The COVID-19 pandemic that reached Europe in 2020 has often been compared to the Spanish flu pandemic of 1918. In this article, we compare the two pandemics in terms of their respective impacts on the loss of life expectancy at birth in six European countries (France, Italy, the Netherlands, Spain, Sweden, Switzerland) by estimating life expectancy in 2020 using Eurostat data. We found that the loss of life expectancy at birth was up to 20 times larger between 1917 and 1918 than between 2019 and 2020. A decomposition of these losses clearly shows that in all six countries, the main contributors were older age groups in 2020 and younger age groups in 1918. These observations are consistent with evidence indicating that most COVID-19 fatalities were among the elderly, while a majority of Spanish flu fatalities were among the young.

Aims Glomerular damage indicated by proteinuria is a main symptom in diabetic nephropathy. Mineralocorticoid receptor (MR) antagonists (MRAs) are beneficial irrespective of aldosterone availability. Thus, we hypothesized an alternatively activated MR to promote glomerular damage in proteinuric diabetic nephropathy. Specifically, we aimed first to demonstrate the presence of steroid hormones serving as alternative MR targets in type II diabetic patients with proteinuric kidney disease, second whether MR selectivity was modified, third to characterize MR and glucocorticoid receptor (GR) expression and activity in glomerular cell types exposed to eu- and hyperglycemic conditions, fourth to characterize the pro-fibrotic potential of primary human renal mesangial cells (HRMC) upon stimulation with aldosterone and cortisol, and fifth to specify the involvement of the MR and/or GR in pro-fibrotic signaling. Materials and methods Urinary steroid hormone profiles of patients with diabetic kidney disease were analyzed by gas chromatography–mass spectrometry and compared to an age and gender matched healthy control group taken out of a population study. In both cohorts, the activity of the MR pre-receptor enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2), which inactivates cortisol to prevent it from binding to the MR, was assessed to define a change in MR selectivity. Expression of HSD11B2, MR and GR was quantified in HRMC and primary human renal glomerular endothelial cells (HRGEC). Activity of MR and GR was explored in HRMC by measuring the MR/GR down-stream signal SGK1 and the pro-fibrotic genes TGFB1, FN1 and COL1A1 in normal and high glucose conditions with the MR/GR agonists aldosterone/cortisol and the MR/GR antagonists spironolactone/RU486. Results Patients with diabetic kidney disease excreted more tetrahydroaldosterone than the control group reaching significance in men. The excretion of MR-agonistic steroid hormones was only increased for 18-hydroxytetrahydrocorticosterone in diabetic women. The excretion of most glucocorticoids was higher in the diabetic cohort. Higher apparent systemic HSD11B2 activity suggested less activation of the MR by cortisol in diabetic patients. Both cell types, HRMC and HRGEC, lacked expression of HSD11B2. Hyperglycemic conditions did not change MR and GR expression and activity. Stimulation with both aldosterone and cortisol promoted upregulation of pro-fibrotic genes in HRMC. This effect of MR and/or GR activation was more pronounced in high glucose conditions and partially inhibited by MRAs and GR antagonists. Conclusions In patients with diabetic kidney disease alternative MR activation is conceivable as cortisol and cortisone metabolites are increased. Systemic availability of active metabolites is counteracted via an increased HSD11B2 activity. As this cortisol deactivation is absent in HRMC and HRGEC, cortisol binding to the MR is enabled. Both, cortisol and aldosterone stimulation led to an increased expression of pro-fibrotic genes in HRMC. This mechanism was related to the MR as well as the GR and more marked in high glucose conditions linking the benefit of MRAs in diabetic kidney disease to these findings.

AIM OF THE STUDY Important regional differences in uranium exposure exist because of varying uranium concentrations in soil, water and food. Comprehensive data on the exposure of the general population to uranium is, however, scarce. Based on the 24-hour urinary excretion, the uranium exposure of the adult Swiss population was assessed in relation to age, sex, place of residence, body mass index (BMI), smoking habit and type of drinking water, as well as risk factors in relation to kidney impairment and indicators of a possible renal dysfunction. METHODS Uranium was quantified in 24-hour urine from a nationwide population-based sample (n = 1393). The ratio 238U/233U was measured for isotope dilution calibration with a sector field inductively coupled plasma mass spectrometer (HR-ICP-MS). RESULTS Overall median and 95th percentile were 15 and 67 ng/24 h, respectively. The place of residence significantly influenced urinary uranium excretion. However, most of the highest urinary uranium excretion levels could not be associated to areas known for their elevated uranium concentrations in the drinking water. Sources other than the local drinking water (e.g., bottled water) might be important, too. Gender as well as albumin excretion also had a significant effect on uranium excretion. The latter was, however, strongly dependent on the presence of diabetes mellitus. No association was found for age, BMI, smoking habit or the other examined kidney related variables. CONCLUSIONS On the basis of uranium exposure, assessed via 24-hour urinary uranium excretion, and current knowledge of the toxicity of naturally occurring uranium, a substantial corresponding health risk for the general adult population is unlikely. However, as long as no specific sensitive biomarker for the biological impact of low-dose chronic uranium exposure has been identified and validated, assessing subtle health impact of such exposure will remain difficult.

