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.

Occupational heat exposure and the risk of chronic kidney disease of nontraditional origin in the United States.

Occupational heat exposure is linked to the development of kidney injury and disease in individuals who frequently perform physically demanding work in the heat. For instance, in Central America, an epidemic of chronic kidney disease of nontraditional origin (CKDnt) is occurring among manual laborers, whereas potentially related epidemics have emerged in India and Sri Lanka. There is growing concern that workers in the United States suffer with CKDnt, but reports are limited. One of the leading hypotheses is that repetitive kidney injury caused by physical work in the heat can progress to CKDnt. Whether heat stress is the primary causal agent or accelerates existing underlying pathology remains contested. However, the current evidence supports that heat stress induces tubular kidney injury, which is worsened by higher core temperatures, dehydration, longer work durations, muscle damaging exercise, and consumption of beverages containing high levels of fructose. The purpose of this narrative review is to identify occupations that may place US workers at greater risk of kidney injury and CKDnt. Specifically, we reviewed the scientific literature to characterize the demographics, environmental conditions, physiological strain (i.e., core temperature increase, dehydration, heart rate), and work durations in sectors typically experiencing occupational heat exposure, including farming, wildland firefighting, landscaping, and utilities. Overall, the surprisingly limited available evidence characterizing occupational heat exposure in US workers supports the need for future investigations to understand this risk of CKDnt.

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.

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.

Chronic kidney disease of non-traditional origin in Mesoamerica: a disease primarily driven by occupational heat stress.

The death toll of the epidemic of chronic kidney disease of nontraditional origin (CKDnt) in Mesoamerica runs into the tens of thousands, affecting mostly young men. There is no consensus on the etiology. Anecdotal evidence from the 1990s pointed to work in sugarcane; pesticides and heat stress were suspected. Subsequent population-based surveys supported an occupational origin with overall high male-female ratios in high-risk lowlands, but small sex differences within occupational categories, and low prevalence in non-workers. CKDnt was reported in sugarcane and other high-intensity agriculture, and in non-agricultural occupations with heavy manual labor in hot environments, but not among subsistence farmers. Recent studies with stronger designs have shown cross-shift changes in kidney function and hydration biomarkers and cross-harvest kidney function declines related to heat and workload. The implementation of a water-rest-shade intervention midharvest in El Salvador appeared to halt declining kidney function among cane cutters. In Nicaragua a water-rest-shade program appeared sufficient to prevent kidney damage among cane workers with low-moderate workload but not among cutters with heaviest workload. Studies on pesticides and infectious risk factors have been largely negative. Non-occupational risk factors do not explain the observed epidemiologic patterns. In conclusion, work is the main driver of the CKDnt epidemic in Mesoamerica, with occupational heat stress being the single uniting factor shown to lead to kidney dysfunction in affected populations. Sugarcane cutters with extreme heat stress could be viewed as a sentinel occupational population. Occupational heat stress prevention is critical, even more so in view of climate change.

La mortalidad por la epidemia de enfermedad renal crónica de origen no tradicional (ERCnt) en Mesoamérica asciende a decenas de miles de personas, principalmente hombres jóvenes. No existe consenso sobre su etiología. En la década de 1990, informes anecdóticos apuntaban como factor de riesgo al trabajo en plantaciones de caña de azúcar; se consideró como posibles causantes a los plaguicidas y el estrés térmico. Estudios de prevalencia de base poblacional subsiguientes apoyaron un origen ocupacional, con una proporción elevada de hombres respecto de las mujeres en las tierras bajas donde el riesgo era elevado, pero con pequeñas diferencias de sexo dentro de las categorías ocupacionales y baja prevalencia en el ámbito no laboral. Se reportó ERCnt en los trabajadores de la caña de azúcar y otros cultivos con alta exigencia física y en ocupaciones no agrícolas que implican trabajo manual intenso en ambientes calurosos, pero no entre los agricultores de subsistencia. Estudios recientes con diseños más sólidos han demostrado cambios en la función renal y en los biomarcadores de hidratación en el curso de los turnos laborales, y disminución de la función renal relacionada con el calor y la carga de trabajo en el curso de la cosecha. La implementación de una intervención basada en la provisión de agua, descanso y sombra a mitad de la cosecha en El Salvador detuvo la disminución de la función renal en los cortadores de caña. En Nicaragua, un programa de provisión de agua, descanso y sombra evitó la lesión renal en los trabajadores de la caña con una carga de trabajo baja y moderada, pero no entre los cortadores, quienes tienen la mayor carga de trabajo. Los estudios sobre plaguicidas y factores de riesgo infecciosos han sido en gran medida negativos. Los factores de riesgo no ocupacionales no explican los patrones epidemiológicos observados. En conclusión, el trabajo es el principal desencadenante de la epidemia de ERCnt en Mesoamérica, y el estrés térmico ocupacional es el único factor que consistentemente conduce a la disfunción renal en las poblaciones afectadas. Los cortadores que trabajan en los ingenios azucareros y están expuestos a un estrés térmico extremo podrían ser considerados una población ocupacional centinela. La prevención del estrés térmico ocupacional es crítica, más aún si se consideran los efectos del cambio climático.

