The role of lifestyle factors in the association between education and self-reported fibromyalgia: a mediation analysis.

BACKGROUND: Socioeconomic status as measured by education, income, or occupation, has been associated with fibromyalgia but the underlying mechanism and the role of lifestyle factors are unclear. Thus, we examine the role of modifiable lifestyle factors (body mass index, physical activity, alcohol consumption and smoking) in the association between education and self-reported fibromyalgia. METHODS: We used data from 74,157 participants in the population-based prospective Norwegian Women and Cancer (NOWAC) study. Socioeconomic position, operationalized as years of educational attainment, and lifestyle factors were assessed via self-reported questionnaires. Multiple mediation analysis was used to decompose total effects into direct and indirect effects. Estimates were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The cumulative incidence of fibromyalgia was 3.2% after a median follow up time of 13 years. Fibromyalgia was inversely associated with years of educational attainment for ≤ 9 years (HR = 2.56; 95% CI 2.32-2.91) and for 10-12 years (HR = 1.84; 95% CI 1.72-2.02), compared with ≥ 13 years of education. Overall, all lifestyle factors together jointly mediated 17.3% (95% CI 14.3-21.6) and 14.1% (95% CI 11.3-18.9) of the total effect for ≤ 9 years and 10-12 years of education, respectively. Smoking and alcohol consumption contributed the most to the proportion mediated, for ≤ 9 years (5.0% and 7.0%) and 10-12 years (5.6% and 4.5%) of education. CONCLUSION: The association between education and self-reported fibromyalgia was partly explained through lifestyle factors, mainly smoking and alcohol consumption.

Beverages - a scoping review for Nordic Nutrition Recommendations 2023.

Background: Coffee, tea, sugar-sweetened beverages (SSBs), and low- and no-calorie sweetened beverages (LNCSBs) are generally frequently consumed in the Nordic and Baltic countries. These beverages have also been related to potential health effects. This scoping review describes the evidence for the role of coffee, tea, SSBs, and LNCSBs for health-related outcomes as a basis for setting and updating food-based dietary guidelines. We used evidence from several qualified systematic reviews (i.e. World Cancer Research Fund, US Dietary Guidelines Advisory Committee, European Food Safety Authority, and World Health Organization) and performed a search for additional systematic reviews. The evidence suggests that moderate coffee and tea consumption do not have long-term adverse health effects. The long-term favorable effects of coffee consumption are related to reduced risk of endometrial and liver cancer, type 2 diabetes, and cardiovascular deaths. However, results from randomized controlled trials (RCTs) suggest that coffee brews that are rich in diterpenes, such as boiled coffee, increase serum cholesterol concentrations. High caffeine intake in pregnancy is associated with higher risk of pregnancy loss, preterm birth, and low birth weight. High consumption of SSBs has been associated with increased risk of obesity, type 2 diabetes, hypertension, and cardiovascular disease, based on data from RCTs and prospective cohort studies. The consumption of LNCSBs may result in a small reduction in body weight in adults, likely mediated through the effect of reduced energy intake, but has neutral effects on other cardiometabolic risk markers using evidence from RCTs. However, evidence from observational studies indicates increased risk of cardiometabolic diseases among high LNCSB consumers. In conclusion, current evidence suggests that moderate coffee and tea consumption have no long-term adverse health effects. The evidence of beneficial effects of coffee consumption on liver and endometrial cancer risk, and some cardiovascular outcomes, comes from observational studies. High consumption of boiled coffee should be avoided due to negative effect on lipid profile. Pregnant women should not exceed the recommended daily dose of caffeine intake of 200 mg set by the European Food Safety Authority as a safe level for the fetus. High consumption of SSBs has consistently been associated with adverse health effects, which is mainly due to excess energy intake, and should be limited. The conflicting results from RCTs and observational studies regarding LNCSBs may be due to revere causation and should be explored further.

A practical guide for the husbandry of cave and surface invertebrates as the first step in establishing new model organisms.

