Pre- and post-diagnostic blood profiles of chlorinated persistent organic pollutants and metabolic markers in type 2 diabetes mellitus cases and controls; a pilot study.

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.

Chlorinated persistent organic pollutants and type 2 diabetes - A population-based study with pre- and post- diagnostic plasma samples.

BACKGROUND: Persistent organic pollutants (POPs) have been associated with type 2 diabetes (T2D), but causality is uncertain. OBJECTIVE: Within longitudinal population-based data from northern Sweden, we assessed how POPs associated with T2D prospectively and cross-sectionally, and further investigated factors related to individual changes in POP concentrations. METHODS: For 129 case-controls pairs matched by age, sex and date of sampling, plasma concentrations of hexachlorobenzene (HCB), dichlorodiphenyl-dichloroethylene (p,p'-DDE), dioxin-like (DL) polychlorinated biphenyl congeners (PCB-118 and PCB-156), and non-dioxin like (NDL-PCB: PCB-74, -99, -138 -153, -170, -180, -183 and PCB-187) were analyzed twice (baseline and follow-up, 9-20 years apart). The cases received their T2D diagnose between baseline and follow-up. Prospective (using baseline data) and cross-sectional (using follow-up data) odds ratios (ORs) for T2D on lipid standardized POPs (HCB, p,p'-DDE, ∑DL-PCBs, ∑NDL-PCBs) were estimated using conditional logistic regression, adjusting for body mass index (BMI) and plasma lipids. The influence of BMI, weight-change, and plasma lipids on longitudinal changes in POP concentrations were evaluated among non-diabetic individuals (n = 306). RESULTS: POPs were associated with T2D in both the prospective and cross-sectional assessments. Of a standard deviation increase in POPs, prospective ORs ranged 1.42 (95% CI: 0.99, 2.06) for ∑NDL-PCBs to 1.55 (95% CI: 1.01, 2.38) for HCB (p < 0.05 only for HCB), and cross-sectional ORs ranged 1.62 (95% CI: 1.13; 2.32) for p,p'-DDE to 2.06 (95% CI: 1.29, 3.28) for ∑DL-PCBs (p < 0.05 for all POPs). In analyses of non-diabetic individuals, higher baseline BMI, decreased weight and decreased plasma lipid concentrations were associated with a slower decrease of POPs. Cases had, besides a higher BMI, reduced cholesterol and weight gain at follow-up compared to controls, which can explain the higher ORs in the cross-sectional assessments. DISCUSSION: The association between POPs and T2D was confirmed, but an indication that individuals body fat history might influence POP-T2D associations weakens the epidemiological support for a causal association. It also warrants studies based on other exposure metrics than biomonitoring. In addition, we note that a cross-sectional design overestimates the ORs if T2D cases have successfully intervened on weight and/or blood lipids, as changes in these factors cause changes in POPs.

Hyperglycemia in Extremely Preterm Infants-Insulin Treatment, Mortality and Nutrient Intakes.

OBJECTIVE: To explore the prevalence of hyperglycemia and the associations between nutritional intakes, hyperglycemia, insulin treatment, and mortality in extremely preterm infants. STUDY DESIGN: Prospectively collected data from the Extremely Preterm Infants in Sweden Study (EXPRESS) was used in this study and included 580 infants born <27 gestational weeks during 2004-2007. Available glucose measurements (n = 9850) as well as insulin treatment and nutritional data were obtained retrospectively from hospital records for the first 28 postnatal days as well as 28- and 70-day mortality data. RESULTS: Daily prevalence of hyperglycemia >180 mg/dL (10 mmol/L) of up to 30% was observed during the first 2 postnatal weeks, followed by a slow decrease in its occurrence thereafter. Generalized additive model analysis showed that increasing parenteral carbohydrate supply with 1 g/kg/day was associated with a 1.6% increase in glucose concentration (P < .001). Hyperglycemia was associated with more than double the 28-day mortality risk (P < .01). In a logistic regression model, insulin treatment was associated with lower 28- and 70-day mortality when given to infants with hyperglycemia irrespective of the duration of the hyperglycemic episode (P < .05). CONCLUSIONS: Hyperglycemia is common in extremely preterm infants throughout the first postnatal month. Glucose infusions seem to have only a minimal impact on glucose concentrations. In the EXPRESS cohort, insulin treatment was associated with lower mortality in infants with hyperglycemia. Current practices of hyperglycemia treatment in extremely preterm infants should be reevaluated and assessed in randomized controlled clinical trials.