A mortalidade devida à epidemia de doença renal crônica de origem não tradicional (DRCnt) na Mesoamérica atinge dezenas de milhares de pessoas, principalmente homens jovens. Não há consenso sobre a sua etiologia. Na década de 1990, informações empíricas apontavam o trabalho em plantações de cana de açúcar como um fator de risco; pesticidas e estresse térmico também eram considerados causas possíveis. As pesquisas populacionais subsequentes sustentam uma origem ocupacional da doença, com uma elevada proporção de homens quando comparados à de mulheres, em areas de baixa altitude, onde o risco da doença é mais elevado, mas com pequenas diferenças de gênero quando se consideram as categorias ocupacionais e baixa prevalência no ambiente não-ocupacional. A DRCnt foi identificada em trabalhadores agrícolas da cana de açúcar e de outras culturas que exigem trabalho físico de alta intensidade e em ocupações não agrícolas envolvendo um trabalho manual intenso em ambientes quentes, mas não entre os agricultores de subsistência. Estudos recentes com desenhos mais robustos demonstraram mudanças na função renal e nos biomarcadores de hidratação ao longo dos turnos de trabalho, e diminuição da função renal relacionada à exposição ao calor e à carga de trabalho ao longo da colheita. A implementação de uma intervenção de água-descanso-sombra durante a colheita em El Salvador interrompeu o declínio da função renal em cortadores de cana. Na Nicarágua, intervenções água-descanso-sombra parecem ter sido suficientes para evitar lesões renais em trabalhadores canavieiros com cargas de trabalho baixa e moderada, mas não entre os cortadores de cana que têm carga de trabalho mais pesada. Estudos sobre exposição a pesticidas e a fatores de risco de origem infecciosa têm sido largamente negativos. Os fatores de risco não-ocupacionais não explicam os padrões epidemiológicos observados. Em conclusão, ocupação é o principal desencadeador da epidemia de DRCnt na Mesoamérica, e o estresse térmico ocupacional é o único fator comprovado que leva à disfunção renal nas populações afetadas. Os cortadores de cana que trabalham em engenhos de açúcar e expostos a um estresse térmico extremo podem ser considerados uma população ocupacional sentinela. A prevenção do estresse térmico ocupacional é crítica, especialmente considerando os efeitos das mudanças climáticas.

Workload and cross-harvest kidney injury in a Nicaraguan sugarcane worker cohort.

