Occupational risk of SARS-CoV-2 infection: a nationwide register-based study of the Danish workforce during the COVID-19 pandemic, 2020-2021.

OBJECTIVE: Most earlier studies on occupational risk of COVID-19 covering the entire workforce are based on relatively rare outcomes such as hospital admission and mortality. This study examines the incidence of SARS-CoV-2 infection by occupational group based on real-time PCR (RT-PCR) tests. METHODS: The cohort includes 2.4 million Danish employees, 20-69 years of age. All data were retrieved from public registries. The incidence rate ratios (IRRs) of first-occurring positive RT-PCR test from week 8 of 2020 to week 50 of 2021 were computed by Poisson regression for each four-digit Danish Version of the International Standard Classification of Occupations job code with more than 100 male and 100 female employees (n=205). Occupational groups with low risk of workplace infection according to a job exposure matrix constituted the reference group. Risk estimates were adjusted by demographic, social and health characteristics including household size, completed COVID-19 vaccination, pandemic wave and occupation-specific frequency of testing. RESULTS: IRRs of SARS-CoV-2 infection were elevated in seven healthcare occupations and 42 occupations in other sectors, mainly social work activities, residential care, education, defence and security, accommodation and transportation. No IRRs exceeded 2.0. The relative risk in healthcare, residential care and defence/security declined across pandemic waves. Decreased IRRs were observed in 12 occupations. DISCUSSION: We observed a modestly increased risk of SARS-CoV-2 infection among employees in numerous occupations, indicating a large potential for preventive actions. Cautious interpretation of observed risk in specific occupations is needed because of methodological issues inherent in analyses of RT-PCR test results and because of multiple statistical tests.

Exposure to high levels of PFAS through drinking water is associated with increased risk of type 2 diabetes-findings from a register-based study in Ronneby, Sweden.

BACKGROUND: Epidemiological studies linking type 2 diabetes (T2D) and exposure to per- and polyfluoroalkyl substances (PFAS), are limited and have yielded conflicting results. This register-based study aimed to investigate the risk of T2D among Swedish adults who had been exposed to PFAS from highly contaminated drinking water for decades. METHODS: The study included 55,032 adults (aged ≥18 years) from the Ronneby Register Cohort, who ever lived in Ronneby during 1985-2013. Exposure was assessed using the yearly residential address and the absence ("never-high") or presence ("ever-high") of high PFAS contamination in the municipal drinking water supply; the latter was subdivided into "early-high" and "late-high" exposure with cut-off at 2005. Incident T2D cases were retrieved from the National Patient Register and the Prescription Register. Cox proportional hazard models with time-varying exposure were used to estimate hazard ratios (HRs). Stratified analyses were performed based on age (18-45 vs > 45). RESULTS: Elevated HRs for T2D were observed when comparing "ever-high" to "never-high" exposure (HR 1.18, 95% CI 1.03-1.35), as well as when comparing "early-high" (HR 1.12, 95% CI 0.98-1.50) or "late-high" (HR 1.17, 95% CI 1.00-1.37) to "never-high", after adjusting for age and sex. Individuals aged 18-45 years had even higher HRs. Adjusting for the highest-achieved education level attenuated the estimates, but the directions of associations remained. Elevated HRs were also found among those who had lived in areas with a heavily contaminated water supply for 1-5 years (HR 1.26, 95% CI 0.97-1.63) and 6-10 years (HR 1.25, 95% CI 0.80-1.94). CONCLUSION: This study suggests an increased risk of T2D after long-term high PFAS exposure through drinking water. In particular, a higher risk of early onset diabetes was found, indicating increased susceptibility to PFAS-related health effects at younger ages.

High exposure to perfluoroalkyl substances in drinking water is associated with increased risk of osteoporotic fractures - A cohort study from Ronneby, Sweden.

