Moniek C.M. de Goeij

Favorable Glucose Tolerance and Lower Prevalence of Metabolic Syndrome in Offspring without Diabetes Mellitus of Nonagenarian Siblings: The Leiden Longevity Study

OBJECTIVES: To explore measures of metabolic syndrome and glucose metabolism in families with exceptional longevity.

How economic crises affect alcohol consumption and alcohol-related health problems: A realist systematic review

Economic crises are complex events that affect behavioral patterns (including alcohol consumption) via opposing mechanisms. With this realist systematic review, we aimed to investigate evidence from studies of previous or ongoing crises on which mechanisms (How?) play a role among which individuals (Whom?). Such evidence would help understand and predict the potential impact of economic crises on alcohol consumption. Medical, psychological, social, and economic databases were used to search for peer-reviewed qualitative or quantitative empirical evidence (published January 1, 1990-May 1, 2014) linking economic crises or stressors with alcohol consumption and alcohol-related health problems. We included 35 papers, based on defined selection criteria. From these papers, we extracted evidence on mechanism(s), determinant, outcome, country-level context, and individual context. We found 16 studies that reported evidence completely covering two behavioral mechanisms by which economic crises can influence alcohol consumption and alcohol-related health problems. The first mechanism suggests that psychological distress triggered by unemployment and income reductions can increase drinking problems. The second mechanism suggests that due to tighter budget constraints, less money is spent on alcoholic beverages. Across many countries, the psychological distress mechanism was observed mainly in men. The tighter budget constraints mechanism seems to play a role in all population subgroups across all countries. For the other three mechanisms (i.e., deterioration in the social situation, fear of losing ones job, and increased non-working time), empirical evidence was scarce or absent, or had small to moderate coverage. This was also the case for important influential contextual factors described in our initial theoretical framework. This realist systematic review suggests that among men (but not among women), the net impact of economic crises will be an increase in harmful drinking. Such a different net impact between men and women could potentially contribute to growing gender-related health inequalities during a crisis.

Multiple imputation: dealing with missing data

In many fields, including the field of nephrology, missing data are unfortunately an unavoidable problem in clinical/epidemiological research. The most common methods for dealing with missing data are complete case analysis-excluding patients with missing data--mean substitution--replacing missing values of a variable with the average of known values for that variable-and last observation carried forward. However, these methods have severe drawbacks potentially resulting in biased estimates and/or standard errors. In recent years, a new method has arisen for dealing with missing data called multiple imputation. This method predicts missing values based on other data present in the same patient. This procedure is repeated several times, resulting in multiple imputed data sets. Thereafter, estimates and standard errors are calculated in each imputation set and pooled into one overall estimate and standard error. The main advantage of this method is that missing data uncertainty is taken into account. Another advantage is that the method of multiple imputation gives unbiased results when data are missing at random, which is the most common type of missing data in clinical practice, whereas conventional methods do not. However, the method of multiple imputation has scarcely been used in medical literature. We, therefore, encourage authors to do so in the future when possible.

Allele-specific regulation of FGFR2 expression is cell type-dependent and may increase breast cancer risk through a paracrine stimulus involving FGF10

IntroductionSNPs rs2981582 and rs2981578, located in a linkage disequilibrium block (LD block) within intron 2 of the fibroblast growth factor receptor 2 gene (FGFR2), are associated with a mildly increased breast cancer risk. Allele-specific regulation of FGFR2 mRNA expression has been reported previously, but the molecular basis for the association of these variants with breast cancer has remained elusive to date.MethodsmRNA levels of FGFR2 and three fibroblast growth factor genes (FGFs) were measured in primary fibroblast and epithelial cell cultures from 98 breast cancer patients and correlated to their rs2981578 genotype. The phosphorylation levels of downstream FGFR2 targets, FGF receptor substrate 2α (FRS2α) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), were quantified in skin fibroblasts exposed to FGF2. Immunohistochemical markers for angiogenesis and lymphocytic infiltrate were semiquantitatively assessed in 25 breast tumors.ResultsThe risk allele of rs2981578 was associated with increased FGFR2 mRNA levels in skin fibroblasts, but not in skin epithelial cell cultures. FGFR2 mRNA levels in skin fibroblasts and breast fibroblasts correlated strongly in the patients from whom both cultures were available. Tumor-derived fibroblasts expressed, on average, eight times more FGFR2 mRNA than the corresponding fibroblasts from normal breast tissue. Fibroblasts with higher FGFR2 mRNA expression showed more FRS2α and ERK1/2 phosphorylation after exposure to FGF2. In fibroblasts, higher FGFR2 expression correlated with higher FGF10 expression. In 25 breast tumors, no associations between breast tumor characteristics and fibroblast FGFR2 mRNA levels were found.ConclusionsThe influence of rs2981578 genotypes on FGFR2 mRNA expression levels is cell type-dependent. Expression differences correlated well with signaling levels of the FGFR2 pathway. Our results suggest that the increased breast cancer risk associated with SNP rs2981578 is due to increased FGFR2 signaling activity in stromal fibroblasts, possibly also involving paracrine FGF10 signaling.

