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Background: Individuals with type 2 diabetes (T2D) have an increased risk of cognitive symptoms and Alzheimer's disease (AD). Mis-metabolism with aggregation of amyloid-β peptides (Aβ) play a key role in AD pathophysiology. Therefore, human studies on Aβ metabolism and T2D are warranted.

Objective: The objective of this study was to examine whether acute hyperglycemia affects plasma Aβ1-40 and Aβ1-42 concentrations in individuals with T2D and matched controls.

Methods: Ten participants with T2D and 11 controls (median age, 69 years; range, 66-72 years) underwent hyperglycemic clamp and placebo clamp (saline infusion) in a randomized order, each lasting 4 hours. Aβ1-40, Aβ1-42, and insulin-degrading enzyme (IDE) plasma concentrations were measured in blood samples taken at 0 and 4 hours of each clamp. Linear mixed-effect regression models were used to evaluate the 4-hour changes in Aβ1-40 and Aβ1-42 concentrations, adjusting for body mass index, estimated glomerular filtration rate, and 4-hour change in insulin concentration.

Results: At baseline, Aβ1-40 and Aβ1-42 concentrations did not differ between the two groups. During the hyperglycemic clamp, Aβ decreased in the control group, compared to the placebo clamp (Aβ1-40: p = 0.034, Aβ1-42: p = 0.020), IDE increased (p = 0.016) during the hyperglycemic clamp, whereas no significant changes in either Aβ or IDE was noted in the T2D group.

Conclusions: Clamp-induced hyperglycemia was associated with increased IDE levels and enhanced Aβ40 and Aβ42 clearance in controls, but not in individuals with T2D. We hypothesize that insulin-degrading enzyme was inhibited during hyperglycemic conditions in people with T2D.

Aim: The burden of respiratory disease is great among children. This study aimed to examine the temporal relationship between hospitalisation for respiratory syncytial virus (RSV) and bacterial pneumonia.

Methods: A Swedish population-based cohort was created by combining data from the Swedish Medical Birth Register, the National Inpatient Register, the Cause of Death Register, the Total Population Register, and the Longitudinal Integration Database for Health Insurance and Labour Market Studies. Children born between 1998 and 2015 were included and followed for 2 years. We examined the temporal relationship between RSV hospitalisation and bacterial pneumonia using piecewise exponential models.

Results: The final cohort comprised 1 641 747 children, 48.5% were females. There were 23 632 RSV and 4722 bacterial pneumonia hospitalisations, with mean age of 137.8 and 424.2 days, respectively. RSV hospitalisation was associated with bacterial pneumonia with an adjusted incidence rate ratio (aIRR) of 3.18. The risk was highest in the first month after RSV hospitalisation, aIRR 11.19. The risk of bacterial pneumonia was elevated for 4 months after RSV hospitalisation and before RSV hospitalisation.

Conclusion: We found an increased risk for bacterial pneumonia hospitalisation in children hospitalised for RSV both before and after RSV hospitalisation, indicating a bidirectional relationship.

Context: Adrenal insufficiency (AI) is usually diagnosed by low plasma cortisol levels following a short Synacthen test (SST). Most plasma cortisol is bound to corticosteroid-binding globulin, which is increased by estrogen in combined estrogen-progestin oral contraceptives (COCs). Women with AI using COCs are therefore at risk of having an apparently normal plasma cortisol level during SST, which would not adequately reflect AI.

Objective: To test whether salivary cortisol or cortisone during SST is more robust against the COC effect and to calculate the lower reference limits (LRLs) for these to be used as tentative diagnostic cutoffs to exclude AI.

Methods: Forty-one healthy women on COCs and 46 healthy women without exogenous estrogens performed an SST with collection of plasma and salivary samples at 0, 30, and 60 min after Synacthen injection. The groups were compared using regression analysis with age as covariate and the LRLs were calculated parametrically.

Results: SST-stimulated plasma cortisol levels were significantly higher in the COC group versus controls, while mean salivary cortisol and cortisone levels were slightly lower in the COC group. Importantly, COC use did not significantly alter LRLs for salivary cortisol or cortisone. The smallest LRL difference between groups was seen for salivary cortisone.

Conclusion: Salivary cortisol and especially salivary cortisone are considerably less affected by COC use than plasma cortisol during SST. Due to similar LRLs, a common cutoff for salivary cortisol and cortisone during SST can be used to exclude AI in premenopausal women irrespective of COC use.