OBJECTIVES: To examine the association between workload and kidney injury in a fieldworker cohort with different levels of physically demanding work over a sugarcane harvest, and to assess whether the existing heat prevention efforts at a leading occupational safety and health programme are sufficient to mitigate kidney injury. METHODS: Biological and questionnaire data were collected before (n=545) and at the end (n=427) of harvest among field support staff (low workload), drip irrigation workers (moderate), seed cutters (high) and burned sugarcane cutters (very high). Dropouts were contacted (87%) and reported the reason for leaving work. Cross-harvest incident kidney injury (IKI) was defined as serum creatinine increase ≥0.30 mg/dL or ≥1.5 times the baseline value, or among dropouts reporting kidney injury leading to leaving work. RESULTS: Mean cross-harvest estimated glomerular filtration rate change was significantly associated with workload, increasing from 0 mL/min/1.73 m2 in the low-moderate category to -5 mL/min/1.73 m2 in the high and -9 mL/min/1.73 m2 in the very high workload group. A similar pattern occurred with IKI, where low-moderate workload had 2% compared with 27% in the very high workload category. A healthy worker selection effect was detected, with 32% of dropouts reporting kidney injury. Fever and C reactive protein elevation were associated with kidney injury. CONCLUSIONS: Workers considered to have the highest workload had more cross-harvest kidney damage than workers with less workload. Work practices preventing heat stress should be strengthened and their role in preventing kidney damage examined further. Future occupational studies on chronic kidney disease of unknown aetiology should account for a healthy worker effect by pursuing those lost to follow-up.

Herpes zoster risk after 21 specific cancers: population-based case-control study.

BACKGROUND: Some malignancies are known to be associated with increased risk of herpes zoster, but little is known about how associations between cancer and subsequent zoster risk vary by cancer site, by time since cancer diagnosis, and by age. METHODS: An age-, sex-, calendar time-, and practice-matched case-control study, nested in the broadly UK representative Clinical Practice Research Datalink (CPRD) primary care database, was analysed using conditional logistic regression to estimate the association between 21 of the most common specific malignancies and subsequent zoster risk. We adjusted for comorbid conditions and other potential confounders, and investigated effect modification by age and time since malignancy diagnosis. RESULTS: A total of 192 081 adult zoster patients and 732 035 controls were included. Malignancy overall was positively associated with zoster risk (adjusted OR 1.29, 95% CI 1.27-1.32), and the association was especially strong for haematological malignancies (OR 2.46, 2.33-2.60). Among specific malignancies, there was evidence that oral, oesophageal, stomach, colorectal, lung, breast, ovarian, prostate, kidney, bladder, and CNS cancers, as well as lymphoma, myeloma, and leukaemia were associated with increased zoster odds (P⩽0.05 in each case), but the magnitude of associations varied widely. The association was typically strongest within 2 years of malignancy diagnosis and decreased with older age for both haematological and solid malignancies. CONCLUSIONS: Several cancers were associated with an increased risk of zoster, particularly within the first 2 years after diagnosis and among younger individuals. Knowledge that patients with a recent diagnosis of cancer are at high risk of zoster may encourage initiation of antiviral therapy earlier in the course of zoster when the benefits are greater. Evaluation of whether patients diagnosed with cancer would benefit from early zoster vaccination is warranted.

Impact of heat and a rest-shade-hydration intervention program on productivity of piece-paid industrial agricultural workers at risk of chronic kidney disease of nontraditional origin.

OBJECTIVES: Assess the impact of environmental heat and a rest-shade-hydration (RSH) intervention against heat stress on productivity of piece-paid Mesoamerican sugarcane cutters. These workers are at a high risk of chronic kidney disease of non-traditional origin (CKDnt), from the severe heat stress they experience due to heavy work under hot conditions. RSH interventions in these populations improve kidney health outcomes, but their impact on productivity has yet to be examined. METHODS: We accessed routine productivity data from seed (SC, N = 749) and burned (BCC, N = 535) sugarcane cutters observed over five harvest seasons with increasing RSH intervention at a large Nicaraguan sugarcane mill. Hourly field-site wet-bulb globe temperature (WBGT) was recorded by mill staff and summarized as a daily mean. Mixed linear regression was used to model daily productivity, adjusting for age (18-29, 30-44, and >45 years), sex, WBGT (<28, 28-29, 29-30, 30-31, and >31 °C) on the same and preceding day, harvest season (2017-18 to 2021-22), month, and acclimatization status (<1, 1-2, and >2 weeks). RESULTS: There was an inverse dose-response relationship between SC productivity and WBGT on the same and preceding days, decreasing by approximately 3%/°C WBGT. Productivity increased during the study period, i.e. coinciding with RSH scale-up, by approximately 19% in SC and 9% in BCC. CONCLUSION: Agricultural worker productivity was expected lower on hotter days, strengthening the interest in all stakeholders to mitigate increasing global temperatures and their impact. Despite decreasing the total time allocated for work each day, an RSH intervention appears to result in increased productivity and no apparent loss in productivity.

