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Introduction: The COVID-19 pandemic led to a dramatic increase in telemedicine use for direct patient care. Inequities in device/internet access can limit the extent to which patients can engage with telemedicine care and exacerbate health disparities. In this review, we examined existing literature on interventions designed to improve patient telemedicine access by providing digital devices including tablets, smartphones, and computers and/or internet connectivity. Methods: In this systematic scoping review, we searched four databases for peer-reviewed studies published 1/1/2000-10/19/2021 that described healthcare interventions that provided patients with devices and/or internet connectivity and reported outcomes related to telemedicine access and/or usage. Data extraction elements included: study population, setting, intervention design, details on device/connectivity provision, and outcomes evaluated. Results: Twelve articles reflecting seven unique interventions met inclusion criteria. Ten articles examined telemedicine utilization (83%) and reported improved patient show rates/utilization. Seven articles examined patient satisfaction with the interventions (58%) and reported positive experiences. Fewer articles examined health outcomes (17%; 2/12) though these also demonstrated positive results. Across included studies, study quality was low. There were no controlled trials, and the most rigorously designed studies (n = 4) involved pre/post-intervention assessments. Discussion: Findings from this review indicate that providing material technology supports to patients can facilitate telemedicine access, is acceptable to patients and clinicians, and can contribute to improved health outcomes. The low number and quality of existing studies limits the strength of this evidence. Future research should explore interventions that can increase equitable access to telemedicine services. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=183442, identifier, PROSPERO: CRD42020183442.
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The diagnosis of prostate cancer using histopathology is reliant on the accurate interpretation of prostate tissue sections. Current standards rely on the assessment of Haematoxylin and Eosin (H&E) staining, which can be difficult to interpret and introduce inter-observer variability. Here, we present a digital pathology atlas and online resource of prostate cancer tissue micrographs for both H&E and the reinterpretation of samples using a novel set of three biomarkers as an interactive tool, where clinicians and scientists can explore high resolution histopathology from various case studies. The digital pathology prostate cancer atlas when used in conjunction with the biomarkers, will assist pathologists to accurately grade prostate cancer tissue samples.
Subject(s)
Adaptor Proteins, Signal Transducing , Adaptor Proteins, Vesicular Transport , Biomarkers, Tumor , Prostatic Neoplasms , Syndecan-1 , Prostatic Neoplasms/pathology , Male , Humans , Syndecan-1/analysisABSTRACT
In 2023, the Canadian Society of Abdominal Radiology (CSAR) and Canadian Emergency, Trauma, and Acute Care Radiology Society (CETARS) received Canadian Association of Radiologists (CAR) member feedback that there was an unmet educational need for guidance in the imaging investigation of right lower quadrant (RLQ) pain. Members requested specific guidance on how to handle controversial scenarios including which test to order when, specifics of imaging protocols, and managing pregnant patients who have RLQ pain-all from a Canadian perspective. After conducting an exhaustive literature review, the working group agreed that a Canadian-specific set of guidelines was warranted. The management recommendations presented in this guideline were discussed as a group to achieve expert consensus. As the workup for RLQ pain can vary considerably in the paediatric population, the scope of this paper was restricted to adults (18 years of age or older). Whenever possible, the best evidence was used to inform the clinical guidance, and where gaps existed, the guidelines reflect consensus among experts in the field. The result is a framework to aid in this process of managing patients with RLQ pain across various clinical scenarios while addressing current questions and controversies, particularly those most relevant to the Canadian healthcare system.
