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There are carcinogenic effects of sun exposure that increase the risk for skin cancer, especially for fair-skinned individuals. Therefore, there are recommendations to avoid sun exposure and to apply sun blockers. A more nuanced and balanced message for sun safety guidelines is now advocated. Despite an increased risk of death due to skin cancer, fair skinned women seem to have an overall survival advantage. In addition, an inverse association between sun exposure and hypertension, thromboembolism, and type 2 diabetes mellitus has been shown. Furthermore, low sun exposure habits result in increased risk of cardiovascular disease (CVD), and non-CVD/non-cancer mortality among women. There are also data supporting that the prognosis of cancer is improved with increasing levels of vitamin D/sun exposure. In this narrative review we will provide a brief update of hazards and benefits of sun exposure focused on an updated, balanced, and evidence-based view., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX )., Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence., Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I 2  = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis., Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care., (© 2021. The Author(s).)

Background: Type 1 diabetes mellitus (T1D) is a metabolic disease causing hyperglycemia due to β-cell destruction. Despite adequate treatment, complications such as diabetic retinopathy (DR) are common. The first aim was to investigate if acute onset of type 1 diabetes differed between those who had developed retinopathy and who had not after 15 years from diagnosis. The second aim was to investigate if mean glycosylated hemoglobin (HbA1c) levels affect the time to development of DR., Methods: The medical records of all children and adolescents diagnosed with type 1 diabetes during 1993-2001 in our area in Sweden were studied retrospectively and the mean HbA1c each year until the development of retinopathy was investigated. In total 72 patients were included and the follow-up time was between 15 and 23 years. Gender, p-glucose, age and HbA1c at diagnosis were analyzed for possible correlations to years to retinopathy., Results: HbA1c was significantly higher among those who had developed DR after 15 years from diagnosis, 98±9.2 (n=25) vs. 86±9.2 (n=46; p=0.025). A negative correlation was found between age at diagnosis and years to DR (rs=-0.376; p=0.026). Mean HbA1c levels at years 6-10 after diabetes diagnosis correlated significantly (rs=-0.354, p=0.037) to years until retinopathy. Mean HbA1c levels at years 1-15 after diabetes diagnosis were significantly higher at years 2-3 and years 5-8 for those who had developed retinopathy after 15 years from diagnosis., Conclusions: Higher HbA1c levels shortened the time to development of retinopathy. It is therefore important to keep HbA1c as close to normal as possible.

We aimed to conduct a narrative review of the rapid advances in knowledge regarding sun exposure and all-cause mortality. Data support the hypothesis that sun exposure avoidance is a major risk factor for all-cause mortality in adjusted analysis (age, income, education, marital status, smoking, and comorbidity). This was caused by an increased risk of death due to cardiovascular disease (CVD) and noncancer/non-CVD. However, the increased life span among those with high sun exposure naturally results in an increased prevalence of cancer death. In addition, sun exposure increases the incidence, but is related to better prognosis of skin cancer. The new findings indicate that there is a need for modification of guidelines regarding sun exposure. They may also add to our knowledge regarding the increasing incidence of diabetes mellitus and increased mortality among non-Caucasians in western countries. According to the present knowledge, in a low solar intensity region we should aim for sound and safe sun exposure habits, especially for those at increased risk of CVD or noncancer/non-CVD.

Context: Studies of the clinical and immunological features of autoimmune Addison disease (AAD) are needed to understand the disease burden and increased mortality., Objective: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles, and cardiovascular risk factors., Design, Setting, and Participants: A cross-sectional, population-based study that included 660 AAD patients from the Swedish Addison Registry (2008-2014). When analyzing the cardiovascular risk factors, 3594 individuals from the population-based survey in Northern Sweden, MONICA (monitoring of trends and determinants of cardiovascular disease), served as controls., Main Outcome Measures: The endpoints were the prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined., Results: The proportion of 21-hydroxylase autoantibody-positive patients was 83%, and 62% of patients had ≥1 associated autoimmune diseases, more frequently coexisting in females (P < 0.0001). AAD patients had a lower body mass index (P < 0.0001) and prevalence of hypertension (P = 0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of the patients, with a mean dose of 28.1 ± 8.5 mg/d. The mean hydrocortisone equivalent dose normalized to the body surface was 14.8 ± 4.4 mg/m2/d. A greater hydrocortisone equivalent dose was associated with a greater incidence of hypertension (P = 0.046)., Conclusions: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients did not have an increased prevalence of overweight, hypertension, type 2 diabetes mellitus, or hyperlipidemia. However, high glucocorticoid replacement doses could be a risk factor for hypertension., (Copyright © 2017 by the Endocrine Society)

