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Masaki Kato,1 Toshiaki Kikuchi,2 Koichiro Watanabe,3 Tomiki Sumiyoshi,4 Yoshiya Moriguchi,5 Daniel Oudin Åström,6 Michael Cronquist Christensen6 1Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan; 2Department of Neuropsychiatry, Keio University School of Medicine, Department of Neuropsychiatry, Tokyo, Japan; 3Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan; 4Department of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan; 5Lundbeck Japan K.K, Tokyo, Japan; 6H. Lundbeck A/S, Valby, DenmarkCorrespondence: Yoshiya Moriguchi, Medical Affairs, Lundbeck Japan, K.K, Kamiyacho Prime Place 8F, 4-1-17 Toranomon, Minato-ku, Tokyo, 105-0001, Japan, Email yomo@lundbeck.comPurpose: Goal attainment scaling (GAS) has been proposed as a person-centric, semi-quantitative measure that assimilates achievement of individually set goals into a single standardized “goal attainment score” that can be compared at the population level. We aimed to examine the reliability and validity of the Japanese version of the GAS for depression (GAS-D) tool in assessing goal attainment in people living with major depressive disorder (MDD).Patients and Methods: This was a prespecified analysis of a prospective, 24-week, multicenter, observational cohort study of employed Japanese outpatients with MDD initiating treatment with vortioxetine according to the Japanese label (JRCT1031210200). Participants were assessed using the Japanese version of the GAS-D and other clinical rating scales at baseline and Weeks 8, 12 and 24.Results: Goal attainment was significantly associated with symptom severity as assessed by the Montgomery–Åsberg Depression Rating Scale (MADRS) scale, confirming convergent validity. In particular, GAS-D scores were significantly related to MADRS total score at Weeks 12 and 24, indicating that improvements in overall symptom severity with vortioxetine treatment were likely to be reflected in the achievement of individualized treatment goals. With an intraclass correlation coefficient of 0.67 (95% CI 0.45– 0.82), the GAS-D also showed moderate test–retest reliability between Weeks 8 and 12 while proving independent of demographic characteristics.Conclusion: The results of this open-label study support the use of the GAS-D as a valid and sensitive outcome measure in the assessment of treatment response in MDD.Keywords: major depressive disorder, goal attainment scaling, goal setting, validation, vortioxetine

Abstract Background Despite accumulating evidence of an association between air pollution and renal disease, studies on the association between long-term exposure to air pollution and renal function are still contradictory. This study aimed to investigate this association in a large population with relatively low exposure and with improved estimation of renal function as well as renal injury biomarkers. Methods We performed a cross-sectional analysis in the middle-aged general population participating in the Swedish CardioPulmonary bioImaging Study (SCAPIS; n = 30 154). Individual 10-year exposure to total and locally emitted fine particulate matter (PM2.5), inhalable particulate matter (PM10), and nitrogen oxides (NOx) were modelled using high-resolution dispersion models. Linear regression models were used to estimate associations between exposures and estimated glomerular filtration rate (eGFR, combined creatinine and cystatin C) and serum levels of renal injury biomarkers (KIM-1, MCP-1, IL-6, IL-18, MMP-2, MMP-7, MMP-9, FGF-23, and uric acid), with consideration of potential confounders. Results Median long-term PM2.5 exposure was 6.2 µg/m3. Almost all participants had a normal renal function and median eGFR was 99.2 mL/min/1.73 m2. PM2.5 exposure was associated with 1.3% (95% CI 0.6, 2.0) higher eGFR per 2.03 µg/m3 (interquartile range, IQR). PM2.5 exposure was also associated with elevated serum matrix metalloproteinase 2 (MMP-2) concentration, with 7.2% (95% CI 1.9, 12.8) higher MMP-2 per 2.03 µg/m3. There was a tendency towards an association between PM10 and higher levels of uric acid, but no associations were found with the other biomarkers. Associations with other air pollutants were null or inconsistent. Conclusion In this large general population sample at low exposure levels, we found a surprising association between PM2.5 exposure and a higher renal filtration. It seems unlikely that particle function would improve renal function. However, increased filtration is an early sign of renal injury and may be related to the relatively healthy population at comparatively low exposure levels. Furthermore, PM2.5 exposure was associated with higher serum concentrations of MMP-2, an early indicator of renal and cardiovascular pathology.

