Persistent fatigue in post-acute COVID syndrome is associated with altered T1 MRI texture in subcortical structures: a preliminary investigation.

Post-acute COVID syndrome (PACS) is a global health concern and is often associated with debilitating symptoms. Post-COVID fatigue is a particularly frequent and troubling issue, and its underlying mechanisms remain incompletely understood. One potential contributor is micropathological injury of subcortical and brainstem structures, as has been identified in other patient populations. Texture-based analysis (TA) may be used to measure such changes in anatomical MRI data. The present study develops a methodology of voxel-wise TA mapping in subcortical and brainstem regions, which is then applied to T1-weighted MRI data from a cohort of 48 individuals who had PACS (32 with and 16 without ongoing fatigue symptoms) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19. Both groups were assessed an average of 4-5 months post-infection. There were no significant differences between PACS and control groups, but significant differences were observed within the PACS groups, between those with and without fatigue symptoms. This included reduced texture energy and increased entropy, along with reduced texture correlation, cluster shade and profile in the putamen, pallidum, thalamus and brainstem. These findings provide new insights into the neurophysiological mechanisms that underlie PACS, with altered tissue texture as a potential biomarker of this debilitating condition.

The neurorehabilitation of post-stroke dysphagia: Physiology and pathophysiology.

Swallowing is a complex process involving the precise contractions of numerous muscles of the head and neck, which act to process and shepherd ingested material from the oral cavity to its eventual destination, the stomach. Over the past five decades, information from animal and human studies has laid bare the complex network of neurones in the brainstem, cortex and cerebellum that are responsible for orchestrating each normal swallow. Amidst this complexity, problems can and often do occur that result in dysphagia, defined as impaired or disordered swallowing. Dysphagia is common, arising from multiple varied disease processes that can affect any of the neuromuscular structures involved in swallowing. Post-stroke dysphagia (PSD) remains the most prevalent and most commonly studied form of dysphagia and, as such, provides an important disease model to assess dysphagia physiology and pathophysiology. In this review, we explore the complex neuroanatomical processes that occur during normal swallowing and PSD. This includes how strokes cause dysphagia, the mechanisms through which natural neuroplastic recovery occurs, current treatments for patients with persistent dysphagia and emerging neuromodulatory treatments.

Characteristics and outcomes of patients with COVID-19 who return to the emergency department: a multicentre observational study by the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN).

OBJECTIVE: Unplanned return emergency department (ED) visits can reflect clinical deterioration or unmet need from the original visit. We determined the characteristics and outcomes of patients with COVID-19 who return to the ED for COVID-19-related revisits. METHODS: This retrospective observational study used data for all adult patients visiting 47 Canadian EDs with COVID-19 between 1 March 2020 and 31 March 2022. Multivariable logistic regression assessed the characteristics associated with having a no return visit (SV=single visit group) versus at least one return visit (MV=return visit group) after being discharged alive at the first ED visit. RESULTS: 39 809 patients with COVID-19 had 44 862 COVID-19-related ED visits: 35 468 patients (89%) had one visit (SV group) and 4341 (11%) returned to the ED (MV group) within 30 days (mean 2.2, SD=0.5 ED visit). 40% of SV patients and 16% of MV patients were admitted at their first visit, and 41% of MV patients not admitted at their first ED visit were admitted on their second visit. In the MV group, the median time to return was 4 days, 49% returned within 72 hours. In multivariable modelling, a repeat visit was associated with a variety of factors including older age (OR=1.25 per 10 years, 95% CI (1.22 to 1.28)), pregnancy (1.86 (1.46 to 2.36)) and presence of comorbidities (eg, 1.72 (1.40 to 2.10) for cancer, 2.01 (1.52 to 2.66) for obesity, 2.18 (1.42 to 3.36) for organ transplant), current/prior substance use, higher temperature or WHO severe disease (1.41 (1.29 to 1.54)). Return was less likely for females (0.82 (0.77 to 0.88)) and those boosted or fully vaccinated (0.48 (0.34 to 0.70)). CONCLUSIONS: Return ED visits by patients with COVID-19 within 30 days were common during the first two pandemic years and were associated with multiple factors, many of which reflect known risk for worse outcomes. Future studies should assess reasons for revisit and opportunities to improve ED care and reduce resource use. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04702945.

Future leaders in a Learning Health System: Exploring the Health System Impact Fellowship.