BACKGROUND: Perfluoroalkyl substances (PFAS) have been reported to be related to decreased bone mineral density, but the relationship with osteoporosis and fractures is less studied. This study aimed to investigate the risks of osteoporotic fractures in a Swedish population with long-term exposure to PFAS through drinking water. METHODS: The Ronneby Register Cohort, including 61,504 individuals who had ever lived in Ronneby during 1985-2013, was used. Exposure to PFAS was assessed according to the yearly residential address with or without highly contaminated water supply and was categorized as 'never-high' and 'ever-high' exposure. The 'ever-high' exposure was further divided into 'early-high' and 'late-high' depending on if the exposure was before or after 2005. Inpatient and outpatient hospital diagnoses of fractures were retrieved from the National Patient Register. Major osteoporotic fractures (MOF, i.e., hip, vertebrae, proximal humerus and distal forearm fractures), and hip fractures were considered as the primary outcomes. Cox proportional hazard models with time-varying exposure were used to estimate the hazard ratios (HRs). Stratified analyses were performed in each sex and age group (<50 yrs and ≥ 50 yrs). RESULTS: Elevated risks of MOF (HR 1.11, 95% CI 1.03-1.19) and hip fractures (1.12, 1.00-1.24) were observed when comparing 'ever-high' to 'never-high' exposure. The HRs were even higher for 'late-high' exposure (MOF: 1.29, 1.16-1.44; hip fractures: 1.22, 1.01-1.47). Further adjustment for highest achieved education slightly attenuated the estimates. Individuals above 50 years old showed even higher HR estimates. Similar patterns were found for all fractures. CONCLUSION: Our results provide further evidence supporting the adverse effects of PFAS on osteoporosis. A better understanding of dose-response relationships as a basis for risk assessment is warranted.

Gestational hypertension, preeclampsia, and gestational diabetes mellitus after high exposure to perfluoroalkyl substances from drinking water in Ronneby, Sweden.

BACKGROUND: Leakage of fire-fighting foam from an airfield caused contamination of the drinking water supplied to a third of the population in Ronneby, resulting in very high serum levels of predominantly perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS). The results of studies investigating the association between exposure to perfluorinated alkyl substances (PFAS) and pregnancy complications are inconsistent, and studies at high exposures of PFOS and PFHxS are lacking. OBJECTIVES: To investigate the association between exposure to high levels of PFAS and gestational hypertension and preeclampsia, and gestational diabetes mellitus. METHODS: We retrieved data on 27 292 childbirths between 1995 and 2013 from the National Medical Birth Register for women that had a residential address in Blekinge county for at least one year before delivery. Residential history was used as a proxy for exposure by categorizing women into high-, intermediate-, or background exposed based on their residential address during the five-year period before childbirth. Data on confounders were retrieved from administrative registers. The outcomes were defined based on International Classification of Diseases codes. We used logistic regression to estimate odds ratios (OR) for gestational hypertension and preeclampsia, and gestational diabetes mellitus. We also investigated effect modification by fetal sex. RESULTS: We found no evidence of increased risk of gestational hypertension and preeclampsia (OR 0.80; CI 0.63-1.03), nor gestational diabetes (OR 1.03; CI 0.67-1.58) after high PFAS exposure. There was no effect modification by fetal sex. DISCUSSION: This was the first study to investigate the association between high exposure to PFOS and PFHxS and pregnancy complications. The results from this study add important knowledge to public health management as new hotspots with high levels of PFAS are continuously discovered.

Changes in perfluoroalkyl substances (PFAS) concentrations in human milk over the course of lactation: A study in Ronneby mother-child cohort.

BACKGROUND: Little is known about how PFAS concentrations in human milk change over the course of lactation, although this is an important determinant of cumulative infant exposure from breastfeeding. OBJECTIVE: To estimate changes in PFAS concentrations in human milk over the course of lactation in a population with a wide range of exposure from background-to high-exposed. METHODS: We measured PFAS concentrations in colostrum and mature milk samples from women in the Ronneby Mother-Child Cohort. For each PFAS, we estimated the change in concentration from colostrum collected 3-4 days postpartum to mature milk collected 4-12 weeks postpartum using linear mixed-effects models. We evaluated whether this estimated change varied by quartiles of colostrum concentrations. In a subset of mothers with at least three mature milk samples, we estimated the change in concentration per month over the first eight months of lactation. RESULTS: Our study included 77 mother-child pairs, of whom 74 had colostrum and initial mature milk samples and 11 had three or more repeated samples. The concentration change from colostrum to mature milk varied by PFAS. While PFOS increased by 21% (95% CI: 8.9, 35), PFOA decreased by 17% (95% CI: -28, -3.5) and PFHxS decreased by 12% (95% CI: -24, 3.3). In addition, PFAS concentrations tended to increase in women with lower colostrum levels, but decreased or remained the same in women with high colostrum concentrations. When we estimated changes over the course of lactation, we found that PFOA concentrations decreased the most (-12% per month; 95% CI: -22, -1.5), whereas PFHxS and PFOS showed small nonsignificant decreases. CONCLUSIONS: Models for cumulative infancy exposure from breastfeeding need to account for differences in concentration trajectories by PFAS and possibly by maternal exposure level. Additional research is needed to evaluate the relative exposure from breastfeeding vs prenatal exposure, especially in highly exposed communities where breastfeeding guidance is urgently needed.