Salivary Cortisol and Cortisone Can Circumvent Confounding Effects of Oral Contraceptives in the Short Synacthen Test.

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: This work aimed 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 underwent an SST with collection of plasma and salivary samples at 0, 30, and 60 minutes 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 vs 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.

Acute Hyperglycemia Induced by Hyperglycemic Clamp Affects Plasma Amyloid-ß in Type 2 Diabetes.

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-ß peptides (Aß) play a key role in AD pathophysiology. Therefore, human studies on Aß metabolism and T2D are warranted. Objective: The objective of this study was to examine whether acute hyperglycemia affects plasma Aß1-40 and Aß1-42 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. Aß1-40, Aß1-42, 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 Aß1-40 and Aß1-42 concentrations, adjusting for body mass index, estimated glomerular filtration rate, and 4-hour change in insulin concentration. Results: At baseline, Aß1-40 and Aß1-42 concentrations did not differ between the two groups. During the hyperglycemic clamp, Aß decreased in the control group, compared to the placebo clamp (Aß1-40: p = 0.034, Aß1-42: p = 0.020), IDE increased (p = 0.016) during the hyperglycemic clamp, whereas no significant changes in either Aß or IDE was noted in the T2D group. Conclusions: Clamp-induced hyperglycemia was associated with increased IDE levels and enhanced Aß40 and Aß42 clearance in controls, but not in individuals with T2D. We hypothesize that insulin-degrading enzyme was inhibited during hyperglycemic conditions in people with T2D.

Increase in daily asthma medication sales in association with air pollution levels in Greater Stockholm.

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-3 increase in PM10 the 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-3 increase in NOx and 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.

Diet and lifestyle factors associated with fish consumption in men and women: a study of whether gender differences can result in gender-specific confounding.

BACKGROUND: Fish consumption and intake of omega-3 fatty acids from fish are associated with a lower risk of cardiovascular disease. However, a prospective study from northern Sweden showed that high consumption of fish is associated with an increased risk of stroke in men, but not in women. The current study aimed to determine if fish consumption is differently related to lifestyle in men compared with women in northern Sweden. METHODS: Lifestyle information on 32,782 men and 34,866 women (aged 30-60 years) was collected between 1992 and 2006 within the Västerbotten Intervention Programme (a health intervention in northern Sweden). Spearman correlations coefficients (Rs) were calculated between self-reported consumption of fish and other food items. Lifestyle variables were compared between fish consumption categories. RESULTS: Fish consumption was positively associated with other foods considered healthy (e.g., root vegetables, lettuce/cabbage/spinach/broccoli, chicken, and berries; Rs = 0.21-0.30), as well as with other healthy lifestyle factors (e.g., exercise and not smoking) and a higher educational level, in both men and women. The only gender difference found, concerned the association between fish consumption and alcohol consumption. Men who were high consumers of fish had a higher intake of all types of alcohol compared with low to moderate fish consumers. For women, this was true only for wine. CONCLUSIONS: Except for alcohol, the association between fish consumption and healthy lifestyle did not differ between men and women in northern Sweden. It is important to adjust for other lifestyle variables and socioeconomic variables in studies concerning the effect of fish consumption on disease outcome.

Short-Term Associations between PM10 and Respiratory Health Effects in Visby, Sweden.

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.

Respiratory Health Effects of Wildfire Smoke during Summer of 2018 in the Jämtland Härjedalen Region, Sweden.

During the summer of 2018 Sweden experienced a high occurrence of wildfires, most intense in the low-densely populated Jämtland Härjedalen region. The aim of this study was to investigate any short-term respiratory health effects due to deteriorated air quality generated by the smoke from wildfires. For each municipality in the region Jämtland Härjedalen, daily population-weighted concentrations of fine particulate matter (PM2.5) were calculated through the application of the MATCH chemistry transport model. Modelled levels of PM2.5 were obtained for two summer periods (2017, 2018). Potential health effects of wildfire related levels of PM2.5 were examined by studying daily health care contacts concerning respiratory problems in each municipality in a quasi-Poisson regression model, adjusting for long-term trends, weekday patterns and weather conditions. In the municipality most exposed to wildfire smoke, having 9 days with daily maximum 1-h mean of PM2.5 > 20 µg/m3, smoke days resulted in a significant increase in daily asthma visits the same and two following days (relative risk (RR) = 2.64, 95% confidence interval (CI): 1.28-5.47). Meta-estimates for all eight municipalities revealed statistically significant increase in asthma visits (RR = 1.68, 95% CI: 1.09-2.57) and also when grouping all disorders of the lower airways (RR = 1.40, 95% CI: 1.01-1.92).

Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes - A nested case-control study.

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.

Field validation of the Ogawa diffusive sampler for NO2 and NOx in a cold climate.

A small-scale field trial in Umeå, Sweden with Ogawa samplers and a chemiluminescence instrument indicated that the NO(2) concentration was underestimated with respect to the reference monitor, if calculated according to the manufacturer's Ogawa sampling protocol. By co-locating Ogawa samplers and reference monitors at six sites in two Swedish cities, uptake rates were determined for NO(2) and NO(x) better applicable to the Swedish conditions and climate. The concentrations of NO(2) and NO(x) calculated according to the instruction manual of the sampler and using the field-determined uptake rates were compared with values derived from chemiluminescence monitors for each week over which samples were taken. When calculated according to the manufacturer's suggested protocol, the Ogawa sampler underestimated the NO(2) concentrations by 9.1% on average for all samples (N = 53), with respect to the reference monitor. In contrast, NO(x) concentrations were overestimated by a mean value of 15% for all samples (N = 45). By using the field determined uptake rates for the calculation of NO(2) and NO(x) a better estimation of the concentrations was obtained. The ratio between concentrations determined with the Ogawa samplers and chemiluminescence monitors was then 1.02 for all measurements of NO(2) and 1.00 for NO(x). Precision, expressed as the mean coefficient of variation, was 6.4% for six, 6-replicate measurements of NO(2) and 3.7% for five, 6-replicate measurements of NO(x).

A Multi-Pollutant Air Quality Health Index (AQHI) Based on Short-Term Respiratory Effects in Stockholm, Sweden.

In this study, an Air Quality Health Index (AQHI) for Stockholm is introduced as a tool to capture the combined effects associated with multi-pollutant exposure. Public information regarding the expected health risks associated with current or forecasted concentrations of pollutants and pollen can be very useful for sensitive persons when planning their outdoor activities. For interventions, it can also be important to know the contribution from pollen and the specific air pollutants, judged to cause the risk. The AQHI is based on an epidemiological analysis of asthma emergency department visits (AEDV) and urban background concentrations of NOx, O3, PM10 and birch pollen in Stockholm during 2001⁻2005. This analysis showed per 10 µg·m⁻3 increase in the mean of same day and yesterday an increase in AEDV of 0.5% (95% CI: -1.2⁻2.2), 0.3% (95% CI: -1.4⁻2.0) and 2.5% (95% CI: 0.3⁻4.8) for NOx, O3 and PM10, respectively. For birch pollen, the AEDV increased with 0.26% (95% CI: 0.18⁻0.34) for 10 pollen grains·m⁻3. In comparison with the coefficients in a meta-analysis, the mean values of the coefficients obtained in Stockholm are smaller. The mean value of the risk increase associated with PM10 is somewhat smaller than the mean value of the meta-coefficient, while for O3, it is less than one fifth of the meta-coefficient. We have not found any meta-coefficient using NOx as an indicator of AEDV, but compared to the mean value associated with NO2, our value of NOx is less than half as large. The AQHI is expressed as the predicted percentage increase in AEDV without any threshold level. When comparing the relative contribution of each pollutant to the total AQHI, based on monthly averages concentrations during the period 2015⁻2017, there is a tangible pattern. The AQHI increase associated with NOx exhibits a relatively even distribution throughout the year, but with a clear decrease during the summer months due to less traffic. O3 contributes to an increase in AQHI during the spring. For PM10, there is a significant increase during early spring associated with increased suspension of road dust. For birch pollen, there is a remarkable peak during the late spring and early summer during the flowering period. Based on monthly averages, the total AQHI during 2015⁻2017 varies between 4 and 9%, but with a peak value of almost 16% during the birch pollen season in the spring 2016. Based on daily mean values, the most important risk contribution during the study period is from PM10 with 3.1%, followed by O3 with 2.0%.

Perfluoroalkyl substances and risk of type II diabetes: A prospective nested case-control study.

