A dual-energy computed tomography-based radiomics nomogram for predicting time since stroke onset: a multicenter study.

OBJECTIVES: We aimed to develop and validate a radiomics nomogram based on dual-energy computed tomography (DECT) images and clinical features to classify the time since stroke (TSS), which could facilitate stroke decision-making. MATERIALS AND METHODS: This retrospective three-center study consecutively included 488 stroke patients who underwent DECT between August 2016 and August 2022. The eligible patients were divided into training, test, and validation cohorts according to the center. The patients were classified into two groups based on an estimated TSS threshold of ≤ 4.5 h. Virtual images optimized the visibility of early ischemic lesions with more CT attenuation. A total of 535 radiomics features were extracted from polyenergetic, iodine concentration, virtual monoenergetic, and non-contrast images reconstructed using DECT. Demographic factors were assessed to build a clinical model. A radiomics nomogram was a tool that the Rad score and clinical factors to classify the TSS using multivariate logistic regression analysis. Predictive performance was evaluated using receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA) was used to compare the clinical utility and benefits of different models. RESULTS: Twelve features were used to build the radiomics model. The nomogram incorporating both clinical and radiomics features showed favorable predictive value for TSS. In the validation cohort, the nomogram showed a higher AUC than the radiomics-only and clinical-only models (AUC: 0.936 vs 0.905 vs 0.824). DCA demonstrated the clinical utility of the radiomics nomogram model. CONCLUSIONS: The DECT-based radiomics nomogram provides a promising approach to predicting the TSS of patients. CLINICAL RELEVANCE STATEMENT: The findings support the potential clinical use of DECT-based radiomics nomograms for predicting the TSS. KEY POINTS: Accurately determining the TSS onset is crucial in deciding a treatment approach. The radiomics-clinical nomogram showed the best performance for predicting the TSS. Using the developed model to identify patients at different times since stroke can facilitate individualized management.

Cardiac, possible cardiac, and likely non-cardiac origin of chest pain : A hitherto underestimated parameter in German chest pain units.

BACKGROUND: Current guidelines emphasize the diagnostic value of non-cardiac or possibly cardiac chest pain. The goal of this analysis was to determine whether German chest pain units (CPUs) adequately address conditions with "atypical" chest pain in existing diagnostic structures. METHOD: A total of 11,734 patients from the German CPU registry were included. The analyses included mode of admission, critical time intervals, diagnostic steps, and differential diagnoses. RESULTS: Patients with unspecified chest pain were younger, more often female, were less likely to have classic cardiovascular risk factors and tended to present more often as self-referrals. Patients with acute coronary syndrome (ACS) mostly had prehospital medical contact. Overall, there was no difference between these two groups regarding the time from the onset of first symptoms to arrival at the CPU. In the CPU, the usual basic diagnostic measures were performed irrespective of ACS as the primary working diagnosis. In the non-ACS group, further ischemia-specific diagnostics were rarely performed. Extra-cardiac differential diagnoses were not specified. CONCLUSION: The establishment of broader awareness programs and opening CPUs for low-threshold evaluation of self-referring patients should be discussed. Regarding the rigid focus on the clarification of cardiac causes of chest pain, a stronger interdisciplinary approach should be promoted.

Relationship Between Quantitative Tracheal Geometry and Clinical Course in Various Types of Vascular Ring.