Association Between Acute Kidney Injury Hospital Visits and Environmental Heat Stress at a Nicaraguan Sugarcane Plantation.

BACKGROUND: Mesoamerican sugarcane cutters are at a high risk of chronic kidney disease of non-traditional origin, a disease likely linked to heat-related acute kidney injury (AKI). Studies in general populations have described a positive association between high environmental temperatures and clinically assessed kidney outcomes, but there are no studies in occupational settings. METHOD: We accessed routine records of clinically diagnosed AKI (AKI-CD) and wet bulb globe temperatures (WBGT) at a large Nicaraguan sugarcane plantation and modeled the relationship between these using negative binomial regression. A rest-shade-hydration intervention was gradually enhanced during the study period, and efforts were made to increase the referral of workers with suspected AKI to healthcare. RESULTS: Each 1°C WBGT was associated with an 18% (95% confidence interval [CI]: [4, 33%]) higher AKI-CD rate on the same day and a 14% (95% CI [-5, 37%]) higher rate over a week. AKI-CD rates and severity, and time between symptoms onset and diagnosis decreased during the study period, that is, with increasing rest-shade-hydration intervention. Symptoms and biochemical signs of systemic inflammation were common among AKI-CD cases. DISCUSSION: Occupational heat stress, resulting from heavy work in environmental heat, was associated with a higher rate of clinically diagnosed AKI in a population at risk of CKDnt. Promoting rest-shade-hydration may have contributed to reducing AKI rates during the study period. Occupational health and safety personnel have key roles to play in enforcing rest, shade, and hydration practices, referring workers with suspected AKI to healthcare as well as collecting and analyzing the data needed to support workplace heat stress interventions.

Targeting workload to ameliorate risk of heat stress in industrial sugarcane workers.

OBJECTIVE: The aim of this study was to quantify the physiological workload of manual laborers in industrial sugarcane and assess the effect of receiving a rest, shade, and hydration intervention to reduce heat stress exposure risk. METHODS: In an observational study, physiological workload was evaluated for burned cane cutters (BCC), seed cutters (SC) and drip irrigation repair workers (DIRW) using heart rate (HR) recorded continuously (Polar®) across a work shift. Workers' percentage of maximal HR (%HRmax), time spent in different HR zones, and estimated core temperature (ECTemp) were calculated. The effect of increasing rest across two harvests was evaluated for BCC and SC. RESULTS: A total of 162 workers participated in this study [52 BCC (all male), 71 SC (13 female) and 39 DIRW (16 female)]. Average %HRmax across a work shift was similar between BCC and SC (BCC: 58%, SC: 59%), but lower in DIRW (51%). BCC and SC spent similar proportions of work shifts at hard/very hard intensities (BCC: 13%, SC: 15%), versus DIRW who worked mostly at light (46%) or light-moderate (39%) intensities. SC maximum ECTemp reached 38.2°C, BCC 38.1°C; while DIRW only reached 37.7°C. Females performed at a higher %HRmax than males across work shifts (SC 64% versus 58%; DIRW 55% versus 49%). An additional rest period was associated with a lower average %HRmax across a work shift in BCC. CONCLUSION: In this setting, BCC and SC both undertake very physiologically demanding work. Females maintained a higher workload than male co-workers. Regulated rest periods each hour, with water and shade access, appears to reduce physiological workload/strain.

Point-of-care biomarkers for prediction of kidney function trajectory among sugarcane cutters: a comparative test accuracy study.

