Is metabolic-healthy obesity associated with risk of dementia? An age-stratified analysis of the Whitehall II cohort study

BACKGROUND: Metabolically healthy obesity is hypothesized to be a benign condition but whether this is the case for dementia remains debated. We examined the role of age at assessment of metabolic-obesity phenotypes in associations with incident dementia. METHODS: Obesity (body mass index ≥ 30 kg/m2) and poor metabolic health (≥ 2 of elevated serum triglycerides, low HDL-C, elevated blood pressure, and elevated serum fasting glucose) were used to define four metabolic-obesity phenotypes (metabolically healthy (MHNO) and unhealthy non-obesity (MUNO), metabolically healthy (MHO) and unhealthy obesity (MUO)) at < 60, 60 to < 70, and ≥ 70 years using 6 waves of data from the Whitehall II study and their associations with incident dementia was examined using Cox regression. RESULTS: Analyses with exposures measured < 60, 60 to < 70, and ≥ 70 years involved 410 (5.8%), 379 (5.6%), and 262 (7.4%) incident dementia cases over a median follow-up of 20.8, 10.3, and 4.2 years respectively. In analyses of individual components, obesity before 60 years (HR 1.41, 95% CI: [1.08, 1.85]) but not at older ages was associated with dementia; unhealthy metabolic status when present < 60 years (HR 1.33, 95% CI: [1.08, 1.62]) and 60 to < 70 years (HR 1.32, 95% CI: [1.07, 1.62]) was associated with dementia. Compared to the metabolically healthy non-obesity group, the risk of dementia was higher in those with metabolically healthy obesity before 60 years (1.69; 95% CI: [1.16, 2.45]); this was not the case when metabolic-obesity phenotype was present at 60 to < 70 years or ≥ 70 years. Analyses at older ages were on smaller numbers due to death and drop-out but inverse probability weighting to account for missing data yielded similar results. CONCLUSIONS: Individuals with metabolically healthy obesity before age 60 had a higher risk of incident dementia over a 27-year follow-up; the excess risk dissipates when metabolic health and obesity are measured after 70 years

Association Between Retinal Nerve Fiber Layer Thickness and Incident Dementia in the European Prospective Investigation into Cancer in Norfolk Cohort

BACKGROUND: Retinal nerve fiber layer (RNFL) thickness may reflect cerebral status. OBJECTIVE: This study assessed the relationship between RNFL thickness and incident all-cause dementia in the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) Eye Study. METHODS: Glaucoma detection with variable corneal compensation (GDx-VCC) and Heidelberg Retinal Tomograph II (HRT II) derived global mean RNFL thickness from dementia-free participants at baseline within the EPIC-Norfolk Eye Study were analyzed. Incident dementia was identified through linkage to electronic medical records. Cox proportional hazard mixed-effects regression models adjusted for key confounders were used to examine the associations between RNFL thickness and incident dementia in four separate models. RESULTS: 6,239 participants were included with 322 cases of incident dementia and mean age of 67.5-years old, with 49.7% women (median follow-up 13.2-years, interquartile range (11.7 to 14.6 years). Greater RNFL thickness (GDx-VCC) was not significantly associated with a lower risk of incident dementia in the full adjusted model [HR per quartile increase 0.95; 95% CI 0.82-1.10]. Similarly, RNFL thickness assessed with HRT II was also not associated with incident dementia in any model (full adjusted model; HR per quartile increase: 1.06; [95% CI 0.93-1.19]. Gender did not modify any associations under study. CONCLUSION: GDx-VCC and HRT II derived RNFL thickness are unlikely to be useful predictors of incident dementia. Higher resolution optical imaging technologies may clarify whether there are useful relationships between neuro-retinal morphology and brain measures

Towards a standardised informed consent procedure for live donor nephrectomy: The PRINCE (Process of Informed Consent Evaluation) project-study protocol for a nationwide prospective cohort study

Introduction: Informed consent is mandatory for all (surgical) procedures, but it is even more important when it comes to living kidney donors undergoing surgery for the benefit of others. Donor education, leading to informed consent, needs to be carried out according to certain standards. Informed consent procedures for live donor nephrectomy vary per centre, and even per individual healthcare professional. The basis for a standardised, uniform surgical informed consent procedure for live donor nephrectomy can be created by assessing what information donors need to hear to prepare them for the operation and convalescence. Methods and analysis: The PRINCE (Process of In formed Consent Evaluation) project is a prospective, multicentre cohort study, to be carried out in all eight Dutch kidney transplant centres. Donor knowledge of the procedure and postoperative course will be evaluated by means of pop quizzes. A baseline cohort (prior to receiving any information from a member of the transplant team in one of the transplant centres) will be compared with a control group, the members of which receive the pop quiz on the day of admission for donor nephrectomy. Donor satisfaction will be evaluated for all donors who completed the admission pop-quiz. The primary end point is donor knowledge. In addition, those elements that have to be included in the standardized format informed consent procedure will be identified. Secondary end points are donor satisfaction, current informed consent practices in the different centres (eg, how many visits, which personnel, what kind of information is di

