Acceptable performance of blood biomarker tests of amyloid pathology - recommendations from the Global CEO Initiative on Alzheimer's Disease.

Anti-amyloid treatments for early symptomatic Alzheimer disease have recently become clinically available in some countries, which has greatly increased the need for biomarker confirmation of amyloid pathology. Blood biomarker (BBM) tests for amyloid pathology are more acceptable, accessible and scalable than amyloid PET or cerebrospinal fluid (CSF) tests, but have highly variable levels of performance. The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to consider the minimum acceptable performance of BBM tests for clinical use. Amyloid PET status was identified as the reference standard. For use as a triaging test before subsequent confirmatory tests such as amyloid PET or CSF tests, the BBM Workgroup recommends that a BBM test has a sensitivity of ≥90% with a specificity of ≥85% in primary care and ≥75-85% in secondary care depending on the availability of follow-up testing. For use as a confirmatory test without follow-up tests, a BBM test should have performance equivalent to that of CSF tests - a sensitivity and specificity of ~90%. Importantly, the predictive values of all biomarker tests vary according to the pre-test probability of amyloid pathology and must be interpreted in the complete clinical context. Use of BBM tests that meet these performance standards could enable more people to receive an accurate and timely Alzheimer disease diagnosis and potentially benefit from new treatments.

Complication rates rise with age and Haller index in minimally invasive correction of pectus excavatum: A high-volume, single-center retrospective cohort study.

OBJECTIVES: The study objectives were to describe the compounded complication rate of minimally invasive repair of pectus excavatum, identify predisposing risk factors, and evaluate the optimal timing of correction. Minimally invasive repair of pectus excavatum is the standard treatment for pectus excavatum and consists of 2 invasive procedures, for example, correction with bar insertion followed by bar removal after 2 to 3 years. METHODS: A retrospective cohort study identifying children, adolescents, and adults of both genders corrected for pectus excavatum with minimally invasive repair of pectus excavatum between 2001 and 2022. Information on complications related to bar insertion and removal procedures for each individual patient was compiled into a compounded complication rate. Complication severities were categorized according to the Clavien-Dindo classification. RESULTS: A total of 2013 patients were corrected by minimally invasive repair of pectus excavatum with a median age (interquartile range) for correction of 16.6 (5) years. Overall compounded complication rate occurred at a frequency of 16.4%, of which 9.3% required invasive reinterventions (Clavien-Dindo classification ≥IIIa). The complication rate related to bar insertion was 2.6-fold higher compared with bar removal (11.8% vs 4.5%, respectively). Multivariable analysis revealed age (adjusted odds ratio, 1.05; P < .001), precorrection Haller Index (adjusted odds ratio, 1.10; P < .033), and early-phase institutional experience (adjusted odds ratio, 1.59; P < .002) as independent predisposing risk factors. The optimal age of correction was 12 years, and the compounded complication rate correlated exponentially with age with a doubling time of 7.2 years. Complications increased 2.2-fold when the Haller index increased to 5 or more units. CONCLUSIONS: Minimally invasive repair of pectus excavatum is associated with a high compounded complication rate that increases exponentially with age and high Haller Index. Consequently, we recommend repair during late childhood and early adolescence, and emphasize the importance of informing patients and relatives about the significant risks of adult correction as well as the need of 2 consecutive procedures taking the complication profile into account before planning surgery.

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.

Impact of Levothyroxine on Lipid Profile in Patients with Hypothyroidism.

Hypothyroidism is a common endocrine disorder and requires lifelong treatment. Hypothyroidism is often associated with dyslipidemia in some populations. The present study was designed to evaluate the impact of levothyroxine (LT4) on lipid profile in hypothyroid patients. This cross-sectional analytical study was conducted in the Department of Pharmacology & Therapeutics, Rajshahi Medical College in collaboration with the Institute of Nuclear Medicine and Allied Sciences (INMAS), Rajshahi from July 2018 to June 2019 to compare serum total cholesterol (TC), serum triglyceride (TG), serum LDL-C and serum HDL-C levels among euthyroids, newly diagnosed hypothyroid patients and levothyroxine (LT4) treated hypothyroid patients. A total of 30 patients with newly diagnosed hypothyroidism and an equal number of age-matched healthy controls (n=30, control group) of both sexes were recruited in the present study. Thirty (30) hypothyroid patients were reevaluated after 6 month of LT4 therapy. The fasting blood samples were collected from the subjects for the estimation of lipid profile. Significantly higher values were observed in total cholesterol (TC) 198.5±19.2mg/dl, triglycerides (TG) 147.0±14.5mg/dl, low density lipoprotein cholesterol (LDL-C) 133.9±19.7mg/dl (p<0.001) and a significant decreased value was seen in high density lipoprotein-cholesterol (HDL-C) levels (35.1±3.67mg/dl) in newly diagnosed hypothyroid patients as compared to after LT4 therapy and normal healthy individuals (p=0.009). These observations suggest that people with hypothyroidism have high risk of development of atherosclerosis which may lead to coronary heart diseases (CHD) due to persistent dyslipidemia. Hypothyroidism induces dyslipidemia or expedites the process of existing dyslipidemia, LT4 therapy corrects it to a significant level thus reduce the risk for atherosclerosis.