OBJECTIVES: Heat-stressed Mesoamerican workers, such as sugarcane cutters, suffer from high rates of chronic kidney disease of non-traditional origin (CKDnt). We aimed to identify easily available early markers of rapid kidney function decline in a population at high risk of CKDnt. DESIGN: The accuracy of different biomarkers measured during harvest for prediction of cross-harvest kidney function decline were assessed in an exploratory study group, and the performance of the most promising biomarker was then assessed in an independent confirmation group. SETTING: Male sugarcane cutters in El Salvador and Nicaragua. PARTICIPANTS: 39 male Salvadoran sugarcane cutters sampled fortnightly at ≤9 occasions before and after work shift during harvest. 371 male Nicaraguan sugarcane cutters were sampled as part of routine monitoring during two harvests. Cutters worked at high physical intensity at wet-bulb globe temperatures mostly above 29°C for 6-8 hours per day 6 days a week during the 5-6 months harvest season. PRIMARY OUTCOMES: Change in estimated glomerular filtration rate (CKD Epidemiology Collaboration) across the harvest season (ΔeGFRcross-harvest). RESULTS: Dipstick leukocyturia after work shift in the El Salvadoran group was the most promising marker, explaining >25% of ΔeGFRcross-harvest variance at 8/9 occasions during harvest. Leukocyturia was associated with experiencing fever, little or dark urine, cramps, headache, dizziness and abdominal pain in the preceding 2-week period. Decreasing blood haemoglobin (Hb) and eGFR during harvest were also predictive of ΔeGFRcross-harvest. In the Nicaraguan confirmation dataset, those having ≥++ leukocyturia at any sampling during harvest had a 13 mL/min/1.73 m2 (95% CI 10 to 16 mL/min/1.73 m2) worse ΔeGFRcross-harvest than those without recorded leukocyturia. CONCLUSION: Leukocyturia and Hb, both measurable with point-of-care methods, may be early indicators for kidney injury and risk for eGFR decline among heat-stressed male workers, thereby facilitating individual-level prevention and research aiming to understand the causes of CKDnt.

Workplace Intervention for Heat Stress: Essential Elements of Design, Implementation, and Assessment.

Heat stress is associated with numerous health effects that potentially harm workers, especially in a warming world. This investigation occurred in a setting where laborers are confronted with occupational heat stress from physically demanding work in high environmental temperatures. Collaboration with a major Nicaraguan sugarcane producer offered the opportunity to study interventions to prevent occupational heat-stress-related kidney disease. Two aims for this study of a rest-shade-water intervention program were: (1) describe the evolving intervention, summarize findings that motivated proposed improvements, assess impact of those improvements, and identify challenges to successful implementation and (2) extract primary lessons learned about intervention research that have both general relevance to investigations of work-related disease prevention and specific relevance to this setting. The learning curve for the various stakeholders as well as the barriers to success demonstrate that effectiveness of an intervention cannot be adequately assessed without considerations of implementation. Designing, effectively implementing, and assessing both health impacts and implementation quality is a resource-intensive endeavor requiring a transdisciplinary approach. Both general and specific lessons learned are presented for decisions on study design and study elements, implementation assessment, and management engagement in understanding how productivity and health can be successfully balanced and for building effective communication between investigators and all levels of management.

Relationship between commuting and health outcomes in a cross-sectional population survey in southern Sweden.

BACKGROUND: The need for a mobile workforce inevitably means that the length of the total work day (working and traveling time) will increase, but the health effects of commuting have been surprisingly little studied apart from perceived stress and the benefits of physically active commuting. METHODS: We used data from two cross-sectional population-based public health surveys performed in 2004 and 2008 in Scania, Sweden (56% response rate). The final study population was 21, 088 persons aged 18-65, working > 30 h/week. Duration (one-way) and mode of commuting were reported. The outcomes studied were perceived poor sleep quality, everyday stress, low vitality, mental health, self-reported health, and absence from work due to sickness during the past 12 months. Covariates indicating socioeconomic status and family situation, overtime, job strain and urban/rural residency were included in multivariate analyses. Subjects walking or cycling to work < 30 min were used as a reference category. RESULTS: Monotonous relations were found between duration of public transport commuting and the health outcomes. For the category commuting > 60 min odds ratios (ORs) ranged from 1.2 - 1.6 for the different outcomes. For car commuting, the relationships were concave downward or flat, with increasing subjective health complaints up to 30-60 min (ORs ranging from 1.2 - 1.4), and lower ORs in the > 60 min category. A similar concave downward relationship was observed for sickness absence, regardless of mode of transport. CONCLUSIONS: The results of this study are concordant with the few earlier studies in the field, in that associations were found between commutation and negative health outcomes. This further demonstrates the need to consider the negative side-effects of commuting when discussing policies aimed at increasing the mobility of the workforce. Studies identifying population groups with increased susceptibility are warranted.