OBJECTIVE To assess the association of low socioeconomic status and risk factors for non-communicable diseases (diabetes, high alcohol intake, high blood pressure, obesity, physical inactivity, smoking) with loss of physical functioning at older ages. DESIGN Multi-cohort population based study. SETTING 37 cohort studies from 24 countries in Europe, the United States, Latin America, Africa, and Asia, 1990-2017. PARTICIPANTS 109 107 men and women aged 45-90 years. MAIN OUTCOME MEASURE Physical functioning assessed using the walking speed test, a valid index of overall functional capacity. Years of functioning lost was computed as a metric to quantify the difference in walking speed between those exposed and unexposed to low socioeconomic status and risk factors. RESULTS According to mixed model estimations, men aged 60 and of low socioeconomic status had the same walking speed as men aged 66.6 of high socioeconomic status (years of functioning lost 6.6 years, 95% confidence interval 5.0 to 9.4). The years of functioning lost for women were 4.6 (3.6 to 6.2). In men and women, respectively, 5.7 (4.4 to 8.1) and 5.4 (4.3 to 7.3) years of functioning were lost by age 60 due to insufficient physical activity, 5.1 (3.9 to 7.0) and 7.5 (6.1 to 9.5) due to obesity, 2.3 (1.6 to 3.4) and 3.0 (2.3 to 4.0) due to hypertension, 5.6 (4.2 to 8.0) and 6.3 (4.9 to 8.4) due to diabetes, and 3.0 (2.2 to 4.3) and 0.7 (0.1 to 1.5) due to tobacco use. In analyses restricted to high income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was 8.0 (5.7 to 13.1) for men and 5.4 (4.0 to 8.0) for women, whereas in low and middle income countries it was 2.6 (0.2 to 6.8) for men and 2.7 (1.0 to 5.5) for women. Within high income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was greater in the United States than in Europe. Physical functioning continued to decline as a function of unfavourable risk factors between ages 60 and 85. Years of functioning lost were greater than years of life lost due to low socioeconomic status and non-communicable disease risk factors. CONCLUSIONS The independent association between socioeconomic status and physical functioning in old age is comparable in strength and consistency with those for established non-communicable disease risk factors. The results of this study suggest that tackling all these risk factors might substantially increase life years spent in good physical functioning.

Switzerland is a multilingual country located between Germany, France and Italy, which differ by dietary habits and related outcomes. We explored differences in food consumption as well as compliance to the Swiss food-based dietary guidelines (FBDG) across the German-, French-, and Italian-speaking regions. The 2014–2015 nationwide cross-sectional survey was conducted among a stratified random sample of 2057 adults aged 18 to 75 years. Trained dietitians assessed food consumption via two non-consecutive 24-h dietary recalls using the international validated software GloboDiet®. Recorded foods and beverages were classified into six groups and 31 subgroups relevant for assessing compliance to the FBDG (Swiss Food Pyramid). Usual daily intake distributions were modelled and weighted for sampling design, non-response, weekdays and season. Participation rate was 38%. Significant differences across regions were observed in 18 of 31 food subgroups (p ≤ 0.01). Weighted mean daily intakes in the German-, French- and Italian-speaking regions were, respectively, 245 g, 155 g, 140 g for soft drinks, 273 g, 214 g, 135 g for coffee, 127 g, 72 g, 109 g for milk, 32 g, 45 g, 43 g for red meat, 18 g, 29 g, 34 g for fish/seafood, 8.1 g, 6.4 g, 3.7 g for butter, and 206 g, 214 g, 168 g for vegetables. The seven FBDGs were followed by <1% of the population. Four in 10 participants met ≥3 FBDG. Eighteen percent of participants ate ≥5 portions of fruit and vegetables a day, without regional differences. Food consumption substantially differed across the three linguistic regions of Switzerland. Adherence to FBDG was uniformly low. This highlights the potential influence of culture on diet. Nutritional education along with public health interventions are needed and may be most efficient if regionally targeted.