IntroductionAir pollution is a significant contributor to morbidity and mortality globally and has been linked to an increased risk of dementia. Previous studies within the Betula cohort in Northern Sweden have demonstrated associations between air pollution and dementia, as well as distinctive metabolomic profiles in dementia patients compared to controls. This study aimed to investigate whether air pollution is associated with quantitative changes in metabolite levels within this cohort, and whether future dementia status would modify this association.MethodsBoth short-term and long-term exposure to air pollution were evaluated using high spatial resolution models and measured data. Air pollution from vehicle exhaust and woodsmoke were analyzed separately. Metabolomic profiling was conducted on 321 participants, including 58 serum samples from dementia patients and a control group matched for age, sex, and education level, using nuclear magnetic resonance spectroscopy.ResultsNo statistically significant associations were found between any metabolites and any measures of short-term or long-term exposure to air pollution. However, there were trends potentially suggesting associations between both long-term and short-term exposure to air pollution with lactate and glucose metabolites. Notably, these associations were observed despite the lack of correlation between long-term and short-term air pollution exposure in this cohort. There were also tendencies for associations between air pollution from woodsmoke to be more pronounced in participants that would later develop dementia, suggesting a potential effect depending on urban/rural factors.DiscussionWhile no significant associations were found, the trends observed in the data suggest potential links between air pollution exposure and changes in lactate and glucose metabolites. These findings provide some new insights into the link between air pollution and metabolic markers in a low-exposure setting. However, addressing existing limitations is crucial to improve the robustness and applicability of future research in this area. The pronounced associations in participants who later developed dementia may indicate an influence of urban/rural factors, warranting further investigation.

Planetary health is being or should be added to medical training curricula in accordance with association consensus. Several articles published in recent years have addressed concern on the implementation, and the challenges that can occur if not addressed properly. This scoping narrative literature review focuses on planetary health as a concept, as well as challenges and suggested solutions to address these challenges. Planetary health is an important concept and needs to be addressed in all medical training. We found that one main challenge is implementation without ensuring the right competences and resources. Medically trained teachers set out to understand and teach complex natural and social systems. At some institutions the time allocated to teach planetary health is limited or non-existent. Case studies and student led teaching are solutions suggested, while other argue that true interdisciplinarity by inviting experts are more in line with what we expect from other subjects. In conclusion, the roots of planetary health, the enormous health risks at stake and nature of the subject requires medical training to adopt a true inter/trans-disciplinary approach to succeed. It might not be expected for all students to become planetary health experts, but all need a general understanding of the most important aspects and values.

Study region: French part of the Moselle catchmentStudy focus: By relying on hydrological simulations forced by climate change scenarios, stakeholders can assess the magnitude of future changes in the rainfall–runoff relationship. The inclusion of human influences in water resources modelling in a non-stationary context is a way to improve the accuracy and usefulness of climate change impact studies. Here, we propose a modelling approach that explicitly considers water uses to evaluate adaptation measures for water management at the French Moselle catchment scale.New hydrological insights for the region: The results highlight the decrease in future low flows but also the change in the balance between demand and supply. Over the Moselle catchment, whatever the water use scenario considered, climate change induces lower water availability both for environmental flows and for human uses. This leads to a potential increase in the duration of water restriction of up to 8 weeks for RCP 8.5 in the long term (2070–2099) compared to 1976–2005. This study could provide water managers with more appropriate climate impact results and potentially help them to design adequate adaptation measures.

