Serum kidney injury molecule 1 and β2-microglobulin perform as well as larger biomarker panels for prediction of rapid decline in renal function in type 2 diabetes

Aims/hypothesis: As part of the Surrogate Markers for Micro- and Macrovascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) programme we previously reported that large panels of biomarkers derived from three analytical platforms maximised prediction of progression of renal decline in type 2 diabetes. Here, we hypothesised that smaller (n ≤ 5), platform-specific combinations of biomarkers selected from these larger panels might achieve similar prediction performance when tested in three additional type 2 diabetes cohorts. Methods: We used 657 serum samples, held under differing storage conditions, from the Scania Diabetes Registry (SDR) and Genetics of Diabetes Audit and Research Tayside (GoDARTS), and a further 183 nested case–control sample set from the Collaborative Atorvastatin in Diabetes Study (CARDS). We analysed 42 biomarkers measured on the SDR and GoDARTS samples by a variety of methods including standard ELISA, multiplexed ELISA (Luminex) and mass spectrometry. The subset of 21 Luminex biomarkers was also measured on the CARDS samples. We used the event definition of loss of >20% of baseline eGFR during follow-up from a baseline eGFR of 30–75 ml min−1 [1.73 m]−2. A total of 403 individuals experienced an event during a median follow-up of 7 years. We used discrete-time logistic regression models with tenfold cross-validation to assess association of biomarker panels with loss of kidney function. Results: Twelve biomarkers showed significant association with eGFR decline adjusted for covariates in one or more of the sample sets when evaluated singly. Kidney injury molecule 1 (KIM-1) and β2-microglobulin (B2M) showed the most consistent effects, with standardised odds ratios for progression of at least 1.4 (p < 0.0003) in all cohorts. A combination of B2M and KIM-1 added to clinical covariates, including baseline eGFR and albuminuria, modestly improved prediction, increasing the area under the curve in the SDR, Go-DARTS and CARDS by 0.079, 0.073 and 0.239, respectively. Neither the inclusion of additional Luminex biomarkers on top of B2M and KIM-1 nor a sparse mass spectrometry panel, nor the larger multiplatform panels previously identified, consistently improved prediction further across all validation sets. Conclusions/interpretation: Serum KIM-1 and B2M independently improve prediction of renal decline from an eGFR of 30–75 ml min−1 [1.73 m]−2 in type 2 diabetes beyond clinical factors and prior eGFR and are robust to varying sample storage conditions. Larger panels of biomarkers did not improve prediction beyond these two biomarkers

How has internet addiction research evolved since the advent of internet gaming disorder? An overview of cyberaddictions from a psychological perspective

During the past two decades, Internet addiction (IA) has been the most commonly used term in research into online activities and their influence on the development of behavioral addictions. The aim of this review is to assess the impact of the concept of Internet gaming disorder (IGD), proposed by the American Psychiatric Association, on the scientific literature regarding IA. It presents a bibliometric analysis of the IA literature starting from the time IGD was first proposed, with the objective of observing and comparing the topics that have arisen during this period among the different IA themes researched. The findings demonstrate a steady evolution, particularly regarding publications related to the general aspects of IA: its clinical component, its prevalence and psychometric measures, the growing interest in the contextual factors promoting this addictive behavior, scientific progress in its conceptualization based on existing theoretical models, and neuropsychological studies. Nevertheless, many of the studies (22 %) focus on specific IA behaviors and show heterogeneity among the cyberaddictions, with online gaming (related to IGD) most common, followed by cybersex and social networking. Although research on the general concept of IA continues, investigators have begun to pay attention to the diverse spectrum of specific cyberaddictions and their psychological components

An umbrella review of the evidence associating diet and cancer risk at 11 anatomical sites

There is evidence that diet and nutrition are modifiable risk factors for several cancers, but associations may be flawed due to inherent biases. Nutritional epidemiology studies have largely relied on a single assessment of diet using food frequency questionnaires. We conduct an umbrella review of meta-analyses of observational studies to evaluate the strength and validity of the evidence for the association between food/nutrient intake and risk of developing or dying from 11 primary cancers. It is estimated that only few single food/nutrient and cancer associations are supported by strong or highly suggestive meta-analytic evidence, and future similar research is unlikely to change this evidence. Alcohol consumption is positively associated with risk of postmenopausal breast, colorectal, esophageal, head & neck and liver cancer. Consumption of dairy products, milk, calcium and wholegrains are inversely associated with colorectal cancer risk. Coffee consumption is inversely associated with risk of liver cancer and skin basal cell carcinoma

Cryoglobulinemic vasculitis in primary Sj\uf6gren's Syndrome: Clinical presentation, association with lymphoma and comparison with Hepatitis C-related disease