Towards a standardised informed consent procedure for live donor nephrectomy:the PRINCE (Process of Informed Consent Evaluation) project-study protocol for a nationwide prospective cohort study

Introduction: Informed consent is mandatory for all (surgical) procedures, but it is even more important when it comes to living kidney donors undergoing surgery for the benefit of others. Donor education, leading to informed consent, needs to be carried out according to certain standards. Informed consent procedures for live donor nephrectomy vary per centre, and even per individual healthcare professional. The basis for a standardised, uniform surgical informed consent procedure for live donor nephrectomy can be created by assessing what information donors need to hear to prepare them for the operation and convalescence. Methods and analysis: The PRINCE (Process of Informed Consent Evaluation) project is a prospective, multicentre cohort study, to be carried out in all eight Dutch kidney transplant centres. Donor knowledge of the procedure and postoperative course will be evaluated by means of pop quizzes. A baseline cohort (prior to receiving any information from a member of the transplant team in one of the transplant centres) will be compared with a control group, the members of which receive the pop quiz on the day of admission for donor nephrectomy. Donor satisfaction will be evaluated for all donors who completed the admission pop-quiz. The primary end point is donor knowledge. In addition, those elements that have to be included in the standardised format informed consent procedure will be identified. Secondary end points are donor satisfaction, current informed consent practices in the different centres (eg, how many visits, which personnel, what kind of information is disclosed, in which format, etc) and correlation of donor knowledge with surgeons' estimation thereof. Ethics and dissemination: Approval for this study was obtained from the medical ethical committee of the Erasmus MC, University Medical Center, Rotterdam, on 18 February 2015. Secondary approval has been obtained from the local ethics committees in six participating centres. Approval in the last centre has been sought. Results: Outcome will be published in a scientific journal

Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies

INTRODUCTION - Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD). METHODS - We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8–11.5] years). RESULTS - General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes. DISCUSSION - These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia

Elevated levels of numerous cytokines in drainage fluid after primary total hip arthroplasty

As cytokines are involved in wound healing and other inflammatory processes, it could be valuable to measure their levels at the operative site. This study was conducted to investigate whether different cytokines are measurable in drainage fluid and, when measurable, whether we can find a difference in cytokine levels between one and six hours postoperatively. Samples from the drainage system in 30 consecutive patients undergoing primary total hip replacement were collected at one and six hours after closure of the wound. Levels of several cytokines were measured in the drainage fluids. A significant elevation of almost all cytokines was observed between the sample after one hour and six hours postoperatively. We found a strong correlation between the different pro-inflammatory cytokines. The IL-6 to IL-10 ratio were also raised, showing a pro-inflammatory predominance. Levels were much higher than those previously shown in serum

Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies

INTRODUCTION: Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD). METHODS: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years). RESULTS: General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes. DISCUSSION: These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia

Blood pressure variability and microvascular dysfunction:the Maastricht Study

Background: Microvascular dysfunction (MVD) contributes to stroke, dementia, depression, retinopathy and chronic kidney disease. However, the determinants of MVD are incompletely understood. Greater blood pressure variability (BPV) may be one such determinant. Methods and results: We used cross-sectional data of The Maastricht Study (n = 2773, age 59.9 years; 51.9% men) to investigate whether greater very short- to mid-term BPV is associated with various MVD measures. We standardized and averaged within-visit, 24-h and 7-day BPV into a systolic and a diastolic BPV composite score. MVD measures included a composite score of MRI cerebral small vessel disease (CSVD) features (total brain parenchymal volume, white matter hyperintensity volume, lacunar infarcts and cerebral microbleeds), a composite score of flicker light-induced retinal arteriolar and venular dilation response, albuminuria, heat-induced skin hyperemia and a composite score of plasma biomarkers of MVD (sICAM-1, sVCAM-1, sE-selectin and von Willebrand Factor). We used linear regression adjusted for age, sex, glucose metabolism status, mean 24-h systolic or DBP, cardiovascular risk factors and antihypertensive medication. We found that higher systolic and diastolic BPV composite scores (per SD) were associated with higher albuminuria [higher ratio, 1.04 (95% CI 1.00–1.08) and 1.07 (1.03–1.11), respectively], but not with other measures of MVD tested. Conclusion: Greater systolic and diastolic BPV was associated with higher albuminuria, but not with CSVD features, flicker light-induced retinal arteriolar and venular dilation response, heat-induced skin hyperemia and plasma biomarkers of MVD. This suggests that the microvasculature of the kidneys is most vulnerable to the detrimental effects of greater BPV

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to—or adding—another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies