Recommendations for clinical implementation of blood-based biomarkers for Alzheimer's disease.

Blood-based biomarkers (BBM) for Alzheimer's disease (AD) are being increasingly used in clinical practice to support an AD diagnosis. In contrast to traditional diagnostic modalities, such as amyloid positron emission tomography and cerebrospinal fluid biomarkers, BBMs offer a more accessible and lower cost alternative for AD biomarker testing. Their unique scalability addresses the anticipated surge in demand for biomarker testing with the emergence of disease-modifying treatments (DMTs) that require confirmation of amyloid pathology. To facilitate the uptake of BBMs in clinical practice, The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to provide recommendations for two clinical implementational pathways for BBMs: one for current use for triaging and another for future use to confirm amyloid pathology. These pathways provide a standardized diagnostic approach with guidance on interpreting BBM test results. Integrating BBMs into clinical practice will simplify the diagnostic process and facilitate timely access to DMTs for eligible patients.

The Impact of Simulation Based Training on the Fundamentals of Endoscopic Surgery Performance Examination.

OBJECTIVE: To determine if simulation training is required to pass the FES skills test and assess the relationship between simulation training, clinical training, and FES skills test performance. SUMMARY OF BACKGROUND DATA: The ABS began requiring completion of the Flexible Endoscopy Curriculum for all applicants beginning in 2018. The role of simulation-based training in FES skills test performance after this requirement has not been evaluated. METHODS: De-identified data from the initial FES skills tests after the Flexible Endoscopy Curriculum requirement was reviewed, and 731 unique participants with reported simulation experience demographics were identified. Self-reported data included sex, upper (UE) and lower (LE) endoscopy experience, and simulator training hours (SE). Final FES skills exam scores and pass/fail designations for each participant were reported by the FES program staff. RESULTS: There was a statistically discernible difference in mean FES total scores between those reporting no SE and more experienced groups ( P = 0.002), and between less and more experienced UE and LE groups ( P < 0.001). There was no statistically discernible difference in FES skills exam pass rates between SE groups ( P = 0.2), but there was a strong relationship between clinical experience (UE & LE) and pass rate ( P < 0.001). Finally, on logistic regression analysis, LE was a discernible predictor of passing [odds ratio (OR) = 1.4, 95% confidence interval (CI) 1.1-1.8, P = 0.02], while UE [odds ratio (OR) = 1, 95% CI 0.8-1.3, P = 0.9] and SE (OR = 1,95% CI 0.9- 1.3, P = 0.7) were not. CONCLUSIONS: There is no threat to the validity of the FES skills test from a need for simulation training to pass the FES skills test. Similarly, the amount of simulation practice is not predictive of passing, but can improve performance on certain FES tasks.

The Mycobiome of Bats in the American Southwest Is Structured by Geography, Bat Species, and Behavior.

Bats are widespread mammals that play key roles in ecosystems as pollinators and insectivores. However, there is a paucity of information about bat-associated microbes, in particular their fungal communities, despite the important role microbes play in host health and overall host function. The emerging fungal disease, white-nose syndrome, presents a potential challenge to the bat microbiome and understanding healthy bat-associated taxa will provide valuable information about potential microbiome-pathogen interactions. To address this knowledge gap, we collected 174 bat fur/skin swabs from 14 species of bats captured in five locations in New Mexico and Arizona and used high-throughput sequencing of the fungal internal transcribed (ITS) region to characterize bat-associated fungal communities. Our results revealed a highly heterogeneous bat mycobiome that was structured by geography and bat species. Furthermore, our data suggest that bat-associated fungal communities are affected by bat foraging, indicating the bat skin microbiota is dynamic on short time scales. Finally, despite the strong effects of site and species, we found widespread and abundant taxa from several taxonomic groups including the genera Alternaria and Metschnikowia that have the potential to be inhibitory towards fungal and bacterial pathogens.

Clinical research in dementia: A perspective on implementing innovation.