Translational research in nephrology: chronic kidney disease prevention and public health.

This narrative review evaluates translational research with respect to five important risk factors for chronic kidney disease (CKD): physical inactivity, high salt intake, smoking, diabetes and hypertension. We discuss the translational research around prevention of CKD and its complications both at the level of the general population, and at the level of those at high risk, i.e. people at increased risk for CKD or CKD complications. At the population level, all three lifestyle risk factors (physical inactivity, high salt intake and smoking) have been translated into implemented measures and clear population health improvements have been observed. At the ‘high-risk’ level, the lifestyle studies reviewed have tended to focus on the individual impact of specific interventions, and their wider implementation and impact on CKD practice are more difficult to establish. The treatment of both diabetes and hypertension appears to have improved, however the impact on CKD and CKD complications was not always clear. Future studies need to investigate the most effective translational interventions in low and middle income countries.

Uric acid: association with rate of renal function decline and time until start of dialysis in incident pre-dialysis patients

BackgroundIn patients with chronic kidney disease (CKD) hyperuricemia is common. Evidence that hyperuricemia might also play a causal role in vascular disease, hypertension and progression of CKD is accumulating. Therefore, we studied the association between baseline uric acid (UA) levels and the rate of decline in renal function and time until start of dialysis in pre-dialysis patients.MethodsData from the PREPARE-2 study were used. The PREPARE-2 study is an observational prospective cohort study including incident pre-dialysis patients with CKD stages IV-V in the years between 2004 and 2011. Patients were followed for a median of 14.9 months until start of dialysis, kidney transplantation, death, or censoring. Main outcomes were the change in the rate of decline in renal function (measured as estimated glomerular filtration rate (eGFR)) estimated using linear mixed models, and time until start of dialysis estimated using Cox proportional hazards models.ResultsIn this analysis 131 patients were included with a baseline UA level (mean (standard deviation (SD)) of 8.0 (1.79) mg/dl) and a mean decline in renal function of -1.61 (95% confidence interval (CI), -2.01; -1.22) ml/min/1.73 m2/year. The change in decline in GFR associated with a unit increase in UA at baseline was -0.14 (95% CI -0.61;0.33, p = 0.55) ml/min/1.73 m2/year. Adjusted for demography, comorbidities, diet, body mass index (BMI), blood pressure, lipids, proteinuria, diuretic and/or allopurinol usage the change in decline in eGFR did not change. The hazard ratio (HR) for starting dialysis for each mg/dl increase in UA at baseline was 1.08 (95% CI, 0.94;1.24, p = 0.27). After adjustment for the same confounders the HR became significant at 1.26 (95% CI, 1.06;1.49, p = 0.01), indicating an earlier start of dialysis with higher levels of UA.ConclusionAlthough high UA levels are not associated with an accelerated decline in renal function, a high serum UA level in incident pre-dialysis patient is a risk factor for an earlier start of dialysis.

The impact of extended closing times of alcohol outlets on alcohol‐related injuries in the nightlife areas of Amsterdam: a controlled before‐and‐after evaluation

BACKGROUND AND AIMS The municipality of Amsterdam implemented a new alcohol policy allowing alcohol outlets in two of the five nightlife areas to extend their closing times from 1 April 2009 onwards. We investigated how levels and trends of alcohol-related injuries changed after implementation of this alcohol policy, by comparing areas with extended closing times to those without. DESIGN A controlled before-and-after evaluation to compare changes in alcohol-related injuries between intervention and control areas. SETTING Central district of Amsterdam, The Netherlands. PARTICIPANTS Alcohol-related ambulance attendances for control and intervention areas between 1 April 2006 and 1 April 2009 (respectively, n = 544 and n = 499) and between 1 April 2009 and 1 April 2011 (respectively, n = 357 and n = 480). MEASUREMENTS Alcohol-related injuries were defined as ambulance attendances for people who suffered from direct or indirect consequences of alcohol consumption. Injuries were counted per month in two intervention and three control nightlife areas. We used Poisson regression to assess changes in injuries. FINDINGS After 1 April 2009, intervention areas showed a larger change in the level of alcohol-related injuries than control areas [incidence rate ratio 1.34, 95% confidence interval (CI) = 1.12, 1.61], but trends remained stable in all areas. This increase was only statistically significant for the following subgroups: 2.00-5.59 a.m., weekend days, men, individuals aged 25-34 years, and people transported to a hospital. However, the increase did not differ between subgroups with statistical significance. CONCLUSIONS A 1-hour extension of alcohol outlet closing times in some of Amsterdams nightlife areas was associated with 34% more alcohol-related injuries.