Human Papillomavirus (HPV) vaccine coverage was

Abstract Background Measured or modeled levels of outdoor air pollution are being used as proxies for individual exposure in a growing number of epidemiological studies. We studied the accuracy of such approaches, in comparison with measured individual levels, and also combined modeled levels for each subject’s workplace with the levels at their residence to investigate the influence of living and working in different places on individual exposure levels. Methods A GIS-based dispersion model and an emissions database were used to model concentrations of NO2 at the subject’s residence. Modeled levels were then compared with measured levels of NO2. Personal exposure was also modeled based on levels of NO2 at the subject’s residence in combination with levels of NO2 at their workplace during working hours. Results There was a good agreement between measured façade levels and modeled residential NO2 levels (rs = 0.8, p > 0.001); however, the agreement between measured and modeled outdoor levels and measured personal exposure was poor with overestimations at low levels and underestimation at high levels (rs = 0.5, p > 0.001 and rs = 0.4, p > 0.001) even when compensating for workplace location (rs = 0.4, p > 0.001). Conclusion Modeling residential levels of NO2 proved to be a useful method of estimating façade concentrations. However, the agreement between outdoor levels (both modeled and measured) and personal exposure was, although significant, rather poor even when compensating for workplace location. These results indicate that personal exposure cannot be fully approximated by outdoor levels and that differences in personal activity patterns or household characteristics should be carefully considered when conducting exposure studies. This is an important finding that may help to correct substantial bias in epidemiological studies.

Abstract Background The relationship between fish intake and stroke incidence has been inconsistent in previous Swedish studies. Here, we report the risk of stroke and fish intake in a cohort from southern Sweden. Findings Data were obtained from an already available population based case-control study where the cases were defined as incident first-time ischemic stroke patients. Complete data on all relevant variables were obtained for 2722 controls and 2469 cases. The data were analyzed with logistic regression analysis. Stroke risk decreased with fat fish intake ([greater than or equal to] 1/week versus Conclusions The results suggest fat fish intake to decrease ischemic stroke risk and lean fish intake to increase women's stroke risk. The inconsistent relationship between fish intake and stroke risk reported in previous studies is further stressed by the results of this study.

Abstract Background Long-term exposure to air pollution is a hypothesized risk factor for ischemic stroke. In a large case-control study with a complete study base, we investigated whether hospital admissions for ischemic stroke were associated with residential concentrations of outdoor NOx, as a proxy for exposure to air pollution, in the region of Scania, Southern Sweden. Methods We used a two-phase case-control study design, including as first-phase controls all individuals born between 1923 and 1965 and residing in Scania in 2002 (N = 556 912). We defined first-phase cases as first-time ischemic stroke patients residing in Scania and registered in the Swedish stroke register between 2001 and 2005 (N = 4 904) and second-phase cases as cases for whom we had information on smoking status, diabetes, and medication for hypertension (N = 4 375). For the controls, information on these covariables was collected from a public health survey, resulting in 4 716 second-phase controls. With a geographical information system and an emission database, individual residential outdoor annual mean NOx concentration was modelled. The data were analyzed with logistic regression. Results We found no evident association between NOx and ischemic stroke. For example, the odds ratio for ischemic stroke associated with the NOx category 20–30 μg/m3 compared to the reference category of 3 was 0.95 (95% CI 0.86–1.06). Conclusion In this study area, with generally low levels of air pollution, using a complete study base, high-quality ascertainment of cases, and individually modelled exposure, we did not observe any clear association between NOx and ischemic stroke hospital admissions.