Quantitative relationships of perfluoroalkyl acids in drinking water associated with serum concentrations above background in adults living near contamination hotspots in Sweden.

Contaminated drinking water (DW) is a major source of exposure to per- and polyfluoroalkyl substances (PFAS) at locations around PFAS production/use facilities and military airports. This study aimed to investigate quantitative relationships between concentrations in DW and serum of nine perfluoroalkyl acids (PFAAs) in Swedish adult populations living near contamination hotspots. Short-chained (PFPeA, PFHxA, PFHpA, and PFBS) and long-chained PFAAs (PFOA, PFNA, PFDA, PFHxS and PFOS) were measured in DW and serum. We matched DW and serum concentrations for a total of 398 subjects living or working in areas receiving contaminated DW and in one non-contaminated area. Thereafter, linear regression analysis with and without adjustments for co-variates was conducted. This enabled to derive (i) serum concentrations at background exposure (CB) from sources other than local DW exposure (i.e. food, dust and textiles) at 0 ng/L DW concentration, (ii) population-mean PFAA serum:water ratios (SWR) and (iii) PFAA concentrations in DW causing observable elevated serum PFAA concentrations above background variability. Median concentrations of the sum of nine PFAAs ranged between 2.8 and 1790 ng/L in DW and between 7.6 and 96.9 ng/mL in serum. DW concentration was the strongest predictor, resulting in similar unadjusted and adjusted regression coefficients. Mean CB ranged from <0.1 (PFPeA, PFHpA, PFBS) to 5.1 ng/mL (PFOS). Serum concentrations increased significantly with increasing DW concentrations for all PFAAs except for PFPeA with SWRs ranging from <10 (PFHxA, PFHpA and PFBS) to 111 (PFHxS). Observed elevated serum concentrations above background variability were reached at DW concentrations between 24 (PFOA) and 357 ng/L (PFHxA). The unadjusted linear regression predictions agreed well with serum concentrations previously reported in various populations exposed to low and high DW levels of PFOA, PFHxS and PFOS. The quantitative relationships derived herein should be helpful to translate PFAA concentrations in DW to concentrations in serum at the population level.

An investigation of child health in relation to housing renovations for a disadvantaged immigrant population in Malmö, Sweden.

AIMS: The aim of the study was to describe child health in relation to housing renovations in more than 800 rental units, consisting of repairs of dilapidated kitchens and bathrooms, in the disadvantaged neighbourhood of Herrgården in Rosengård, Malmö, Sweden. METHODS: Data on housing conditions and self-reported health were collected during home visits to families living in Herrgården (building renovations area) and a comparison area (neighbouring Törnrosen, with generally better housing conditions). At baseline, 130 families with 359 children participated, while 51 families with 127 children participated at follow-up. All data were collected between 2010 and 2012. Additionally, regional register data on health-care usage/in- and outpatient contacts within the public health-care system between 2008 and 2013 were also collected for all 8715 children registered as living in the two areas. RESULTS: Self-reported health seemed to somewhat improve in both areas, with 74% versus 86% and 78% versus 88% reporting good or very good health in Herrgården and in the comparison area at baseline and follow-up, respectively. In Herrgården, crowdedness increased, while it decreased in the comparison area. The number of health-care contacts remained stable over time in Herrgården, while it decreased in the comparison area. CONCLUSIONS: Partial housing renovations did not seem to result in clear health improvements as measured with the indicators used in the present study. This could possibly be due to persisting health effects due to increased crowdedness or persisting poor housing conditions, as only kitchens and bathrooms were renovated.

An explorative study of inflammation-related proteins associated with kidney injury in male heat-stressed workers.

