Association of CSF α-Synuclein Seeding Amplification Assay Results With Clinical Features of Possible and Probable Dementia With Lewy Bodies.

BACKGROUND AND OBJECTIVES: The clinical diagnosis of dementia with Lewy bodies (DLB) depends on identifying significant cognitive decline accompanied by core features of parkinsonism, visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder (RBD). Hyposmia is one of the several supportive features. α-Synuclein seeding amplification assays (αSyn-SAAs) may enhance diagnostic accuracy by detecting pathologic αSyn seeds in CSF. In this study, we examine how different clinical features associate with CSF αSyn-SAA positivity in a large group of clinically diagnosed participants with DLB. METHODS: Cross-sectional and longitudinal CSF samples from the multicentered observational cohort study of the DLB Consortium and similar studies within the Parkinson's Disease Biomarker Program, contributed by academic medical centers in the United States, underwent αSyn-SAA testing. Participants included those clinically diagnosed with DLB and 2 control cohorts. Associations between core DLB features and olfaction with αSyn-SAA positivity were evaluated using logistic regression. RESULTS: CSF samples from 191 participants diagnosed with DLB (mean age 69.9 ± 6.8, 15% female), 50 age-matched and sex-matched clinical control participants, and 49 younger analytical control participants were analyzed. Seventy-two percent (137/191) of participants with DLB had positive αSyn-SAAs vs 4% of the control groups. Among participants with DLB, those who were αSyn-SAA-positive had lower Montreal Cognitive Assessment scores (18.8 ± 5.7 vs 21.2 ± 5.2, p = 0.01), had worse parkinsonism on the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (33.8 ± 15.1 vs 25.6 ± 16.4, p = 0.001), were more likely to report RBD (114/133 [86%] vs 33/53 [62%], p < 0.0001), and had worse hyposmia on the University of Pennsylvania Smell Identification Test (UPSIT) (94/105 [90%] below 15th percentile vs 14/44 [32%], p < 0.0001). UPSIT percentile had the highest area under the curve (0.87, 95% CI 0.81-0.94) in predicting αSyn-SAA positivity and participants scoring at or below the 15th percentile of age and sex normative values had 18.3 times higher odds (95% CI 7.52-44.6) of having a positive αSyn-SAA test. Among 82 participants with longitudinal CSF samples, 81 (99%) had the same αSyn-SAA result for initial and follow-up specimens. DISCUSSION: A substantial proportion of clinically diagnosed participants with DLB had negative αSyn-SAA results. Hyposmia was the strongest clinical predictor of αSyn-SAA positivity. Hyposmia and αSyn-SAA may have utility in improving the diagnostic assessment of individuals with potential DLB. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that CSF αSyn-SAA distinguishes patients with clinically diagnosed DLB from normal controls.

Targeting Gut Microbiome With Prebiotic in Patients With CKD: The TarGut-CKD Study.

Introduction: Disruption of gut microbiota underpins some of the metabolic alterations observed in chronic kidney disease (CKD). Methods: In a nonrandomized, open-label, 3-phase pilot trial, with repeated measures within each phase, we examined the efficacy of oligofructose-enriched inulin (p-inulin) in changing the gut microbiome and their metabolic products in 15 patients with CKD. The stability of microbiome and metabolome was studied during the pretreatment phase (8 weeks), a p-inulin treatment phase (12 weeks), and a post treatment phase (8 weeks) of the study. Results: Study participants completed 373 of the 420 expected study visits (88.8%). Adherence to p-inulin was 83.4%. 16S rRNA sequencing was performed in 368 stool samples. A total of 1085 stool, urine, and plasma samples were subjected to untargeted metabolomic studies. p-inulin administration altered the composition of the gut microbiota significantly, with an increase in abundance of Bifidobacterium and Anaerostipes. Intersubject variations in microbiome and metabolome were larger than intrasubject variation, indicating the stability of the gut microbiome within each phase of the study. Overall metabolite compositions assessed by beta diversity in urine and stool metabolic profiles were significantly different across study phases. Several specific metabolites in stool, urine, and plasma were significant at false discovery rate (FDR) ≤ 0.1 over phase. Specifically, there was significant enrichment in microbial metabolites derived from saccharolysis. Conclusion: Results from our study highlight the stability of the gut microbiome and the expansive effect of p-inulin on microbiome and host cometabolism in patients with CKD. Findings from this study will enable rigorous design of microbiome-based intervention trials.

Professionalization of the public health workforce: scoping review and call to action.