The increasing global prevalence of dementia demands concrete actions that are aimed strategically at optimizing processes that drive clinical innovation. The first step in this direction requires outlining hurdles in the transition from research to practice. The different parties needed to support translational processes have communication mismatches; methodological gaps hamper evidence-based decision-making; and data are insufficient to provide reliable estimates of long-term health benefits and costs in decisional models. Pilot projects are tackling some of these gaps, but appropriate methods often still need to be devised or adapted to the dementia field. A consistent implementation perspective along the whole translational continuum, explicitly defined and shared among the relevant stakeholders, should overcome the "research-versus-adoption" dichotomy, and tackle the implementation cliff early on. Concrete next steps may consist of providing tools that support the effective participation of heterogeneous stakeholders and agreeing on a definition of clinical significance that facilitates the selection of proper outcome measures.

A roadmap to advance delirium research: Recommendations from the NIDUS Scientific Think Tank.

Delirium is an acute disorder of attention and cognition. It occurs across the life span, yet it is particularly common among older adults, and is closely linked with underlying neurocognitive disorders. Evidence is mounting that intervening on delirium may represent an important opportunity for delaying the onset or progression of dementia. To accelerate the current understanding of delirium, the Network for Investigation of Delirium: Unifying Scientists (NIDUS) held a conference "Advancing Delirium Research: A Scientific Think Tank" in June 2019. This White Paper encompasses the major knowledge and research gaps identified at the conference: advancing delirium definition and measurement, understanding delirium pathophysiology, and prevention and treatment of delirium. A roadmap of research priorities is proposed to advance the field in a systematic, interdisciplinary, and coordinated fashion. A call is made for an international consortium and biobank targeted to delirium, as well as a public health campaign to advance the field.

The cholinergic system in the pathophysiology and treatment of Alzheimer's disease.

Cholinergic synapses are ubiquitous in the human central nervous system. Their high density in the thalamus, striatum, limbic system, and neocortex suggest that cholinergic transmission is likely to be critically important for memory, learning, attention and other higher brain functions. Several lines of research suggest additional roles for cholinergic systems in overall brain homeostasis and plasticity. As such, the brain's cholinergic system occupies a central role in ongoing research related to normal cognition and age-related cognitive decline, including dementias such as Alzheimer's disease. The cholinergic hypothesis of Alzheimer's disease centres on the progressive loss of limbic and neocortical cholinergic innervation. Neurofibrillary degeneration in the basal forebrain is believed to be the primary cause for the dysfunction and death of forebrain cholinergic neurons, giving rise to a widespread presynaptic cholinergic denervation. Cholinesterase inhibitors increase the availability of acetylcholine at synapses in the brain and are one of the few drug therapies that have been proven clinically useful in the treatment of Alzheimer's disease dementia, thus validating the cholinergic system as an important therapeutic target in the disease. This review includes an overview of the role of the cholinergic system in cognition and an updated understanding of how cholinergic deficits in Alzheimer's disease interact with other aspects of disease pathophysiology, including plaques composed of amyloid-ß proteins. This review also documents the benefits of cholinergic therapies at various stages of Alzheimer's disease and during long-term follow-up as visualized in novel imaging studies. The weight of the evidence supports the continued value of cholinergic drugs as a standard, cornerstone pharmacological approach in Alzheimer's disease, particularly as we look ahead to future combination therapies that address symptoms as well as disease progression.

Prevalence of prescription errors in general practice in Jeddah, Saudi Arabia.

PURPOSE: Prescription errors are a common cause of adverse drug events (ADEs). Recognizing ADEs can significantly contribute to the reduction of morbidity and mortality. This study aims to investigate the type and prevalence of errors in prescription writing, directed toward a needs assessment for developing educational interventions. MATERIALS AND METHODS: A cross-sectional descriptive study was conducted in Jeddah community pharmacies (January-February 2016). A random sample of 117 prescriptions were reviewed and analyzed by community pharmacists for legibility and omission of the information in the prescription. RESULTS: Results revealed that 51% of the prescriptions included diagnosis, in which 62% included the recommended drug dosage. Only 7% of drug interactions were reported between the prescribed drugs, 17% of the physicians prescribed drugs that prevented the adverse effects used for diagnosis. Prescriptions for chronic conditions were scrutinized to be 18%. It was noteworthy that 29% of the pharmacists reported difficulty in reading the handwriting of prescriptions. CONCLUSIONS: The quality of prescription writing is deficient in some elements and strategies for improvement are needed. These findings underscore a crucial requirement to upgrade the quality of prescription writing by encouraging continuous medical education programs to facilitate delivery of excellent therapeutic outcomes.