Chronic kidney disease of non-traditional origin (CKDnt) and acute kidney injury (AKI) often affect heat-stressed Mesoamerican manual workers. Inflammation occurs concurrently with AKI in this population, but its role remains unknown. To explore links between inflammation and kidney injury in heat stress, we compared levels of inflammation-related proteins in cutters with and without increasing serum creatinine levels during sugarcane harvest. These sugarcane cutters have previously been identified to be repeatedly exposed to severe heat stress during the five month harvest season. A nested case-control study was conducted among male Nicaraguan sugarcane cutters in a CKDnt hotspot. Cases (n = 30) were defined as having an increase in creatinine of ≥0.3 mg/dL across the five-month harvest. Controls (n = 57) had stable creatinine levels. Ninety-two inflammation-related proteins in serum were measured before and after harvest using Proximity Extension Assays. Mixed linear regression was used to identify differences in protein concentrations between cases and controls before harvest, differential trends during harvest, and association between protein concentrations and the urine kidney injury markers Kidney Injury Molecule (KIM)-1, Monocyte Chemoattractant Protein (MCP)-1 and albumin. One protein, chemokine (C-C motif) ligand 23 (CCL23), was elevated among cases at pre-harvest. Changes in seven inflammation-related proteins (CCL19, CCL23, colony-stimulating factor 1 [CSF1], hepatocyte and fibroblast growth factors [HGF and FGF23], and tumor necrosis factor beta [TNFB] and TNF-related activation-induced cytokine [TRANCE]) were associated with case status and at least two out of three urine kidney injury markers (KIM-1, MCP-1 and albumin). Several of these have been implicated in myofibroblast activation, which likely is an important step in kidney interstitial fibrotic disease such as CKDnt. This study provides an initial exploration of immune system determinants of, and activation during, kidney injury experienced during prolonged heat stress.

Markers of kidney tubular and interstitial injury and function among sugarcane workers with cross-harvest serum creatinine elevation.

OBJECTIVES: Serum creatinine (SCr) is a routine marker of kidney injury but also increases with dehydration and muscular work. This study was to elucidate whether increase in SCr is associated with more specific markers of kidney tubular and interstitial injury and function, during prolonged heat stress among workers at high risk of chronic kidney disease of non-traditional origin (CKDnt). METHODS: Urine monocyte chemoattractant protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), calbindin, glutathione S-transferase-π (GST-π), clusterin, interleukin 18 and albumin, fractional excretion of potassium (FEK), blood haemoglobin, serum potassium, ferritin and erythropoietin were measured before and after harvest in a sample of 30 workers with a ≥0.3 mg/dL SCr increase across harvest (cases), and 53 workers with stable SCr (controls). RESULTS: Urine MCP-1 (p for differential cross-harvest trend <0.001), KIM-1 (p=0.002), calbindin (p=0.02), GST-π (p=0.04), albumin (p=0.001) and FEK (p<0.001) increased in cases, whereas blood haemoglobin (p<0.001) and serum erythropoietin (p<0.001) decreased. CONCLUSION: Several markers of tubular and interstitial injury and function changed as SCr increased across a harvest season, supporting the use of SCr as an indicator of kidney injury in physically active workers regularly exposed to heat stress. Repeated injury similar to that described here, and continued work under strenuous and hot conditions with similarly elevated injury markers is likely to worsen and possibly initiate CKDnt.

Large difference but high correlation between creatinine and cystatin C estimated glomerular filtration rate in Mesoamerican sugarcane cutters.

OBJECTIVES: To explore the relationship between creatinine and cystatin C based estimated glomerular filtration rate (eGFR) in actively working sugarcane cutters. METHODS: This cohort study included 458 sugarcane cutters from Nicaragua and El Salvador. Serum samples were taken before and at end of harvest seasons and analysed for creatinine and cystatin C. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were used to calculate eGFRs based on creatinine (eGFRcr), cystatin C (eGFRcys) and both creatinine and cystatin C (eGFRcrcys) at each time point. Bland-Altman plots and paired t-tests were used to compare the difference between eGFRcr and eGFRcys, and the difference in eGFRs between before and at end of the harvest seasons. RESULTS: The mean eGFRcr was higher than eGFRcys in both cohorts; absolute difference 22 mL/min/1.73 m2 (95% CI 21 to 23) in Nicaragua and 13 mL/min/1.73 m2 (95% CI 11 to 15) in El Salvador. Correlations between eGFRcr and eGFRcys were high, with r=0.69, 0.77 and 0.67 in Nicaragua at pre-harvest, end-harvest and cross-harvest, and r=0.89, 0.89 and 0.49 in El Salvador. CONCLUSIONS: Creatinine increases among heat-stressed workers reflect reduced glomerular filtration as estimated using eGFRcys, a marker independent of muscle mass and metabolism. The discrepancy between eGFRcr and eGFRcys may indicate reduced glomerular filtration of larger molecules and/or systemic bias in CKD-EPI performance in this population.