Objective: To investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes., Design: Observational study., Setting: Swedish National Diabetes Register, Sweden 2005-12., Participants: 18,168 people with type 1 diabetes, 2441 using insulin pump therapy and 15,727 using multiple daily insulin injections., Main Outcome Measures: Cox regression analysis was used to estimate hazard ratios for the outcomes, with stratification of propensity scores including clinical characteristics, risk factors for cardiovascular disease, treatments, and previous diseases., Results: Follow-up was for a mean of 6.8 years until December 2012, with 114,135 person years. With multiple daily injections as reference, the adjusted hazard ratios for insulin pump treatment were significantly lower: 0.55 (95% confidence interval 0.36 to 0.83) for fatal coronary heart disease, 0.58 (0.40 to 0.85) for fatal cardiovascular disease (coronary heart disease or stroke), and 0.73 (0.58 to 0.92) for all cause mortality. Hazard ratios were lower, but not significantly so, for fatal or non-fatal coronary heart disease and fatal or non-fatal cardiovascular disease. Unadjusted absolute differences were 3.0 events of fatal coronary heart disease per 1000 person years; corresponding figures were 3.3 for fatal cardiovascular disease and 5.7 for all cause mortality. When lower body mass index and previous cardiovascular diseases were excluded, results of subgroup analyses were similar to the results from complete data. A sensitivity analysis of unmeasured confounders in all individuals showed that an unmeasured confounders with hazard ratio of 1.3 would have to be present in >80% of the individuals treated with multiple daily injections versus not presence in those treated with pump therapy to invalidate the significantly lower hazard ratios for fatal cardiovascular disease. Data on patient education and frequency of blood glucose monitoring were missing, which might have influenced the observed association., Conclusion: Among people with type 1 diabetes use of insulin pump therapy is associated with lower cardiovascular mortality than treatment with multiple daily insulin injections., (© Steineck et al 2015.)

Background: A possible downstream effect of high in-hospital bed occupancy is that patients in the emergency department (ED) who would benefit from in-hospital care are denied admission. The present study aimed at evaluating this hypothesis through investigating associations between in-hospital bed occupancy at the time of presentation in the ED and the probability for unplanned 72-hour (72-h) revisits to the ED among patients discharged at index. A second outcome was unplanned 72-h revisits resulting in admission., Methods: All visits to the ED of a 420-bed emergency hospital in southern Sweden between 1 January 2011 and 31 December 2012, which did not result in admission, death, or transfer to another hospital were included. Revisiting fractions were computed for in-hospital occupancy intervals <85%, 85% to 90%, 90% to 95%, 95% to 100%, 100% to 105%, and ≥105%. Multivariate models were constructed in an attempt to take confounding factors from, e.g., presenting complaints, age, referral status, and triage priority into account., Results: Included in the study are 81,878 visits. The fraction of unplanned 72-h revisits/unplanned 72-h revisits resulting in admission was 5.8%/1.4% overall, 6.2%/1.4% for occupancy <85%, 6.4%/1.5% for occupancy 85% to 90%, 5.8%/1.4% for occupancy 90% to 95%, 6.0%/1.6% for occupancy 95% to 100%, 5.4%/1.6% for occupancy 100% to 105%, and 4.9%/1.4% for occupancy ≥105%. In the multivariate models, a trend to lower probability of unplanned 72-h revisits was observed at occupancy ≥105% compared to occupancy <95% (OR 0.88, CI 0.76 to 1.01). No significant associations between in-hospital occupancy at index and the probability of making unplanned 72-h revisits resulting in admission were observed., Conclusions: The lack of associations between in-hospital occupancy and unplanned 72-h revisits does not support the hypothesis that ED patients are inappropriately discharged when in-hospital beds are scarce. The results are reassuring as they indicate that physicians are able to make good decisions, also while resources are constrained.

