Mortality and Function After Hip Fracture or Pneumonia in People With and Without Dementia.

Background: The extent to which disruptive surgical or medical events impact mortality and function is critical for anticipatory planning and informing goal-aligned care.

Methods: Using Health and Retirement Study data (2008-2018), we employed propensity score matching to compare the impact of hospitalization for hip fracture (a surgical event) or pneumonia (a medical event) among people with dementia to two groups: (1) people with dementia who did not experience these events; and (2) people without dementia who experienced an event. Dementia status was determined using validated cognitive assessments (Hurd method); hip fracture and pneumonia were identified from Medicare claims.

Mortality and Function After Widowhood Among Older Adults With Dementia, Cancer, or Organ Failure.

Importance: The widowhood effect, in which mortality increases and function decreases in the period following spousal death, may be heightened in older adults with functional impairment and serious illnesses, such as cancer, dementia, or organ failure, who are highly reliant on others, particularly spouses, for support. Yet there are limited data on widowhood among people with these conditions.

Objective: To determine the association of widowhood with function and mortality among older adults with dementia, cancer, or organ failure.

Soluble biomarkers for Neuromyelitis Optica Spectrum Disorders: a mini review.

The Neuromyelitis Optica Spectrum Disorders (NMOSD) constitute a spectrum of rare autoimmune diseases of the central nervous system characterized by episodes of transverse myelitis, optic neuritis, and other demyelinating attacks. Previously thought to be a subtype of multiple sclerosis, NMOSD is now known to be a distinct disease with unique pathophysiology, clinical course, and treatment options. Although there have been significant recent advances in the diagnosis and treatment of NMOSD, the field still lacks clinically validated biomarkers that can be used to stratify disease severity, monitor disease activity, and inform treatment decisions.

A case of immunotherapy-responsive autoimmune hemichorea.

Introduction: Subacute adult-acquired hemichorea is a striking presentation with a broad differential, including ischemic, metabolic, and inflammatory causes.

Case: We encountered a 74-year-old woman with rapid onset of hemichorea and associated encephalopathy. Following a thorough workup without identification of clear imaging or laboratory abnormalities, we empirically treated with IVIg.

Dissemination and implementation of clinical practice guidelines: a longitudinal, mixed-methods evaluation of the Canadian Task Force on Preventive Health Care's knowledge translation efforts.

Background: The Canadian Task Force on Preventive Health Care (task force) develops evidence-based preventive health care guidelines and knowledge translation (KT) tools to facilitate guideline dissemination and implementation. We aimed to determine practitioners' awareness of task force guidelines and KT tools and explore barriers and facilitators to their use.

Methods: The task force's KT team completed annual evaluations using surveys and interviews with primary care providers in Canada from 2014 to 2020, to assess practitioners' awareness and determinants of use of task force guidelines and tools.

The impact of vaccination status on importation of COVID-19 among international travellers.

Governments worldwide are looking for ways to safely enable international travel while mitigating the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated coronavirus disease 2019 (COVID-19). However, few data describe the impact of vaccination on importation of COVID-19. We took advantage of the sequential introduction of two government policies in Canada to evaluate the real-world evidence of vaccine effectiveness among 30,361 international travellers arriving by air in Alberta, Canada.

Population surveillance approach to detect and respond to new clusters of COVID-19.

Background: To maintain control of the coronavirus disease 2019 (COVID-19) epidemic as lockdowns are lifted, it will be crucial to enhance alternative public health measures. For surveillance, it will be necessary to detect a high proportion of any new cases quickly so that they can be isolated, and people who have been exposed to them traced and quarantined. Here we introduce a mathematical approach that can be used to determine how many samples need to be collected per unit area and unit time to detect new clusters of COVID-19 cases at a stage early enough to control an outbreak.

The Oral Case Presentation: Time for a "Refresh".

Despite enormous changes in medicine over the last 50 years, the oral presentation of newly admitted patients remains a core activity in academic teaching hospitals. With increased pace and complexity of care, it is time to refresh this tradition, as its efficiency and utility in contemporary practice are open to question. In this paper, we suggest a revised structure to help presenters organize their thoughts before the oral presentation and provide an online tool for doing so.

COVID-19 infection among international travellers: a prospective analysis.

Objectives: This report estimates the risk of COVID-19 importation and secondary transmission associated with a modified quarantine programme in Canada.

Design And Participants: Prospective analysis of international asymptomatic travellers entering Alberta, Canada.

Interventions: All participants were required to receive a PCR COVID-19 test on arrival.

Comprehensive identification of somatic nucleotide variants in human brain tissue.

Background: Post-zygotic mutations incurred during DNA replication, DNA repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. However, detecting mosaic variants in DNA from non-cancerous somatic tissues poses significant challenges, particularly if the variants only are present in a small fraction of cells.

MIPP-Seq: ultra-sensitive rapid detection and validation of low-frequency mosaic mutations.

Background: Mosaic mutations contribute to numerous human disorders. As such, the identification and precise quantification of mosaic mutations is essential for a wide range of research applications, clinical diagnoses, and early detection of cancers. Currently, the low-throughput nature of single allele assays (e.

The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing.

We characterize the landscape of somatic mutations-mutations occurring after fertilization-in the human brain using ultra-deep (~250×) whole-genome sequencing of prefrontal cortex from 59 donors with autism spectrum disorder (ASD) and 15 control donors. We observe a mean of 26 somatic single-nucleotide variants per brain present in ≥4% of cells, with enrichment of mutations in coding and putative regulatory regions. Our analysis reveals that the first cell division after fertilization produces ~3.

Large mosaic copy number variations confer autism risk.

Although germline de novo copy number variants (CNVs) are known causes of autism spectrum disorder (ASD), the contribution of mosaic (early-developmental) copy number variants (mCNVs) has not been explored. In this study, we assessed the contribution of mCNVs to ASD by ascertaining mCNVs in genotype array intensity data from 12,077 probands with ASD and 5,500 unaffected siblings. We detected 46 mCNVs in probands and 19 mCNVs in siblings, affecting 2.

Developing trustworthy recommendations as part of an urgent response (1-2 weeks): a GRADE concept paper.

Objectives: The aim of this study is to propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 week) in the clinical, public health, and health systems fields.

Study Design And Setting: We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the Grading of Recommendations Assessment, Development and Evaluation Rapid Guidelines project group, and obtained feedback from the larger Grading of Recommendations Assessment, Development and Evaluation working group.

Results: A request for developing recommendations within 2 week is the usual trigger for an urgent response.

Accurate detection of mosaic variants in sequencing data without matched controls.

Detection of mosaic mutations that arise in normal development is challenging, as such mutations are typically present in only a minute fraction of cells and there is no clear matched control for removing germline variants and systematic artifacts. We present MosaicForecast, a machine-learning method that leverages read-based phasing and read-level features to accurately detect mosaic single-nucleotide variants and indels, achieving a multifold increase in specificity compared with existing algorithms. Using single-cell sequencing and targeted sequencing, we validated 80-90% of the mosaic single-nucleotide variants and 60-80% of indels detected in human brain whole-genome sequencing data.