The Canadian health system is reeling following the COVID-19 pandemic. Strains have become growing cracks, with long emergency department wait times, shortage of human health resources, and growing dissatisfaction from both clinicians and patients. To address long needed health system reform in Canada, a modernization of training is required for the next generation health leaders. The Canadian Institutes of Health Research Health System Impact Fellowship is an example of a well-funded and connected training program which prioritizes embedded research and embedding technically trained scholars with health system partners. The program has been successful in the scope and impact of its training outcomes as well as providing health system partners with a pool of connected and capable scholars. Looking forward, integrating aspects of evidence synthesis from both domestic and international sources and adapting a general contractor approach to implementation within the HSIF could help catalyze Learning Health System reform in Canada.

Persistent post-COVID headache is associated with suppression of scale-free functional brain dynamics in non-hospitalized individuals.

INTRODUCTION: Post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) is a growing concern, with headache being a particularly debilitating symptom with high prevalence. The long-term effects of COVID-19 and post-COVID headache on brain function remain poorly understood, particularly among non-hospitalized individuals. This study focused on the power-law scaling behavior of functional brain dynamics, indexed by the Hurst exponent (H). This measure is suppressed during physiological and psychological distress and was thus hypothesized to be reduced in individuals with post-COVID syndrome, with greatest reductions among those with persistent headache. METHODS: Resting-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data were collected for 57 individuals who had COVID-19 (32 with no headache, 14 with ongoing headache, 11 recovered) and 17 controls who had cold and flu-like symptoms but  tested negative for COVID-19. Individuals were assessed an average of 4-5 months after COVID testing, in a cross-sectional, observational study design. RESULTS: No significant differences in H values were found between non-headache COVID-19 and control groups., while those with ongoing headache had significantly reduced H values, and those who had recovered from headache had elevated H values, relative to non-headache groups. Effects were greatest in temporal, sensorimotor, and insular brain regions. Reduced H in these regions was also associated with decreased BOLD activity and local functional connectivity. CONCLUSIONS: These findings provide new insights into the neurophysiological mechanisms that underlie persistent post-COVID headache, with reduced BOLD scaling as a potential biomarker that is specific to this debilitating condition.

Impact of a high sensitivity troponin accelerated diagnostic protocol on the safety and emergency department length of stay of chest pain in an academic tertiary hospital: a quality improvement study.

PURPOSE: High-sensitivity troponin (hsTn) accelerated diagnostic protocols are highly recommended for evaluating acute coronary syndromes. Our goal was to improve care for chest pain patients through the safe adoption of an accelerated diagnostic protocol in our academic Emergency Department (ED) with an aim to reduce mean ED length of stay for chest pain patients by 1 h over 1.5 years. Pre-accelerated diagnostic protocol, our mean ED length of stay for chest pain patients was 9.0 h. METHODS: Using the Model for Improvement, we implemented a two-hour accelerated diagnostic protocol and conducted two Plan-Do-Study-Act cycles and education efforts to improve accelerated diagnostic protocol compliance and decrease ED length of stay. Using control charts, we measured the mean monthly ED length of stay for chest pain patients to look for special cause evidence of improvement. Process measures measured compliance with the accelerated diagnostic protocol. Balancing measures included the ED length of stay for abdominal pain patients and the number of admissions and deaths at 7 days for chest pain patients. RESULTS: Mean ED length of stay for chest pain patients decreased from 9.0 to 8.2 h post-accelerated diagnostic protocol. The mean time between troponins decreased from 3.9 to 3.0 h, and the percentage of second troponins repeated at < 2.75 h increased from 22.3% to 58.6%. For abdominal pain patients, ED length of stay decreased from 10.8 to 10.5 h. No chest pain patients died within 7 days pre- or post-accelerated diagnostic protocol. Pre-accelerated diagnostic protocol, 0.84% (41/4,905) were admitted within 7 days. Post-accelerated diagnostic protocol and accelerated diagnostic protocol compliant, 0.70% (13/1,844) were admitted. Post-accelerated diagnostic protocol and accelerated diagnostic protocol non-compliant, 1.1% (13/1,183) were admitted. CONCLUSION: We safely introduced a hsTn accelerated diagnostic protocol in an academic ED. ED length of stay decreased for chest pain patients but did not meet our 1-h goal.