While extensive research on traditional model species has significantly advanced the biological sciences, the ongoing search for new model organisms is essential to tackle contemporary challenges such as human diseases or climate change, and fundamental phenomena including adaptation or speciation. Recent methodological advances such as next-generation sequencing, gene editing, and imaging are widely applicable and have simplified the selection of species with specific traits from the wild. However, a critical milestone in this endeavor remains the successful cultivation of selected species. A historically overlooked but increasingly recognized group of non-model organisms are cave dwellers. These unique animals offer invaluable insights into the genetic basis of human diseases like eye degeneration, metabolic and neurological disorders, and basic evolutionary principles and the origin of adaptive phenotypes. However, to take advantage of the beneficial traits of cave-dwelling animals, laboratory cultures must be established-a practice that remains extremely rare except for the cavefish Astyanax mexicanus. For most cave-dwelling organisms, there are no published culturing protocols. In this study, we present the results of our multi-year effort to establish laboratory cultures for a variety of invertebrate groups. We have developed comprehensive protocols for housing, feeding, and husbandry of cave dwellers and their surface relatives. Our recommendations are versatile and can be applied to a wide range of species. Hopefully our efforts will facilitate the establishment of new laboratory animal facilities for cave-dwelling organisms and encourage their greater use in experimental biology.

Circulating endogenous sex steroids and risk of differentiated thyroid carcinoma in men and women.

Thyroid cancer (TC) is substantially more common in women than in men, pointing to a possible role of sex steroid hormones. We investigated the association between circulating sex steroid hormones, sex hormone binding globulin (SHBG) and the risk of differentiated TC in men and women within the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. During follow-up, we identified 333 first primary incident cases of differentiated TC (152 in pre/peri-menopausal women, 111 in post-menopausal women, and 70 in men) and 706 cancer-free controls. Women taking exogenous hormones at blood donation were excluded. Plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estradiol, estrone and progesterone (in pre-menopausal women only) were performed using liquid chromatography/mass spectrometry method. SHBG concentrations were measured by immunoassay. Odds ratios (ORs) were estimated using conditional logistic regression models adjusted for possible confounders. No significant associations were observed in men and postmenopausal women, while a borderline significant increase in differentiated TC risk was observed with increasing testosterone (adjusted OR T3 vs T1: 1.68, 95% CI: 0.96-2.92, ptrend = .06) and androstenedione concentrations in pre/perimenopausal women (adjusted OR T3 vs T1: 1.78, 95% CI: 0.96-3.30, ptrend = .06, respectively). A borderline decrease in risk was observed for the highest progesterone/estradiol ratio (adjusted OR T3 vs T1: 0.54, 95% CI: 0.28-1.05, ptrend = .07). Overall, our results do not support a major role of circulating sex steroids in the etiology of differentiated TC in post-menopausal women and men but may suggest an involvement of altered sex steroid production in pre-menopausal women.

Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis.

PURPOSE: To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Our study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome. RESULTS: During a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14-1.34) and OAC (HR = 1.24, 95% CI 1.05-1.47). WHR mediated 5% (95% CI 3-10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6-53%) and 15% (95% CI 8-72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis. CONCLUSIONS: We reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).

Lifestyle risk factors of self-reported fibromyalgia in the Norwegian Women and Cancer (NOWAC) study.