Purpose: At northern latitudes, vitamin D is not synthesized endogenously during winter, causing low plasma 25-hydroxyvitamin D (25(OH)D) concentrations. Therefore, we evaluated the effects of a healthy Nordic diet based on Nordic nutrition recommendations (NNR) on plasma 25(OH)D and explored its dietary predictors., Methods: In a Nordic multi-centre trial, subjects (n = 213) with metabolic syndrome were randomized to a control or a healthy Nordic diet favouring fish (≥300 g/week, including ≥200 g/week fatty fish), whole-grain products, berries, fruits, vegetables, rapeseed oil and low-fat dairy products. Plasma 25(OH)D and parathyroid hormone were analysed before and after 18- to 24-week intervention., Results: At baseline, 45 % had vitamin D inadequacy (<50 nmol/l), whereas 8 % had deficiency (<25 nmol/l). Dietary vitamin D intake was increased by the healthy Nordic diet (P < 0.001). The healthy Nordic and the control diet reduced the prevalence of vitamin D inadequacy by 42 % (P < 0.001) and 19 % (P = 0.002), respectively, without between-group difference (P = 0.142). Compared with control, plasma 25(OH)D (P = 0.208) and parathyroid hormone (P = 0.207) were not altered by the healthy Nordic diet. Predictors for 25(OH)D were intake of vitamin D, eicosapentaenoic acids (EPA), docosahexaenoic acids (DHA), vitamin D supplement, plasma EPA and plasma DHA. Nevertheless, only vitamin D intake and season predicted the 25(OH)D changes., Conclusion: Consuming a healthy Nordic diet based on NNR increased vitamin D intake but not plasma 25(OH)D concentration. The reason why fish consumption did not improve vitamin D status might be that many fish are farmed and might contain little vitamin D or that frying fish may result in vitamin D extraction. Additional ways to improve vitamin D status in Nordic countries may be needed.

Background: The association between emergency department (ED) overcrowding and poor patient outcomes is well described, with recent work suggesting that the phenomenon causes delays in time-sensitive interventions, such as resuscitation. Even though most researchers agree on the fact that admitted patients boarding in the ED is a major contributing factor to ED overcrowding, little work explicitly addresses whether in-hospital occupancy is associated to the probability of patients being admitted from the ED. The objective of the present study is to investigate whether such an association exists., Methods: Retrospective analysis of data on all ED visits to Helsingborg General Hospital in southern Sweden between January 1, 2011, and December 31, 2012, was undertaken. The fraction of admitted patients was calculated separately for strata of in-hospital occupancy <95%, 95-100%, 100-105%, and >105%. Multivariate models were constructed in an attempt to take confounding factors, e.g., presenting complaints, age, referral status, triage priority, and sex into account. Subgroup analysis was performed for each specialty unit within the ED., Results: Overall, 118,668 visits were included. The total admitted fraction was 30.9%. For levels of in-hospital occupancy <95%, 95-100%, 100-105%, and >105% the admitted fractions were 31.5%, 30.9%, 29.9%, and 28.7%, respectively. After taking confounding factors into account, the odds ratio for admission were 0.88 (CI 0.84-0.93, P >0.001) for occupancy level 95-100%, 0.82 (CI 0.78-0.87, P >0.001) for occupancy level 100-105%, and 0.74 (CI 0.67-0.81, P >0.001) for occupancy level >105%, relative to the odds ratio for admission at occupancy level <95%. A similar pattern was observed upon subgroup analysis., Conclusions: In-hospital occupancy was significantly associated with a decreased odds ratio for admission in the study population. One interpretation is that patients who would benefit from inpatient care instead received suboptimal care in outpatient settings at times of high in-hospital occupancy. A second interpretation is that physicians admit patients who could be managed safely in the outpatient setting, in times of good in-hospital bed availability. Physicians thereby expose patients to healthcare-associated infections and other hazards, in addition to consuming resources better needed by others.

Type 2 diabetes is associated with a higher cardiovascular risk and there has been a growing interest in using dietary intervention to improve lipid profile and glucose control. The present work aims at analysing the effects of the enrichment of a normal diet with beta-glucan (3.5 g/d) in free-living type 2 diabetic subjects for 2 months, using a palatable soup. This trial was a parallel, placebo-controlled, double-blinded randomised study performed in fifty-three type 2 diabetic subjects. During a 3-week run-in period, subjects daily consumed a ready meal control soup (without beta-glucan). For the following 8 weeks, subjects were randomly assigned to consume daily either a control soup or a beta-glucan soup. Changes in lipid profile (total cholesterol (TC), HDL- and LDL-cholesterol (HDLc and LDLc), apo B and TAG) and in glucose control (HbA1c and fasting glucose) were measured. There was no significant alteration in lipid profile in the two groups (TC, HDLc, LDLc and apo B). TAG decreased significantly in the beta-glucan group compared with the control group ( - 0.12 (SD 0.38) v. 0.12 (SD 0.44) mmol/l, P = 0.03). HbA1c and fasting glucose were not reduced in any group. A single daily ingestion of 3.5 g beta-glucan, as required by official dietary recommendations, for 8 weeks did not change the lipid profile and HbA1c in type 2 diabetic subjects. To improve the metabolic profile of type 2 diabetic subjects in the long term, the quantity, the food vectors and the tolerability of beta-glucan products may be re-evaluated.

SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.