BACKGROUND: Perfluoroalkyl substances (PFAS) have drawn much attention due to bioaccumulation potential and their current omnipresence in human blood. We assessed whether plasma PFAS, suspected to induce endocrine-disrupting effects, were prospectively associated with clinical type 2 diabetes (T2D) risk. METHODS: We established a nested case-control study within the Swedish prospective population-based Västerbotten Intervention Programme cohort. Several PFAS were measured in plasma from a subset of 124 case-control pairs at baseline (during 1990-2003) and at 10-year follow-up. T2D cases were matched (1:1) according to gender, age and sample date with participants without T2D (controls). Conditional logistic regressions were used to prospectively assess risk of T2D by baseline PFAS plasma concentrations. Associations between long-term PFAS plasma levels (mean of baseline and follow-up) and insulin resistance (HOMA2-IR) and beta-cell function (HOMA2-B%) at follow-up were prospectively explored among 178 and 181 controls, respectively, by multivariable linear regressions. RESULTS: After adjusting for gender, age, sample year, diet and body mass index, the odds ratio of T2D for the sum of PFAS (Σ z-score PFAS) was 0.52 (95% confidence interval, CI: 0.20, 1.36), comparing third with first tertile; and 0.92 (95% CI: 0.84, 1.00) per one standard deviation increment of sum of log-transformed PFAS. Among the controls, the adjusted ß of HOMA2-IR and HOMA-B% for the sum of PFAS were -0.26 (95% CI: -0.52, -0.01) and -9.61 (95% CI: -22.60, 3.39) respectively comparing third with first tertile. CONCLUSIONS: This prospective nested case-control study yielded overall inverse associations between individual PFAS and risk of T2D, although mostly non-significant. Among participants without T2D, long-term PFAS exposure was prospectively associated with lower insulin resistance.

Associations between repeated measure of plasma perfluoroalkyl substances and cardiometabolic risk factors.

BACKGROUND: Perfluoroalkyl substances (PFAS) are persistent synthetic chemicals that may affect components of metabolic risk through the peroxisome proliferator-activated receptor but epidemiological data remain scarce and inconsistent. OBJECTIVE: To estimate associations between repeated measurements of the main PFAS in plasma and total cholesterol, triglycerides and hypertension among the control subjects from a population-based nested case-control study on diabetes type 2 in middle-aged women and men. METHODS: Participants (n = 187) were free of diabetes at both baseline and follow-up visits to the Västerbotten Intervention Programme, 10 years apart: during 1990 to 2003 (baseline) and 2001 to 2013 (follow-up). Participants left blood samples, completed questionnaires on diet and lifestyle factors, and underwent medical examinations, including measurement of blood pressure. PFAS and lipids were later determined in stored plasma samples. Associations for the repeated measurements were assessed using generalized estimating equations. RESULTS: Six PFAS exceeded the limit of quantitation. Repeated measures of PFAS in plasma, cardiometabolic risk factors and confounders, showed an average decrease of triglycerides from -0.16 mmol/l (95% confidence interval [CI]: -0.33, 0.02 for PFOA) to -0.26 mmol/l (95% CI: -0.50, -0.08 for PFOS), when comparing the highest tertile of PFAS plasma levels with the lowest. Associations based on average PFAS measurements and follow-up triglycerides revealed similar inverse associations, although attenuated. The estimates for cholesterol and hypertension were inconsistent and with few exception non-significant. CONCLUSIONS: This study found inverse associations between PFAS and triglycerides, but did not support any clear link with either cholesterol or hypertension.

Persistent Organochlorine Pollutants in Plasma, Blood Pressure, and Hypertension in a Longitudinal Study.

Persistent organochlorine pollutants (POPs) have shown to be involved in the atherosclerotic process and to cause endothelial cell dysfunction. To assess longitudinally whether plasma concentrations of different POPs were associated with blood pressure and risk of hypertension in middle-aged women and men. Study subjects were 850 participants in the VIP (Västerbotten Intervention Programme) with 2 blood samples and blood pressure measurements, 10 years apart, during 1990 to 2003 (baseline) and during 2000 to 2013 (follow-up). Dioxin-like and nondioxin-like polychlorinated biphenyls (DL-PCBs, NDL-PCBs) and p,p'-dichlorodiphenyldichloroethylene (DDE) were measured. Associations were assessed using generalized estimating equations. At baseline sampling 49% and at follow-up 64% had hypertension. DL-PCBs and DDE, but not NDL-PCBs or hexachlorobenzene, were associated with hypertension. Only the association for DL-PCBs remained statistically significant after lipid-standardization and adjustment for body mass index and total serum lipids. The multivariable-adjusted odds ratio of hypertension based on repeated measurements were 1.52 (95% confidence interval, 1.08-2.13) for DL-PCBs (third versus first tertile of lipid-standardized POPs). In stratified adjusted analyses, odds ratio for those born after 1950 increased to 3.99 (95% confidence interval, 2.15-7.43), whereas no association was observed among those born earlier. Based on repeated measurements, the accumulated exposure to DL-PCBs and DDE, although less clear for the latter, may disrupt the normal blood pressure levels and increase the odds of hypertension. Moreover, individuals experiencing early-life POP exposure may be at elevated risk of vascular POP effects.