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To investigate how host and pathogen diversity govern immunity against Mycobacterium tuberculosis (Mtb), we performed a large-scale screen of vaccine-mediated protection against aerosol Mtb infection using three inbred mouse strains [C57BL/6 (B6), C3HeB/FeJ (C3H), Balb/c x 129/SvJ (C129F1)] and three Mtb strains (H37Rv, CDC1551, SA161) representing two lineages and distinct virulence properties. We compared three protective modalities, all of which involve inoculation with live mycobacteria: Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, delivered either subcutaneously or intravenously, and concomitant Mtb infection (CoMtb), a model of pre-existing immunity in which a low-level Mtb infection is established in the cervical lymph node following intradermal inoculation. We examined lung bacterial burdens at early (Day 28) and late (Day 98) time points after aerosol Mtb challenge and histopathology at Day 98. We observed substantial heterogeneity in the reduction of bacterial load afforded by these modalities at Day 28 across the combinations and noted a strong positive correlation between bacterial burden in unvaccinated mice and the degree of protection afforded by vaccination. Although we observed variation in the degree of reduction in bacterial burdens across the nine mouse/bacterium strain combinations, virtually all protective modalities performed similarly for a given strain-strain combination. We also noted dramatic variation in histopathology changes driven by both host and bacterial genetic backgrounds. Vaccination improved pathology scores for all infections except CDC1551. However, the most dramatic impact of vaccination on lesion development occurred for the C3H-SA161 combination, where vaccination entirely abrogated the development of the large necrotic lesions that arise in unvaccinated mice. In conclusion, we find that substantial TB heterogeneity can be recapitulated by introducing variability in both host and bacterial genetics, resulting in changes in vaccine-mediated protection as measured both by bacterial burden as well as histopathology. These differences can be harnessed in future studies to identify immune correlates of vaccine efficacy.
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Mycobacterium tuberculosis , Animals , Mycobacterium tuberculosis/immunology , Mycobacterium tuberculosis/genetics , Mice , Genetic Variation , Female , Tuberculosis/prevention & control , Tuberculosis/immunology , Tuberculosis/microbiology , Tuberculosis Vaccines/immunology , Mice, Inbred C57BL , Mice, Inbred BALB C , Host-Pathogen Interactions/immunology , BCG Vaccine/immunology , Lung/microbiology , Lung/pathology , Lung/immunology , Disease Models, Animal , Bacterial Load , VaccinationABSTRACT
An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.5% (6/11) CyCMV/Flu-vaccinated MCM survived. Survival correlates with the magnitude of lung-resident influenza-specific CD4 + T cells prior to challenge. These data demonstrate that CD4 + T cells targeting conserved internal influenza proteins can protect against highly pathogenic heterologous influenza challenge and support further exploration of effector memory T cell-based vaccines for universal influenza vaccine development.
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CD4-Positive T-Lymphocytes , Cytomegalovirus , Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Macaca fascicularis , Animals , Influenza Vaccines/immunology , Influenza Vaccines/administration & dosage , CD4-Positive T-Lymphocytes/immunology , Influenza A Virus, H1N1 Subtype/immunology , Cytomegalovirus/immunology , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/prevention & control , Influenza A Virus, H5N1 Subtype/immunology , Lung/immunology , Lung/virology , Lung/pathology , Genetic Vectors/genetics , Genetic Vectors/immunology , Male , Female , Memory T Cells/immunology , Immunologic Memory/immunology , VaccinationABSTRACT
An integrated health system including 12 hospitals, an expansive network of ambulatory settings, and health insurance plans began a systematic review of the existing nursing professional practice model (PPM) created in 2007 to assess current relevancy. The goal was to determine PPM concepts and imagery that represent present-day nursing workforce. This article shares how a formal review of literature, utilization of focus groups, and system-wide shared decision-making influenced creation and evaluation of a revised PPM.
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The association between SARS-CoV-2 humoral immunity and post-acute sequelae of COVID-19 (long COVID) remains uncertain. The objective of this population-based cohort study was to assess the association between SARS-CoV-2 seropositivity and symptoms consistent with long COVID. English and Spanish-speaking members ≥ 18 years old with SARS-CoV-2 serologic testing conducted prior to August 2021 were recruited from Kaiser Permanente Southern California and Kaiser Permanente Colorado. Between November 2021 and April 2022, participants completed a survey assessing symptoms, physical health, mental health, and cognitive function consistent with long COVID. Survey results were linked to SARS-CoV-2 antibody (Ab) and viral (RNA) lab results in electronic health records. Weighted descriptive analyses were generated for five mutually exclusive patient groups: (1) +Ab/+RNA; (2) +Ab/- or missing RNA; (3) -Ab/+RNA; (4a) -Ab/-RNA reporting no prior infection; and (4b) -Ab/-RNA reporting prior infection. The proportions reporting symptoms between the +Ab/+RNA and -Ab/+RNA groups were compared, adjusted for covariates. Among 3,946 participants, the mean age was 52.1 years old (SD 15.6), 68.3% were female, 28.4% were Hispanic, and the serologic testing occurred a median of 15 months prior (IQR = 12-18). Three quarters (74.5%) reported having had COVID-19. Among people with laboratory-confirmed COVID-19, there was no association between antibody positivity (+Ab/+RNA vs. -Ab/+RNA) and any symptoms, physical health, mental health, or cognitive function. As expected, physical health, cognitive function, and fatigue were worse, and palpitations and headaches limiting the ability to work were more prevalent among people with laboratory-confirmed prior infection and positive serology (+Ab/+RNA) compared to those without reported or confirmed prior infection and negative serology (-Ab/-RNA/no reported COVID-19). Among people with laboratory-confirmed COVID-19, SARS-CoV-2 serology from practice settings were not associated with long COVID symptoms and health status suggesting limited utility of serology testing for long COVID.