Breastfeeding initiation and duration after high exposure to perfluoroalkyl substances through contaminated drinking water: A cohort study from Ronneby, Sweden.

BACKGROUND: The drinking water in parts of Ronneby was heavily contaminated with perfluoroalkyl substances (PFAS) for decades. Although PFAS has endocrine-disrupting properties and may interfere with breastfeeding, the effects in populations with a point source of high exposure are unknown. OBJECTIVES: To investigate associations between high PFAS exposure and 1) initiation and 2) duration of breastfeeding. METHODS: We retrieved data on infant feeding practices for 2374 children born between 1999 and 2009 from Child Health Care centers in Ronneby and a reference municipality. Residential address before delivery was used as a proxy for exposure, and confounders were obtained from charts and registers. We used modified Poisson regressions to estimate the relative risks (RR) of not initiating breastfeeding, not breastfeeding exclusively after 3 months, and not breastfeeding at all at 6 months. We also estimated hazard ratios (HR) of cessation of exclusive breastfeeding before 6 months and any breastfeeding before 12 months. RESULTS: Mothers who had received contaminated water seemed to have a higher risk of not initiating breastfeeding (RR = 2.4; 95% CI: 0.8, 6.7). Primiparous mothers from the exposed area were at a 1.2 times increased risk (95% CI: 0.9, 1.6) of not exclusively breastfeeding at 3 months and a 1.6 times increased risk (95% CI: 1.2, 2.1) of not breastfeeding at 6 months. The results were confirmed by the Cox regressions, which further showed that the HR for cessation of any breastfeeding was time dependent and higher in early lactation, thereafter decreasing as lactation progressed. We observed no overall associations in multiparous mothers. DISCUSSION: Exposure to high levels of PFAS seemed to be associated with increased risks of not initiating breastfeeding and shorter breastfeeding duration in primiparous mothers. The findings imply that the ability of first-time mothers to establish breastfeeding is a sensitive outcome after high exposure to PFAS.

Cancer incidence in a Swedish cohort with high exposure to perfluoroalkyl substances in drinking water.

BACKGROUND: The use of firefighting foams at a military airport resulted in high levels of perfluorinated substances (PFAS) in the drinking water distributed to one-third of households in the Swedish municipality of Ronneby between the mid-1980s and the end of 2013. METHOD: The Ronneby Register Cohort, a large cohort comprising all individuals (N = 60,507) who ever lived in the Ronneby municipality during the period of drinking water contamination, was linked to the Swedish Cancer Register 1985-2016. Individual exposure was classified based on comprehensive data on yearly residential address and water distribution. External analysis explored standardized cancer incidence ratios (SIR) for residents never, or ever, residing in the contaminated water district, compared with those residing in other towns in the same county as reference population. Cox models provided hazard ratios (HR) for different exposure groups within the cohort. RESULTS: 5,702 individuals with cancer were identified. SIR for overall cancer was 1.04 for men (95%CI 0.96-1.12) and 0.89 for women (95%CI 0.82-0.96) who ever lived in the contaminated drinking water area. Kidney cancer, which was reported with increased risk in C8 study, showed somewhat elevated HR in this study (HR 1.27; 95%CI 0.85-1.89). The HR was modestly elevated for bladder cancer (HR 1.32; 95%CI 1.01-1.72), and reduced for prostate cancer (HR 0.83; 95%CI 0.71-0.98). In subjects who ever lived in the contaminated water area during 2005-2013, when exposure was estimated to be highest, higher risks for kidney cancer (HR 1.84; 95%CI 1.00-3.37) but lower for prostate cancer (HR 0.76; 95%CI 0.59-0.98) were observed. CONCLUSION: Analysis of this large cohort exposed to high levels of PFAS, dominated by PFHxS and PFOS, revealed no evidence for an overall increased risk of cancer. A moderately increased risk of kidney cancer was observed, in accordance with previous findings after PFAS exposure dominated by PFOA.