BACKGROUND:Frail older people with multiple interacting conditions, polypharmacy, and complex care needs are particularly exposed to health care-related adverse events. Among these, anticoagulant-related thromboembolic and hemorrhagic events are particularly frequent and serious in older inpatients. The growing use of anticoagulants in this population and their substantial risk of toxicity and inefficacy have therefore become an important patient safety and public health concern worldwide. Anticoagulant-related adverse events and the quality of anticoagulation management should thus be routinely assessed to improve patient safety in vulnerable older inpatients.OBJECTIVE:This project aims to develop and validate a set of outcome and process indicators based on linked administrative health data (ie, insurance claims data linked to hospital discharge data) assessing older inpatient safety related to anticoagulation in both Switzerland and France, and enabling comparisons across time and among hospitals, health territories, and countries. Geriatric patient safety indicators (GPSIs) will assess anticoagulant-related adverse events. Geriatric quality indicators (GQIs) will evaluate the management of anticoagulants for the prevention and treatment of arterial or venous thromboembolism in older inpatients.METHODS:GPSIs will measure cumulative incidences of thromboembolic and bleeding adverse events based on hospital discharge data linked to insurance claims data. Using linked administrative health data will improve GPSI risk adjustment on patients' conditions that are present at admission and will capture in-hospital and postdischarge adverse events. GQIs will estimate the proportion of index hospital stays resulting in recommended anticoagulation at discharge and up to various time frames based on the same electronic health data. The GPSI and GQI development and validation process will comprise 6 stages: (1) selection and specification of candidate indicators, (2) definition of administrative data-based algorithms, (3) empirical measurement of indicators using linked administrative health data, (4) validation of indicators, (5) analyses of geographic and temporal variations for reliable and valid indicators, and (6) data visualization.RESULTS:Study populations will consist of 166,670 Swiss and 5,902,037 French residents aged 65 years and older admitted to an acute care hospital at least once during the 2012-2014 period and insured for at least 1 year before admission and 1 year after discharge. We will extract Swiss data from the Helsana Group data warehouse and French data from the national health insurance information system (SNIIR-AM). The study has been approved by Swiss and French ethics committees and regulatory organizations for data protection.CONCLUSIONS:Validated GPSIs and GQIs should help support and drive quality and safety improvement in older inpatients, inform health care stakeholders, and enable international comparisons. We discuss several limitations relating to the representativeness of study populations, accuracy of administrative health data, methods used for GPSI criterion validity assessment, and potential confounding bias in comparisons based on GQIs, and we address these limitations to strengthen study feasibility and validity.