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.

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.

Feasibility of and experience using a portable MRI scanner in the neonatal intensive care unit.

OBJECTIVE: A portable, low-field MRI system is now Food and Drug Administration cleared and has been shown to be safe and useful in adult intensive care unit settings. No neonatal studies have been performed. The objective is to assess our preliminary experience and assess feasibility of using the portable MRI system at the bedside in a neonatal intensive care unit (NICU) at a quaternary children's hospital. STUDY DESIGN: This was a single-site prospective cohort study in neonates ≥2 kg conducted between October and December 2020. All parents provided informed consent. Neonates underwent portable MRI examination in the NICU with support equipment powered on and attached to the neonate during the examination. A paediatric radiologist interpreted each portable MRI examination. The study outcome variable was percentage of portable MRI examinations completed without artefacts that would hinder diagnosis. Findings were compared between portable MRI examinations and standard of care examinations. RESULTS: Eighteen portable, low-field MRI examinations were performed on 14 neonates with an average age of 29.7 days (range 1-122 days). 94% (17 of 18) of portable MRI examinations were acquired without significant artefact. Significant intracranial pathology was visible on portable MRI, but subtle abnormalities were missed. The examination reads were concordant in 59% (10 of 17) of cases and significant pathology was missed in 12% (2 of 17) of cases. CONCLUSION: This single-centre series demonstrated portable MRI examinations can be performed safely with standard patient support equipment present in the NICU. These findings demonstrate that portable MRI could be used in the future to guide care in the NICU setting. TRIAL REGISTRATION NUMBER: NCT04629469.

Great diversity of KSα sequences from bat-associated microbiota suggests novel sources of uncharacterized natural products.

Polyketide synthases (PKSs) are multidomain enzymes in microorganisms that synthesize complex, bioactive molecules. PKS II systems are iterative, containing only a single representative of each domain: ketosynthase alpha (KS[Formula: see text]), ketosynthase beta and the acyl carrier protein. Any gene encoding for one of these domains is representative of an entire PKS II biosynthetic gene cluster (BGC). Bat skin surfaces represent an extreme environment prolific in Actinobacteria that may constitute a source for bioactive molecule discovery. KS[Formula: see text] sequences were obtained from culturable bacteria from bats in the southwestern United States. From 467 bat bacterial isolates, we detected 215 (46%) had KS[Formula: see text] sequences. Sequencing yielded 210 operational taxonomic units, and phylogenetic placement found 45 (21%) shared <85% homology to characterized metabolites. Additionally, 16 Actinobacteria genomes from the bat microbiome were analyzed for biosynthetic capacity. A range of 69-93% of the BGCs were novel suggesting the bat microbiome may contain valuable uncharacterized natural products. Documenting and characterizing these are important in understanding the susceptibility of bats to emerging infectious diseases, such as white-nose syndrome. Also noteworthy was the relationship between KS [Formula: see text] homology and total BGC novelty within each fully sequenced strain. We propose amplification and detection of KS[Formula: see text] could predict a strain's global biosynthetic capacity.

Epidural analgesia and abnormal coagulation in patients undergoing minimal invasive repair of pectus excavatum.

Background: Epidural analgesia (EA) is effective in patients undergoing minimal invasive repair of pectus excavatum (MIRPE) but is associated with major complications such as epidural hematomas. It is recommended to assess coagulation status in patients receiving anticoagulant therapy prior to EA, although no consensus exists in patients without a history of bleeding tendency or anticoagulant therapy. Thus, the aim of this paper was to assess 1) the prevalence of abnormal routine coagulation parameters, i.e., international normalized ratio (INR) and platelet count, and 2) the safety of EA in patients undergoing MIRPE. Methods: In this retrospective study, we identified 1,973 patients undergoing MIRPE at our center between 2001 and 2019. Complications related to EA were registered for all patients. Information on coagulation parameters was present in 929 patients. Patients with spontaneously elevated INR ≥1.5 were referred for assessment of coagulation factor VII in order to assess the cause of the elevated INR. Results: Of 929 patients with coagulation information available, 18 patients had spontaneously elevated INR ≥1.5 (1.9%). In patients with INR ≥1.5, 12 patients underwent further assessment of factor VII, with all patients having a slightly reduced factor VII close to the lower reference range. The majority of the 1,973 patients undergoing MIRPE received EA (99.6%) with very low complication rates (0.2%) and no incidence of epidural hematomas. Conclusion: In patients undergoing MIRPE, coagulation screening prior to EA should not be mandatory as it revealed no clinically relevant consequences. EA is safe with very low complication rates.