RéSUMé : OBJECTIF : Les protocoles de diagnostic accélérés à haute sensibilité de la troponine (hsTn) sont fortement recommandés pour évaluer les syndromes coronariens aigus. Notre objectif était d'améliorer les soins pour les patients souffrant de douleurs thoraciques grâce à l'adoption en toute sécurité d'un protocole de diagnostic accéléré dans notre service d'urgence universitaire (ED) dans le but de réduire la durée moyenne de séjour des patients souffrant de douleurs thoraciques d'une heure sur 1,5 an. Protocole de diagnostic pré-accéléré, notre durée moyenne de séjour aux urgences pour les patients souffrant de douleurs thoraciques était de 9 heures. MéTHODES: À l'aide du Modèle d'amélioration, nous avons mis en œuvre un protocole de diagnostic accéléré de deux heures et mené deux cycles Plan-Do-Study-Act et des efforts d'éducation pour améliorer la conformité du protocole de diagnostic accéléré et réduire la durée du séjour aux urgences. À l'aide de tableaux de contrôle, nous avons mesuré la durée moyenne mensuelle du séjour aux urgences pour les patients souffrant de douleurs thoraciques afin de rechercher des preuves d'amélioration de cause spéciale. Le processus mesure la conformité au protocole de diagnostic accéléré. Les mesures d'équilibrage comprenaient la durée du séjour aux urgences pour les patients souffrant de douleurs abdominales et le nombre d'admissions et de décès à sept jours pour les patients souffrant de douleurs thoraciques. RéSULTATS: La durée moyenne du séjour aux urgences chez les patients souffrant de douleurs thoraciques a diminué de 9,0 à 8,2 heures après le protocole de diagnostic accéléré. Le temps moyen entre les troponines a diminué de 3,9 à 3,0 heures, et le pourcentage de deuxième troponines répétées à moins de 2,75 heures a augmenté de 22,3 % à 58,6 %. Pour les patients souffrant de douleurs abdominales, la durée du séjour aux urgences a diminué de 10,8 à 10,5 heures. Aucun patient souffrant de douleurs thoraciques n'est décédé dans les sept jours précédant ou suivant le protocole de diagnostic accéléré. Protocole de diagnostic pré-accéléré, 0,84 % (41/4905) ont été admis dans les sept jours. Protocole de diagnostic post-accéléré et protocole de diagnostic accéléré conforme, 0,70% (13/1844) ont été admis. Le protocole diagnostique post-accéléré et le protocole diagnostique accéléré non conforme, 1,1% (13/1,183) ont été admis. CONCLUSION: Nous avons introduit en toute sécurité un protocole de diagnostic accéléré hsTn dans un ED académique. La durée de séjour des patients souffrant de douleurs thoraciques a diminué, mais n'a pas atteint notre objectif d'une heure.

Comparing methods to classify admitted patients with SARS-CoV-2 as admitted for COVID-19 versus with incidental SARS-CoV-2: A cohort study.

INTRODUCTION: Not all patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection develop symptomatic coronavirus disease 2019 (COVID-19), making it challenging to assess the burden of COVID-19-related hospitalizations and mortality. We aimed to determine the proportion, resource utilization, and outcomes of SARS-CoV-2 positive patients admitted for COVID-19, and assess the impact of using the Center for Disease Control's (CDC) discharge diagnosis-based algorithm and the Massachusetts state department's drug administration-based classification system on identifying admissions for COVID-19. METHODS: In this retrospective cohort study, we enrolled consecutive SARS-CoV-2 positive patients admitted to one of five hospitals in British Columbia between December 19, 2021 and May 31,2022. We completed medical record reviews, and classified hospitalizations as being primarily for COVID-19 or with incidental SARS-CoV-2 infection. We applied the CDC algorithm and the Massachusetts classification to estimate the difference in hospital days, intensive care unit (ICU) days and in-hospital mortality and calculated sensitivity and specificity. RESULTS: Of 42,505 Emergency Department patients, 1,651 were admitted and tested positive for SARS-CoV-2, with 858 (52.0%, 95% CI 49.6-54.4) admitted for COVID-19. Patients hospitalized for COVID-19 required ICU admission (14.0% versus 8.2%, p<0.001) and died (12.6% versus 6.4%, p<0.001) more frequently compared with patients with incidental SARS-CoV-2. Compared to case classification by clinicians, the CDC algorithm had a sensitivity of 82.9% (711/858, 95% CI 80.3%, 85.4%) and specificity of 98.1% (778/793, 95% CI 97.2%, 99.1%) for COVID-19-related admissions and underestimated COVID-19 attributable hospital days. The Massachusetts classification had a sensitivity of 60.5% (519/858, 95% CI 57.2%, 63.8%) and specificity of 78.6% (623/793, 95% CI 75.7%, 81.4%) for COVID-19-related admissions, underestimating total number of hospital and ICU bed days while overestimating COVID-19-related intubations, ICU admissions, and deaths. CONCLUSION: Half of SARS-CoV-2 hospitalizations were for COVID-19 during the Omicron wave. The CDC algorithm was more specific and sensitive than the Massachusetts classification, but underestimated the burden of COVID-19 admissions. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04702945.