Leprosy reactions in postelimination stage: the Bangladesh experience.

BACKGROUND: Leprosy reactions are immunologically mediated conditions and a major cause of disability before, during and after multidrug therapy (MDT). Little data have been published on the epidemiology of leprosy reactions in Bangladesh. OBJECTIVES: To describe the pattern and prevalence of leprosy reactions in the postelimination stage. METHODS: A descriptive retrospective cross-sectional study was carried out in Chittagong Medical College Hospital using the registered records of patients in the period between 2004 and 2013. RESULTS: Of the 670 patients with leprosy, 488 (73.38%) were males and 182 (27.37%) were females. The prevalence of reaction was in 300 (44.78%) patients with a male:female ratio of 3.55 : 1. The age-specific cumulative reaction cases at >40 years were 115 (38.33%) among all age groups. The prevalence of reaction was found to be in 166 (55.33%) patients for the reversal reaction, 49 (16.57%) for the erythema nodosum leprosum (ENL) and 85 (28.33%) for the neuritis. Borderline tuberculoid was most common (106, 35.33%)in the reversal reaction group, while lepromatous leprosy was most common (37, 12.33%) in ENL group. More than half of the patients (169, 56.33%) had reactions at the time of presentations, while 85 (28.33%) and 46 (15.33%) patients developed reaction during and after MDT, respectively. The reversal reaction group presented with ≥six skin lesions in 96 (57.83%) patients and ≥two nerve function impairments (NFIs) in 107 (64.46%) patients. The ENL was present chiefly as papulo-nodular lesions in 45 (91.84%) patients followed by pustule-necrotic lesions in four (8.16%), neuritis in 33 (67.35%), fever in 24 (48.98%), lymphadenitis in six (12.24%), arthritis in five (10.20%) and iritis in two (4.08%). Bacterial index ≥3 had been demonstrated in 34 (60.71%) patients in ENL group. CONCLUSION: The incidence of leprosy reaction seemed to be more than three times common in borderline tuberculoid (52.33%) group than in lepromatous leprosy (14%) group. Reactions with NFI and disability still occur among multibacillary patients during and after MDT. Early detection and management of leprosy reaction are very important in preventing disability and deformity, and patients should be educated to undergo regular follow-up examinations. Developing reinforced new therapies to curb leprosy reactions is crucial for improving leprosy healthcare services.

Master's degrees: Meeting the standards for medical and health professions education.

Increasing numbers of educators are finding it necessary to obtain advanced training in medical and health professions education. This demand has been met by a wide variety of postgraduate courses. In this Guide, we present an international consensus statement of the standards to which Master's courses in medical and health professions education should aspire.

Patients come from populations and populations contain patients. A two-stage scientific and ethics review: The next adaptation for single institutional review boards.

INTRODUCTION: For nearly 50 years, institutional review boards (IRB) and independent ethics committees have featured local oversight as a core function of research ethics reviews. However growing complexity in Alzheimer's clinical research suggests current approaches to research volunteer safety is hampering development of new therapeutics. As a partial response to this challenge, the NIH has mandated that all NIH-funded multi-site studies will use a single Institutional Review Board. The perspective describes a joint program to provide a single IRB of record (sIRB) for phases of multi-site studies. METHODS: The approach follows two steps. One, an expert Scientific Review Committee (SRC) of senior researchers in the field will conduct the review principally of scientific merit, significance, feasibility, and the likelihood of meaningful results. The second step will be the IRB's regulatory and ethics review. The IRB will apply appropriate regulatory criteria for approval including minimization of risks to subjects and risks reasonable in relation to anticipated benefits, equitable subject selection, informed consent, protections for vulnerable populations, and application of local context considerations, among others. RESULTS: There is a steady demand for scientific, ethical and regulatory review of planned Alzheimer's studies. As of January 15, 2017, there are nearly 400 open studies, Phase II and III, industry and NIH sponsored trials on disease indications affecting memory, movement and mood in the US. CONCLUSIONS: The effort will initially accept protocols for studies of Alzheimer's disease, dementia, and related disorders effecting memory, movement and mood. Future aims will be to provide scientific review and, where applicable, regulatory and ethical review in an international context outside North America with sites possibly in Asia, Europe and Australia.

WITHDRAWN: Revisiting the cholinergic hypothesis in Alzheimer's disease: Emerging evidence from translational and clinical research.

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2014 Report on the Milestones for the US National Plan to Address Alzheimer's Disease.

With increasing numbers of people with Alzheimer's and other dementias across the globe, many countries have developed national plans to deal with the resulting challenges. In the United States, the National Alzheimer's Project Act, signed into law in 2011, required the creation of such a plan with annual updates thereafter. Pursuant to this, the US Department of Health and Human Services (HHS) released the National Plan to Address Alzheimer's Disease in 2012, including an ambitious research goal of preventing and effectively treating Alzheimer's disease by 2025. To guide investments, activities, and the measurement of progress toward achieving this 2025 goal, in its first annual plan update (2013) HHS also incorporated into the plan a set of short, medium and long-term milestones. HHS further committed to updating these milestones on an ongoing basis to account for progress and setbacks, and emerging opportunities and obstacles. To assist HHS as it updates these milestones, the Alzheimer's Association convened a National Plan Milestone Workgroup consisting of scientific experts representing all areas of Alzheimer's and dementia research. The workgroup evaluated each milestone and made recommendations to ensure that they collectively constitute an adequate work plan for reaching the goal of preventing and effectively treating Alzheimer's by 2025. This report presents these Workgroup recommendations.

Cadaver study of the volume of the ovary in Bangladeshi women.

Reproductive age, ovarian reserve and reproductive capability may be determined from the volume of the ovary. A cross-sectional, descriptive study was done in the Department of Anatomy, Dhaka Medical College, Dhaka, from January to December 2009, to see the variation in the volume of the ovary with age in Bangladeshi women. The study was performed on 140 post mortem human ovaries collected from 70 unclaimed female dead bodies which were in the morgue under examination in the Department of Forensic Medicine, Dhaka Medical College, Dhaka. The samples were divided into three age-groups including group A (10-13 years), group B (1445 years) & group C (46-52 years). Group A is pre-menarche group, group B represents reproductive age and group C is post menopausal group. The length, breadth and thickness of each ovary were measured by using a slide calipers. Then the volume of each ovary was determined by the product of its length, breadth and thickness multiplied by 0.524, according to the Prolate ellipsoid formula. The mean volume of the right ovary was found higher than that of the left one in all age groups (p < 0.001). The difference in mean volume of the ovary between group A & group B, group B & group C (p < 0.001) and group A & group C (p < 0.01) were also statistically significant. The volume of the ovary increases with age and then gradually starts to decrease from menopause.

The Return of Biomarker Results in Research: Balancing Complexity, Precision, and Ethical Responsibility.

Recent research aimed at the discovery, integration, and communication of health outcome measures (or "biomarkers") in Alzheimer's disease has raised challenging questions related to whether, how and when results from these investigations should be disclosed to research participants. Reflecting the apparent heterogeneity of many neurodegenerative diseases, biomarker or other risk factor results are often probabilistic, interactive, multi-modal, and selective. Such characteristics make it very complex to summarize and communicate to clinicians, researchers, and research participants. Whereas the format and content of academic literature is well-managed by the peer-review process, reporting individualized results to participants involves complex, sensitive, and ethical considerations. This paper describes three key factors to consider in decisions about the return of results to research participants: complexity, precision, and responsibility. The paper also presents six practical recommendations for implementing meaningful and ethical communication with research participants.