Background: Limited data are available in the African region on trends in blood pressure (BP) and awareness, treatment and control rates. Objective: We examined trends in these indicators for a 25-year period in the Seychelles, a rapidly developing small island state in the African region. Methods: Population-based surveys of adults aged 25–64 years were performed in 1989, 1994, 2004 and 2013 using nearly identical methods for all surveys. BP was based on the average of the second and third readings. Data were age-standardized. Results: Between 1989 and 2013, mean SBP decreased in older adults (but increased in younger adults) and mean DBP decreased in all age categories, despite a marked secular increase in mean BMI. At age 25–64 years, the proportions with BP at least 140/90 mmHg decreased from 44%/33% (men/women) in 1989 to 37%/22% in 2013. The proportions of persons aware of having high BP (among those with BP ≥ 140/90 or treatment) increased from 40%/63% (men/women) in 1989 to 65%/80% in 2013; the proportions under treatment (among aware) increased from 37%/49% to 64%/78%; and the proportions with controlled BP (among treated) increased from 10%/16% to 34%/61%. Awareness was associated with female sex, age, obesity and diabetes; treatment with age, obesity, low alcohol consumption and diabetes; and control with female sex, age and high socio-economic status. In 2013, the main classes of antihypertensive medications were used in similar proportions, and 64.5% received at least two medications. Conclusion: The prevalence of high BP (≥140/90 mmHg) decreased over time, which paralleled improved detection and control of hypertension. The identified associated factors should be considered when strengthening BP control programs.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Objective: Genome wide association studies have shown that the gene encoding for uromodulin (UMOD) is associated with hypertension. Recently, animal studies have demonstrated that UMOD modulates NaCl reabsorption driven by NKCC2. We hypothesised that the NaCl effect on blood pressure may be modulated by UMOD levels in the general population. Design and method: Urinary UMOD levels were measured in 994 participants of the SKIPOGH population-based study who completed 24 h blood pressure monitoring and 24 h urinary collection. We used mixed linear regression models to determine the association between 24 h sodium excretion and 24 h systolic (SBP) or diastolic (DBP) blood pressure. Family association was taken into account. Sodium excretion was square root transformed. Age, gender, smoking, treated hypertension, center, BMI, eGFR and 24 h urine variables (volume, creatinine, potassium) were entered as covariates in the models. As there was an interaction between sodium and UMOD excretion for SBP (p interaction = 0.002) and DBP (p interaction = 0.0012), we divided UMOD levels into low or high according to the median and stratified the analyses by UMOD groups. Results: Participants mean age was 47.5 ± 17.5 years; 51.8% were women. The mean 24 h SBP and DBP were 119.9 ± 13.9 and 78.2 ± 8.7 mmHg. Median 24 h sodium excretion was 136.0mmol (IQR 100.4–177.5) and median UMOD 40.1 mg/24 h (IQR 28.0–56.2). In multivariate analysis, sodium excretion was not associated with SBP in the lower UMOD group [n = 495; coefficient −0.21 (95% CI −0.74 to 0.32), p = 0.44] but was strongly associated in the higher one [n = 499; coefficient 0.87 (95% CI 0.36 to 1.38), p = 0.001]. Regarding DBP, we observed no significant association in the higher UMOD group [coef 0.21 (95% CI −0.10 to 0.51), p = 0.19] although there was an inverse one in the lower group [coef −0.39 (95% CI −0.73 to −0.04), p = 0.027]. Figure 1 shows the adjusted association between the sodium excretion and SBP (A) or DBP (B) according to UMOD levels. Figure. No caption available. Conclusions: These data show that the association of NaCl with blood pressure is modified by urinary UMOD levels. This is consistent with animal studies demonstrating that UMOD modulates NKCC2 activity and sodium reabsorption by the renal tubule, influencing salt sensitivity.

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate homeostasis. Circulating FGF23 is elevated in chronic kidney disease (CKD) and independently associated with poor renal and cardiovascular outcomes and mortality. Because the study of FGF23 in individuals with normal renal function has received little attention, we examined in a large, population based study of 1128 participants the associations of FGF23 with markers of mineral metabolism and renal function. The median estimated glomerular filtration rate (eGFR) of the cohort was 105 ml/min per 1.73 m(2), and the median plasma FGF23 was 78.5 RU/ml. FGF23 increased and plasma 1,25-dihydroxyvitamin D3 decreased significantly below an eGFR threshold of 102 and 99 ml/min per 1.73 m(2), respectively. In contrast, plasma parathyroid hormone increased continuously with decreasing eGFR and was first significantly elevated at an eGFR of 126 ml/min per 1.73 m(2). On multivariable analysis adjusting for sex, age, body mass index, and GFR, FGF23 was negatively associated with 1,25-dihydroxyvitamin D3, and urinary absolute and fractional calcium excretion but not with serum calcium or parathyroid hormone. We found a positive association of FGF23 with plasma phosphate, but no association with urinary absolute or fractional phosphate excretion and, unexpectedly, a positive association with tubular maximum phosphate reabsorption/GFR. Thus, in the absence of CKD, parathyroid hormone increases earlier than FGF23 when the eGFR decreases. The increase in FGF23 occurs at a higher eGFR threshold than previously reported and is closely associated with a decrease in 1,25-dihydroxyvitamin D3. We speculate that the main demonstrable effect of FGF23 in the setting of preserved renal function is suppression of 1,25-dihydroxyvitamin D3 rather than stimulation of renal phosphate excretion.

BACKGROUND:In high income countries, low socioeconomic status (SES) is related to unhealthier dietary patterns, while evidence on the social patterning of diet in low and middle income countries is scarce. OBJECTIVE:In this study, we assess dietary patterns in the general population of a middle income country in the African region, the Republic of Seychelles, and examine their distribution according to educational level and income. METHODS:Data was drawn from two independent national surveys conducted in the Seychelles among adults aged 25-64 years in 2004 (n = 1236) and 2013 (n = 1240). Dietary patterns were assessed by principal component analysis (PCA). Educational level and income were used as SES indicators. Data from both surveys were combined as no interaction was found between SES and year. RESULTS:Three dietary patterns were identified: "snacks and drinks", "fruit and vegetables" and "fish and rice". No significant associations were found between SES and the "snacks and drinks" pattern. Low vs. high SES individuals had lower adherence to the "fruit and vegetables" pattern [prevalence ratio (95% CI) 0.71 (0.60-0.83)] but a higher adherence to the traditional "fish and rice" pattern [1.58 (1.32-1.88)]. Income modified the association between education and the "fish and rice" pattern (p = 0.02), whereby low income individuals had a higher adherence to this pattern in both educational groups. CONCLUSION:Low SES individuals have a lower consumption of fruit and vegetables, but a higher consumption of traditional foods like fish and rice. The Seychelles may be at a degenerative diseases stage of the nutrition transition.

We aimed to assess the associations of socioeconomic factors with dietary patterns in a Guatemalan population.

Global health has attracted growing attention from academic institutions. Its emergence corresponds to the increasing interdependence that characterizes our time and provides a new worldview to address health challenges globally. There is still a large potential to better delineate the limits of the field, drawing on a wide perspective across sciences and geographical areas. As an implementation and integration science, academic global health aims primarily to respond to societal needs through research, education, and practice. From five academic institutions closely engaged with international Geneva, we propose here a definition of global health based on six core principles: 1) cross–border/multilevel approach, 2) inter–/trans–disciplinarity, 3) systems thinking, 4) innovation, 5) sustainability, and 6) human rights/equity. This definition aims to reduce the century–old divide between medicine and public health while extending our perspective to other highly relevant fields. Overall, this article provides an intellectual framework to improve health for all in our contemporary world with implications for academic institutions and science policy. Health and well–being are major challenges for the 21st century. While these key areas of societal development have gained prominence worldwide by receiving more political attention and funding than ever, the expression ‘global health’ has emerged to describe the profound shift in the nature of health within the context of globalization. Becoming ubiquitous, global health has generated increasing interest from academic institutions, which, as places of knowledge innovation, validation, transmission, and application, have a critical role to play in global health education, research, and practice [1,2]. In this article we use the terms ‘academic global health’ (AGH) to focus on the key role of academic institutions including university hospitals in the global health system. As an integration and implementation science [3], the primary goal of AGH is to foster transformative knowledge, which implies both new models of thinking and new types of research. At the operational level, this translates into a process of mutual learning for change and health improvement, through sharing and comparing across systems and cultures, using both qualitative and quantitative methods, validating new evidence internally and externally, and making interdisciplinary and international collaborations a prerequisite. From the viewpoint of five academic institutions closely engaged with Geneva, a leading city in global health and global governance, the present article attempts to reflect on the core principles, definition, and significance of AGH.

OBJECTIVE: Electrolytes handling by the kidney is essential for volume and blood pressure (BP) homeostasis but their distribution and heritability are not well described. We estimated the heritability of kidney function as well as of serum and urine concentrations, renal clearances and fractional excretions for sodium, chloride, potassium, calcium, phosphate and magnesium in a Swiss population-based study. DESIGN AND METHOD: Nuclear families were randomly selected from the general population in Switzerland. We estimated glomerular filtration rate (eGFR) using the CKD-EPI and MDRD equations. Urine was collected separately during day and night over 24-hour. We used the ASSOC program (S.A.G.E.) to estimate narrow sense heritability, including as covariates in the model: age, sex, body mass index and study center. RESULTS: The 1128 participants (537 men and 591 women from 273 families), had mean (sd) age of 47.4(17.5) years, body mass index of 25.0 (4.5) kg/m2 and CKD-EPI of 98.0(18.5) mL/min/1.73 m2. Heritability estimates (SE) were 46.0% (0.06), 48.0% (0.06) and 18.0% (0.06) for CKD-EPI, MDRD and 24-hour creatinine clearance (P u003c 0.05), respectively. Heritability [SE] of serum concentration was highest for calcium (37%[0.06]) and lowest for sodium (13%[0.05]). Heritabilities [SE] of 24-h urine concentrations and excretions, and of fractional excretions were highest for calcium (51%[0.06], 44%[0.06] and 51%[0.06], respectively) and lowest for potassium (11%[0.05], 10%[0.05] and 16%[0.06], respectively). All results were statistically different from zero.(Figure is included in full-text article.) CONCLUSIONS: : Serum and urine levels, urinary excretions and renal handling of electrolytes, particularly calcium, are heritable in the general adult population. Identifying genetic variants involved in electrolytes homeostasis may provide useful insight into the pathophysiological mechanisms involved in common chronic diseases such as kidney diseases, hypertension and diabetes.