Abstract Background Blood lead concentrations (B-Pb) were measured in 3 879 Swedish school children during the period 1978–2007. The objective was to study the effect of the proximity to lead sources based on the children's home and school location. Methods The children's home address and school location were geocoded and their proximity to a lead smelter and major roads was calculated using geographical information system (GIS) software. All the statistical analyses were carried out using means of generalized log-linear modelling, with natural-logarithm-transformed B-Pb, adjusted for sex, school year, lead-exposing hobby, country of birth and, in the periods 1988–1994 and 1995–2007, parents' smoking habits. Results The GIS analysis revealed that although the emission from the smelter and children's B-Pb levels had decreased considerably since 1978, proximity to the lead smelter continued to affect levels of B-Pb, even in recent years (geometric mean: near smelter: 22.90 μg/l; far from smelter 19.75 μg/l; p = 0.001). The analysis also revealed that proximity to major roads noticeably affected the children's B-Pb levels during the period 1978–1987 (geometric mean near major roads: 44.26 μg/l; far from roads: 38.32 μg/l; p = 0.056), due to the considerable amount of lead in petrol. This effect was, however, not visible after 1987 due to prohibition of lead in petrol. Conclusion The results show that proximity to the lead smelter still has an impact on the children's B-Pb levels. This is alarming since it could imply that living or working in the vicinity of a former lead source could pose a threat years after reduction of the emission. The analysis also revealed that urban children exposed to lead from traffic were only affected during the early period, when there were considerable amounts of lead in petrol, and that the prohibition of lead in petrol in later years led to reduced levels of lead in the blood of urban children.

Abstract Background We plan to conduct a case-control study to investigate whether exposure to nitrogen dioxide (NO2) increases the risk of stroke. In case-control studies, selective participation can lead to bias and loss of efficiency. A two-phase design can reduce bias and improve efficiency by combining information on the non-participating subjects with information from the participating subjects. In our planned study, we will have access to individual disease status and data on NO2 exposure on group (area) level for a large population sample of Scania, southern Sweden. A smaller sub-sample will be selected to the second phase for individual-level assessment on exposure and covariables. In this paper, we simulate a case-control study based on our planned study. We develop a two-phase method for this study and compare the performance of our method with the performance of other two-phase methods. Methods A two-phase case-control study was simulated with a varying number of first- and second-phase subjects. Estimation methods: Method 1: Effect estimation with second-phase data only. Method 2: Effect estimation by adjusting the first-phase estimate with the difference between the adjusted and unadjusted second-phase estimate. The first-phase estimate is based on individual disease status and residential address for all study subjects that are linked to register data on NO2-exposure for each geographical area. Method 3: Effect estimation by using the expectation-maximization (EM) algorithm without taking area-level register data on exposure into account. Method 4: Effect estimation by using the EM algorithm and incorporating group-level register data on NO2-exposure. Results The simulated scenarios were such that, unbiased or marginally biased (< 7%) odds ratio (OR) estimates were obtained with all methods. The efficiencies of method 4, are generally higher than those of methods 1 and 2. The standard errors in method 4 decreased further when the case/control ratio is above one in the second phase. For all methods, the standard errors do not become substantially reduced when the number of first-phase controls is increased. Conclusion In the setting described here, method 4 had the best performance in order to improve efficiency, while adjusting for varying participation rates across areas.

Abstract Background Numerous studies have shown that exposure to air pollutants in the area of residence and the socio-economic status of an individual may be related. Therefore, when conducting an epidemiological study on the health effect of air pollution, socio-economy may act as a confounding factor. In this paper we examine to what extent socio-economic status and concentrations of NO2 in the county/region of Scania, southern Sweden, are associated and if such associations between these factors differ when studying them at county or city level. To perform this study we used high-resolution census data and modelled the annual exposure to NO2 using an emission database, a dispersion modelling program and a geographical information system (GIS). Results The results from this study confirm that socio-economic status and the levels of NO2 in the area of residence are associated in some cities. The associations vary considerably between cities within the same county (Scania). Even for cities of similar sizes and population bases the associations observed are different. Studying the cities together or separately yields contradictory results, especially when education is used as a socio-economic indicator. Conclusion Four conclusions have been drawn from the results of this study. 1) Adjusting for socio-economy is important when investigating the health effects of air pollution. 2) The county of Scania seems to be heterogeneous regarding the association between air pollution and socio-economy. 3) The relationship between air pollution and socio-economy differs in the five cities included in our study, depending on whether they are analysed separately or together. It is therefore inadvisable to determine and analyse associations between socio-economy and exposure to air pollutants on county level. This study indicates that the size and choice of study area is of great importance. 4) The selection of socio-economic indices (in this study: country of birth and education level) is important.