Differences in Progression to ESRD between Black and White Patients Receiving Predialysis Care in a Universal Health Care System

BACKGROUND AND OBJECTIVES Studies performed in the United States showed that blacks progress from CKD to ESRD faster than do whites. Possible explanations are differences in health care system factors. This study investigated whether progression is also faster in a universal health care system, where all patients receive comparable care. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data from the PREdialysis PAtient REcord study, a multicenter follow-up study of patients with CKD who started predialysis care in The Netherlands (1999-2011), were analyzed. Time-dependent Cox proportional hazards models were used to estimate the hazard ratio (HR) for starting renal replacement therapy (RRT), and linear mixed models were used to compare renal function decline (RFD) between blacks and whites. To explore possible mechanisms, analyses were adjusted for patient characteristics. RESULTS At initiation of predialysis care, blacks (n=49) were younger and had more diabetes mellitus, higher proteinuria levels, and a higher estimated GFR than whites (n=946). Median follow-up time in months was similar (blacks: 13.9 [boundaries of interquartile range (IQR), 5.3 to 19.5]; whites: 13.1 [IQR, 5.1 to 24.0]). For blacks compared with whites, the crude HR for starting RRT within the first 15 months was 0.86 (95% confidence interval [CI], 0.55 to 1.34) and from 15 months onward, 1.93 (95% CI, 1.02 to 3.68), which increased after adjustment. RFD was faster by 0.18 (95% CI, 0.05 to 0.32) ml/min per 1.73 m(2) per month in blacks compared with whites. CONCLUSION Blacks receiving predialysis care in a universal health care system have faster disease progression than whites, suggesting that health care system factors have a less influential role than had been thought in explaining black-white differences.

Association of blood pressure with decline in renal function and time until the start of renal replacement therapy in pre-dialysis patients: a cohort study.

BackgroundTo investigate whether high blood pressure accelerates renal function decline in patients with advanced chronic kidney disease (CKD), we studied the association of systolic (SBP) and diastolic blood pressure (DBP) with decline in renal function and time until the start of renal replacement therapy (RRT) in patients with CKD stages IV-V on pre-dialysis care.MethodsIn the PREPARE-1 cohort 547 incident pre-dialysis patients, referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included between 1999 and 2001 and followed until the start of RRT, mortality, or end of follow-up (January 1st 2008). Main outcomes were rate of decline in renal function, estimated as the slope of available eGFR measurements, and time until the start of RRT.ResultsA total of 508 patients, 57% men and median (IQR) age of 63 (50-73) years, were available for analyses. Mean (SD) decline in renal function was 0.35 (0.75) ml/min/1.73 m2/month. Every 10 mmHg increase in SBP or DBP resulted in an accelerated decline in renal function (adjusted additional decline 0.04 (0.02;0.07) and 0.05 (0.00;0.11) ml/min/1.73 m2/month respectively) and an earlier start of RRT (adjusted HR 1.09 (1.04;1.14) and 1.16 (1.05;1.28) respectively). Furthermore, patients with SBP and DBP above the BP target goal of < 130/80 mmHg experienced a faster decline in renal function (adjusted additional decline 0.31 (0.08;0.53) ml/min/1.73 m2/month) and an earlier start of RRT (adjusted HR 2.08 (1.25;3.44)), compared to patients who achieved the target goal (11%). Comparing the decline in renal function and risk of starting RRT between patients with only SBP above the target (≥ 130 mmHg) and patients with both SBP and DBP below the target (< 130/80 mmHg), showed that the results were almost similar as compared to patients with both SBP and DBP above the target (adjusted additional decline 0.31 (0.04;0.58) ml/min/1.73 m2/month and adjusted HR 2.24 (1.26;3.97)). Therefore, it seems that especially having SBP above the target is harmful.ConclusionsIn pre-dialysis patients with CKD stages IV-V, having blood pressure (especially SBP) above the target goal for CKD patients (< 130/80 mmHg) was associated with a faster decline in renal function and a later start of RRT.

How economic recessions and unemployment affect illegal drug use: A systematic realist literature review

BACKGROUND Economic recessions may influence illegal drug use via different mechanisms, for example increased use due to more psychological distress or decreased use due to lower incomes and purchasing power. This paper reviews the literature on how economic recessions and unemployment affect the use of illegal drugs among adults. METHODS We conducted a systematic realist literature review, which is an explanatory method that aims to understand underlying mechanisms that connect an event to an outcome in a specific context. A systematic search was performed in EconLit, Embase, Medline, PsycINFO, SocIndex, and Web of Science for studies examining mechanisms explaining how recessions or unemployment affect illegal drug use. RESULTS We synthesized 28 studies published between 1990 and 2015. Most evidence (17 studies) was found for the counter-cyclical mechanism that recessions and unemployment increase psychological distress, which increases drug use. Mainly supportive evidence for this mechanism was found in several high quality studies, in different contexts, and in a diverse number of countries and samples. In contrast, decreased income did not seem to decrease drug use (10 studies). Little evidence was available on the non-working time mechanism (4 studies) and the social exclusion mechanism (5 studies). Most of the studies that did examine these latter mechanisms confirmed the hypothesized counter-cyclical associations. CONCLUSION The current evidence is in line with the hypothesis that drug use increases in times of recession because unemployment increases psychological distress which increases drug use. During times of recession, psychological support for those who lost their job and are vulnerable to drug use (relapse) is likely to be important.