Objective: To describe the clinical spectrum of cryoglobulinemic vasculitis (CV) in primary Sj\uf6gren's syndrome (pSS), investigate its relation to lymphoma and identify the differences with hepatitis C virus (HCV) related CV. Methods: From a multicentre study population of consecutive pSS patients, those who had been evaluated for cryoglobulins and fulfilled the 2011 classification criteria for CV were identified retrospectively. pSS-CV patients were matched with pSS patients without cryoglobulins (1:2) and HCV-CV patients (1:1). Clinical, laboratory and outcome features were analyzed. A data driven logistic regression model was applied for pSS-CV patients and their pSS cryoglobulin negative controls to identify independent features associated with lymphoma. Results: 1083 pSS patients were tested for cryoglobulins. 115 (10.6%) had cryoglobulinemia and 71 (6.5%) fulfilled the classification criteria for CV. pSS-CV patients had higher frequency of extraglandular manifestations and lymphoma (OR=9.87, 95% CI: 4.7\u201320.9) compared to pSS patients without cryoglobulins. Purpura was the commonest vasculitic manifestation (90%), presenting at disease onset in 39% of patients. One third of pSS-CV patients developed B-cell lymphoma within the first 5 years of CV course, with cryoglobulinemia being the strongest independent lymphoma associated feature. Compared to HCV-CV patients, pSS-CV individuals displayed more frequently lymphadenopathy, type II IgMk cryoglobulins and lymphoma (OR = 6.12, 95% CI: 2.7\u201314.4) and less frequently C4 hypocomplementemia and peripheral neuropathy. Conclusion: pSS-CV has a severe clinical course, overshadowing the typical clinical manifestations of pSS and higher risk for early lymphoma development compared to HCV related CV. Though infrequent, pSS-CV constitutes a distinct severe clinical phenotype of pSS

Nutrient-wide association study of 92 foods and nutrients and breast cancer risk

Background:&nbsp;Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study. Methods:&nbsp;Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS). Results:&nbsp;Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake&thinsp;=&thinsp;1.05, 95% CI 1.03&ndash;1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment&thinsp;=&thinsp;1.05, 95% CI 1.03&ndash;1.06 and 1.04, 95% CI 1.02&ndash;1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment&thinsp;=&thinsp;0.96, 95% CI 0.94&ndash;0.98; 0.96, 95% CI 0.94&ndash;0.99; and 0.96, 95% CI 0.95&ndash;0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS. Conclusions:&nbsp;Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.</p

Diet-wide association study of 92 foods and nutrients and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study

Diet-wide association study of 92 foods and nutrients and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Stud

Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study

Introduction: Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). Methods: We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients &lt;18 years of age were screened, and 706 with severe sepsis defined either by physician diagnosis or on the basis of 2005 International Pediatric Sepsis Consensus Conference consensus criteria were enrolled. The primary endpoint was agreement of pediatric severe sepsis between physician diagnosis and consensus criteria as measured using Cohen's ?. Secondary endpoints included characteristics and clinical outcomes for patients identified using physician diagnosis versus consensus criteria. Results: Of the 706 patients, 301 (42.6 %) met both definitions. The inter-rater agreement (? ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02. Of the 438 patients with a physician's diagnosis of severe sepsis, only 69 % (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. Conclusions: Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis

Development of a common scale for measuring healthy ageing across the world: results from the ATHLOS consortium

Background: Research efforts to measure the concept of healthy ageing have been diverse and limited to specific populations. This diversity limits the potential to compare healthy ageing across countries and/or populations. In this study, we developed a novel measurement scale of healthy ageing using worldwide cohorts. Methods: In the Ageing Trajectories of Health-Longitudinal Opportunities and Synergies (ATHLOS) project, data from 16 international cohorts were harmonized. Using ATHLOS data, an item response theory (IRT) model was used to develop a scale with 41 items related to health and functioning. Measurement heterogeneity due to intra-dataset specificities was detected, applying differential item functioning via a logistic regression framework. The model accounted for specificities in model parameters by introducing cohort-specific parameters that rescaled scores to the main scale, using an equating procedure. Final scores were estimated for all individuals and converted to T-scores with a mean of 50 and a standard deviation of 10. Results: A common scale was created for 343 915 individuals above 18 years of age from 16 studies. The scale showed solid evidence of concurrent validity regarding various sociodemographic, life and health factors, and convergent validity with healthy life expectancy (r = 0.81) and gross domestic product (r = 0.58). Survival curves showed that the scale could also be predictive of mortality. Conclusions: The ATHLOS scale, due to its reliability and global representativeness, has the potential to contribute to worldwide research on healthy ageing