Brain-derived neurotrophic factor as a biomarker in cancer-related cognitive impairment among adolescent and young adult cancer patients.

Brain-derived neurotrophic factor (BDNF) improves cognitive function by stimulating neurogenesis and neuroplasticity. We hypothesize that higher plasma BDNF levels are protective against cognitive toxicity among adolescent and young adult cancer patients (15-39 years old). In a prospective, longitudinal study, we recruited 74 newly diagnosed cancer and 118 age-matched non-cancer controls who completed the Cambridge Neuropsychological Test Automated Battery (CANTAB), Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog) and blood draws. Plasma BDNF was quantified using an enzyme-linked immunosorbent assay. Genomic DNA from buffy coat was genotyped for BDNF Val66Met. Most cancer participants were diagnosed with breast (24%) and head/neck (22%) cancers. After adjusting for sociodemographic variables (age, gender, race, marital status, education years), cancer participants had lower BDNF levels (ng/mL) at baseline (median: 10.7 vs 21.6, p < 0.001) and 6-months post-baseline (median: 8.2 vs 15.3, p = 0.001) compared to non-cancer controls. Through linear mixed modelling adjusted for sociodemographic variables, baseline cognition, fatigue, psychological distress, and time, we observed that among cancer participants, lower baseline BDNF levels were associated with worse attention (p = 0.029), memory (p = 0.018) and self-perceived cognitive abilities (p = 0.020) during cancer treatment. Met/Met was associated with enhanced executive function compared to Val/Val (p = 0.012). Plasma BDNF may serve as a predictive biomarker of cancer-related cognitive impairment.

Drivers of Emergency Department Use Among Oncology Patients in the Era of Novel Cancer Therapeutics: A Systematic Review.

BACKGROUND: Patients diagnosed with cancer are frequent users of the emergency department (ED). While many visits are unavoidable, a significant portion may be potentially preventable ED visits (PPEDs). Cancer treatments have greatly advanced, whereby patients may present with unique toxicities from targeted therapies and are often living longer with advanced disease. Prior work focused on patients undergoing cytotoxic chemotherapy, and often excluded those on supportive care alone. Other contributors to ED visits in oncology, such as patient-level variables, are less well-established. Finally, prior studies focused on ED diagnoses to describe trends and did not evaluate PPEDs. An updated systematic review was completed to focus on PPEDs, novel cancer therapies, and patient-level variables, including those on supportive care alone. METHODS: Three online databases were used. Included publications were in English, from 2012-2022, with sample sizes of ≥50, and reported predictors of ED presentation or ED diagnoses in oncology. RESULTS: 45 studies were included. Six studies highlighted PPEDs with variable definitions. Common reasons for ED visits included pain (66%) or chemotherapy toxicities (69.1%). PPEDs were most frequent amongst breast cancer patients (13.4%) or patients receiving cytotoxic chemotherapy (20%). Three manuscripts included immunotherapy agents, and only one focused on end-of-life patients. CONCLUSION: This updated systematic review highlights variability in oncology ED visits during the last decade. There is limited work on the concept of PPEDs, patient-level variables and patients on supportive care alone. Overall, pain and chemotherapy toxicities remain key drivers of ED visits in cancer patients. Further work is needed in this realm.

Feasibility of diffusion-tensor and correlated diffusion imaging for studying white-matter microstructural abnormalities: Application in COVID-19.