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.

Three-Jaw Chuck Pinch Strength and its Correlation with Hand Depth in Electronics Technicians.

The three jaw chuck pinch is a variety of pinch technique where thumb opposes both middle and index fingers. Pinch strength is generally influenced by the health status and level of physical activity of a person. The present study was conducted to measure the correlation of three-jaw chuck pinch strength with hand depth in electronics technicians working in Dhaka Metropolitan City. The data obtained from the study may be used as a base line for other professions as well as for research in our country. This cross sectional, analytical study was carried out in the department of Anatomy, Dhaka Medical College, Dhaka, Bangladesh from July 2015 to June 2016 on 100 adults male electronics technicians and 100 adult sedentary workers. Electronics technicians were considered as case group and sedentary workers were considered as control group. Case group was further subdivided according to their working experiences. Study subjects were selected by convenient purposive sampling technique. Hand depth was measured by digital slide calipers and pinch gauge was used to measure the three-jaw chuck pinch strength. The mean three-jaw chuck pinch strength was significantly higher (p<0.05) in case group than in the control group. Significant difference were also observed between case group and control group in the mean hand depth (p<0.05). Mean hand depth was greater in case group than that of control group. Three-jaw chuck pinch strength showed significant positive correlation with hand depth in case group. Case group was further subdivided according to their working experiences, the mean three-jaw chuck pinch strength and hand depth was significantly higher (p<0.05) in more working experience group than in less working experience group. Three-jaw chuck pinch strength showed significant positive correlation with hand depth.

Combined use of the ketogenic diet and vagus nerve stimulation in pediatric drug-resistant epilepsy.

Objective: Patients with drug-resistant epilepsy (DRE) pose considerable management challenges for patients, their families, and providers. Both the vagus nerve stimulator (VNS) and the ketogenic diet (KD) have been shown to be safe and effective in treating DRE. Nevertheless, information is lacking regarding treatment with combination of both modalities. This study reports the efficacy and tolerability of combining VNS and KD in a pediatric cohort with intractable epilepsy. Methods: This is a retrospective review of 33 patients (0-17 years) with DRE treated with VNS and KD at a single pediatric level IV epilepsy center. We compared seizure reduction rates for each patient at baseline and at every clinic visit for 24 months after adding the second nonpharmacological therapy. The frequency of adverse events on the combined therapy was collected to assess safety and tolerability. Results: There were a total of 170 visits for all patients while on the combined therapy. At 88% (95% CI: 83%-93%) of the visits, patients reported some reduction in seizure frequency. The proportion of patients reporting a greater than 50% seizure reduction over all visits was 62% (95% CI: 55%-69%). The proportion of a patient's visits with at least a greater than 50% reduction in seizure frequency had a median of 71% (IQR 33%-100%). Continued improvement was seen over time of combined treatment; for every one-unit time unit change (one month), there was a 6% increase in the odds of having a reduction in seizure frequency of >50% (OR = 1.06, 95% CI: 1.01-1.11). Significance: This study shows that combining the VNS and KD in patients with drug-resistant epilepsy is well tolerated and reduces seizure frequency more than either one modality used alone and that the benefits in terms of seizure reduction continue to increase with the length of treatment.

Effectiveness of an adaptive eLearning intervention on dental students' learning in comparison to traditional instruction.

There is a great deal of excitement in higher education about the value of adaptive learning to personalize learning paths according to students' individual needs. The authors explored the impact of an Adaptive Learning Platform (ALP) on learning, by comparing learning effectiveness between dental students who used the ALP in a blended learning environment formatively and summatively compared with students who did not use the ALP (i.e., face-to-face), as measured by students' performance on the final exam in a single review preparatory course during the academic years 2013-2018. Paired t-tests showed significant improvement in post-test scores across different course instructional modalities (P < 0.01). The learning gain was greater for students who studied using the ALP summatively (t = 26.20) than those who used it formatively or studied using a face-to-face format (t = 13.10 and 14.13, respectively). Controlling for pre-test scores, analysis of covariance tests indicate that: (1) intervention groups (formative and summative ALP) scored significantly higher than the traditional group (B = 9.34 points, P < 0.01, for summative ALP group) and (B = 4.47 points, P < 0.05, for formative ALP group), and (2) summative ALP group scored significantly higher than formative ALP group (B = 4.84 points, P < 0.05). This study provides empirical evidence that an adaptive learning intervention can have a significant impact on student learning performance. The success of any adaptive learning system relies mainly on sound instructional design. Technology will continue to grow at an overwhelming pace; the cautionary note the authors highlight is that conceptions of pedagogy, complemented by technology, must guide the development of adaptive learning systems.