BACKGROUND: While the aetiology of fibromyalgia syndrome (FM) remains unknown, lifestyle factors have been linked to the disorder. However, there are few studies on the association between lifestyle factors and FM, thus we examine the risk of self-reported fibromyalgia given selected lifestyle factors. METHODS: We used data from 75,485 participants in the Norwegian Women and Cancer study. Information on FM and the lifestyle factors body mass index (BMI), physical activity level, smoking status/intensity, and alcohol consumption were obtained from baseline and follow-up questionnaires. We used Cox proportional hazards model to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: After a median follow-up time of 10 years, we observed 2,248 cases of self-reported fibromyalgia. Overweight (BMI 25-29.9 kg/m2) and obese (BMI ≥ 30 kg/m2) women had a relative risk of 1.34 (95% CI 1.21-1.47) and 1.62 (95% CI 1.41-1.87), respectively, compared to women with normal weight (BMI 18.5-24.9 kg/m2). Very low physical activity level (1-2) was associated with a 31% higher risk of self-reported fibromyalgia (HR 1.31, 95% CI 1.09-1.57) when compared to moderate physical activity level (5-6). There was a strong dose-response relationship between smoking status/intensity and self-reported fibromyalgia (p for trend < 0.001). Compared with moderate alcohol consumption (4.0-10 g/day), the risk of self-reported FM was 72% (HR 1.72; 95% CI 1.45-2.03) higher among teetotallers, and 38% (HR 1.38, 95% CI 1.23-1.54) higher among those with low consumption (0.1-3.9 g/day). CONCLUSIONS: Overweight and obesity, very low physical activity level, smoking, and alcohol consumption were associated with an increased risk of self-reported FM.

The educational gradient in dental caries experience in Northern- Norway: a cross-sectional study from the seventh survey of the Tromsø study.

BACKGROUND: Although, studies from Norway indicate a reduction in dental caries experience, in Northern-Norway this non-communicable oral condition is still prevalent. There is conflicting evidence of presence of social inequalities in dental caries in an adult population. Therefore, the aim of this study was to assess an association between educational level and dental caries experience in adults in urban Tromsø municipality, Northern-Norway, using The World Health Organization (WHO) Commission on Social Determinants of Health (CSDH) framework of health determinants. METHODS: Data from 3752 participants having recorded dental caries status and educational level in the seventh survey of the Tromsø Study: Tromsø7 were included. Dental status was examined clinically as decayed-, missing-, filled-teeth (DMFT score). For statistical analyses DMFT score was grouped into lower (DMFT < 19) and higher (DMFT ≥ 20). Educational level was obtained from a questionnaire and categorized as primary/partly secondary education, upper secondary education, tertiary education, short and tertiary education, long. Data on social and intermediary determinants was also self-reported. Univariable and multivariable binary logistic regression analyses were applied. RESULT: This study included 1939 (52%) women and the mean age of the participants was 57.11. The mean DMFT score was 18.03. The odds of having higher DMFT score followed a gradient based on educational level. Participants who reported lower than secondary education had 2.06 -fold increased odds of having higher DMFT score than those with tertiary education, long (OR: 2.06, 95% CI: 1.50-2.83). Those with upper secondary education had 60% higher odds of having higher DMFT score (OR: 1.60, 95% CI: 1.21-2.11), and those with tertiary education, short had 66% higher odds of having higher DMFT score (OR: 1.66, 95% CI: 1.24-2.22). CONCLUSION: The current cross-sectional study suggested an educational gradient in dental caries experience in an adult population of Northern- Norway. Further studies validating our results and investigating mechanisms of educational inequalities in oral health are warranted.

The first cavefish in the Dinaric Karst? Cave colonization made possible by phenotypic plasticity in Telestes karsticus.

Cave animals are an excellent model system for studying adaptive evolution. At present, however, little is known about the mechanisms that enable surface colonizers to survive in the challenging environment of caves. One possibility is that these species have the necessary genetic background to respond with plastic changes to the pressures of underground habitats. To gain insight into this process, we conducted a comparative study with the fish species Telestes karsticus, which occurs in a hydrological system consisting of an interconnected stream and a cave. Results showed that T. karsticus resided year-round and spawned in Susik cave, making it the first known cavefish in the Dinaric Karst. Cave and surface populations differed in morphological and physiological characteristics, as well as in patterns of gene expression without any evidence of genetic divergence. To test whether observed trait differences were plastic or genetic, we placed adult fish from both populations under light/dark or constant dark conditions. Common laboratory conditions erased all morphometric differences between the two morphs, suggesting phenotypic plasticity is driving the divergence of shape and size in wild fish. Lighter pigmentation and increased fat deposition exhibited by cave individuals were also observed in surface fish kept in the dark in the laboratory. Our study also revealed that specialized cave traits were not solely attributed to developmental plasticity, but also arose from adult responses, including acclimatization. Thus, we conclude that T. karsticus can adapt to cave conditions, with phenotypic plasticity playing an important role in the process of cave colonization.