There has been growing attention on the effect of COVID-19 on white-matter microstructure, especially among those that self-isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single-shell diffusion magnetic resonance imaging (MRI) methods for detecting such effects. In this work, the performances of three single-shell-compatible diffusion MRI modeling methods are compared for detecting the effect of COVID-19, including diffusion-tensor imaging, diffusion-tensor decomposition of orthogonal moments and correlated diffusion imaging. Imaging was performed on self-isolated patients at the study initiation and 3-month follow-up, along with age- and sex-matched controls. We demonstrate through simulations and experimental data that correlated diffusion imaging is associated with far greater sensitivity, being the only one of the three single-shell methods to demonstrate COVID-19-related brain effects. Results suggest less restricted diffusion in the frontal lobe in COVID-19 patients, but also more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID-19 infection. These results, taken together with the simulation results, suggest that a significant proportion of COVID-19 related white-matter microstructural pathology manifests as a change in tissue diffusivity. Interestingly, different b-values also confer different sensitivities to the effects. No significant difference was observed in patients at the 3-month follow-up, likely due to the limited size of the follow-up cohort. To summarize, correlated diffusion imaging is shown to be a viable single-shell diffusion analysis approach that allows us to uncover opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID-19 patients, suggesting the two regions react differently to viral infection.

Implementation of the YEARS algorithm to optimise pulmonary embolism diagnostic workup in the emergency department.

BACKGROUND: Excessive use of CT pulmonary angiography (CTPA) to investigate pulmonary embolism (PE) in the emergency department (ED) contributes to adverse patient outcomes. Non-invasive D-dimer testing, in the context of a clinical algorithm, may help decrease unnecessary imaging but this has not been widely implemented in Canadian EDs. AIM: To improve the diagnostic yield of CTPA for PE by 5% (absolute) within 12 months of implementing the YEARS algorithm. MEASURES AND DESIGN: Single centre study of all ED patients >18 years investigated for PE with D-dimer and/or CTPA between February 2021 and January 2022. Primary and secondary outcomes were the diagnostic yield of CTPA and frequency of CTPA ordered compared with baseline. Process measures included the percentage of D-dimer tests ordered with CTPA and CTPAs ordered with D-dimers <500 µg/L Fibrinogen Equivalent Units (FEU). The balancing measure was the number of PEs identified on CTPA within 30 days of index visit. Multidisciplinary stakeholders developed plan- do-study-act cycles based on the YEARS algorithm. RESULTS: Over 12 months, 2695 patients were investigated for PE, of which 942 had a CTPA. Compared with baseline, the CTPA yield increased by 2.9% (12.6% vs 15.5%, 95% CI -0.06% to 5.9%) and the proportion of patients that underwent CTPA decreased by 11.4% (46.4% vs 35%, 95% CI -14.1% to -8.8%). The percentage of CTPAs ordered with a D-dimer increased by 26.3% (30.7% vs 57%, 95% CI 22.2% 30.3%) and there were two missed PE (2/2695, 0.07%). IMPACT: Implementing the YEARS criteria may safely improve the diagnostic yield of CTPAs and reduce the number of CTPAs completed without an associated increase in missed clinically significant PEs. This project provides a model for optimising the use of CTPA in the ED.

Effects of post-acute COVID-19 syndrome on the functional brain networks of non-hospitalized individuals.

Introduction: The long-term impact of COVID-19 on brain function remains poorly understood, despite growing concern surrounding post-acute COVID-19 syndrome (PACS). The goal of this cross-sectional, observational study was to determine whether there are significant alterations in resting brain function among non-hospitalized individuals with PACS, compared to symptomatic individuals with non-COVID infection. Methods: Data were collected for 51 individuals who tested positive for COVID-19 (mean age 41±12 yrs., 34 female) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19 (mean age 41±14 yrs., 9 female), with both groups assessed an average of 4-5 months after COVID testing. None of the participants had prior neurologic, psychiatric, or cardiovascular illness. Resting brain function was assessed via functional magnetic resonance imaging (fMRI), and self-reported symptoms were recorded. Results: Individuals with COVID-19 had lower temporal and subcortical functional connectivity relative to controls. A greater number of ongoing post-COVID symptoms was also associated with altered functional connectivity between temporal, parietal, occipital and subcortical regions. Discussion: These results provide preliminary evidence that patterns of functional connectivity distinguish PACS from non-COVID infection and correlate with the severity of clinical outcome, providing novel insights into this highly prevalent disorder.

A systematic review and meta-analysis on the prevalence and clinical characteristics of dysphagia in patients with dermatomyositis.

