Outcome after proton beam therapy versus photon-based radiation therapy in childhood-onset craniopharyngioma patients — results of KRANIOPHARYNGEOM 2007

Background: Proton beam therapy (PBT) is being increas16ingly used to treat residual craniopharyngioma (CP) after hypothalamus-sparing surgery. Compared to photon-based radiation therapy (XRT) with PBT, less irradiation in the penumbra reduces the scattered dose to critical organs neighboring but outside the area of treatment, minimizing the risk of sequelae. Patients and methods: Between 2007 and 2019, 99 of 290 (34%) childhood-onset CP patients recruited in KRANIOPHARYNGEOM 2007 received external radiation therapy (RT) (65% PBT, 35% XRT). Outcome was analyzed in terms of survival, endocrinological and anthropometric parameters (BMI and height SDS), quality of life (QoL using PEDQOL), and functional capacity (FMH) with special regard to irradiation technique. Results: PBT became predominant (used in 43% and 72% of all irradiated patients registered within the first and second halves of the recruitment period, between 2008 and 2013 and 2013 and 2018, respectively). Five-year event-free survival rates after PBT or XRT were comparable (92% ± 4% vs. 91% ± 4%, p = 0.42) and higher than for the whole cohort since diagnosis, including non-RT patients (37% ± 4%). Radiation doses to the hypothalamus and pituitary did not differ between PBT and XRT. Endocrine deficits due to disturbances of the hypothalamic-pituitary axis (HPA) were already common before irradiation. During the first 5 years after CP diagnosis/RT, no differences between PBT, XRT, and non-RT CP patients concerning functional capacity and anthropometric parameters have been obtained. Only for the PEDQOL domain “physical function”, parental-assessed QoL was lower 12 months after PBT versus XRT or non-RT patients. Conclusion: QoL, functional capacity, degree of obesity, and endocrinopathy varied over time from diagnosis, but by 5 years, there was no significant difference between PBT and XRT upfront or delayed, nor was there any compromise in historic survival rates, which remained high >90%. RT of any type is extremely effective at stabilizing disease after hypothalamic-sparing surgery. The purported specific benefits of PBT-reducing sequelae are not proven in this study where the organ of critical interest is itself diseased, increasing an urgent need to better address and treat the tumor-induced endocrine harm from diagnosis in dedicated pituitary services. Other hypothesized benefits of PBT versus XRT on vascular events and secondary cancers await longer comparison. Clinical trial registration number: https://clinicaltrials.gov/study/, identifier NCT01272622

Vitamin A and D intake in pregnancy, infant supplementation, and asthma development:the Norwegian Mother and Child Cohort

Background Western diets may provide excess vitamin A, which is potentially toxic and could adversely affect respiratory health and counteract benefits from vitamin D. Objective The aim of this study was to examine child asthma at age 7 y in relation to maternal intake of vitamins A and D during pregnancy, infant supplementation with these vitamins, and their potential interaction. Design We studied 61,676 school-age children (born during 2002–2007) from the Norwegian Mother and Child Cohort with data on maternal total (food and supplement) nutrient intake in pregnancy (food-frequency questionnaire validated against biomarkers) and infant supplement use at age 6 mo (n = 54,142 children). Linkage with the Norwegian Prescription Database enabled near-complete follow-up (end of second quarter in 2015) for dispensed medications to classify asthma. We used log-binomial regression to calculate adjusted RRs (aRRs) for asthma with 95% CIs. Results Asthma increased according to maternal intake of total vitamin A [retinol activity equivalents (RAEs)] in the highest (≥2031 RAEs/d) compared with the lowest (≤779 RAEs/d) quintile (aRR: 1.21; 95% CI: 1.05, 1.40) and decreased for total vitamin D in the highest (≥13.6 µg/d) compared with the lowest (≤3.5 µg/d) quintile (aRR: 0.81; 95% CI: 0.67, 0.97) during pregnancy. No association was observed for maternal intake in the highest quintiles of both nutrients (aRR: 0.99; 95% CI: 0.83, 1.18) and infant supplementation with vitamin D or cod liver oil. Conclusions Excess vitamin A (≥2.5 times the recommended intake) during pregnancy was associated with increased risk, whereas vitamin D intake close to recommendations was associated with a reduced risk of asthma in school-age children. No association for high intakes of both nutrients suggests antagonistic effects of vitamins A and D. This trial was registered at http://www.clinicaltrials.gov as NCT03197233. © 2018 American Society for Nutrition. This work is written by (a) US Government employee(s) and is in the public domain in the US

The use and applicability of Internet search queries for infectious disease surveillance in low- to middle-income countries

Uncontrolled outbreaks of emerging infectious diseases can pose threats to livelihoods and can undo years of progress made in developing regions, such as Sub-Saharan Africa. Therefore, the surveillance and early outbreak detection of infectious diseases, e.g., Dengue fever, is crucial. As a low-cost and timely source, Internet search queries data [e.g., Google Trends data (GTD)] are used and applied in epidemiological surveillance. This review aims to identify and evaluate relevant studies that used GTD in prediction models for epidemiological surveillance purposes regarding emerging infectious diseases. A comprehensive literature search in PubMed/MEDLINE was carried out, using relevant keywords identified from up-to-date literature and restricted to low- to middle-income countries. Eight studies were identified and included in the current review. Three focused on Dengue fever, three analyzed Zika virus infections, and two were about COVID-19. All studies investigated the correlation between GTD and the cases of the respective infectious disease; five studies used additional (time series) regression analyses to investigate the temporal relation. Overall, the reported positive correlations were high for Zika virus (0.75-0.99) or Dengue fever (0.87-0.94) with GTD, but not for COVID-19 (-0.81 to 0.003). Although the use of GTD appeared effective for infectious disease surveillance in low- to middle-income countries, further research is needed. The low costs and availability remain promising for future surveillance systems in low- to middle-income countries, but there is an urgent need for a standard methodological framework for the use and application of GTD

Intake of dietary fats and fatty acids and the incidence of type 2 diabetes: A systematic review and dose-response meta-analysis of prospective observational studies.

