a gestational hypertensive disorder was not associated with breast cancer risk (HR=1.0, 95% CI 0.90, 1.1). We did not observe clear evidence of effect measure modification or etiologic heterogeneity. Conclusions: History of a gestational hypertensive disorder was not associated with breast cancer risk in a cohort of women with a first-degree family history of breast cancer. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. View on Web

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