BACKGROUND: Dermatomyositis (DM) is a rare autoimmune disease characterized by distinctive skin rash, muscle inflammation with symmetrical and progressive muscle weakness, and elevated serum levels of muscle-associated enzymes. DM may affect skeletal muscles involved in swallowing, leading to dysphagia, which can negatively impact individual's physical and psychosocial well-being. Despite this, dysphagia in patients with DM remains poorly understood. This systematic review and meta-analysis aimed to evaluate the prevalence and clinical features of dysphagia in patients with DM and juvenile DM (JDM). METHODS: Four electronic databases were systematically searched until September 2022. Studies with patients with DM or JDM and dysphagia were included. The pooled prevalence of all included studies was calculated, and the clinical characteristics of dysphagia were qualitatively analyzed. KEY RESULTS: Thirty-nine studies with 3335 patients were included. The overall pooled prevalence of dysphagia was 32.3% (95% CI: 0.270, 0.373) in patients with DM and 37.7% (95% CI: -0.031, 0.785) in patients with JDM. Subgroup analyses revealed that Sweden had the highest prevalence (66.7% [95% CI: 0.289, 1.044]), whereas Tunisia had the lowest prevalence (14.3% [95% CI: -0.040, 0.326]). Moreover, South America had the highest prevalence (47.0% [95% CI: 0.401, 0.538]), whereas Africa had the lowest prevalence (14.3% [95% CI: -0.040, 0.326]). Dysphagia in patients with DM and JDM was characterized by both oropharyngeal and esophageal dysfunctions, with predominant difficulties in motility. CONCLUSIONS & INFERENCES: Our findings showed that dysphagia affects one in three patients with DM or JDM. However, the documentation on the diagnosis and management of dysphagia in the literature is inadequate. Our results highlighted the need to use both clinical and instrumental assessments to evaluate swallowing function in this population.

The burden of incidental SARS-CoV-2 infections in hospitalized patients across pandemic waves in Canada.

Many health authorities differentiate hospitalizations in patients infected with SARS-CoV-2 as being "for COVID-19" (due to direct manifestations of SARS-CoV-2 infection) versus being an "incidental" finding in someone admitted for an unrelated condition. We conducted a retrospective cohort study of all SARS-CoV-2 infected patients hospitalized via 47 Canadian emergency departments, March 2020-July 2022 to determine whether hospitalizations with "incidental" SARS-CoV-2 infection are less of a burden to patients and the healthcare system. Using a priori standardized definitions applied to hospital discharge diagnoses in 14,290 patients, we characterized COVID-19 as (i) the "Direct" cause for the hospitalization (70%), (ii) a potential "Contributing" factor for the hospitalization (4%), or (iii) an "Incidental" finding that did not influence the need for admission (26%). The proportion of incidental SARS-CoV-2 infections rose from 10% in Wave 1 to 41% during the Omicron wave. Patients with COVID-19 as the direct cause of hospitalization exhibited significantly longer LOS (mean 13.8 versus 12.1 days), were more likely to require critical care (22% versus 11%), receive COVID-19-specific therapies (55% versus 19%), and die (17% versus 9%) compared to patients with Incidental SARS-CoV-2 infections. However, patients hospitalized with incidental SARS-CoV-2 infection still exhibited substantial morbidity/mortality and hospital resource use.

Dysphagia treatments in Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: The majority of patients with Parkinson's disease (PD) develop oropharyngeal dysphagia during the course of their disease. However, the efficacy of dysphagia treatments for these patients remains controversial. Therefore, we conducted this systematic review and meta-analysis to evaluate treatment efficacy based on the evidence from randomized controlled trials (RCTs). METHODS: Five electronic databases were systematically searched from inception date to April 2022. Two reviewers independently extracted and analyzed the data. The outcome measures were changes in swallowing-related characteristics based on instrumental swallowing assessments. KEY RESULTS: An initial search identified 187 RCT studies of relevance. After screening, nine studies with a total sample size of 286 were included in the meta-analysis. The pooled effect size for all dysphagia treatments compared with control comparators was significant and medium (SMD [95% CI] = 0.58 [0.22, 0.94], p = 0.001; I2  = 50%). Subgroup analysis revealed a significant and medium pooled effect size for stimulation treatments (brain stimulation, peripheral neurostimulation and acupuncture) (SMD [95% CI] = 0.54 [0.15, 0.92]; p = 0.006; I2  = 22%). Specifically, the effect sizes for the single RCTs on neuromuscular stimulation (SMD [95% CI] = 1.58 [0.49, 2.86]; p = 0.005) and acupuncture (SMD [95% CI] = 0.82 [0.27, 1.37]; p = 0.003) were significant and large. CONCLUSIONS AND INFERENCES: Our results showed that overall, dysphagia treatments, particularly stimulation treatments, can potentially benefit PD patients. However, given the limited number of small RCTs for each type of treatment, the evidence remains weak and uncertain. Further large-scale, multicenter RCTs are warranted to fully explore their clinical efficacy in the PD population.