Reproductive and hormonal factors and risk of renal cell carcinoma among women in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology. MATERIALS & METHODS: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. RESULTS: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use. CONCLUSION: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.

Cohort profile: The Clinical and Multi-omic (CAMO) cohort, part of the Norwegian Women and Cancer (NOWAC) study.

INTRODUCTION: Breast cancer is the most common cancer worldwide and the leading cause of cancer related deaths among women. The high incidence and mortality of breast cancer calls for improved prevention, diagnostics, and treatment, including identification of new prognostic and predictive biomarkers for use in precision medicine. MATERIAL AND METHODS: With the aim of compiling a cohort amenable to integrative study designs, we collected detailed epidemiological and clinical data, blood samples, and tumor tissue from a subset of participants from the prospective, population-based Norwegian Women and Cancer (NOWAC) study. These study participants were diagnosed with invasive breast cancer in North Norway before 2013 according to the Cancer Registry of Norway and constitute the Clinical and Multi-omic (CAMO) cohort. Prospectively collected questionnaire data on lifestyle and reproductive factors and blood samples were extracted from the NOWAC study, clinical and histopathological data were manually curated from medical records, and archived tumor tissue collected. RESULTS: The lifestyle and reproductive characteristics of the study participants in the CAMO cohort (n = 388) were largely similar to those of the breast cancer patients in NOWAC (n = 10 356). The majority of the cancers in the CAMO cohort were tumor grade 2 and of the luminal A subtype. Approx. 80% were estrogen receptor positive, 13% were HER2 positive, and 12% were triple negative breast cancers. Lymph node metastases were present in 31% at diagnosis. The epidemiological dataset in the CAMO cohort is complemented by mRNA, miRNA, and metabolomics analyses in plasma, as well as miRNA profiling in tumor tissue. Additionally, histological analyses at the level of proteins and miRNAs in tumor tissue are currently ongoing. CONCLUSION: The CAMO cohort provides data suitable for epidemiological, clinical, molecular, and multi-omics investigations, thereby enabling a systems epidemiology approach to translational breast cancer research.

Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study.

BACKGROUND: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive. METHODS: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method. RESULTS: Of 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HRQ5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HRQ5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HRQ5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HRQ5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HRQ5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HRQ5vs.Q1:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99). CONCLUSIONS: Our findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.

Baseline and lifetime alcohol consumption and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).

Experimental evidence suggests that alcohol induces cutaneous carcinogenesis, yet epidemiological studies on the link between alcohol intake and skin cancer have been inconsistent. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort initiated in 1992 in 10 European countries. Alcohol intake at baseline and average lifetime alcohol intake were assessed using validated country-specific dietary and lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in Cox models. A total of 14 037 skin cancer cases (melanoma: n = 2457; basal-cell carcinoma (BCC): n = 8711; squamous-cell carcinoma (SCC): n = 1928; unknown: n = 941) were identified among 450 112 participants (average follow-up: 15 years). Baseline alcohol intake was positively associated with SCC (>15 vs 0.1-4.9 g/day: HR = 1.44, 95% CI = 1.17-1.77; Ptrend  = .001), BCC (HR = 1.12, 95% CI = 1.01-1.23; Ptrend  = .04), and melanoma risks in men (HR = 1.17, 95% CI = 0.95-1.44; Ptrend  = .17), while associations were more modest in women (SCC: HR = 1.09, 95% CI = 0.90-1.30; Ptrend  = .13; BCC: HR = 1.08, 95% CI = 1.00-1.17, Ptrend  = .03; melanoma: HR = 0.93, 95% CI = 0.80-1.08, Ptrend  = .13). Associations were similar for lifetime alcohol intake, with an attenuated linear trend. Lifetime liquor/spirit intake was positively associated with melanoma (fourth vs first quartile: HR = 1.47, 95% CI = 1.08-1.99; Ptrend  = .0009) and BCC risks in men (HR = 1.17, 95% CI = 1.04-1.31; Ptrend  = .14). Baseline and lifetime intakes of wine were associated with BCC risk (HR = 1.25 in men; HR = 1.11-1.12; in women). No statistically significant associations were found between beverage types and SCC risk. Intake of beer was not associated with skin cancer risk. Our study suggests positive relationships between alcohol intake and skin cancer risk, which may have important implications for the primary prevention of skin cancer.