Challenges in conducting epidemiological field studies evaluating associations between heat stress and renal health among workers in informal sectors: experiences from India.

Well-designed Environmental Epidemiological Studies (EES) play a crucial role in quantifying the influence of environmental exposures and their associated risks on health in the wider population. They provide critical research evidence for identifying and developing interventions to avert adverse health consequences from those exposures. However, uncertainty and variability inherent to any field based EES could hinder the nature and magnitude of association between an exposure and health outcome. This is particularly pronounced in resource limited settings and resource-tight research projects. The present study evaluated the association between occupational heat stress and renal health among informal work sectors in India which had some significant challenges. Informal workers exposed to chronic occupational heat stress had significantly higher adverse renal health outcomes than the unexposed workers. Our field challenges included gaining access and permissions to conduct the study, participant recalls bias and attrition, accurately estimating exposures, confounding from causes of both exposure and disease, and to a large extent tight-funding. Though opportunities are abundant, we must ensure field conditions are optimized to attain study objectives. A keen understanding and sensitivity towards the cultural and work settings is essential for successful project completion. Based on our experiences, we provide strategies to adopt to improve fieldwork and provide recommendations to help overcome the field challenges and achieve better results for future EES studies in developing country settings.

Associations between perfluoroalkyl substances and thyroid hormones after high exposure through drinking water.

BACKGROUND: The reported associations for several per- and polyfluoroalkyl substance (PFAS) with thyroid hormones are inconsistent in epidemiological studies. The purpose of the current study was to investigate the possible association of thyroid hormones in relation to serum levels of perfluorohexane sulfonate, perfluorooctane sulfonate and perfluorooctanoic acid, in a Swedish general population, highly exposed through contaminated drinking water, and if the associations with PFAS remained in a comparison to a reference group based only on residency in areas with contrasting PFAS levels. METHOD: 3297 participants from Ronneby, a municipality with drinking water highly contaminated by PFAS (exposed group), and a reference group (N = 226) from a nearby municipality with non-contaminated drinking water supply were included. Regression analysis was used to investigate the associations between PFAS exposure, assessed as exposure groups (Ronneby and reference groups) and measured serum PFAS levels, and thyroid hormone levels, with adjustments for age, sex and BMI. RESULT: No cross-sectional associations were found between PFAS and thyroid hormones in adults and seniors except for a positive association between PFAS and fT4 in males over 50. Higher thyroid hormone levels were found in the preteen children from Ronneby compared to the reference group. In contrast, within Ronneby, there was weak evidence of associations between increased PFAS levels and decreased fT3 in preteen boys, and decreased TSH in teenage males. No such pattern was found in preteen and teenage girls. CONCLUSION: The present study found no consistent evidence to support association of PFAS with thyroid hormones.

An ecological study of chronic kidney disease in five Mesoamerican countries: associations with crop and heat.

BACKGROUND: Mesoamerica is severely affected by an epidemic of Chronic Kidney Disease of non-traditional origin (CKDnt), an epidemic with a marked variation within countries. We sought to describe the spatial distribution of CKDnt in Mesoamerica and examine area-level crop and climate risk factors. METHODS: CKD mortality or hospital admissions data was available for five countries: Mexico, Guatemala, El Salvador, Nicaragua and Costa Rica and linked to demographic, crop and climate data. Maps were developed using Bayesian spatial regression models. Regression models were used to analyze the association between area-level CKD burden and heat and cultivation of four crops: sugarcane, banana, rice and coffee. RESULTS: There are regions within each of the five countries with elevated CKD burden. Municipalities in hot areas and much sugarcane cultivation had higher CKD burden, both compared to equally hot municipalities with lower intensity of sugarcane cultivation and to less hot areas with equally intense sugarcane cultivation, but associations with other crops at different intensity and heat levels were not consistent across countries. CONCLUSION: Mapping routinely collected, already available data could be a first step to identify areas with high CKD burden. The finding of higher CKD burden in hot regions with intense sugarcane cultivation which was repeated in all five countries agree with individual-level studies identifying heavy physical labor in heat as a key CKDnt risk factor. In contrast, no associations between CKD burden and other crops were observed.