BACKGROUND AND OBJECTIVESAllelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSUrinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age±SD, 45±17 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology Collaboration formula and by 24-hour creatinine clearance.RESULTSIn both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and osmolality. In SKIPOGH, 24-hour uromodulin excretion (median, 41 [interquartile range, 29-57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24-hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR<90 ml/min per 1.73 m(2).CONCLUSIONAge, creatinine excretion, diabetes, and urinary volume are independent clinical correlates of urinary uromodulin excretion. The associations of uromodulin excretion with markers of tubular functions and kidney dimensions suggest that it may reflect tubule activity in the general population.

Objective: Genome wide association studies have shown that the gene encoding for uromodulin (UMOD) is associated with hypertension. Recently, animal studies have demonstrated that UMOD modulates NaCl reabsorption driven by NKCC2. We hypothesised that the NaCl effect on blood pressure may be modulated by UMOD levels in the general population. Design and method: Urinary UMOD levels were measured in 994 participants of the SKIPOGH population-based study who completed 24 h blood pressure monitoring and 24 h urinary collection. We used mixed linear regression models to determine the association between 24 h sodium excretion and 24 h systolic (SBP) or diastolic (DBP) blood pressure. Family association was taken into account. Sodium excretion was square root transformed. Age, gender, smoking, treated hypertension, center, BMI, eGFR and 24 h urine variables (volume, creatinine, potassium) were entered as covariates in the models. As there was an interaction between sodium and UMOD excretion for SBP (p interaction = 0.002) and DBP (p interaction = 0.0012), we divided UMOD levels into low or high according to the median and stratified the analyses by UMOD groups. Results: Participants mean age was 47.5 ± 17.5 years; 51.8% were women. The mean 24 h SBP and DBP were 119.9 ± 13.9 and 78.2 ± 8.7 mmHg. Median 24 h sodium excretion was 136.0mmol (IQR 100.4–177.5) and median UMOD 40.1 mg/24 h (IQR 28.0–56.2). In multivariate analysis, sodium excretion was not associated with SBP in the lower UMOD group [n = 495; coefficient −0.21 (95% CI −0.74 to 0.32), p = 0.44] but was strongly associated in the higher one [n = 499; coefficient 0.87 (95% CI 0.36 to 1.38), p = 0.001]. Regarding DBP, we observed no significant association in the higher UMOD group [coef 0.21 (95% CI −0.10 to 0.51), p = 0.19] although there was an inverse one in the lower group [coef −0.39 (95% CI −0.73 to −0.04), p = 0.027]. Figure 1 shows the adjusted association between the sodium excretion and SBP (A) or DBP (B) according to UMOD levels. Conclusions: These data show that the association of NaCl with blood pressure is modified by urinary UMOD levels. This is consistent with animal studies demonstrating that UMOD modulates NKCC2 activity and sodium reabsorption by the renal tubule, influencing salt sensitivity.

Background: Meticulous steps and procedures are proposed in planning guidelines for the development of comprehensive multiyear plans for national immunization programmes. However, we know very little about whether the real-life experience of those who adopt these guidelines involves following these procedures as expected. Are these steps and procedures followed in practice? We examined the adoption and usage of the guidelines in planning national immunization programmes and assessed whether the recommendations in these guidelines are applied as consistently as intended.Methods: We gathered information from the national comprehensive multiyear plans developed by 77 low-income countries. For each of the 11 components, we examined how each country applied the four recommended steps of situation analysis, problem prioritization, selection of interventions, and selection of indicators. We then conducted an analysis to determine the patterns of alignment of the comprehensive multiyear plans with those four recommended planning steps.Results: Within the first 3 years following publication of the guidelines, 66 (86%) countries used the tool to develop their comprehensive multiyear plans. The funding conditions attached to the use of these guidelines appeared to influence their rapid adoption and usage. Overall, only 33 (43%) countries fully applied all four recommended planning steps of the guidelines.Conclusions: Adoption and usage of the guidelines for the development of comprehensive multiyear plans for national immunization programmes were rapid. However, our findings show substantial variation between the proposed planning ideals set out in the guidelines and actual use in practice. A better understanding of factors that influence how recommendations in public health guidelines are applied in practice could contribute to improvements in guidelines design. It could also help adjust strategies used to introduce them into public health programmes, with the ultimate goal of a greater health impact.