To investigate the relationship between quantitative tracheal geometry and clinical course among various types of vascular ring and to identify factors correlating with symptom presentation. Patients with vascular ring diagnosed between April 2010 and December 2022 were included. All the patients were classified as type 1 (complete double aortic arch); type 2 (incomplete double aortic arch); type 3 (circumflex aorta); type 4 (right aortic arch and aberrant left subclavian artery with a left retroesophageal diverticulum of Kommerell); or type 5 (mirror-imaged right aortic arch with retroesophageal aortic diverticulum). Their clinical characteristics and quantitative variables on computed tomography (CT) were compared. Of the 50 patients enrolled, those with type 1 tended to have a smaller luminal tracheal diameter at the level of the ring. The median symptom-free survival time was shortest in this group (16.0 days [95% confidence interval (CI): 9.4-51.0]), followed by type 3 (138.0 days [95% CI: 0.0-851.4]). Type 1 (hazard ratio [HR]: 9.0; 95% CI: 2.3-35.0; P = 0.001), type 3 (HR: 4.2; 95% CI: 1.4-13.2; P = 0.013), and the percentage of tracheal narrowing in the anteroposterior projection (HR: 0.87; 95% CI: 0.78-0.96; P = 0.008) were significantly associated with symptom presentation in the time-dependent course. The aortic arch encircling the entire circumference in type 1 and high-pressure vasculature in front of the vertebral body in types 1 and 3 may contribute to raising the risk of symptom presentation.

Factors impacting D-dimer levels in patients with acute ischemic cerebrovascular events.

BACKGROUND AND OBJECTIVES: A better understanding of the factors influencing D-dimer levels in code stroke patients is needed to guide further investigations of concomitant thrombotic conditions. This study aimed to investigate the impact of time from symptom onset and other factors on D-dimer levels in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). METHODS: Data on consecutive AIS and TIA patients treated at our tertiary-care stroke center between January 2015 and December 2020 were retrospectively assessed. Patients with available D-dimer levels were evaluated for eligibility. Multivariable non-linear regression analyses were performed. RESULTS: In total, 2467 AIS patients and 708 TIA patients were included. The median D-dimer levels differed between the AIS and TIA groups (746 µg/L [interquartile range 381-1468] versus 442 µg/L [interquartile range 244-800], p<0.001). In AIS patients, an early increase in D-dimer levels was demonstrated within the first 6 h (standardized beta coefficient [ß] 0.728; 95% confidence interval [CI] 0.324-1.121). This was followed by an immediate decrease (ß -13.022; 95% CI -20.401 to -5.643) and then by a second, late increase after 35 h (ß 11.750; 95% CI 4.71-18.791). No time-dependent fluctuation in D-dimer levels was observed in TIA patients. CONCLUSION: The time from symptom onset may affect D-dimer levels in patients with AIS but not those with TIA. Further studies confirming these findings and validating time-specific variations are needed to enable D-dimer levels to be used efficiently as an acute stroke and thrombotic risk biomarker.

The APOE4 effect: structural brain differences in Alzheimer's disease according to the age at symptom onset.

BACKGROUND AND PURPOSE: How the APOE genotype can differentially affect cortical and subcortical memory structures in biomarker-confirmed early-onset (EOAD) and late-onset (LOAD) Alzheimer's disease (AD) was assessed. METHOD: Eighty-seven cerebrospinal fluid (CSF) biomarker-confirmed AD patients were classified according to their APOE genotype and age at onset. 28 were EOAD APOE4 carriers (+EOAD), 21 EOAD APOE4 non-carriers (-EOAD), 23 LOAD APOE4 carriers (+LOAD) and 15 LOAD APOE4 non-carriers (-LOAD). Grey matter (GM) volume differences were analyzed using voxel-based morphometry in Papez circuit regions. Multiple regression analyses were performed to determine the relation between GM volume loss and cognition. RESULTS: Significantly more mammillary body atrophy in +EOAD compared to -EOAD is reported. The medial temporal and posterior cingulate cortex showed less GM in +LOAD compared to -LOAD. Medial temporal GM volume loss was also found in +EOAD compared to -LOAD. With an exception for +EOAD, medial temporal GM was strongly associated with episodic memory in the three groups, whilst posterior cingulate cortex GM volume was more related with visuospatial abilities. Visuospatial abilities and episodic memory were also associated with the anterior thalamic nucleus in -LOAD. CONCLUSIONS: Our results show that the APOE genotype has a significant effect on GM integrity as a function of age of disease onset. Specifically, whilst LOAD APOE4 genotype is mostly associated with increased medial temporal and parietal atrophy compared to -LOAD, for EOAD APOE4 might have a more specific effect on subcortical (mammillary body) structures. The findings suggest that APOE genotype needs to be taken into account when classifying patients by age at onset.

Rapid review and meta-analysis of serial intervals for SARS-CoV-2 Delta and Omicron variants.

BACKGROUND: The serial interval is the period of time between symptom onset in the primary case and symptom onset in the secondary case. Understanding the serial interval is important for determining transmission dynamics of infectious diseases like COVID-19, including the reproduction number and secondary attack rates, which could influence control measures. Early meta-analyses of COVID-19 reported serial intervals of 5.2 days (95% CI: 4.9-5.5) for the original wild-type variant and 5.2 days (95% CI: 4.87-5.47) for Alpha variant. The serial interval has been shown to decrease over the course of an epidemic for other respiratory diseases, which may be due to accumulating viral mutations and implementation of more effective nonpharmaceutical interventions. We therefore aggregated the literature to estimate serial intervals for Delta and Omicron variants. METHODS: This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A systematic literature search was conducted of PubMed, Scopus, Cochrane Library, ScienceDirect, and preprint server medRxiv for articles published from April 4, 2021, through May 23, 2023. Search terms were: ("serial interval" or "generation time"), ("Omicron" or "Delta"), and ("SARS-CoV-2" or "COVID-19"). Meta-analyses were done for Delta and Omicron variants using a restricted maximum-likelihood estimator model with a random effect for each study. Pooled average estimates and 95% confidence intervals (95% CI) are reported. RESULTS: There were 46,648 primary/secondary case pairs included for the meta-analysis of Delta and 18,324 for Omicron. Mean serial interval for included studies ranged from 2.3-5.8 days for Delta and 2.1-4.8 days for Omicron. The pooled mean serial interval for Delta was 3.9 days (95% CI: 3.4-4.3) (20 studies) and Omicron was 3.2 days (95% CI: 2.9-3.5) (20 studies). Mean estimated serial interval for BA.1 was 3.3 days (95% CI: 2.8-3.7) (11 studies), BA.2 was 2.9 days (95% CI: 2.7-3.1) (six studies), and BA.5 was 2.3 days (95% CI: 1.6-3.1) (three studies). CONCLUSIONS: Serial interval estimates for Delta and Omicron were shorter than ancestral SARS-CoV-2 variants. More recent Omicron subvariants had even shorter serial intervals suggesting serial intervals may be shortening over time. This suggests more rapid transmission from one generation of cases to the next, consistent with the observed faster growth dynamic of these variants compared to their ancestors. Additional changes to the serial interval may occur as SARS-CoV-2 continues to circulate and evolve. Changes to population immunity (due to infection and/or vaccination) may further modify it.

Demographic and geographic variations in the access time of pediatric patients presenting with staring spells.

OBJECTIVE: To assess the demographic and geographic variations in access time - defined as years between the date of symptom onset and initial date of neurological care - in pediatric patients presenting with staring spells. MATERIALS AND METHODS: We conducted a secondary analysis of a retrospective chart review study from 2011 to 2021. A total of 1,353 staring spell patients, aged 0 to 17.9 years, were analyzed for age, sex, race/ethnicity, insurance, county, average county annual per capita personal income, and access time. RESULTS: Patients aged 0-2.9 years had the shortest median access time of 0.3 years, compared to 1.2 years in patients aged 3-12.9 years and 1.0 year in patients aged 13-17.9 years. Statistically significant differences were seen based on race/ethnicity and insurance with White patients having shorter access time of 0.5 years compared to Black patients with 1.0 year and self-pay patients having the shortest access time of 0.4 years compared to patients with private insurance (0.7 years). Warren County had the largest annual per capita personal income of $65,855 and access time of 0.5 years compared to Preble county with the least annual per capita personal income of $45,016 and access time of 1.1 years. CONCLUSION: Demographic parameters of age, race/ethnicity, insurance, and annual county per capita personal income appeared to be associated with access time to initial neurological care in patients with staring spells. These associations need to be investigated further to ensure timely access to neurological care and to ensure equity in health care.