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Antibodies, Viral , COVID-19 , SARS-CoV-2 , Humans , Female , Male , COVID-19/immunology , COVID-19/epidemiology , Middle Aged , Antibodies, Viral/blood , SARS-CoV-2/immunology , Adult , Aged , Post-Acute COVID-19 Syndrome , Colorado/epidemiology , Cohort Studies , RNA, Viral/blood , California/epidemiology , Immunity, HumoralABSTRACT
Low-cost markerless motion capture systems offer the potential for 3D measurement of joint angles during human movement. This study aimed to validate a smartphone-based markerless motion capture system's (OpenCap) derived lower extremity kinematics during common return-to-sport tasks, comparing it to an established optoelectronic motion capture system. Athletes with prior anterior cruciate ligament reconstruction (12-18 months post-surgery) performed three movements: a jump-landing-rebound, single-leg hop, and lateral-vertical hop. Kinematics were recorded concurrently with two smartphones running OpenCap's software and with a 10-camera, marker-based motion capture system. Validity of lower extremity joint kinematics was assessed across 437 recorded trials using measures of agreement (coefficient of multiple correlation: CMC) and error (mean absolute error: MAE, root mean squared error: RMSE) across the time series of movement. Agreement was best in the sagittal plane for the knee and hip in all movements (CMC > 0.94), followed by the ankle (CMC = 0.84-0.93). Lower agreement was observed for frontal (CMC = 0.47-0.78) and transverse (CMC = 0.51-0.6) plane motion. OpenCap presented a grand mean error of 3.85° (MAE) and 4.34° (RMSE) across all joint angles and movements. These results were comparable to other available markerless systems. Most notably, OpenCap's user-friendly interface, free software, and small physical footprint have the potential to extend motion analysis applications beyond conventional biomechanics labs, thus enhancing the accessibility for a diverse range of users.
Subject(s)
Return to Sport , Humans , Biomechanical Phenomena , Male , Female , Adult , Movement/physiology , Knee Joint/physiology , Knee Joint/surgery , Lower Extremity/physiology , Anterior Cruciate Ligament Reconstruction/methods , Range of Motion, Articular/physiology , Young Adult , Smartphone , Motion CaptureABSTRACT
A 69-year-old female presented with symptomatic atrial fibrillation. Cardiac amyloidosis was suspected due to an artificial intelligence clinical tool applied to the presenting electrocardiogram predicting a high probability for amyloidosis, and the subsequent unexpected finding of left atrial appendage thrombus reinforced this clinical suspicion. This facilitated an early diagnosis by the biopsy of AL cardiac amyloidosis and the prompt initiation of targeted therapy. This case highlights the utilization of an AI clinical tool and its impact on clinical care, particularly for the early detection of a rare and difficult to diagnose condition where early therapy is critical.
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Background: White matter loss is a well-documented phenomenon in Alzheimer's disease (AD) patients that has been recognized for decades. However, the underlying reasons for the failure of oligodendrocyte progenitor cells (OPCs) to repair myelin deficits in these patients remain elusive. A single nucleotide polymorphism (SNP) in Clusterin has been identified as a risk factor for late-onset Alzheimer's disease and linked to a decrease in white matter integrity in healthy adults, but its specific role in oligodendrocyte function and myelin maintenance in Alzheimer's disease pathology remains unclear. Methods: To investigate the impact of Clusterin on OPCs in the context of Alzheimer's disease, we employed a combination of immunofluorescence and transmission electron microscopy techniques, primary culture of OPCs, and an animal model of Alzheimer's disease. Results: Our findings demonstrate that Clusterin, a risk factor for late-onset AD, is produced by OPCs and inhibits their differentiation into oligodendrocytes. Specifically, we observed upregulation of Clusterin in OPCs in the 5xFAD mouse model of AD. We also found that the phagocytosis of debris, including amyloid beta (Aß), myelin, and apoptotic cells leads to the upregulation of Clusterin in OPCs. In vivo experiments confirmed that Aß oligomers stimulate Clusterin upregulation and that OPCs are capable of phagocytosing Aß. Furthermore, we discovered that Clusterin significantly inhibits OPC differentiation and hinders the production of myelin proteins. Finally, we demonstrate that Clusterin inhibits OPC differentiation by reducing the production of IL-9 by OPCs. Conclusion: Our data suggest that Clusterin may play a key role in the impaired myelin repair observed in AD and could serve as a promising therapeutic target for addressing AD-associated cognitive decline.