BACKGROUND: The 'WHO-ASPHER Roadmap to Professionalizing the Public Health Workforce in the European Region' provides recommendations for strategic and systematic workforce planning around professionalization levers including: (i) competencies, (ii) training and education, (iii) formal organization, (iv) professional credentialing and (v) code of ethics and professional conduct as well as taxonomy and enumeration. It was based on a literature review till 2016. This scoping review aims to explore how the professionalization was documented in the literature between 2016 and 2022. METHODS: Following the Joanna Briggs Institute guidelines, we searched Medline via PubMed, Web of Science, ERIC via EBSCO and Google Scholar and included studies on professionalization levers. Four critical appraisal tools were used to assess qualitative, quantitative, mixed methods studies and grey literature. The PRISMA Extension for Scoping Reviews (PRISMA-ScR) was used for reporting. RESULTS: Eleven articles included in this review spanned 61 countries, targeting undergraduate, master's, doctoral degrees and continuing professional development. Most of these documents were reviews. About half provided a definition of the public health workforce; more than half covered the taxonomy and included information about competences, but the use of frameworks was sporadic and inconsistent. Formal organization and the necessity of a code of conduct for the public health workforce were acknowledged in only two studies. CONCLUSIONS: In spite of some efforts to professionalize the public health workforce, this process is fragmented and not fully recognized and supported. There is an urgent need to engage policymakers and stakeholders to prioritize investments in strengthening the public health workforce worldwide.

Seed amplification assay results illustrate discrepancy in Parkinson's disease clinical diagnostic accuracy and error rates.

Parkinson's disease (PD) may be misdiagnosed due to the clinical overlap between PD and atypical parkinsonism. The utility of α-Synuclein (αSyn) Seed Amplification Assay (SAA) as a diagnostic indicator for PD has been reported in numerous studies, but never when administered as a validated clinical laboratory test. This study compares results from αSyn-SAA validation testing performed using well-characterized cohorts from two biorepositories to better understand the accuracy of PD clinical diagnosis. Blinded cerebrospinal fluid (CSF) specimens from a repository that included cohorts of subjects clinically diagnosed as PD or healthy controls, both with confirmatory dopamine transporter single-photon emission computed tomography (DAT SPECT) imaging, and blinded CSF specimens from a repository that included cohorts of subjects clinically diagnosed as PD or healthy controls based on clinical diagnosis alone, were tested as part of the validation studies for the diagnostic αSyn-SAA test (SYNTap® Biomarker Test). Measured αSyn-SAA test accuracy was 83.9% using clinical diagnosis as comparator, and 93.6% using clinical diagnosis with confirmatory DAT- SPECT imaging as comparator. The statistically significant discordance between accuracy determinations using specimens classified using different diagnostic inclusion criteria indicates that there is some symbiosis between dopamine-weighted imaging and αSyn-SAA results, both of which are associated with higher accuracy compared with the clinical diagnosis alone.

Number of bottles of esophageal biopsies in the evaluation of eosinophilic esophagitis and clinical outcomes.

BACKGROUND: The number of bottles of esophageal biopsies needed for the evaluation of eosinophilic esophagitis (EoE) is unclear, despite cost differences. AIMS: Assess the clinical outcomes between patients with one and two bottles of esophageal biopsies for the assessment of EoE. METHODS: Retrospective study of adults who underwent esophagogastroduodenoscopy (EGD) for esophageal symptoms between January 2015 and June 2021 and findings of ≥15 eosinophils per high power field (eos/hpf). Patients with one bottle (1 bottle-EoE) had biopsies from the entire or proximal esophagus. Patients with two bottles had biopsies separated from the distal and proximal esophagus and were separated into those with ≥ 15 eos/hpf in both bottles (2 bottle Dif-EoE), or the distal bottle alone (2 bottle Lim-EoE). The primary outcomes were endoscopic findings at follow-up EGD as assessed by the Eosinophilic Esophagitis Endoscopic Reference Score (EREFS) and the presence of ≥15 eos/hpf. RESULTS: Of 85 patients with esophageal eosinophilia who met inclusion criteria, 49 had 2 bottle Dif-EoE, 18 had 2 bottle Lim-EoE, and 18 had 1 bottle-EoE. At median follow-up of 3.3-5.6 months, more patients with 1 bottle EoE had dysphagia (p = 0.029), however there were no differences in the EREFS (p = 0.14) or presence of ≥15 eos/hpf (p = 0.39). More patients with 2 bottle Dif-EoE were treated with topical steroids (16.3% vs. 0% vs. 0%, p = 0.039) and diet (20.4% vs. 0% vs. 5.6%, p = 0.05). CONCLUSION: Endoscopic and histologic outcomes were similar in patients who had one and two bottles for esophageal biopsies in the evaluation of EoE.

Comparison of incisional gastropexy with and without addition of two full-thickness stomach to body wall sutures.

OBJECTIVE: To compare complications between a modified incisional gastropexy (MIG) technique and standard incisional gastropexy (SIG). ANIMALS: 347 client-owned dogs. PROCEDURES: Dogs that had undergone SIG or MIG from March 2005 through April 2019 were identified through a medical record search of the University of Missouri Veterinary Health Center. The MIG technique is identical to SIG except 2 additional simple interrupted sutures are added, 1 cranial and 1 caudal to the continuous suture line, going full thickness into the stomach to ensure engagement of submucosa. Medical record information was used to identify intraoperative, postoperative, and short-term complications, and telephone or email communication to pet owners and/or referring veterinarians was used to identify complications (short-term and long-term) after discontinuance of care at the University of Missouri Veterinary Health Center. Intraoperative, postoperative, short-term, and long-term complications were analyzed in aggregate within 6 matched groupings: (1) gastropexy for gastric dilatation-volvulus, (2) prophylactic gastropexy without other procedures, (3) gastropexy with ovariohysterectomy, (4) gastropexy with castration, (5) gastropexy with splenectomy, and (6) gastropexy with celiotomy other than splenectomy. Overall rates of complications potentially attributed to gastropexy were compared between SIG and MIG using the Fisher exact test. Overall rates of complications not attributed to gastropexy were compared between SIG and MIG using the χ2 test. RESULTS: There were no significant differences in overall complication rates between SIG and MIG. CLINICAL RELEVANCE: Surgeons who feel that engagement of gastric submucosa is important for gastropexy success may use the MIG technique with minimal fear of complications. However, superiority of one technique over the other cannot be determined on the basis of this study.

Perspectives on implementing veterinary clinical studies committees.

To address the limitations of traditional IACUC review of clinical research studies involving client-owned animals, the AVMA issued a policy describing the use of a veterinary clinical studies committee (VCSC), analogous to an institutional review board, as a way to ensure the adequate review and oversight of such studies. While IACUC composition, review, approval processes, and responsibilities are well established, uniform guidance for VCSCs is not readily available and not included in the guidance for IACUCs. In this manuscript we describe suggested best practices for scientific and ethical review of veterinary clinical research studies, regardless of the specific research setting. This resource complements the AVMA policy mentioned above by providing additional thoughts on aspects of VCSCs, including considerations necessary for the adequate review and oversight of clinical research studies using client-owned animals by VCSCs or IACUCs.

Revolutionizing the Public Health Workforce-A Policy Brief in Retrospect of the World Congress on Public Health Rome 2020.

Background: The COVID-19 pandemic dramatically illustrates the consequences of inadequate prioritization of the Public Health Workforce (PHW). This Policy Brief introduces a Call for Action following the plenary session entitled "Revolutionising the Public Health Workforce (PHW) as Agents of Change" as part of the 2020 World Congress on Public Health. Policy Options and Recommendations: In order to revolutionize the PHW, five long-term key approaches are proposed: 1. Transforming public health competencies through transdisciplinary education and inter-professional training; 2. Revolutionizing educational systems by shifting the public health paradigm; 3. Linking public health education and work opportunities; 4. Overcoming the paradoxical shortage and overproduction of graduates and 5. Developing adaptable, multisectoral agents of change. Conclusion: Public health education of the future requires a paradigm shift towards a holistic understanding of public health, characterized by transdisciplinary education, inter-professional training and a closer integration of academia, health services, and communities.

Invited review: Selective treatment of clinical mastitis in dairy cattle.

Treatment of clinical mastitis (CM) and use of antimicrobials for dry cow therapy are responsible for the majority of animal-defined daily doses of antimicrobial use (AMU) on dairy farms. However, advancements made in the last decade have enabled excluding nonsevere CM cases from antimicrobial treatment that have a high probability of cure without antimicrobials (no bacterial causes or gram-negative, excluding Klebsiella spp.) and cases with a low bacteriological cure rate (chronic cases). These advancements include availability of rapid diagnostic tests and improved udder health management practices, which reduced the incidence and infection pressure of contagious CM pathogens. This review informed an evidence-based protocol for selective CM treatment decisions based on a combination of rapid diagnostic test results, review of somatic cell count and CM records, and elucidated consequences in terms of udder health, AMU, and farm economics. Relatively fast identification of the causative agent is the most important factor in selective CM treatment protocols. Many reported studies did not indicate detrimental udder health consequences (e.g., reduced clinical or bacteriological cures, increased somatic cell count, increased culling rate, or increased recurrence of CM later in lactation) after initiating selective CM treatment protocols using on-farm testing. The magnitude of AMU reduction following a selective CM treatment protocol implementation depended on the causal pathogen distribution and protocol characteristics. Uptake of selective treatment of nonsevere CM cases differs across regions and is dependent on management systems and adoption of udder health programs. No economic losses or animal welfare issues are expected when adopting a selective versus blanket CM treatment protocol. Therefore, selective CM treatment of nonsevere cases can be a practical tool to aid AMU reduction on dairy farms.

Current and Emerging Diagnostic Approaches to Bacterial Diseases of Ruminants.

The diagnostic approaches and methods to detect bacterial pathogens in ruminants are discussed, with a focus on cattle. Conventional diagnostic methods using culture, isolation, and characterization are being replaced or supplemented with new methods. These include molecular diagnostics such as real-time polymerase chain reaction and whole-genome sequencing. In addition, methods such as matrix-assisted laser desorption ionization-time-of-flight mass spectrometry enable rapid identification and enhanced pathogen characterization. These emerging diagnostic tools can greatly enhance the ability to detect and characterize pathogens, but performance and interpretation vary greatly across sample and pathogen types, disease syndromes, assay performance, and other factors.

Core competencies in applied infectious disease epidemiology: a framework for countries in Europe.

In 2009, the European Centre for Disease Prevention and Control (ECDC) developed a competency framework to support European Union countries and the European Commission in ensuring a competent public health workforce for Europe. The coronavirus disease (COVID-19) pandemic emphasised the importance of harmonised public health strategies and competencies across international boundaries, specifically for infectious diseases. This perspective presents the process to update the competency framework for applied infectious disease epidemiology, highlighting ECDC's efforts to support countries with using the framework. ECDC commissioned the Association of Schools of Public Health in the European Region (ASPHER) to update the framework through publication and dissemination of a technical report and a self-assessment tool linked to training resources. A mixed methods approach to gather input from experts in relevant specialities included qualitative interviews with 42 experts, workshops with ECDC Technical Advisory Group and an online survey of 212 public health professionals across Europe and beyond. Modifications resulted in 157 core competencies in 23 domains, each mapping to one of six subject areas of importance in applied infectious disease epidemiology. The framework serves as a basis to update the curriculum of the ECDC Fellowship programme with two alternative paths: intervention epidemiology or public health microbiology.

Study protocol of a randomized controlled trial of fistula vs. graft arteriovenous vascular access in older adults with end-stage kidney disease on hemodialysis: the AV access trial.

BACKGROUND: Treatment of end-stage kidney disease (ESKD) with hemodialysis requires surgical creation of an arteriovenous (AV) vascular access-fistula (AVF) or graft (AVG)-to avoid (or limit) the use of a central venous catheter (CVC). AVFs have long been considered the first-line vascular access option, with AVGs as second best. Recent studies have suggested that, in older adults, AVGs may be a better strategy than AVFs. Lacking evidence from well-powered randomized clinical trials, integration of these results into clinical decision making is challenging. The main objective of the AV Access Study is to compare, between the two types of AV access, clinical outcomes that are important to patients, physicians, and policy makers. METHODS: This is a prospective, multicenter, randomized controlled trial in adults ≥ 60 years old receiving chronic hemodialysis via a CVC. Eligible participants must have co-existing cardiovascular disease, peripheral arterial disease, and/or diabetes mellitus; and vascular anatomy suitable for placement of either type of AV access. Participants are randomized, in a 1:1 ratio, to a strategy of AVG or AVF creation. An estimated 262 participants will be recruited across 7 healthcare systems, with average follow-up of 2 years. Questionnaires will be administered at baseline and semi-annually. The primary outcome is the rate of CVC-free days per 100 patient-days. The primary safety outcome is the cumulative incidence of vascular access (CVC or AV access)-related severe infections-defined as access infections that lead to hospitalization or death. Secondary outcomes include access-related healthcare costs and patients' experiences with vascular access care between the two treatment groups. DISCUSSION: In the absence of studies using robust and unbiased research methodology to address vascular access care for hemodialysis patients, clinical decisions are limited to inferences from observational studies. The goal of the AV Access Study is to generate evidence to optimize vascular access care, based on objective, age-specific criteria, while incorporating goals of care and patient preference for vascular access type in clinical decision-making. TRIAL REGISTRATION: This study is being conducted in accordance with the tenets of the Helsinki Declaration, and has been approved by the central institutional review board (IRB) of Wake Forest University Health Sciences (approval number: 00069593) and local IRB of each participating clinical center; and was registered on Nov 27, 2020, at ClinicalTrials.gov (NCT04646226).