Evolution of Minimum Mortality Temperature in Stockholm, Sweden, 1901-2009.

BACKGROUND: The mortality impacts of hot and cold temperatures have been thoroughly documented, with most locations reporting a U-shaped relationship with a minimum mortality temperature (MMT) at which mortality is lowest. How MMT may have evolved over previous decades as the global mean surface temperature has increased has not been thoroughly explored. OBJECTIVE: We used observations of daily mean temperatures to investigate whether MMT changed in Stockholm, Sweden, from the beginning of the 20th century until 2009. METHODS: Daily mortality and temperature data for the period 1901-2009 in Stockholm, Sweden, were used to model the temperature-mortality relationship. We estimated MMT using distributed lag nonlinear Poisson regression models considering lags up to 21 days of daily mean temperature as the exposure variable. To avoid large influences on the MMT from intra- and interannual climatic variability, we estimated MMT based on 30-year periods. Furthermore, we investigated whether there were trends in the absolute value of the MMT and in the relative value of the MMT (the corresponding percentile of the same-day temperature distribution) over the study period. RESULTS: Our findings suggest that both the absolute MMT and the relative MMT increased in Stockholm, Sweden, over the course of the 20th century. CONCLUSIONS: The increase in the MMT over the course of the 20th century suggests autonomous adaptation within the context of the large epidemiological, demographical, and societal changes that occurred. Whether the rate of increase will be sustained with climate change is an open question. CITATION: Oudin Åström D, Tornevi A, Ebi KL, Rocklöv J, Forsberg B. 2016. Evolution of minimum mortality temperature in Stockholm, Sweden, 1901-2009. Environ Health Perspect 124:740-744; http://dx.doi.org/10.1289/ehp.1509692.

Efficacy of water treatment processes and endemic gastrointestinal illness - A multi-city study in Sweden.

Outbreaks of acute gastrointestinal illnesses (AGI) have been linked to insufficient drinking water treatment on numerous occasions in the industrialized world, but it is largely unknown to what extent public drinking water influences the endemic level of AGI. This paper aimed to examine endemic AGI and the relationship with pathogen elimination efficacy in public drinking water treatment processes. For this reason, time series data of all telephone calls to the Swedish National Healthcare Guide between November 2007 and February 2014 from twenty Swedish cities were obtained. Calls concerning vomiting, diarrhea or abdominal pain (AGI calls) were separated from other concerns (non-AGI calls). Information on which type of microbial barriers each drinking water treatment plant in these cities have been used were obtained, together with the barriers' theoretical pathogen log reduction efficacy. The total log reduction in the drinking water plants varied between 0.0 and 6.1 units for viruses, 0.0-14.6 units for bacteria and 0.0-7.3 units regarding protozoans. To achieve one general efficacy parameter for each plant, a weighted mean value of the log reductions (WLR) was calculated, with the weights based on how commonly these pathogen groups cause AGI. The WLR in the plants varied between 0.0 and 6.4 units. The effect of different pathogen elimination efficacy on levels of AGI calls relative non-AGI calls was evaluated in regression models, controlling for long term trends, population size, age distribution, and climatological area. Populations receiving drinking water produced with higher total log reduction was associated with a lower relative number of AGI calls. In overall, AGI calls decreased by 4% (OR = 0.96, CI: 0.96-0.97) for each unit increase in the WLR. The findings apply to both groundwater and surface water study sites, but are particularly evident among surface water sites during seasons when viruses are the main cause of AGI. This study proposes that the endemic level of gastroenteritis can indeed be reduced with more advanced treatment processes at many municipal drinking water treatment plants.

Precipitation and primary health care visits for gastrointestinal illness in Gothenburg, Sweden.