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BACKGROUND: Childhood obesity is a devastating disease process disproportionately affecting minority and low-income populations. Though bariatric surgery leads to durable weight loss and reversal of multiple obesity-related comorbidities, only a small fraction of pediatric patients undergoes the procedure. We sought to identify factors associated with non-completion in a pediatric bariatric surgery program. METHODS: Retrospective review of consecutive patients ≤18-years-old referred to an academic adolescent bariatric surgery program between 2017 and 2022 (n = 20 completers, 40 non-completers) was completed. Demographics and medical and psychosocial histories were summarized by completion status. RESULTS: Of the 33% (20/60; 85% female, 30% racial minorities) who successfully completed the program, the median age was 16 years [IQR 16, 17]. The median age of non-completers was 16 years [IQR 15, 17] (55% female, 56% racial minorities). Non-completion was associated with male gender (15% of completers vs 45% of non-completers, p = 0.022), neighborhood income <150% poverty level (0 completers vs 17.5% of non-completers, p = 0.047), and presence of environmental or family stressors (22% of completers vs 65% of non-completers, p = 0.008). Though not statistically significant, non-completers tended to be racial minorities (p = 0.054). CONCLUSIONS: Non-completion of the bariatric surgery pathway was more prevalent among male patients from lower-income neighborhoods with significant environmental or family stressors. These patients also tended to be racial and ethnic minorities. The findings underscore the need for further investigation into barriers to pediatric bariatric surgery. LEVEL OF EVIDENCE: Level III.
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Background: In Australia, invasive meningococcal disease (IMD) incidence rapidly increased between 2014 and 2017 due to rising serogroup W (MenW) and MenY infections. We aimed to better understand the genetic diversity of IMD during 2017 and 2018 using whole genome sequencing data. Methods: Whole genome sequencing data from 440 Australian IMD isolates collected during 2017 and 2018 and 1737 international MenW:CC11 isolates collected in Europe, Africa, Asia, North America, and South America between 1974 and 2020 were used in phylogenetic analyses; genetic relatedness was determined from single-nucleotide polymorphisms. Results: Australian isolates were as follows: 181 MenW (41%), 144 MenB (33%), 88 MenY (20%), 16 MenC (4%), 1 MenW/Y (0.2%), and 10 nongenogroupable (2%). Eighteen clonal complexes (CCs) were identified, and 3 (CC11, CC23, CC41/44) accounted for 78% of isolates (343/440). These CCs were associated with specific serogroups: CC11 (n = 199) predominated among MenW (n = 181) and MenC (n = 15), CC23 (n = 80) among MenY (n = 78), and CC41/44 (n = 64) among MenB (n = 64). MenB isolates were highly diverse, MenY were intermediately diverse, and MenW and MenC isolates demonstrated the least genetic diversity. Thirty serogroup and CC-specific genomic clusters were identified. International CC11 comparison revealed diversification of MenW in Australia. Conclusions: Whole genome sequencing comprehensively characterized Australian IMD isolates, indexed their genetic variability, provided increased within-CC resolution, and elucidated the evolution of CC11 in Australia.
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T cells producing IFN-γ have long been considered a stalwart for immune protection against Mycobacterium tuberculosis (Mtb), but their relative importance to pulmonary immunity has been challenged by murine studies that achieved protection by adoptively transferred Mtb-specific IFN-γ-/- T cells. Using IFN-γ-/- T cell chimeric mice and adoptive transfer of IFN-γ-/- T cells into TCRß-/-δ-/- mice, we demonstrate that control of lung Mtb burden is in fact dependent on T cell-derived IFN-γ, and, furthermore, mice selectively deficient in T cell-derived IFN-γ develop exacerbated disease compared with T cell-deficient control animals, despite equivalent lung bacterial burdens. Deficiency in T cell-derived IFN-γ skews infected and bystander monocyte-derived macrophages to an alternative M2 phenotype and promotes neutrophil and eosinophil influx. Our studies support an important role for T cell-derived IFN-γ in pulmonary immunity against tuberculosis.