Background: Daily air pollution levels are known to influence the number of patients with acute asthma. We investigated the short-term effects of air pollution exposure on the daily number of asthma medication purchases in the Greater Stockholm area, Sweden.

Methods: We conducted a time-series study with data on asthma medication purchases and daily mean values of particulate matter ≤10 µm (PM10), nitrogen oxides (NOx), and ozone during 2018-2019. We used nonlinear distributed lag quasi-Poisson regression models to estimate the associations between air pollution levels and medication purchases, adjusting for meteorological variables, pollen levels, day of the week, and long-term trends. The models established linear relationships between air pollutants and the outcome, and potential delayed effects were smoothed with a spline across a lag period of 2 weeks. We applied separate models for each municipality (n = 21) in Greater Stockholm, and calculated pooled estimates to achieve combined results for the whole region.

Results: We observed associations between daily levels of air pollution and purchases of asthma medications, most clearly for PM10. The pooled estimates of the relative risks for asthma medication purchases across all 21 municipalities associated with a 10 μg m-3increase in PM10the same day (lag 0) was 1.7% [95% confidence interval (CI): 1.2%, 2.1%], a cumulative increase of 4.6% (95% CI: 3.7%, 5.6%) over one week (lag 0-6), and a 6.5% (95% CI: 5%, 8%) increase over 2 weeks (lag 0-13). The corresponding pooled effect per 10 μg m-3increase in NOxand ozone were 2.8% (95% CI: 1.6%, 4.1%) and 0.7% (95% CI: 0%, 1.4%) over 2 weeks (lag 0-13), respectively.

Conclusions: Our study revealed short-term associations between air pollution, especially PM10, and purchases of asthma medications.

In the summer of 2018, Sweden experienced widespread wildfires, particularly in the region of Jämtland Härjedalen during the final weeks of July. We previously conducted an epidemiological study and investigated acute respiratory health effects in eight municipalities relation to the wildfire air pollution. In this study, we aimed to estimate the potential health impacts under less favorable conditions with different locations of the major fires. Our scenarios focused on the most intense plume from the 2018 wildfire episode affecting the largest municipality, which is the region’s only city. Combining modeled PM2.5 concentrations, gridded population data, and exposure–response functions, we assessed the relative increase in acute health effects. The cumulative population-weighted 24 h PM2.5 exposure during the nine highest-level days reached 207 μg/m3 days for 63,227 inhabitants. We observed a small number of excess cases, particularly in emergency unit visits for asthma, with 13 additional cases compared to the normal 12. Overall, our scenario-based health impact assessment indicates minor effects on the studied endpoints due to factors such as the relatively small population, limited exposure period, and moderate increase in exposure compared to similar assessments. Nonetheless, considering the expected rise in fire potential due to global warming and the long-range transport of wildfire smoke, raising awareness of the potential health risks in this region is important.

Nedstängningen av samhällen på grund av pandemin våren 2020 skedde tämligen globalt, varför åtföljande förändringar av utsläpp både lokalt och på långt avstånd kan ha påverkat luftkvaliteten i Stockholm. Denna rapport redovisar tre delstudier: en analys av hur föroreningshalterna i Stockholmsområdet påverkades av den inledande nedstängningen av samhället, en hälsokonsekvensberäkning av vilka hälsoeffekter en sådan förändring av halterna antas medföra, samt en epidemiologisk tidsseriestudie av sambanden mellan registrerat dagligt antal utköp av astmamediciner och halter av luftföroreningar under den inledande nedstängningen och före/efter denna period.

Vi har i detta projekt använt två metoder, spridningsmodellering med emissionsdata respektive regressionsanalys med mätdata, för att beräkna hur främst kväveoxidhalterna påverkades av minskade emissioner lokalt, samt hur bl.a halterna av kvävedioxid och ozon i staden avvek ifrån förväntade värden efter hänsyn till meteorologins inverkan på halterna.

Spridningsberäkningarna visade att halterna av kvävedioxid minskade med 0,7 μg/m3 under mars-juli till följd av minskad lokal trafik. Utifrån sammanvägningar av publicerade epidemiologiska samband skulle detta leda till cirka 2 dödsfall färre i 9 kommuner med totalt drygt 1,5 miljoner invånare, medan besök och inläggningar på sjukhus för andningsorganen förväntas minska med drygt 24 fall genom minskade lokala utsläpp.