The burden of colon cancer attributable to modifiable factors-The Norwegian Women and Cancer Study.

Colon cancer is the second most frequently diagnosed cancer in women in Norway, where incidence rates of colon cancer increased 3-fold between 1955 and 2014, for unknown reasons. We aimed to assess the burden of colon cancer attributable to modifiable risk factors in Norwegian women using the data from the Norwegian Women and Cancer (NOWAC) study. Self-reported information from 35 525 women from the NOWAC study were available. These included the following exposures: smoking status, alcohol consumption, body mass index, physical activity, intake of calcium, fibers, and red and processed meat. Colon cancer cases were identified from the Cancer Registry of Norway. A parametric piecewise constant hazards model was used to estimate the strength of exposure-cancer associations. Population attributable fractions with 95% confidence intervals (CIs) were calculated considering competing risk of death. The fraction of incident colon cancer attributable to ever smoking was 18.7% (95% CI 4.7%-30.6%), low physical activity 10.8% (95% CI -0.7% to 21.0%), alcohol consumption 14.5% (95% CI -2.8% to 28.9%), and low intake of calcium 10.0% (95% CI -7.8% to 24.8%). A small proportion of colon cancer cases was attributable to combined intake of red and processed meat over 500 g/week, overweight/obesity, and low intake of fibers. Jointly, these seven risk factors could explain 46.0% (95% CI 23.0%-62.4%) of the colon cancer incidence burden. Between 23% and 62% of the colon cancer burden among women in Norway was attributable to modifiable risk factors, indicating an important preventive potential of a healthy lifestyle.

A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk.

BACKGROUND: Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. OBJECTIVE: Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. METHODS: Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. RESULTS: Mean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. CONCLUSIONS: Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.

Seroprevalence of antibodies against SARS-CoV-2 in the adult population during the pre-vaccination period, Norway, winter 2020/21.

BackgroundSince March 2020, 440 million people worldwide have been diagnosed with COVID-19, but the true number of infections with SARS-CoV-2 is higher. SARS-CoV-2 antibody seroprevalence can add crucial epidemiological information about population infection dynamics.AimTo provide a large population-based SARS-CoV-2 seroprevalence survey from Norway; we estimated SARS-CoV-2 seroprevalence before introduction of vaccines and described its distribution across demographic groups.MethodsIn this population-based cross-sectional study, a total of 110,000 people aged 16 years or older were randomly selected during November-December 2020 and invited to complete a questionnaire and provide a dried blood spot (DBS) sample.ResultsThe response rate was 30% (31,458/104,637); compliance rate for return of DBS samples was 88% (27,700/31,458). National weighted and adjusted seroprevalence was 0.9% (95% CI (confidence interval): 0.7-1.0). Seroprevalence was highest among those aged 16-19 years (1.9%; 95% CI: 0.9-2.9), those born outside the Nordic countries 1.4% (95% CI: 1.0-1.9), and in the counties of Oslo 1.7% (95% CI: 1.2-2.2) and Vestland 1.4% (95% CI: 0.9-1.8). The ratio of SARS-CoV-2 seroprevalence (0.9%) to cumulative incidence of virologically detected cases by mid-December 2020 (0.8%) was slightly above one. SARS-CoV-2 seroprevalence was low before introduction of vaccines in Norway and was comparable to virologically detected cases, indicating that most cases in the first 10 months of the pandemic were detected.ConclusionFindings suggest that preventive measures including contact tracing have been effective, people complied with physical distancing recommendations, and local efforts to contain outbreaks have been essential.