Pre-hospital delay, clinical characteristics, angiographic findings, and in-hospital mortality in young and middle-aged adults with acute coronary syndrome: a single-centre registry analysis.

There are several differences between younger and older adults with acute coronary syndrome (ACS). However, few studies have evaluated these differences. We analysed the pre-hospital time interval [symptom onset to first medical contact (FMC)], clinical characteristics, angiographic findings, and in-hospital mortality in patients aged ≤50 (group A) and 51-65 (group B) years hospitalised for ACS. We retrospectively collected data from 2010 consecutive patients hospitalised with ACS between 1 October 2018 and 31 October 2021 from a single-centre ACS registry. Groups A and B included 182 and 498 patients, respectively. ST-segment elevation myocardial infarction (STEMI) was more common in group A than group B (62.6 and 45.6%, respectively; P < 0.001). The median time from symptom onset to FMC in STEMI patients did not significantly differ between groups A and B [74 (40-198) and 96 (40-249) min, respectively; P = 0.369]. There was no difference in the rate of sub-acute STEMI (symptom onset to FMC > 24 h) between groups A and B (10.4% and 9.0%, respectively; P = 0.579). Among patients with non-ST elevation acute coronary syndrome (NSTE-ACS), 41.8 and 50.2% of those in groups A and B, respectively, presented to the hospital within 24 h of symptom onset (P = 0.219). The prevalence of previous myocardial infarction was 19.2% in group A and 19.5% in group B (P = 1.00). Hypertension, diabetes, and peripheral arterial disease were more common in group B than group A. Active smoking was more common in group A than group B (67 and 54.2%, respectively; P = 0.021). Single-vessel disease was present in 52.2 and 37.1% of participants in groups A and B, respectively (P = 0.002). Proximal left anterior descending artery was more commonly the culprit lesion in group A compared with group B, irrespective of the ACS type (STEMI, 37.7 and 24.2%, respectively; P = 0.009; NSTE-ACS, 29.4 and 21%, respectively; P = 0.140). The hospital mortality rate for STEMI patients was 1.8 and 4.4% in groups A and B, respectively (P = 0.210), while for NSTE-ACS patients it was 2.9 and 2.6% in groups A and B, respectively (P = 0.873). No significant differences in pre-hospital delay were found between young (≤50 years) and middle-aged (51-65 years) patients with ACS. Although clinical characteristics and angiographic findings differ between young and middle-aged patients with ACS, the in-hospital mortality rate did not differ between the groups and was low for both of them.

Assessing the impact of temperature and humidity exposures during early infection stages on case-fatality of COVID-19: A modelling study in Europe.

Background Although associations between key weather indicators (i.e. temperature and humidity) and COVID-19 mortality have been reported, the relationship between these exposures at different timings in early infection stages (from virus exposure up to a few days after symptom onset) and the probability of death after infection (also called case fatality rate, CFR) has yet to be determined. Methods We estimated the instantaneous CFR of eight European countries using Bayesian inference in conjunction with stochastic transmission models, taking account of delays in reporting the number of newly confirmed cases and deaths. The exposure-lag-response associations between fatality rate and weather conditions to which patients were exposed at different timings were obtained using distributed lag nonlinear models coupled with mixed-effect models. Results Our results show that the Odds Ratio (OR) of death is negatively associated with the temperature, with two maxima (OR = 1.29 (95% CI: 1.23, 1.35) at -0.1°C; OR = 1.12 (95% CI: 1.08, 1.16) at 0.1°C) occurring at the time of virus exposure and after symptom onset. Two minima (OR = 0.81 (95% CI: 0.71, 0.92) at 23.2°C; OR = 0.71 (95% CI: 0.63, 0.80) at 21.7°C) also occurred at these two distinct periods correspondingly. Low humidity (below 50%) during the early stages and high humidity (approximately 89%) after symptom onset were related to the lower fatality. Conclusion Environmental conditions may affect not only the initial viral load when patients are exposed to the virus, but also individuals' immune response around symptom onset. Warmer temperatures and higher humidity after symptom onset were linked to lower fatality.

Estimated incubation period for monkeypox cases confirmed in the Netherlands, May 2022.

In May 2022, monkeypox outbreaks have been reported in countries not endemic for monkeypox. We estimated the monkeypox incubation period, using reported exposure and symptom-onset times for 18 cases detected and confirmed in the Netherlands up to 31 May 2022. Mean incubation period was 9.0 [corrected] days (5th-95th percentiles: 4.2-17.3), underpinning the current recommendation to monitor or isolate/quarantine case contacts for 21 days. However, as the incubation period may differ between different transmission routes, further epidemiological investigations are needed.

Symptomatic discoid lateral meniscus shows a relationship between types and tear patterns, and between causes of clinical symptom onset and the age distribution.

PURPOSE: Discoid meniscus is a congenital abnormality of the lateral meniscus and is seen more frequently in East Asia. The purpose of this study was to retrospectively assess the relationship between discoid lateral meniscus (DLM) types and tear patterns and causes of age-specific clinical symptom onset. METHODS: Of 1650 arthroscopic surgeries over a 20-year period, 138 (105 patients) were performed for DLM and were evaluated in this study. The mean age at surgery was 21.5 ± 15.8 years. The DLM type was classified by Watanabe's classification, and tear patterns were classified by the modified Bin's classification as simple horizontal, complicated horizontal, longitudinal, radial, complex, and no tear. Additionally, patients were divided by age group (< 10, 10-19, 20-39, 40-59, and ≥ 60 years) and classified according to the causes of clinical symptom onset as follows: sports activities, minor trauma in daily living, and no traumatic episode. RESULTS: The DLM was complete in 78 (56.5%) knees and incomplete in 60 (43.5%); no Wrisberg type DLM was observed. Simple horizontal and complicated horizontal tears were significantly more frequent in complete DLM, whereas radial tears and no tears were significantly more frequent in incomplete DLM (p < 0.0001). When classified by age group, 74 (53.6%) knees with DLMs were found in teenagers. Sports activities caused symptom onset significantly more often in teenagers, no traumatic episode caused symptom onset in patients aged < 10 years, and minor trauma in daily living caused symptom onset in patients aged 40-59 years and ≥ 60 years (p < 0.0001). No relationship was found between the age distribution and tear patterns; however, the absence of tears tended to be more common in teenaged patients, and complicated horizontal tears were more common in patients over 20 years of age. CONCLUSION: Symptomatic DLM occurred most often in teenagers. A relationship was identified between the DLM types and tear patterns, which could be helpful in preoperative planning. Causes of clinical symptom onset in patients with DLM were characterised by age group, which might help clinicians to suspect the presence of DLM. LEVEL OF EVIDENCE: Level IV.

Laterality of motor symptom onset and facial expressivity in Parkinson disease using face digitization.

The onset of motor symptoms in Parkinson disease (PD) is typically unilateral. Previous work has suggested that laterality of motor symptoms may also influence non-motor symptoms including cognition and emotion perception. In line with hemispheric differences in emotion processing, we tested whether left side/right brain motor onset was associated with worse expression of facial affect when compared to right side/left brain motor onset. We evaluated movement changes associated with facial affect in 30 patients with idiopathic PD (15 left-sided motor onset, 15 right-sided motor onset) and 20 healthy controls. Participants were videotaped while posing three facial expressions: fear, anger, and happiness. Expressions were digitized and analyzed using software that extracted three variables: two measures of dynamic movement change (total entropy and entropy percent change) and a measure of time to initiate facial expression (latency). The groups did not differ in overall amount of movement change or percentchange. However, left-sided onset PD patients were significantly slower in initiating anger and happiness facial expressions than were right-sided onset PD patients and controls. Our results indicated PD patients with left-sided symptom onset had greater latency in initiating two of three facial expressions, which may reflect laterality effects in intentional behaviour.

A Meta-Analysis Study of SOD1-Mutant Mouse Models of ALS to Analyse the Determinants of Disease Onset and Progression.

A complex interaction between genetic and external factors determines the development of amyotrophic lateral sclerosis (ALS). Epidemiological studies on large patient cohorts have suggested that ALS is a multi-step disease, as symptom onset occurs only after exposure to a sequence of risk factors. Although the exact nature of these determinants remains to be clarified, it seems clear that: (i) genetic mutations may be responsible for one or more of these steps; (ii) other risk factors are probably linked to environment and/or to lifestyle, and (iii) compensatory plastic changes taking place during the ALS etiopathogenesis probably affect the timing of onset and progression of disease. Current knowledge on ALS mechanisms and therapeutic targets, derives mainly from studies involving superoxide dismutase 1 (SOD1) transgenic mice; therefore, it would be fundamental to verify whether a multi-step disease concept can also be applied to these animal models. With this aim, a meta-analysis study has been performed using a collection of primary studies (n = 137), selected according to the following criteria: (1) the studies should employ SOD1 transgenic mice; (2) the studies should entail the presence of a disease-modifying experimental manipulation; (3) the studies should make use of Kaplan-Meier plots showing the distribution of symptom onset and lifespan. Then, using a subset of this study collection (n = 94), the effects of treatments on key molecular mechanisms, as well as on the onset and progression of disease have been analysed in a large population of mice. The results are consistent with a multi-step etiopathogenesis of disease in ALS mice (including two to six steps, depending on the particular SOD1 mutation), closely resembling that observed in patient cohorts, and revealed an interesting relationship between molecular mechanisms and disease manifestation. Thus, SOD1 mouse models may be considered of high predictive value to understand the determinants of disease onset and progression, as well as to identify targets for therapeutic interventions.

Viral Cultures for Coronavirus Disease 2019 Infectivity Assessment: A Systematic Review.

BACKGROUND: We aimed to review the evidence from studies relating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) culture with the results of reverse-transcription polymerase chain reaction (RT-PCR) and other variables that may influence the interpretation of the test, such as time from symptom onset. METHODS: We searched LitCovid, medRxiv, Google Scholar, and the World Health Organization coronavirus disease 2019 (COVID-19) database for COVID-19 up to 10 September 2020. We included studies attempting to culture or observe SARS-CoV-2 in specimens with RT-PCR positivity. Studies were dual-extracted and the data summarized narratively by specimen type. Where necessary, we contacted corresponding authors of included papers for additional information. We assessed quality using a modified Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2) risk-of-bias tool. RESULTS: We included 29 studies reporting attempts at culturing, or observing tissue infection by, SARS-CoV-2 in sputum, nasopharyngeal or oropharyngeal, urine, stool, blood, and environmental specimens. The quality of the studies was moderate with lack of standardized reporting. The data suggest a relationship between the time from onset of symptom to the timing of the specimen test, cycle threshold (Ct), and symptom severity. Twelve studies reported that Ct values were significantly lower and log copies higher in specimens producing live virus culture. Two studies reported that the odds of live virus culture were reduced by approximately 33% for every 1-unit increase in Ct. Six of 8 studies reported detectable RNA for >14 days, but infectious potential declined after day 8 even among cases with ongoing high viral loads. Four studies reported viral culture from stool specimens. CONCLUSIONS: Complete live viruses are necessary for transmission, not the fragments identified by PCR. Prospective routine testing of reference and culture specimens and their relationship to symptoms, signs, and patient co-factors should be used to define the reliability of PCR for assessing infectious potential. Those with high Ct are unlikely to have infectious potential.

Anti-neutrophil cytoplasmic antibodies predate symptom onset of ANCA-associated vasculitis. A case-control study.

OBJECTIVES: Anti-neutrophil cytoplasmic autoantibodies [ANCA) are important for diagnosis of ANCA-associated vasculitides (AAV). The timing of antibody development is not well established. To investigate the development of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA, blood samples collected before onset of symptoms of AAV were analysed. METHODS: To identify AAV patients with blood samples predating symptoms, the National Patient Register and Cause of Death register were scrutinized for ICD codes for AAV and linked to the registers of five biobanks. Diagnoses of AAV and time point for symptom onset were confirmed by reviewing 504 case-record. Eighty-five AAV cases (34 males, 51 females) with samples >1 month < 10 years from AAV symptom onset and two controls matched for sex, age, and sampling time for each case were included. Samples were screened using ELISAs for ANCA and further analysed for PR3-or MPO- specificities. RESULTS: In ANCA-screen 35.7% of the pre-symptomatic cases and 3.5% of controls tested positive (p < 0.01). 26.2% of the cases were PR3-ANCA+ and 10.7% MPO-ANCA+. Median (Q1-Q3) predating time for PR3-ANCA+ was 2.7 (0.3-7.7) years and MPO-ANCA+ 2.0 (0.9-3.5) years. PR3-ANCA was demonstrated in samples up to nine years before symptom onset. At symptom onset predating PR3-ANCA+ cases were younger than PR3-ANCA- (P < 0.01), and MPO-ANCA+ were older than MPO-ANCA- (p < 0.05). Predating MPO-ANCA+ cases vs. MPO-ANCA- and vs. PR3-ANCA+ cases had more often at symptoms onset manifestations from lungs, kidneys or peripheral nervous system (p < 0.01 and p < 0.05, respectively). CONCLUSION: The PR3-and MPO-ANCAs are present years before AAV symptom onset and represent distinct diseases.

Clinical performance of three fully automated anti-SARS-CoV-2 immunoassays targeting the nucleocapsid or spike proteins.

This study assesses the clinical performance of three anti-SARS-CoV-2 assays, namely EUROIMMUN anti-SARS-CoV-2 nucleocapsid (IgG) ELISA, Elecsys anti-SARS-CoV-2 nucleocapsid (total antibodies) assay, and LIAISON anti-SARS-CoV-2 spike proteins S1 and S2 (IgG) assay. One hundred and thirty-seven coronavirus disease 2019 (COVID-19) samples from 96 reverse-transcription polymerase chain reaction confirmed patients were chosen to perform the sensitivity analysis. Non-SARS-CoV-2 sera (n = 141) with a potential cross-reaction to SARS-CoV-2 immunoassays were included in the specificity analysis. None of these tests demonstrated a sufficiently high clinical sensitivity to diagnose acute infection. Fourteen days since symptom onset, we did not find any significant difference between the three techniques in terms of sensitivities. However, Elecsys performed better in terms of specificity. All three anti-SARS-CoV-2 assays had equivalent sensitivities 14 days from symptom onset to diagnose past-COVID-19 infection. We also confirmed that anti-SARS-CoV-2 determination before Day 14 is of less clinical interest.

Impact of the COVID-19 outbreak on hospitalizations and outcomes in patients with acute myocardial infarction in a Japanese Single Center.

There are a few Japanese data regarding the incidence and outcomes of acute myocardial infarction (AMI) after the coronavirus disease 2019 (COVID-19) outbreak. We retrospectively reviewed the data of AMI patients admitted to the Nihon University Itabashi Hospital after a COVID-19 outbreak in 2020 (COVID-19 period) and the same period from 2017 to 2019 (control period). The patients' characteristics, time course of admission, diagnosis, and treatment of AMI, and 30-day mortality were compared between the two period-groups for both ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI), respectively. The AMI inpatients decreased by 5.7% after the COVID-19 outbreak. There were no differences among most patient backgrounds between the two-period groups. For NSTEMI, the time from the symptom onset to admission was significantly longer, and that from the AMI diagnosis to the catheter examination tended to be longer during the COVID-19 period than the control period, but not for STEMI. The 30-day mortality was significantly higher during the COVID-19 period for NSTEMI (23.1% vs. 1.9%, P = 0.004), but not for STEMI (9.4% vs. 8.3%, P = 0.77). In conclusion, hospitalizations for AMI decreased after the COVID-19 outbreak. Acute cardiac care for STEMI and the associated outcome did not change, but NSTEMI outcome worsened after the COVID-19 outbreak, which may have been associated with delayed medical treatment due to the indirect impact of the COVID-19 pandemic.

A retrospective chart review study of symptom onset, diagnosis, comorbidities, and treatment in patients with binge eating disorder in Canadian clinical practice.

PURPOSE: In the Canadian healthcare setting, there is limited understanding of the pathways to diagnosis and treatment for patients with binge eating disorder (BED). METHODS: This retrospective chart review examined the clinical characteristics, diagnostic pathways, and treatment history of adult patients diagnosed with BED. RESULTS: Overall, 202 charts from 57 healthcare providers (HCPs) were reviewed. Most patients were women (69%) and white (78%). Mean ± SD patient age was 37 ± 12.1 years. Comorbidities identified in > 20% of patients included obesity (50%), anxiety (49%), depression and/or major depressive disorder (46%), and dyslipidemia (26%). Discussions regarding a diagnosis of BED were typically initiated more often by HCPs than patients. Most patients (64%) received a diagnosis of BED ≥ 3 years after symptom onset. A numerically greater percentage of patients received (past or current) nonpharmacotherapy than pharmacotherapy (84% vs. 67%). The mean ± SD number of binge eating episodes/week numerically decreased from pretreatment to follow-up with lisdexamfetamine (5.4 ± 2.8 vs. 1.7 ± 1.2), off-label pharmacotherapy (4.7 ± 3.9 vs. 2.0 ± 1.13), and nonpharmacotherapy (6.3 ± 4.8 vs. 3.5 ± 6.0) Across pharmacotherapies and nonpharmacotherapies, most patients reported improvement in symptoms of BED (84-97%) and in overall well-being (80-96%). CONCLUSIONS: These findings highlight the importance of timely diagnosis and treatment of BED. Although HCPs are initiating discussions about BED, earlier identification of BED symptoms is required. Furthermore, these data indicate that pharmacologic and nonpharmacologic treatment for BED is associated with decreased binge eating and improvements in overall well-being. LEVEL OF EVIDENCE: IV, chart review.

Hypertension Is Associated With an Earlier Age of Onset of Huntington's Disease.

BACKGROUND AND OBJECTIVE: Hypertension (HTN) is associated with worsening clinical outcomes in neurodegenerative diseases. The relationship between HTN and the age of diagnosis (ADx) of Huntington's disease (HD) is not clear, however. This study sought to determine if the presence of HTN in adult patients with premanifest HD was associated with an earlier ADx compared with normotensive patients with HD. METHODS: Premanifest participants from Enroll-HD were included if they had a cytosine-adenine-guanine greater than or equal to 36, baseline diagnostic confidence level less than 4, baseline total functional capacity score greater than 11, and baseline motor score less than 21. There were 3020 premanifest participants with HD, and 293 reported a diagnosis of HTN. HTN was transformed into a time-dependent variable, and a Cox proportional hazard survival model determine if the presence of HTN affected the time to motor conversion. Baseline cytosine-adenine-guanine-age product score, cytosine-adenine-guanine repeat length, baseline age, sex, baseline body mass index, smoking history, and region were included as covariates. RESULTS: Participants with HTN had an increased annualized hazard of motor conversion compared to normotensive participants with HD (hazard ratio, 1.29; 95% confidence interval, 1.02-1.64; P = 0.034). CONCLUSIONS: A previous study reported a protective effect of HTN in HD, but did not account for the fact that the prevalence of HTN increases with age. By controlling for this confounder, we more accurately outline the association between the ADx of HD to demonstrate that a diagnosis of HTN may be associated with an earlier ADx of HD. These results represent an association, however, and further investigation is warranted. © 2020 International Parkinson and Movement Disorder Society.

Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20-28 January 2020.

A novel coronavirus (2019-nCoV) is causing an outbreak of viral pneumonia that started in Wuhan, China. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan in the early outbreak phase, we estimate the mean incubation period to be 6.4 days (95% credible interval: 5.6-7.7), ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values should help inform 2019-nCoV case definitions and appropriate quarantine durations.