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Introduction
Supplementation with spermidine may support healthy aging, but elevated spermidine tissue levels were shown to be an indicator of Alzheimer's disease (AD).
Methods
Data from 659 participants (age range: 21–81 years) of the population-based Study of Health in Pomerania TREND were included. We investigated the association between spermidine plasma levels and markers of brain aging (hippocampal volume, AD score, global cortical thickness [CT], and white matter hyperintensities [WMH]).
Results
Higher spermidine levels were significantly associated with lower hippocampal volume (ß = −0.076; 95% confidence interval [CI]: −0.13 to −0.02; q = 0.026), higher AD score (ß = 0.118; 95% CI: 0.05 to 0.19; q = 0.006), lower global CT (ß = −0.104; 95% CI: −0.17 to −0.04; q = 0.014), but not WMH volume. Sensitivity analysis revealed no substantial changes after excluding participants with cancer, depression, or hemolysis.
Discussion
Elevated spermidine plasma levels are associated with advanced brain aging and might serve as potential early biomarker for AD and vascular brain pathology.
Abstract
Aim
Observational research suggests that periodontitis affects psoriasis. However, observational studies are prone to reverse causation and confounding, which hampers drawing causal conclusions and the effect direction. We applied the Mendelian randomization (MR) method to comprehensively assess the potential bi‐directional association between periodontitis and psoriasis.
Materials and Methods
We used genetic instruments from the largest available genome‐wide association study of European descent for periodontitis (17,353 cases, 28,210 controls) to investigate the relationship with psoriasis (13,229 cases, 21,543 controls), and vice versa. Causal Analysis Using Summary Effect (CAUSE) estimates and inverse variance‐weighted (IVW) MR analyses were used for the primary analysis. Robust MR approaches were used for sensitivity analyses.
Results
Both univariable methods, CAUSE and IVW MR analyses, did not reveal any impact of periodontitis on psoriasis (CAUSE odds ratio [OR] = 1.00, p = 1.00; IVW OR = 1.02, p = .6247), or vice versa (CAUSE OR = 1.01, p = .5135; IVW OR = 1.00, p = .7070). The null association was corroborated by pleiotropy‐robust methods with ORs close to 1 and p‐values >.59. Overall, MR analyses did not suggest any effect of periodontitis on psoriasis. Similarly, there was no evidence to support an effect of psoriasis on periodontitis.
Conclusions
Within the limitations of this MR study, the outcomes supported neither periodontitis affecting psoriasis nor psoriasis affecting periodontitis.
Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and “precision,” data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface–level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.
Background: For years, coagulase-negative staphylococci (CoNS) were not considered a cause of bloodstream infections (BSIs) and were often regarded as contamination. However, the association of CoNS with nosocomial infections is increasingly recognized. The identification of more than 40 different CoNS species has been driven by the introduction of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Yet, treatment guidelines consider CoNS as a whole group, despite increasing antibiotic resistance (ABR) in CoNS. This retrospective study provides an in-depth data analysis of CoNS isolates found in human blood culture isolates between 2013 and 2019 in the entire region of the Northern Netherlands. Methods: In total, 10,796 patients were included that were hospitalized in one of the 15 hospitals in the region, leading to 14,992 CoNS isolates for (ABR) data analysis. CoNS accounted for 27.6% of all available 71,632 blood culture isolates. EUCAST Expert rules were applied to correct for errors in antibiotic test results. Results: A total of 27 different CoNS species were found. Major differences were observed in occurrence and ABR profiles. The top five species covered 97.1% of all included isolates: S. epidermidis, S. hominis, S. capitis, S. haemolyticus, and S. warneri. Regarding ABR, methicillin resistance was most frequently detected in S. haemolyticus (72%), S. cohnii (65%), and S. epidermidis (62%). S. epidermidis and S. haemolyticus showed 50–80% resistance to teicoplanin and macrolides while resistance to these agents remained lower than 10% in most other CoNS species. Conclusion: These differences are often neglected in national guideline development, prompting a focus on ‘ABR-safe’ agents such as glycopeptides. In conclusion, this multi-year, full-region approach to extensively assess the trends in both the occurrence and phenotypic resistance of CoNS species could be used for evaluating treatment policies and understanding more about these important but still too often neglected pathogens.
Objective
Whole-body MRI (wb-MRI) is increasingly used in research and screening but little is known about the effects of incidental findings (IFs) on health service utilisation and costs. Such effects are particularly critical in an observational study. Our principal research question was therefore how participation in a wb-MRI examination with its resemblance to a population-based health screening is associated with outpatient service costs.
Design
Prospective cohort study.
Setting
General population Mecklenburg-Vorpommern, Germany.
Participants
Analyses included 5019 participants of the Study of Health in Pomerania with statutory health insurance data. 2969 took part in a wb-MRI examination in addition to a clinical examination programme that was administered to all participants. MRI non-participants served as a quasi-experimental control group with propensity score weighting to account for baseline differences.Primary and secondary outcome measuresOutpatient costs (total healthcare usage, primary care, specialist care, laboratory tests, imaging) during 24 months after the examination were retrieved from claims data. Two-part models were used to compute treatment effects.
Results
In total, 1366 potentially relevant IFs were disclosed to 948 MRI participants (32% of all participants); most concerned masses and lesions (769 participants, 81%). Costs for outpatient care during the 2-year observation period amounted to an average of €2547 (95% CI 2424 to 2671) for MRI non-participants and to €2839 (95% CI 2741 to 2936) for MRI participants, indicating an increase of €295 (95% CI 134 to 456) per participant which corresponds to 11.6% (95% CI 5.2% to 17.9%). The cost increase was sustained rather than being a short-term spike. Imaging and specialist care related costs were the main contributors to the increase in costs.
Conclusions
Communicated findings from population-based wb-MRI substantially impacted health service utilisation and costs. This introduced bias into the natural course of healthcare utilisation and should be taken care for in any longitudinal analyses.