Treatment of chronic diabetic macular oedema with intravitreal fluocinolone acetonide implant; real-life analysis of outcomes during overall treatment period.

PURPOSE: To assess the clinical efficacy of the fluocinolone acetonide (FA) intravitreal implant (Iluvien, Alimera Sciences) over a 12-month period in a population resistant to treatment with first-line anti-VEGF agents. METHODS: This study is a retrospective cohort study assessing functional and anatomical outcomes in 13 eyes of 12 patients treated for diabetic macular oedema (DMO) with a single fluocinolone implant (FA) (Iluvien) under real-world conditions. The follow-up period includes the time of first intravitreal treatment (incl anti-VEGF or short-lasting steroids) given until 12 months post FA implant insertion. Primary outcomes were best corrected visual acuity (BCVA), measured using the modified Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale, and central foveal thickness (CFT), measured using Topcon 3DOCT-2000 (Topcon Inc) SD-OCT imaging. Mean BCVA and CFT were measured before anti-VEGF treatment, after anti-VEGF treatment, at the time of Iluvien implant insertion, and 6 and 12 months after Iluvien implant insertion. The t-paired sample test was used to ascertain statistical significance of changes in comparison of two samples while the ANOVA analysis was used in comparison of three or more samples. RESULTS: The baseline BCVA (SD) of the cohort prior to initiation of anti-VEGF treatment was 47.45 (12.27) ETDRS letters whilst the mean CFT (SD) was 579 (203) microns. Following completion of anti-VEGF therapy, the mean improvement in vision was 8.9 ETDRS letters (p = 0.1) whilst the mean reduction in CFT was 197 microns (p = 0.028). Mean BCVA (SD) at the time of insertion of the FA implant was 55.15 (11.16) ETDRS letters and mean (SD) CFT at time of insertion of the FA was 454.62 µm (109.51). Following the 12-month treatment period with the FA implant, BCVA (SD) was 62.15 (10.25) ETDRS letters (p = 0.0331) and the mean (SD) CFT was 404.36 µm (142.92), a change of -50.26 µm from baseline (p = 0.0369). CONCLUSIONS: This study has shown that statistically significant improvements in BCVA and CFT can be achieved over a 12-month period with the Iluvien implant. The implant has been shown to be a safe option in the treatment of DMO and may have a role to play in achieving good functional and anatomical outcomes in DMO while also reducing the frequency of follow-up appointments required to maintain stable vision in the working-age population.

Analysis of association of risk factors for age-related macular degeneration.

PURPOSE: To evaluate the significance of risk factors and analyze their interrelationship in developing age-related macular degeneration (AMD). MATERIALS AND DESIGN: This is a multicenter, cross-sectional study conducted in eight ophthalmology centers in Europe. The STARS (Simplified Thea AMD Risk-Assessment Scale) questionnaire was used to assess 12 risk factors grouped in four major categories. We used Welch's t-test/F ratios to determine statistically significant changes. The principal component analysis was done to investigate the association between risk factors. RESULTS: There were 3297 participants included in our data analysis. Nineteen percent of patients had a high risk of developing AMD, whilst 45.92% and 34.85% had moderate and small risk, respectively. Atherosclerosis appeared as the most relevant risk indicator for AMD development (Cohen's d = 0.861). Tukey's post hoc analysis of the smoking variable showed that ex-smokers (p < 0.001) have a significantly high risk of developing AMD. The Welch's t-test showed pseudophakic patients have a higher risk of developing AMD than phakic ones. Then, we conducted the principal component analysis, which revealed a significant connection between smoking and male gender and between smoking and atherosclerosis. Pseudophakic patients were generally older and had more often myocardial infarction as compared to phakic patients. We showed that higher BMI, history of arterial hypertension, hypercholesterolemia, and atherosclerosis tend to occur together as risk factors for AMD. CONCLUSION: Risk factors evaluated in our study should be considered for the development of AMD.