Using network analyses to characterise Australian and Canadian frequent attenders to the emergency department.

OBJECTIVE: To explore and compare the characteristics of frequent attenders to the ED at an Australian and a Canadian tertiary hospitals by utilising a network analysis approach. METHODS: We conducted a retrospective population-based study using administrative data over the 2018 and 2019 calendar years. Participants were from a tertiary hospital in Melbourne, Australia, and Toronto, Canada. Frequent attenders were defined as patients with four or more visits in 12 months. Characteristics of younger (18-39 years), middle-aged (40-69 years) and older (70 years and older) frequent attenders were described using descriptive statistics and network analyses. RESULTS: Younger frequent attenders were characterised by mental illness and substance use, while older frequent attenders had high rates of physical (including chronic) diseases. Middle-aged frequent attenders were characterised by a combination of mental and physical illnesses. These findings were observed at both hospitals. Across all age groups, the network analyses between the Melbourne and Toronto hospitals were different. Among older frequent attender visits, more diagnoses were associated with high triage acuity at the Toronto hospital than at the Melbourne hospital. Some associations were similar at both sites, for example, the negative correlation between high triage acuity and joint pain. CONCLUSION: Younger, middle-aged and older frequent attenders have distinct characteristics, made readily apparent by using network analyses. Future interventions to reduce ED visits should consider the heterogeneity of frequent attenders who have needs specific to their age, presenting problems and jurisdiction.

Cognitive impairment in adolescent and young adult cancer patients: Pre-treatment findings of a longitudinal study.

BACKGROUND: There is little information about cancer-related cognitive impairment (CRCI) in adolescent and young adults (AYA, 15-39 years old) due to its rare incidence. Here, we present the pre-treatment (before chemotherapy or radiotherapy) evaluation of cognitive function and ability of AYA with cancer (AYAC) in a multicentered cohort study. METHODS: Newly diagnosed AYAC and age-matched healthy controls (HC) were recruited between 2018 and 2021. The primary outcome was the comparison of pre-treatment cognitive impairment defined as 2 standard deviations (SDs) below the HC on ≥1 cognitive test, or >1.5 SDs below on ≥2 tests using CANTAB® between AYAC and HC. Secondary outcomes included self-perceived cognitive ability assessed by FACT-Cog v3 and biomarkers (inflammatory cytokines and brain-derived neurotrophic factor [BDNF]). RESULTS: We recruited 74 AYAC (median age = 34) and 118 HC (median age = 32). On objective cognitive testing, we observed three times more AYAC patients performed poorly on at least 2 cognitive tests compared to HC (40.5% vs. 13.6%, p < 0.001). AYAC self-perceived less degree of cognitive impairment than HC (p < 0.001). However, AYAC perceived a greater impact of cognitive changes on their quality of life compared to HC (p = 0.039). Elevated baseline inflammatory markers (IL-2, IL-4, IL-6, IL-8, IL-10 and IFN-γ) were observed among AYAC compared to HC, and baseline BDNF was lower in AYAC compared to HC. Interaction effects between cancer diagnosis and biomarkers were observed in predicting cognitive function. CONCLUSION: With the pre-existence of CRCI and risk factors of neuroinflammation even prior to systemic therapy, AYAC should receive early rehabilitation to prevent further deterioration of cognitive function after initiation of systemic therapies. (ClinicalTrials.gov Identifier: NCT03476070).

Evaluating the Therapeutic Application of Neuromodulation in the Human Swallowing System.

In the last two decades, the focus of neurogenic dysphagia management has moved from passive compensatory strategies to evidence-based rehabilitative approaches. Advances in technology have enabled the development of novel treatment approaches such as neuromodulation techniques, which target the promotion of neurological reorganization for functional recovery of swallowing. Given the rapid pace of development in the field, this review aims to summarize the current findings on the effects of neuromodulation techniques on the human swallowing system and evaluate their therapeutic potential for neurogenic dysphagia. Implications for future clinical research and practical considerations for using neuromodulation in clinical practice will also be discussed.