Den väderjusterade minskningen av totala NO₂ halterna var 2,8 μg/m3, vilket skulle förväntas leda till ungefär 97 färre besök och inläggningar på sjukhus för andningsorganen under samma 5 månader. Men eftersom minskade utsläpp av kväveoxider även följdes av en oväntat stor väderjusterad ökning av marknära ozon förväntas för vissa hälsoutfall en nettoökning av antalet fall, exempelvis av patienter med problem i andningsorganen.

Eftersom utköp av förskrivna läkemedel inte kräver att man besöker sjukvården, inte ens att man besöker ett apotek, studerades dagligt antal utköp av astmaläkemedel i relation till variationer i luftföroreningshalterna. Trots en inledande hamstringsvåg med efterföljande svacka i utköp under maj och lägre uppmätta halter av kväveoxider (NO_x) och partiklar <10 mikrometer (PM10) än normalt, fanns sammantaget även under april-juli 2020 en statistiskt säkerställd effekt av PM10 och NO_x på dagligt antal utköp. När relativa riskökningen per 10 μg/m3 jämförs mellan denna nedstängningsperiod och övrig studieperiod kan konstateras att ökningen av utköp per haltökning var högre under april-juli 2020. För hela perioden 2018 - 2021 visade en meta-skattning över 21 kommuner i Stockholms län på 2,6 procent ökning i uttag av lång- och korttidsverkande astmaläkemedel per 10 μg/m3 ökning av PM10 (medelvärde för samma dygn och det föregående).

The old Swedish city Visby, located on the island Gotland, has, for several years, reported higher PM₁₀ concentrations than any other city in Sweden. In Visby, local limestone is used, both in road paving and as sand used for anti-slip measures, resulting in a clear annual pattern of PM₁₀ with the highest concentrations during winter/spring when studded tires are allowed. This study analyzes the short-term associations between PM₁₀ and daily number of patients with acute respiratory problems (ICD-10 diagnoses: J00-J99) seeking care at the hospital or primary healthcare units in Visby during the period of 2013-2019. The daily mean of PM₁₀ was on average 45 µg m^-3 during winter/spring and 18 µg m^-3 during summer/autumn. Four outcome categories were analyzed using quasi-Poisson regression models, stratifying for period and adjusting for calendar variables and weather. An increase in respiratory visits was associated with increasing concentrations in PM₁₀ during the summer/autumn period, most prominent among children, where asthma visits increased by 5% (95% CI: 2-9%) per 10 µg m^-3 increase in PM₁₀. For the winter/spring period, no significant effects were observed, except for the diagnose group 'upper airways' in adults, where respiratory visits increased by 1% (95% CI: 0.1-1.9%) per 10 µg m^-3 increase. According to the results, limestone in particles seem to be relatively harmless at the exposure concentrations observed in Visby, and this is in line with the results from a few experimental and occupational studies.

Denna studie syftar till att följa upp episoden med skogsbrandrök som drabbade Östersund och Jämtland Härjedalen sommaren 2018, samt att belysa vilka erfarenheter man har från andra länder om nivåer för exponering och risker.

Tyvärr hade ingen av regionens tätorter kontinuerliga partikelmätningar sommaren 2018. En spridningsmodell vid SMHI användes för att beskriva spridning av rök från skogsbränderna 2018, samt en jämförbar period 2017 (då antalet bränder var färre), med fokus på fina partiklar (PM2.5) och sot-partiklar. Utifrån halt- och befolkningsskikt användes befolkningsviktade dygnsmedelhalter som mått på exponeringen i respektive kommun. Statistik över dagligt antal akuta besök för problem från andnings-organen vid sjukhuset i Östersund och regionens olika vårdcentraler och mottagningar, samt över antalet samtal till sjukvårdsupplysningen 1177 om andningsproblem, användes för att studera eventuella akuta hälsoeffekter inom respektive kommuns befolkning.

Enligt beräkningarna förekom befolkningsviktade dygnsmedelhalter på upp till 97 μg/m3. I verkligheten förekom sannolikt, under kortare tid och avgränsade platser, betydligt högre halter. När brand-röksepisoder definierades som dygn med PM2.5>20 μg/m3 beräknades den sammanviktade relativa ökningen av akuta besök gällande astma till 68% (RR=1.68, 95% KI:1.09-2.57). För diagnoser gällande nedre luftvägar totalt observerades en ökning med 40% (RR=1.4, 95% KI:1.01-1.92). I genomsnitt innebar brandröksepisoder en ökning av halten PM2.5 med 28 μg/m3 i jämförelse med referensdygnen.