BackgroundThe role of fat quantity and quality in type 2 diabetes (T2D) prevention is controversial. Thus, this systematic review and meta-analysis aimed to investigate the associations between intake of dietary fat and fatty acids and T2D, and to evaluate the certainty of evidence.Methods and findingsWe systematically searched PubMed and Web of Science through 28 October 2019 for prospective observational studies in adults on the associations between intake of dietary fat and fatty acids and T2D incidence. The systematic literature search and data extraction were conducted independently by 2 researchers. We conducted linear and nonlinear random effects dose-response meta-analyses, calculated summary relative risks (SRRs) with their corresponding 95% confidence intervals (95% CIs), and assessed the certainty of evidence. In total, 15,070 publications were identified in the literature search after the removal of duplicates. Out of the 180 articles screened in full text, 23 studies (19 cohorts) met our inclusion criteria, with 11 studies (6 cohorts) conducted in the US, 7 studies (7 cohorts) in Europe, 4 studies (5 cohorts) in Asia, and 1 study (1 cohort) in Australia. We mainly observed no or weak linear associations between dietary fats and fatty acids and T2D incidence. In nonlinear dose-response meta-analyses, the protective association for vegetable fat and T2D was steeper at lower levels up to 13 g/d (SRR [95% CI]: 0.81 [0.76; 0.88], pnonlinearity = 0.012, n = 5 studies) than at higher levels. Saturated fatty acids showed an apparent protective association above intakes around 17 g/d with T2D (SRR [95% CI]: 0.95 [0.90; 1.00], pnonlinearity = 0.028, n = 11). There was a nonsignificant association of a decrease in T2D incidence for polyunsaturated fatty acid intakes up to 5 g/d (SRR [95% CI]: 0.96 [0.91; 1.01], pnonlinearity = 0.023, n = 8), and for alpha-linolenic acid consumption up to 560 mg/d (SRR [95% CI]: 0.95 [0.90; 1.00], pnonlinearity = 0.014, n = 11), after which the curve rose slightly, remaining close to no association. The association for long-chain omega-3 fatty acids and T2D was approximately linear for intakes up to 270 mg/d (SRR [95% CI]: 1.10 [1.06; 1.15], pnonlinearity ConclusionsThere was no association between total fat intake and the incidence of T2D. However, for specific fats and fatty acids, dose-response curves provided insights for significant associations with T2D. In particular, a high intake of vegetable fat was inversely associated with T2D incidence. Thus, a diet including vegetable fat rather than animal fat might be beneficial regarding T2D prevention

Moderators of exercise effects on self-reported cognitive functioning in cancer survivors: an individual participant data meta-analysis

Purpose: This individual participant data meta-analysis (IPD-MA) assesses exercise effects on self-reported cognitive functioning (CF) and investigates whether effects differ by patient-, intervention-, and exercise-related characteristics. Methods: IPD from 16 exercise RCTs, including 1987 patients across multiple types of non-metastatic cancer, was pooled. A one-stage IPD-MA using linear mixed-effect models was performed to assess exercise effects on self-reported CF (z-score) and to identify whether the effect was moderated by sociodemographic, clinical, intervention- and exercise-related characteristics, or fatigue, depression, anxiety, and self-reported CF levels at start of the intervention (i.e., baseline). Models were adjusted for baseline CF and included a random intercept at study level to account for clustering of patients within studies. A sensitivity analysis was performed in patients who reported cognitive problems at baseline. Results: Minimal significant beneficial exercise effects on self-reported CF (β=−0.09 [−0.16; −0.02]) were observed, with slightly larger effects when the intervention was delivered post-treatment (n=745, β=−0.13 [−0.24; −0.02]), and no significant effect during cancer treatment (n=1,162, β=−0.08 [−0.18; 0.02]). Larger effects were observed in interventions of 12 weeks or shorter (β=−0.14 [−0.25; −0.04]) or 24 weeks or longer (β=−0.18 [−0.32; −0.02]), whereas no effects were observed in interventions of 12–24 weeks (β=0.01 [−0.13; 0.15]). Exercise interventions were most beneficial when provided to patients without anxiety symptoms (β=−0.10 [−0.19; −0.02]) or after completion of treatment in patients with cognitive problems (β=−0.19 [−0.31; −0.06]). No other significant moderators were identified. Conclusions: This cross-cancer IPD meta-analysis observed small beneficial exercise effects on self-reported CF when the intervention was delivered post-treatment, especially in patients who reported cognitive problems at baseline. Implications for Cancer Survivors: This study provides some evidence to support the prescription of exercise to improve cognitive functioning. Sufficiently powered trials are warranted to make more definitive recommendations and include these in the exercise guidelines for cancer survivors