[Large differences in excess mortality in March-May 2020 by country of birth in Sweden]. / Stora skillnader i överdödlighet våren 2020 utifrån födelseland.

The Swedish strategy for dealing with covid-19 has been criticized for not accounting for difficulties of conducting voluntary social distancing in settings with household overcrowding, dependence on public transport and large proportion of service sector workers. In such neighbourhoods there is typically a larger proportion of immigrants. We compared all-cause-mortality data in Sweden by country of origin from 2020 and 2016-2019 and found large disparities. The number of deaths among persons born in countries from which many refugees have migrated to Sweden in the last decades was 220% higher in March-May 2020 compared to the mean in 2016-2019. In contrast, there was no increased mortality among persons aged 40-64 years and a 19% increased number of deaths of those aged above 65 years born in Sweden, EU or North America during these three months. These observations further illustrate the need for a dedicated and more diverse strategy in dealing with the covid-19 pandemic.

Pathophysiological Mechanisms by which Heat Stress Potentially Induces Kidney Inflammation and Chronic Kidney Disease in Sugarcane Workers.

BACKGROUND: Chronic kidney disease of non-traditional origin (CKDnt) is common among Mesoamerican sugarcane workers. Recurrent heat stress and dehydration is a leading hypothesis. Evidence indicate a key role of inflammation. METHODS: Starting in sports and heat pathophysiology literature, we develop a theoretical framework of how strenuous work in heat could induce kidney inflammation. We describe the release of pro-inflammatory substances from a leaky gut and/or injured muscle, alone or in combination with tubular fructose and uric acid, aggravation by reduced renal blood flow and increased tubular metabolic demands. Then, we analyze longitudinal data from >800 sugarcane cutters followed across harvest and review the CKDnt literature to assess empirical support of the theoretical framework. RESULTS: Inflammation (CRP elevation and fever) and hyperuricemia was tightly linked to kidney injury. Rehydrating with sugary liquids and NSAID intake increased the risk of kidney injury, whereas electrolyte solution consumption was protective. Hypokalemia and hypomagnesemia were associated with kidney injury. DISCUSSION: Heat stress, muscle injury, reduced renal blood flow and fructose metabolism may induce kidney inflammation, the successful resolution of which may be impaired by daily repeating pro-inflammatory triggers. We outline further descriptive, experimental and intervention studies addressing the factors identified in this study.

Multiple headspace single-drop microextraction-a new technique for quantitative determination of styrene in polystyrene.

Single-drop microextraction (SDME), an emerging miniaturised extraction technique, was for the first time combined with multiple headspace extraction (MHE) to enable the quantitative determination of volatiles in solid matrixes by SDME technique. The concept of multiple headspace single-drop microextraction (MHS-SDME) was then applied for quantitative determination of styrene in polystyrene (PS) samples. Good linearity for the multiple headspace extraction was obtained when the migration of styrene was facilitated by grinding the samples and incubating them for 1 h at 150 degrees C prior the first extraction. Two microlitres of butyl acetate was used as the single-drop microextraction solvent and the extraction time was 5 min per cycle. The relative standard deviation (RSD) for single-drop microextraction of styrene standard at n=6 was 7.6%. Linearity was shown for styrene concentrations between 0.005 and 0.75 microg/ml (R2=0.999). This corresponds to total amount of styrene between 0.1 and 15 microg. The limit of quantitation for styrene standard at S/N 10 was 0.005 microg/ml. The developed method was validated against and showed good agreement with an earlier reported dissolution-precipitation method.