Preventing kidney injury among sugarcane workers: promising evidence from enhanced workplace interventions.

OBJECTIVES: To assess if improvement of working conditions related to heat stress was associated with improved kidney health outcomes among sugarcane harvest workers in Chichigalpa, Nicaragua, a region heavily affected by the epidemic of chronic kidney disease of non-traditional origin. METHODS: Based on our findings during the 2017-2018 harvest (harvest 1), recommendations that enhanced the rest schedule and improved access to hydration and shade were given before the 2018-2019 harvest (harvest 2). Actual work conditions during harvest 2 were then observed. Serum creatinine (SCr) was measured before and at end-harvest, and cross-harvest changes in estimated glomerular filtration rate (eGFR) and incident kidney injury (IKI, ie, SCr increase by ≥0.30 mg/dL or ≥1.5 times the baseline value) were compared between harvest 1 and harvest 2 for three jobs with different physical workloads using regression modelling. Workers who left during harvest were contacted at home, to address the healthy worker selection effect. RESULTS: In burned cane cutters, mean cross-harvest eGFR decreased 6 mL/min/1.73 m2 (95% CI 2 to 9 mL/min/1.73 m2) less and IKI was 70% (95% CI 90% to 50%) lower in harvest 2 as compared with harvest 1 data. No such improvements were seen among seed cutters groups with less successful intervention implementation. CONCLUSION: Kidney injury risk was again elevated in workers with strenuous jobs. The results support further efforts to prevent kidney injury among sugarcane workers, and other heat-stressed workers, by improving access to water, rest and shade. The distinction between design and implementation of such interventions should be recognised.

Inflammatory bowel disease and biomarkers of gut inflammation and permeability in a community with high exposure to perfluoroalkyl substances through drinking water.

Perfluoroalkyl substances (PFAS) can act as surfactants and have been suggested to be capable of affecting gut mucosa integrity, a possible factor in the pathogenesis of inflammatory bowel disease (IBD). So far, only PFOA has been shown to have a positive association with ulcerative colitis. The present study aimed to investigate the association of PFAS and clinically diagnosed IBD in the Ronneby cohort, a population with high PFAS exposure (especially high PFOS and PFHxS) from Aqueous Film-Forming Foam through drinking water, using registry data. Additionally, to explore associations of PFAS with fecal zonulin and calprotectin, subclinical biomarkers of gut inflammation and permeability, in a sub-set of participants from Ronneby and Karlshamn (a nearby control municipality). The registry study included all people that ever resided in Ronneby municipality at least one year between 1980 and 2013. Yearly exposure to contaminated drinking water was assessed based on residential addresses and waterworks supply data, and the population classified by early, mid and late periods in ascending level of contamination. Diagnosed IBD cases were retrieved from the Swedish National Patient register and cause-of-death register. The Cox proportional hazards model was used to derive the hazard ratios (HRs) for diagnosed IBD. The biomarker study included 189 individuals who provided fecal samples. Serum PFAS were measured using LC-MS/MS. Fecal zonulin and calprotectin were measured using ELISA. Linear regression was used to assess the associations between measured PFAS and biomarker levels. In the registry study, no raised HRs for diagnosed IBD were found for cohort subjects with mid (1995-2004) or late period (2005-2013) exposure compared to never exposure. Early period exposure only (1985-1994) showed raised HRs for Crohn's disease (HR = 1.58, p = 0.048) and other non-specified IBD (HR = 1.38, p = 0.037). In the biomarker study, Karlshamn showed higher fecal calprotectin levels (median = 99.6 mg/kg in Karlshamn vs. 66.8 mg/kg in Ronneby, p = 0.04). A trend of decreased calprotectin with increased serum PFAS indicated higher PFAS was associated with lower degree of gut inflammation (p = 0.002). No association between serum PFAS and fecal zonulin was found. In conclusion, the present study found no consistent evidence to support PFAS exposure as a risk factor for IBD.

Associations between perfluoroalkyl substances and serum lipids in a Swedish adult population with contaminated drinking water.