MRI Assessment of Cerebral Blood Flow in Nonhospitalized Adults Who Self-Isolated Due to COVID-19.

BACKGROUND: Neurological symptoms associated with coronavirus disease 2019 (COVID-19), such as fatigue and smell/taste changes, persist beyond infection. However, little is known of brain physiology in the post-COVID-19 timeframe. PURPOSE: To determine whether adults who experienced flu-like symptoms due to COVID-19 would exhibit cerebral blood flow (CBF) alterations in the weeks/months beyond infection, relative to controls who experienced flu-like symptoms but tested negative for COVID-19. STUDY TYPE: Prospective observational. POPULATION: A total of 39 adults who previously self-isolated at home due to COVID-19 (41.9 ± 12.6 years of age, 59% female, 116.5 ± 62.2 days since positive diagnosis) and 11 controls who experienced flu-like symptoms but had a negative COVID-19 diagnosis (41.5 ± 13.4 years of age, 55% female, 112.1 ± 59.5 since negative diagnosis). FIELD STRENGTH AND SEQUENCES: A 3.0 T; T1-weighted magnetization-prepared rapid gradient and echo-planar turbo gradient-spin echo arterial spin labeling sequences. ASSESSMENT: Arterial spin labeling was used to estimate CBF. A self-reported questionnaire assessed symptoms, including ongoing fatigue. CBF was compared between COVID-19 and control groups and between those with (n = 11) and without self-reported ongoing fatigue (n = 28) within the COVID-19 group. STATISTICAL TESTS: Between-group and within-group comparisons of CBF were performed in a voxel-wise manner, controlling for age and sex, at a family-wise error rate of 0.05. RESULTS: Relative to controls, the COVID-19 group exhibited significantly decreased CBF in subcortical regions including the thalamus, orbitofrontal cortex, and basal ganglia (maximum cluster size = 6012 voxels and maximum t-statistic = 5.21). Within the COVID-19 group, significant CBF differences in occipital and parietal regions were observed between those with and without self-reported on-going fatigue. DATA CONCLUSION: These cross-sectional data revealed regional CBF decreases in the COVID-19 group, suggesting the relevance of brain physiology in the post-COVID-19 timeframe. This research may help elucidate the heterogeneous symptoms of the post-COVID-19 condition. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

Development and pilot testing of a decision aid for navigating breast cancer survivorship care.

BACKGROUND: The predominant oncologist-led model in many countries is unsustainable to meet the needs of a growing cohort of breast cancer survivors (BCS). Despite available alternative models, adoption rates have been poor. To help BCS navigate survivorship care, we aimed to systematically develop a decision aid (DA) to guide their choice of follow-up care model and evaluate its acceptability and usability among BCS and health care providers (HCPs). METHODS: We recruited BCS aged ≥ 21 years who have completed primary treatment and understand English. BCS receiving palliative care or with cognitive impairment were excluded. HCPs who routinely discussed post-treatment care with BCS were purposively sampled based on disciplines. Each participant reviewed the DA during a semi-structured interview using the 'think aloud' approach and completed an acceptability questionnaire. Descriptive statistics and directed content analysis were used. RESULTS: We conducted three rounds of alpha testing with 15 BCS and 8 HCPs. All BCS found the final DA prototype easy to navigate with sufficient interactivity. The information imbalance favouring the shared care option perceived by 60% of BCS in early rounds was rectified. The length of DA was optimized to be 'just right'. Key revisions made included (1) presenting care options side-by-side to improve perceived information balance, (2) creating dedicated sections explaining HCPs' care roles to address gaps in health system contextual knowledge, and (3) employing a multicriteria decision analysis method for preference clarification exercise to reflect the user's openness towards shared care. Most BCS (73%) found the DA useful for decision-making, and 93% were willing to discuss the DA with their HCPs. Most HCPs (88%) agreed that the DA was a reliable tool and would be easily integrated into routine care. CONCLUSIONS: Our experience highlighted the need to provide contextual information on the health care system for decisions related to care delivery. Developers should address potential variability within the care model and clarify inherent biases, such as low confidence levels in primary care. Future work could expand on the developed DA's informational structure to apply to other care models and leverage artificial intelligence to optimize information delivery.