BACKGROUND: The river Göta Älv is a source of freshwater for the City of Gothenburg, Sweden, and we recently identified a clear influence of upstream precipitation on concentrations of indicator bacteria in the river water, as well as an association with the daily number of phone calls to the nurse advice line related to acute gastrointestinal illnesses (AGI calls). This study aimed to examine visits to primary health-care centers owing to similar symptoms (AGI visits) in the same area, to explore associations with precipitation, and to compare variability in AGI visits and AGI calls. METHODS: We obtained data covering six years (2007-2012) of daily AGI visits and studied their association with prior precipitation (0-28 days) using a distributed lag nonlinear Poisson regression model, adjusting for seasonal patterns and covariates. In addition, we studied the effects of prolonged wet and dry weather on AGI visits. We analyzed lagged short-term relations between AGI visits and AGI calls, and we studied differences in their seasonal patterns using a binomial regression model. RESULTS: The study period saw a total of 17,030 AGI visits, and the number of daily visits decreased on days when precipitation occurred. However, prolonged wet weather was associated with an elevated number of AGI visits. Differences in seasonality patterns were observed between AGI visits and AGI calls, as visits were relatively less frequent during winter and relatively more frequent in August, and only weak short-term relations were found. CONCLUSION: AGI visits and AGI calls seems to partly reflect different types of AGI illnesses, and the patients' choice of medical contact (in-person visits versus phone calls) appears to depend on current weather conditions. An association between prolonged wet weather and increased AGI visits supports the hypothesis that the drinking water is related to an increased risk of AGI illnesses.

Precipitation effects on microbial pollution in a river: lag structures and seasonal effect modification.

BACKGROUND: The river Göta Älv is a source of freshwater for 0.7 million swedes. The river is subject to contamination from sewer systems discharge and runoff from agricultural lands. Climate models projects an increase in precipitation and heavy rainfall in this region. This study aimed to determine how daily rainfall causes variation in indicators of pathogen loads, to increase knowledge of variations in river water quality and discuss implications for risk management. METHODS: Data covering 7 years of daily monitoring of river water turbidity and concentrations of E. coli, Clostridium and coliforms were obtained, and their short-term variations in relation with precipitation were analyzed with time series regression and non-linear distributed lag models. We studied how precipitation effects varied with season and compared different weather stations for predictive ability. RESULTS: Generally, the lowest raw water quality occurs 2 days after rainfall, with poor raw water quality continuing for several more days. A rainfall event of >15 mm/24-h (local 95 percentile) was associated with a three-fold higher concentration of E. coli and 30% higher turbidity levels (lag 2). Rainfall was associated with exponential increases in concentrations of indicator bacteria while the effect on turbidity attenuated with very heavy rainfall. Clear associations were also observed between consecutive days of wet weather and decreased water quality. The precipitation effect on increased levels of indicator bacteria was significant in all seasons. CONCLUSIONS: Rainfall elevates microbial risks year-round in this river and freshwater source and acts as the main driver of varying water quality. Heavy rainfall appears to be a better predictor of fecal pollution than water turbidity. An increase of wet weather and extreme events with climate change will lower river water quality even more, indicating greater challenges for drinking water producers, and suggesting better control of sources of pollution.

Intake and macronutrient content of human milk given to extremely preterm infants.

BACKGROUND: Human milk (HM) is the preferred basis of nutrition for infants, including those born prematurely. Information on HM macronutrient content is necessary to optimize nutritional support of preterm infants. OBJECTIVES: This study aimed to describe the types and amounts of enteral feeds given to Swedish extremely preterm infants during hospitalization and to investigate the energy and macronutrient contents in HM given to these infants. METHODS: A population-based study of Swedish extremely preterm infants (n = 586) born before 27 gestational weeks was conducted. Data on ingested volumes of different milk during hospitalization and analyses of macronutrient content in HM samples were obtained from hospital records. Nutritional content of HM was determined by mid-infrared spectrophotometry analysis. RESULTS: During the first 4 weeks of life, 99% of the infants were exclusively fed HM, and at 4 weeks of life, 70% of the infants received only mother's own milk (MOM). Nutritional content in 821 MOM samples was analyzed. Protein content in MOM decreased significantly from 2.2 to 1.2 g/100 mL during the first 112 postpartum days, whereas fat and energy content were highly variable within and between MOM samples. In addition, 354 samples of donor milk were analyzed. Content of protein, fat, and energy in pooled donor milk (n = 129) was lower compared to single donor milk. CONCLUSION: Swedish extremely preterm infants receive MOM to a large extent during hospitalization. Protein, carbohydrates, and energy in MOM changed significantly with time. Weekly analyses of MOM during the first month of lactation would allow more individualized nutritional support for these vulnerable infants.