BACKGROUND: Exposures to perfluoroalkyl substances (PFAS) have shown positive associations with serum lipids in previous studies. While many studies on lipids investigated associations with perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), there are only a few studies regarding other PFAS, such as perfluorohexane sulfonic acid (PFHxS). The purpose of the current study is to investigate if associations with serum lipids were present, not only for serum PFOS and PFOA, but also for PFHxS, and if the associations with PFAS remained also in a comparison based only on residency in areas with contrasting exposure to PFAS. METHODS: 1945 adults aged 20-60 were included from Ronneby, Sweden, a municipality where one out of two waterworks had been heavily contaminated from aqueous fire-fighting foams, and from a nearby control area. The exposure was categorized based on either been living in areas with contrasting PFAS exposure or based on the actual serum PFAS measurements. Regression analyses of serum lipids were fitted against serum PFAS levels, percentile groups, smooth splines and between exposed and reference areas, adjusting for age, sex and BMI. RESULTS: Drinking water contamination caused high serum levels of PFOS (median 157 ng/ml) and PFHxS (median 136 ng/ml) and PFOA (median 8.6 ng/ml). These serum PFAS levels in the exposed groups were 5 to 100-fold higher than in the controls. In this population with mixed PFAS exposure, predominantly PFOS and PFHxS, PFAS exposure were positively associated with serum lipids. This was observed both when quantifying exposure as contrast between exposed and controls, and in terms of serum PFAS. Due to high correlations between each PFAS, we cannot separate them. CONCLUSIONS: In conclusion, the present study provides further evidence of a causal association between PFAS and serum lipids, especially for PFHxS.

Pregnancy-induced changes in serum concentrations of perfluoroalkyl substances and the influence of kidney function.

BACKGROUND: Epidemiological associations between maternal concentrations of perfluoroalkyl substances (PFAS) and birth weight are inconsistent. There is concern that studies based on samples collected in late pregnancy may be confounded by kidney function but studies of the relation between pregnancy-induced changes in PFAS and kidney function are lacking. Our aims were to investigate changes in serum concentrations of perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) from early to late pregnancy and to explore relations to changes in glomerular filtration rate (GFR) and glomerular pore size. METHODS: We conducted the study in a cohort of 73 pregnancies of normal-weight Swedish women without gestational diabetes and preeclampsia, enrolled 2009-2014. Blood was collected in median weeks 11 and 36, respectively, and analysed PFAS using liquid chromatography-tandem-mass-spectrometry. We estimated GFR based on creatinine and cystatin C and used the ratio eGFRcystatin C/eGFRcreatinine to indicate glomerular pore size. We used Wilcoxon signed-rank test to compare early and late measures and partial Spearman rank correlations to explore relations between changes in PFAS and kidney function. RESULTS: Median concentrations of PFNA, PFOA and PFOS decreased by 15-21% but changes were uncorrelated to changes in kidney function (partial R = - 0.06-0.11). The observed increase in median PFHxS concentration of 69% was likely an artefact of systematic measurement error caused by coeluting endogenous inferences. CONCLUSIONS: Serum concentrations of PFNA, PFOA and PFOS decrease during pregnancy but the magnitudes of change are unrelated to parallel changes in eGFR and glomerular pore size, suggesting that changes in these indicators of kidney function are not important confounders in studies of PFAS and birth weight in pregnancies without gestational diabetes and preeclampsia.

Insufficient mixing of thawed serum samples leading to erroneous results - experience from a field study and use of a correction procedure.

Incorrect analysis results that are close to expected might not be recognized in scientific studies or routine patient care. In two field studies we obtained unexpected results in a large number of samples. The present study aimed to identify the source of error in the samples from these studies and to validate a method to obtain correct results. Pre-analytical procedures were scrutinized, giving no indications of inappropriate pre-analytical sample handling in the field or during transport in a tropical climate. Using a new set of samples from volunteers in simulation experiments, we observed the known concentration gradient of analytes sampled in gel as well as plain tubes after freezer storage and thawing. Experiments demonstrated that mixing of samples by vortexing alone was not sufficient to disrupt the gradient formed by freezing and thawing, which appeared to cause the problem encountered when we in field studies analyzed and biobanked large sample sets by robot pipetting. A correction procedure was introduced, in which the obtained value of an analyte was multiplied by a correction factor calculated for each sample using the expected sodium level (140 mmol/L) divided by the measured sodium value. When it was validated on results from the simulation experiments, we repeatedly found that the correction lead to results very close to true values for analytes of different size and charge. Usefulness of the procedure was demonstrated when applied to a large set of field study results.