Smartphone-based remote monitoring of vision in macular disease enables early detection of worsening pathology and need for intravitreal therapy.

BACKGROUND/AIMS: To assess the outcomes of home monitoring of distortion caused by macular diseases using a smartphone-based application (app), and to examine them with hospital-based assessments of visual acuity (VA), optical coherence tomography-derived central macular thickness (CMT) and the requirement of intravitreal injection therapy. DESIGN: Observational study with retrospective analysis of data. METHODS: Participants were trained in the correct use of the app (Alleye, Oculocare, Zurich, Switzerland) in person or by using video and telephone consultations. Automated threshold-based alerts were communicated based on a traffic light system. A 'threshold alarm' was defined as three consecutive 'red' scores, and turned into a 'persistent alarm' if present for greater than a 7-day period. Changes of VA and CMT, and the requirement for intravitreal therapy after an alarm were examined. RESULTS: 245 patients performing a total of 11 592 tests (mean 46.9 tests per user) were included and 85 eyes (164 alarms) examined. Mean drop in VA from baseline was -4.23 letters (95% CI: -6.24 to -2.22; p<0.001) and mean increase in CMT was 29.5 µm (95% CI: -0.08 to 59.13; p=0.051). Sixty-six eyes (78.5%) producing alarms either had a drop in VA, increase in CMT or both and 60.0% received an injection. Eyes with persistent alarms had a greater loss of VA, -4.79 letters (95% CI: -6.73 to -2.85; p<0.001) or greater increase in CMT, +87.8 µm (95% CI: 5.2 to 170.4; p=0.038). CONCLUSION: Smartphone-based self-tests for macular disease may serve as reliable indicators for the worsening of pathology and the need for treatment.

Association of Pre-diagnostic Antibody Responses to Escherichia coli and Bacteroides fragilis Toxin Proteins with Colorectal Cancer in a European Cohort.

Experimental evidence has implicated genotoxic Escherichia coli (E. coli) and enterotoxigenic Bacteroides fragilis (ETBF) in the development of colorectal cancer (CRC). However, evidence from epidemiological studies is sparse. We therefore assessed the association of serological markers of E. coli and ETBF exposure with odds of developing CRC in the European Prospective Investigation into Nutrition and Cancer (EPIC) study.Serum samples of incident CRC cases and matched controls (n = 442 pairs) were analyzed for immunoglobulin (Ig) A and G antibody responses to seven E. coli proteins and two isoforms of the ETBF toxin via multiplex serology. Multivariable-adjusted conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of sero-positivity to E. coli and ETBF with CRC.The IgA-positivity of any of the tested E. coli antigens was associated with higher odds of developing CRC (OR: 1.42; 95% CI: 1.05-1.91). Dual-positivity for both IgA and IgG to E. coli and ETBF was associated with >1.7-fold higher odds of developing CRC, with a significant association only for IgG (OR: 1.75; 95% CI: 1.04, 2.94). This association was more pronounced when restricted to the proximal colon cancers (OR: 2.62; 95% CI: 1.09, 6.29) compared to those of the distal colon (OR: 1.24; 95% CI: 0.51, 3.00) (pheterogeneity = 0.095). Sero-positivity to E. coli and ETBF was associated with CRC development, suggesting that co-infection of these bacterial species may contribute to colorectal carcinogenesis. These findings warrant further exploration in larger prospective studies and within different population groups.