Analyserna av förhöjda partikelhalter i Jämtland-Härjedalen under brandröksperioden sommaren 2018 tyder på att en ökning av akuta problem gällande de nedre luftvägarna kan förväntas från dygns-medelhalter på 20-40 μg/m3 av PM2.5 med ursprung i huvudsak från bränder. För information och varningar under pågående exponering för PM2.5 i skogsbrandrök torde de kriterier för korttidshalter som finns i USA och Kanada vara tillämpliga även för Sverige. Om haltbidraget från branden förväntas bli omkring 60-90 μg/m3 av PM2.5 under 1 timme eller längre bör känsliga grupper uppmanas att begränsa sin exponering.

Perfluoroalkyl substances (PFAS) are widespread persistent environmental pollutants. There is evidence that PFAS induce metabolic perturbations in humans, but underlying mechanisms are still unknown. In this exploratory study, we investigated PFAS-related plasma metabolites for their associations with type 2 diabetes (T2D) to gain potential mechanistic insight in these perturbations. We used untargeted LC-MS metabolomics to find metabolites related to PFAS exposures in a case-control study on T2D (n = 187 matched pairs) nested within the Västerbotten Intervention Programme cohort. Following principal component analysis (PCA), six PFAS measured in plasma appeared in two groups: 1) perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid and 2) perfluorohexane sulfonic acid, perfluorooctane sulfonic acid and perfluorooctanoic acid. Using a random forest algorithm, we discovered metabolite features associated with individual PFAS and PFAS exposure groups which were subsequently investigated for associations with risk of T2D. PFAS levels correlated with 171 metabolite features (0.16 ≤ |r| ≤ 0.37, false discovery rate (FDR) adjusted p < 0.05). Out of these, 35 associated with T2D (p < 0.05), with 7 remaining after multiple testing adjustment (FDR < 0.05). PCA of the 35 PFAS- and T2D-related metabolite features revealed two patterns, dominated by glycerophospholipids and diacylglycerols, with opposite T2D associations. The glycerophospholipids correlated positively with PFAS and associated inversely with risk for T2D (Odds Ratio (OR) per 1 standard deviation (1-SD) increase in metabolite PCA pattern score = 0.2; 95% Confidence Interval (CI) = 0.1-0.4). The diacylglycerols also correlated positively with PFAS, but they associated with increased risk for T2D (OR per 1-SD = 1.9; 95% CI = 1.3-2.7). These results suggest that PFAS associate with two groups of lipid species with opposite relations to T2D risk.

Objective: Several risk factors for type 2 diabetes mellitus (T2DM) are also associated with blood concentrations of persistent organic pollutants (POPs), and factors related to the disease may affect POP concentrations, and subsequent associations between POPs and T2DM. The purpose of this pilot study was to investigate the change in concentrations of lipids, hormones and POPs pre- and post-diagnosis in T2DM cases compared to healthy controls and their associations with T2DM.

Methods: We measured POPs, lipids, and thyroid and steroid hormones in plasma from 44 female cases collected prior to (pre-diagnostic) and following (post-diagnostic) T2DM diagnosis, and in 44 healthy female age-matched controls. We compared cross-sectional differences and longitudinal changes within and between matched cases and controls with t-tests and multivariable linear regression models. Associations between POP concentrations and T2DM were investigated using conditional logistic regression.

Results: Between the pre- and post-diagnostic measurement, cases developed more favorable lipid profiles and the longitudinal changes in lipid-normalized concentrations of non-dioxin-like polychlorinated biphenyls (PCBs), dioxin-like PCBs, beta-hexachlorocyclohexane (HCH), HCB, and 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (p,p'-DDE) differed significantly between cases and controls. The longitudinal changes in POPs were mainly driven by changes in bodyweight, total lipids and T2DM status. Cases had significantly higher pre-diagnostic concentrations of POPs and triglycerides, and lower concentrations of high-density lipoprotein cholesterol and free thyroxin than controls. Pre-diagnostic POP concentrations were not significantly associated with incident T2DM, whereas several post-diagnostic POP concentrations were significantly positively associated with prevalent T2DM.

Conclusions: This pilot study suggests that factors related to T2DM affect blood concentrations of POPs and may partly explain the positive associations between POPs and T2DM.