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Interferon-gamma , Lung , Mice, Knockout , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Animals , Mice , Adoptive Transfer , Interferon-gamma/immunology , Lung/immunology , Lung/microbiology , Macrophages/immunology , Mice, Inbred C57BL , Mycobacterium tuberculosis/immunology , Neutrophils/immunology , T-Lymphocytes/immunology , Tuberculosis, Pulmonary/immunologyABSTRACT
Despite the known detrimental health effects of alcohol use during pregnancy, there are still health care (HCP) and social service providers (SSP) who do not promote complete abstinence. The purpose of this study was to explore the current practices of HCPs and SSPs when discussing alcohol use during pregnancy, and to understand their rationale for their specific recommendations. An online survey was completed by 1123 HCPs (n = 588) and SSPs (n = 535) that asked them to identify their approach to discussing alcohol and pregnancy. Participants had the option to further explain their current recommendations regarding alcohol use during pregnancy in an open-ended format. Open-ended responses were analyzed using a content analysis approach (n = 156). The majority of respondents recommend abstinence (83.9% of HCPs, n = 493; 78.4% of SSPs, n = 419), while 9.8% of HCPs (n = 57) and 2.2% of SSPs (n = 12) responded that low levels of consumption may be acceptable. HCPs may recommend low levels of consumption based on other international guidelines, limited evidence to suggest that one unit of alcohol is harmful, and as a harm reduction strategy. SSPs stated that they refer clients to HCPs for recommendations related to alcohol consumption, and that they prefer to provide information based on public health guidelines. This exploratory work may inform the development of resources to support HCPs and SSPs to recommend abstinence from alcohol throughout gestation.
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Alcohol Abstinence , Humans , Female , Pregnancy , Surveys and Questionnaires , Adult , Social Work , Health Personnel , Alcohol Drinking/prevention & control , Middle Aged , MaleABSTRACT
This cross-sectional study assesses the implication of patients' English language skills for telehealth use and visit experience.
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Limited English Proficiency , Telemedicine , Humans , Telemedicine/methods , Male , Female , Middle Aged , Adult , Aged , Cross-Sectional Studies , Communication BarriersABSTRACT
Imaging of pregnant patients who sustained trauma often causes fear and confusion among patients, their families, and health care professionals regarding the potential for detrimental effects from radiation exposure to the fetus. Unnecessary delays or potentially harmful avoidance of the justified imaging studies may result from this understandable anxiety. This guideline was developed by the Canadian Emergency, Trauma and Acute Care Radiology Society (CETARS) and the Canadian Association of Radiologists (CAR) Working Group on Imaging the Pregnant Trauma Patient, informed by a literature review as well as multidisciplinary expert panel opinions and discussions. The working group included academic subspecialty radiologists, a trauma team leader, an emergency physician, and an obstetriciangynaecologist/maternal fetal medicine specialist, who were brought together to provide updated, evidence-based recommendations for the imaging of pregnant trauma patients, including patient safety aspects (eg, radiation and contrast concerns) and counselling, initial imaging in maternal trauma, specific considerations for the use of fluoroscopy, angiography, and magnetic resonance imaging. The guideline strives to achieve clarity and prevent added anxiety in an already stressful situation of injury to a pregnant patient, who should not be imaged differently.
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OBJECTIVE: To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. BACKGROUND: Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. METHODS: A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. RESULTS: In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338). CONCLUSIONS: In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.
Subject(s)
Botulinum Toxins, Type A , Migraine Disorders , Nerve Block , Humans , Botulinum Toxins, Type A/administration & dosage , Botulinum Toxins, Type A/adverse effects , Botulinum Toxins, Type A/pharmacology , Female , Male , Retrospective Studies , Middle Aged , Adult , Nerve Block/methods , Migraine Disorders/drug therapy , Headache Disorders/drug therapy , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/adverse effects , Neuromuscular Agents/pharmacology , Aged , Anesthetics, Local/administration & dosage , Anesthetics, Local/pharmacologyABSTRACT
Aims: Cardiac amyloidosis (CA) is common in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Cardiac amyloidosis has poor outcomes, and its assessment in all TAVR patients is costly and challenging. Electrocardiogram (ECG) artificial intelligence (AI) algorithms that screen for CA may be useful to identify at-risk patients. Methods and results: In this retrospective analysis of our institutional National Cardiovascular Disease Registry (NCDR)-TAVR database, patients undergoing TAVR between January 2012 and December 2018 were included. Pre-TAVR CA probability was analysed by an ECG AI predictive model, with >50% risk defined as high probability for CA. Univariable and propensity score covariate adjustment analyses using Cox regression were performed to compare clinical outcomes between patients with high CA probability vs. those with low probability at 1-year follow-up after TAVR. Of 1426 patients who underwent TAVR (mean age 81.0 ± 8.5 years, 57.6% male), 349 (24.4%) had high CA probability on pre-procedure ECG. Only 17 (1.2%) had a clinical diagnosis of CA. After multivariable adjustment, high probability of CA by ECG AI algorithm was significantly associated with increased all-cause mortality [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.01-1.96, P = 0.046] and higher rates of major adverse cardiovascular events (transient ischaemic attack (TIA)/stroke, myocardial infarction, and heart failure hospitalizations] (HR 1.36, 95% CI 1.01-1.82, P = 0.041), driven primarily by heart failure hospitalizations (HR 1.58, 95% CI 1.13-2.20, P = 0.008) at 1-year follow-up. There were no significant differences in TIA/stroke or myocardial infarction. Conclusion: Artificial intelligence applied to pre-TAVR ECGs identifies a subgroup at higher risk of clinical events. These targeted patients may benefit from further diagnostic evaluation for CA.
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BACKGROUND: AI models have shown promise in performing many medical imaging tasks. However, our ability to explain what signals these models have learned is severely lacking. Explanations are needed in order to increase the trust of doctors in AI-based models, especially in domains where AI prediction capabilities surpass those of humans. Moreover, such explanations could enable novel scientific discovery by uncovering signals in the data that aren't yet known to experts. METHODS: In this paper, we present a workflow for generating hypotheses to understand which visual signals in images are correlated with a classification model's predictions for a given task. This approach leverages an automatic visual explanation algorithm followed by interdisciplinary expert review. We propose the following 4 steps: (i) Train a classifier to perform a given task to assess whether the imagery indeed contains signals relevant to the task; (ii) Train a StyleGAN-based image generator with an architecture that enables guidance by the classifier ("StylEx"); (iii) Automatically detect, extract, and visualize the top visual attributes that the classifier is sensitive towards. For visualization, we independently modify each of these attributes to generate counterfactual visualizations for a set of images (i.e., what the image would look like with the attribute increased or decreased); (iv) Formulate hypotheses for the underlying mechanisms, to stimulate future research. Specifically, present the discovered attributes and corresponding counterfactual visualizations to an interdisciplinary panel of experts so that hypotheses can account for social and structural determinants of health (e.g., whether the attributes correspond to known patho-physiological or socio-cultural phenomena, or could be novel discoveries). FINDINGS: To demonstrate the broad applicability of our approach, we present results on eight prediction tasks across three medical imaging modalities-retinal fundus photographs, external eye photographs, and chest radiographs. We showcase examples where many of the automatically-learned attributes clearly capture clinically known features (e.g., types of cataract, enlarged heart), and demonstrate automatically-learned confounders that arise from factors beyond physiological mechanisms (e.g., chest X-ray underexposure is correlated with the classifier predicting abnormality, and eye makeup is correlated with the classifier predicting low hemoglobin levels). We further show that our method reveals a number of physiologically plausible, previously-unknown attributes based on the literature (e.g., differences in the fundus associated with self-reported sex, which were previously unknown). INTERPRETATION: Our approach enables hypotheses generation via attribute visualizations and has the potential to enable researchers to better understand, improve their assessment, and extract new knowledge from AI-based models, as well as debug and design better datasets. Though not designed to infer causality, importantly, we highlight that attributes generated by our framework can capture phenomena beyond physiology or pathophysiology, reflecting the real world nature of healthcare delivery and socio-cultural factors, and hence interdisciplinary perspectives are critical in these investigations. Finally, we will release code to help researchers train their own StylEx models and analyze their predictive tasks of interest, and use the methodology presented in this paper for responsible interpretation of the revealed attributes. FUNDING: Google.