Self-Reported Cardiovascular Disease and the Risk of Lung Cancer, the HUNT Study

Introduction:Inflammation is involved in development of lung cancer and cardiovascular disease (CVD), and we hypothesize that self-reported CVD is an independent risk factor for lung cancer.Methods:Data from the Nord-Trøndelag Health Study (1984–2008) linked to the Norwegian Cancer and Death Cause Registry were analyzed stratified by smoking status. In total, 97,087 persons (1,634,967 person years) were included (never smokers 567,575 person years, former smokers 295,685 person years, current smokers 444,922 person years, and unknown 326,785 person years) and followed for an average of 15 years. The proportional hazard model was applied to estimate the hazard ratio (HR) with a 95% confidence interval (CI) for self-reported CVD on lung cancer incidence rate adjusted for age, sex, body mass index, burden of tobacco smoking and chronic cough with phlegm.Results:1080 cases of lung cancer (1.1%) occurred. A total of 5981 (6.9%) participants had at baseline or developed during follow-up self-reported CVD. After adjusting for confounders, self-reported CVD was an independent risk factor for the development of lung cancer in former (HR [95% CI] 1.74 [1.11–2.73]) and current smokers (HR [95% CI] 1.38 [1.04–1.83]), but not in never smokers (HR [95% CI] 0.87 [0.34–2.23]).Conclusions:Self-reported CVD was independently associated with increased occurrence of lung cancer in former and current smokers. CVD may be a novel risk factor for lung cancer screening

Severe bradycardia and hypotension in anaesthetized pigs: Possible interaction between octreotide, xylazine, and atropine: A case series

Pigs are common animal models in diabetes research. Streptozotocin-induced destruction of pancreatic β-cells is used to induce diabetes in conscious pigs. However, in short-term non-recovery experiments, suppression of endogenous insulin secretion can be faster and more easily achieved with somatostatin analogues. We report a series of severe and unexpected episodes of severe bradycardia in eight pigs during non-recovery experiments with the original aim of investigating the pharmacokinetics and pharmacodynamics of intraperitoneal hormone delivery. The adverse events occurred four to five hours into the experiments, and we believe that they were caused by an interaction between the somatostatin analogue octreotide, and the sedative drug xylazine and that atropine delayed the time of occurrence

Basic lifestyle advice to individuals at high risk of type 2 diabetes : a 2-year population-based diabetes prevention study. The DE-PLAN intervention in the HUNT Study, Norway

Objective Among individuals at high risk for diabetes identified through a population survey, we performed an intervention study with basic lifestyle advice aiming to prevent diabetes. Research design and methods Among 50 806 participants in the HUNT3 Survey (2006-2008), 5297 individuals with Finnish Diabetes Risc Score (FINDRISC >= 15 were invited to an oral glucose tolerance test (OGTT) and an education session with lifestyle advice, and 2634 (49.7%) attended. Among them, 2380 people without diabetes were included in the prevention study with repeated examinations and education sessions after 6, 12, and 24 months. We examined participation, diabetes incidence, glycemia, and adiposity during follow-up. Results Of 2380 participants, 1212 (50.9%) participated in >= 3 of the four examinations. Diabetes was detected in 3.5%, 3.1%, and 4.0% of individuals at the 6-month, 12-month, and 24-month examinations, respectively, indicating a 10.3% 2-year diabetes incidence. Mean (95% CI) increases from baseline to 2-year follow-up were 0.30 (0.29 to 0.32) percentage points (3.3 (3.2 to 3.5) mmol/mol) for Hemoglobin A 1c, 0.13 (0.10 to 0.16) mmol/L for fasting serum-glucose, 0.46 (0.36 to 0.56) mmol/L for 2-hour OGTT s-glucose, 0.30 (0.19 to 0.40) kg/m(2) forbody mass index (BMI) (all p 5% weight loss during follow-up; their fasting and 2-hour s-glucose did not increase, and HbA 1c increased less than in other participants. Conclusion Basic lifestyle advice given to high-risk individuals during three group sessions with 6-month intervals was not effective in reducing 2-year diabetes risk.Peer reviewe

Maternal PCOS status and metformin in pregnancy: Steroid hormones in 5–10 years old children from the PregMet randomized controlled study

Objective: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, with potential effects on offspring both genetically and through altered intrauterine environment. Metformin, which ameliorate hormonal disturbances in non-pregnant women with PCOS is increasingly used in pregnancy. It passes the placenta, and the evidence on potential consequences for offspring endocrine development is scarce. We explore the potential effects of maternal PCOS status and intrauterine metformin exposure on offspring steroid hormone levels. Design: This is a follow-up study of 5–10 years old children from the PregMet-study–a randomized controlled trial comparing metformin (2000 mg/day) to placebo during PCOS pregnancies. Of the 255 children invited, 117 (46%) were included. Methods: There was no intervention in this follow-up study. Outcomes were serum levels of androstenedione, testosterone, SHBG, cortisol, 17-hydroxyprogesterone, 11-deoxycortisol and calculated free testosterone converted to gender-and age adjusted z-scores from a Norwegian reference population. These were compared in i) placebo-exposed children versus children from the reference population (z-score zero) by the deviation in z-score by one-sample t-tests and ii) metformin versus placebo-exposed children by two-sample t-tests. Holm-Bonferroni adjustments were performed to account for multiple endpoints. Results: Girls of mothers with PCOS (n = 30) had higher mean z-scores of androstenedione (0.73 (95% confidence interval (CI) 0.41 to 1.06), p<0.0001), testosterone (0.76 (0.51 to 1.00), p<0.0001), and free testosterone (0.99 (0.67 to 1.32), p<0.0001) than the reference population. Metformin-exposed boys (n = 31) tended to have higher 11-deoxycortisol z-score than placebo-exposed boys (n = 24) (mean difference 0.65 (95% CI 0.14–1.17), p = 0.014). Conclusion: Maternal PCOS status was associated with elevated androgens in 5- to 10-year-old daughters, which might indicate earlier maturation and increased risk of developing PCOS. An impact of metformin in pregnancy on steroidogenesis in children born to mothers with PCOS cannot be excluded. Our findings need confirmation in studies that include participants that have entered puberty.publishedVersio

ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity