Impact of Clinician Training Background and Stroke Location on Bedside Diagnostic Test Accuracy in the Acute Vestibular Syndrome - A Meta-Analysis.

OBJECTIVE: Acute dizziness/vertigo is usually due to benign inner-ear causes but is occasionally due to dangerous neurologic ones, particularly stroke. Because symptoms and signs overlap, misdiagnosis is frequent and overuse of neuroimaging is common. We assessed the accuracy of bedside findings to differentiate peripheral vestibular from central neurologic causes. METHODS: We performed a systematic search (MEDLINE and Embase) to identify studies reporting on diagnostic accuracy of physical examination in adults with acute, prolonged dizziness/vertigo ("acute vestibular syndrome" [AVS]). Diagnostic test properties were calculated for findings. Results were stratified by examiner type and stroke location. RESULTS: We identified 6,089 citations and included 14 articles representing 10 study cohorts (n = 800). The Head Impulse, Nystagmus, Test of Skew (HINTS) eye movement battery had high sensitivity 95.3% (95% confidence interval [CI] = 92.5-98.1) and specificity 92.6% (95% CI = 88.6-96.5). Sensitivity was similar by examiner type (subspecialists 94.3% [95% CI = 88.2-100.0] vs non-subspecialists 95.0% [95% CI = 91.2-98.9], p = 0.55), but specificity was higher among subspecialists (97.6% [95% CI = 94.9-100.0] vs 89.1% [95% CI = 83.0-95.2], p = 0.007). HINTS sensitivity was lower in anterior cerebellar artery (AICA) than posterior inferior cerebellar artery (PICA) strokes (84.0% [95% CI = 65.3-93.6] vs 97.7% [95% CI = 93.3-99.2], p = 0.014) but was "rescued" by the addition of bedside hearing tests (HINTS+). Severe (grade 3) gait/truncal instability had high specificity 99.2% (95% CI = 97.8-100.0) but low sensitivity 35.8% (95% CI = 5.2-66.5). Early magnetic resonance imaging (MRI)-diffusion-weighted imaging (DWI; within 24-48 hours) was falsely negative in 15% of strokes (sensitivity 85.1% [95% CI = 79.2-91.0]). INTERPRETATION: In AVS, HINTS examination by appropriately trained clinicians can differentiate peripheral from central causes and has higher diagnostic accuracy for stroke than MRI-DWI in the first 24-48 hours. These techniques should be disseminated to all clinicians evaluating dizziness/vertigo. ANN NEUROL 2023;94:295-308.

Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection.

BACKGROUND: The definition of sudden sensorineural hearing loss (SSNHL) is broadly accepted as acute sensorineural hearing loss of more than 30 dB over at least three consecutive frequencies in a pure-tone audiogram (PTA). Acute audiovestibular loss is common with ischaemic stroke in the territory of the anterior inferior cerebellar artery (AICA). However, cases in which SSNHL and vertigo occur with hypoperfusion alone are very rare. We describe a patient who developed unilateral SSNHL and vertigo as initial symptoms caused by cerebellar hypoperfusion by vertebral artery (VA) dissection without the occurrence of infarction. CASE PRESENTATION: A 51-year-old man suddenly developed acute hearing loss (AHL) in his left ear and vertigo. On neurological examination, he had vibration-induced right-beating nystagmus and left-beating nystagmus after a head-shaking test. Additionally, he had apogeotropic nystagmus during head turns to either side. The head impulse test (HIT) was normal. PTA showed mild unilateral SSNHL in the left ear. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) showed territorial perfusion deficits in the left posterior inferior cerebellar artery (PICA) and anterior inferior cerebellar artery (AICA) without infarction. Two months later, the patient had no vertigo but still had hearing impairment in his left ear. A follow-up PTA documented persistent unilateral SSNHL in the left ear. Additionally, perfusion computed tomography (CT) showed that perfusion deficits remained in the left cerebellum along the PICA and AICA territories. CONCLUSIONS: Our case highlights a case of AHL and vertigo presented by isolated cerebellar hypoperfusion without infarction. It is necessary to consider the possibility of a central cause in patients with AHL and vertigo, and it is important to confirm this possibility through brain magnetic resonance imaging (MRI), including PWI, and magnetic resonance angiography (MRA).

An open-source framework for fast-yet-accurate calculation of quantum mechanical features.

We present the open-source framework kallisto that enables the efficient and robust calculation of quantum mechanical features for atoms and molecules. For a benchmark set of 49 experimental molecular polarizabilities, the predictive power of the presented method competes against second-order perturbation theory in a converged atomic-orbital basis set at a fraction of its computational costs. The calculation of isotropic molecular polarizabilities is robust for a data set of more than 80 000 molecules. We present furthermore a generally applicable van der Waals radius model that is rooted on atomic static polarizabilites. Efficiency tests show that such radii can even be calculated for small- to medium-size proteins where the largest system (SARS-CoV-2 spike protein) has 42 539 atoms. Following the work of Domingo-Alemenara et al. [Domingo-Alemenara et al., Nat. Commun., 2019, 10, 5811], we present computational predictions for retention times for different chromatographic methods and describe how physicochemical features improve the predictive power of machine-learning models that otherwise only rely on two-dimensional features like molecular fingerprints. Additionally, we developed an internal benchmark set of experimental super-critical fluid chromatography retention times. For those methods, improvements of up to 10.6% are obtained when combining molecular fingerprints with physicochemical descriptors. Shapley additive explanation values show furthermore that the physical nature of the applied features can be retained within the final machine-learning models. We generally recommend the kallisto framework as a robust, low-cost, and physically motivated featurizer for upcoming state-of-the-art machine-learning studies.

Evaluation of cardiovascular biomarkers and histopathological alterations in cattle naturally infected by Babesia bigemina.

Hemolytic anemia and secondary hypoxia are characteristics of naturally occurring Babesia bigemina infection in cattle. The anemic phase comes with cardiovascular insufficiency due to hypoxia-induced system dysfunction; but to date there is no description of cardiac damage in the infected animals. Therefore, this study was undertaken to investigate hematological parameters, biomarkers of cardiac function and D-dimer in 13 cattle infected with B. bigemina which were unresponsive to standard treatment. The animals were necropsied and the cardiac tissue was examined for histopathologic alterations. A significant parasitemia burden-dependent increase in the cardiac biomarkers and D-dimer level were recorded in the infected cattle compared to the control animals. Thrombocytes count was also significantly lower in the infected animals than the control. Both macroscopic and microscopic hemorrhage, mononuclear infiltrates, and myocardial necrosis were the evident histopathologic findings. These findings suggest that B. bigemina infection can potentially induce cardiac dysfunction in cattle. Furthermore, mechanistic studies should be conducted to understand the mechanisms beyond cardiac complications.

Consensus on Virtual Management of Vestibular Disorders: Urgent Versus Expedited Care.

The virtual practice has made major advances in the way that we care for patients in the modern era. The culture of virtual practice, consulting, and telemedicine, which had started several years ago, took an accelerated leap as humankind was challenged by the novel coronavirus pandemic (COVID19). The social distancing measures and lockdowns imposed in many countries left medical care providers with limited options in evaluating ambulatory patients, pushing the rapid transition to assessments via virtual platforms. In this novel arena of medical practice, which may form new norms beyond the current pandemic crisis, we found it critical to define guidelines on the recommended practice in neurotology, including remote methods in examining the vestibular and eye movement function. The proposed remote examination methods aim to reliably diagnose acute and subacute diseases of the inner-ear, brainstem, and the cerebellum. A key aim was to triage patients into those requiring urgent emergency room assessment versus non-urgent but expedited outpatient management. Physicians who had expertise in managing patients with vestibular disorders were invited to participate in the taskforce. The focus was on two topics: (1) an adequate eye movement and vestibular examination strategy using virtual platforms and (2) a decision pathway providing guidance about which patient should seek urgent medical care and which patient should have non-urgent but expedited outpatient management.

A retrospective observational population-based study to assess the prevalence and burden of illness of type 2 diabetes with an estimated glomerular filtration rate < 90 mL/min/1.73 m2 in Ontario, Canada.

AIM: To better understand the healthcare burden of people with type 2 diabetes (T2D) and estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 in Ontario, Canada. MATERIALS AND METHODS: We used administrative data to evaluate the prevalence of T2D, eGFR < 90 mL/min/1.73 m2 and adverse cardiovascular co-morbidities in individuals aged ≥ 30 years living in Ontario, Canada. We also examined incremental healthcare costs and healthcare resource utilization (HCRU) for these patients with specific incident cardiovascular and renal outcomes, in comparison with controls without these outcomes. RESULTS: While the prevalence of T2D in the general population aged ≥ 30 years in Ontario increased by 1.8% over a 5-year period (2011-2012 to 2015-2016), the prevalence of eGFR < 90 mL/min/1.73 m2 among people with T2D increased by 35%. In comparison with corresponding controls without these outcomes, the per patient average total costs (Canadian dollars) over a 2-year analysis period were higher for patients with cardiovascular disease/chronic kidney disease related death ($69 827; n = 32 407), doubling of serum creatinine ($52 260; n = 22 825), those who started dialysis ($150 627; n = 3499) or received a kidney transplant ($50 664; n = 651). Similarly, HCRU was significantly greater for patients with these incident outcomes. CONCLUSIONS: This real-world retrospective study highlights an increasing prevalence of T2D, eGFR < 90 mL/min/1.73 m2 , and the substantially higher healthcare costs and HCRU when these patients have adverse cardiovascular and renal outcomes. The existence of such a large economic burden underpins the importance of preventing these diabetes-related complications.

Non-Adherent Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Clinical Manifestations and Inflammation in an Experimental Model of Ulcerative Colitis in Rats.

BACKGROUND: Functional and developmental versatility of mesenchymal stem cells (MSCs) have generated great interest in their clinical application. Recently, it has been proposed that the non-adherent population of bone marrow cells can differentiate to MSCs in vitro. The present study aimed to compare the anti-inflammatory potentials of adherent and non-adherent MSCs in an experimental model of ulcerative colitis (UC) in rats. METHODS: The present experimental study was conducted at the School of Veterinary Medicine, Urmia University (Urmia, Iran) during March-May 2018. UC was induced using acetic acid in three groups of male Wistar rats, namely the control colitis, adherent MSCs treated, and non-adherent MSCs treated groups. Adherent and non-adherent MSCs were collected, characterized, and proliferated. The isolated cells were injected into the peritoneum of the respective groups of colitis rats. After 10 days, the animals were evaluated for gross and microscopic pathology, production of inflammatory mediators, and stress oxidative profile in the gut tissue. The statistical analysis was performed using SPSS software (version 23.0). P<0.05 was considered statistically significant. RESULTS: The non-adherent MSCs had almost similar therapeutic potency compared to the adherent MSCs (P=0.12). They significantly reduced the level of inflammatory mediators and improved the oxidative stress profile in colonic tissue compared to the control colitis group (P=0.0001). CONCLUSION: The molecular assays and histopathological assessment revealed that the non-adherent MSCs not only had anti-inflammatory and regulatory potency but also enhanced tissue regeneration in UC rats. Therefore, the non-adherent fraction of bone marrow-derived MSCs could be used as a complementary source of MSCs in stem cell therapies.

Upregulation of FSHR and PCNA by administration of coenzyme Q10 on cyclophosphamide-induced premature ovarian failure in a mouse model.

Cyclophosphamide (CTX) has been broadly used in the clinic for the treatment of autoimmune disorders and ovarian cancer. The process of chemotherapy has significant toxicity in the reproductive system as it has detrimental effects on folliculogenesis, which leads to an irreversible premature ovarian failure (POF). Coenzyme Q10 (CoQ10) has positive impacts on the reproductive system due to its antioxidant properties, protecting the cells from free-radical oxidative damage and apoptosis. However, little is known about the possible synergistic effect of CTX and CoQ10 on the expression of genes involved in folliculogenesis, such as proliferation cell nuclear antigen (PCNA) and follicle-stimulating hormone receptor (FSHR). A total of 32 NMRI mice were applied and divided into four groups, including healthy control, CTX, CTX + CoQ10, and CoQ10 groups. The effects of CoQ10 on CTX-induced ovarian injury and folliculogenesis were examined by histopathological and real-time quantitative reverse transcription-polymerase chain reaction analyses. The rates of fertilization (in vitro fertilization), embryo development, as well as the level of reactive oxygen species (ROS) in metaphase II (MII) mouse oocytes after PMSG/HCC treatment were also assessed. Results showed that the treatment with CTX decreased the mRNA expression of PCNA and FSHR, IVF rate, and embryo development whereas the application of CoQ10 successfully reversed those factors. CoQ10 administration significantly enhanced histological morphology and decreased ROS levels and the number of atretic follicles in the ovary of CTX-treated mice. In conclusion, it seems that the protective effect of CoQ10 is exerted via the antioxidant and proliferative properties of this substance on CTX-induced ovarian damage.

Closing the Medicare Doughnut Hole: Changes in Prescription Drug Utilization and Out-of-Pocket Spending Among Medicare Beneficiaries With Part D Coverage After the Affordable Care Act.

BACKGROUND: The Affordable Care Act (ACA) include provisions that reduce beneficiaries' cost sharing and eventually closes the coverage gap-known as the "doughnut hole"-that was originally part of Medicare prescription drug coverage implemented in 2006. OBJECTIVES: This study examines changes in overall prescription drug utilization and out-of-pocket spending as well as by manufacturer type (brand vs. generic), through 2013 as a result of the doughnut hole provisions of the ACA. MATERIALS AND METHODS: This analysis is based on data from Medical Expenditure Panel Survey and the sample for this analysis includes all individuals 55 years of age and older. A difference-in-differences methodology was adopted to measure changes in drug utilization and out-of-pocket spending among both the treatment group and the comparison group after the ACA. RESULTS: The findings from this study suggest that overall out-of-pocket spending significantly decreased after closing the coverage gap, mainly because of a significant reduction in out-of-pocket spending on brand-name drugs. Conversely, the results show that generic drug utilization increased after closing the coverage gap. As expected, the effects were considerably larger for people who fell into the doughnut hole. CONCLUSIONS: The ACA doughnut hole provisions likely contributed to a reduction in out-of-pocket spending for prescription drugs for part D beneficiaries, especially for people who fell into the doughnut hole.

Changes in Emergency Department Utilization After Early Medicaid Expansion in California.

BACKGROUND: Medicaid expansions aim to improve access to primary care, which could reduce nonemergent (NE) use of the emergency department (ED). In contrast, Medicaid enrollees use the ED more than other groups, including the uninsured. Thus, the expected impact of Medicaid expansion on ED use is unclear. OBJECTIVES: To estimate changes in total and NE ED visits as a result of California's early Medicaid expansion under the Affordable Care Act. In addition to overall changes in the number of visits, changes by payer and safety net hospital status are examined. METHODS: We used a quasi-experimental approach to examine changes in ED utilization, comparing California expansion counties to comparison counties from California and 2 other states in the same region that did not implement Medicaid expansion during the study period. RESULTS: Regression estimates show no significant change in total number of ED visits following expansion. Medicaid visits increased by 145 visits per hospital-quarter in the first year following expansion and 242 visits subsequent to the first year, whereas visits among uninsured patients decreased by 129 visits per hospital-quarter in the first year and 175 visits in subsequent years, driven by changes at safety net hospitals. We also observe an increase in NE visits per hospital-quarter paid for by Medicaid, and a significant decrease in uninsured NE visits. CONCLUSIONS: Medicaid expansions in California were associated with increases in ED visits paid for by Medicaid and declines in uninsured visits. Expansion was also associated with changes in NE visits among Medicaid enrollees and the uninsured.

Neuroimaging "HINTS" of the Lateral Medullary Syndrome.

A series of neuroimaging studies illustrates many of the key findings of the lateral medullary syndrome.

Clinical outcomes of HIV care delivery models in the US: a systematic review.

With over 1 million people living with HIV, the US faces national challenges in HIV care delivery due to an inadequate HIV specialist workforce and the increasing role of non-communicable chronic diseases in driving morbidity and mortality in HIV-infected patients. Alternative HIV care delivery models, which include substantial roles for advanced practitioners and/or coordination between specialty and primary care settings in managing HIV-infected patients, may address these needs. We aimed to systematically review the evidence on patient-level HIV-specific and primary care health outcomes for HIV-infected adults receiving outpatient care across HIV care delivery models. We identified randomized trials and observational studies from bibliographic and other databases through March 2016. Eligible studies met pre-specified eligibility criteria including on care delivery models and patient-level health outcomes. We considered all available evidence, including non-experimental studies, and evaluated studies for risk of bias. We identified 3605 studies, of which 13 met eligibility criteria. Of the 13 eligible studies, the majority evaluated specialty-based care (9 studies). Across all studies and care delivery models, eligible studies primarily reported mortality and antiretroviral use, with specialty-based care associated with mortality reductions at the clinician and practice levels and with increased antiretroviral initiation or use at the clinician level but not the practice level. Limited and heterogeneous outcomes were reported for other patient-level HIV-specific outcomes (e.g., viral suppression) as well as for primary care health outcomes across all care delivery models. No studies addressed chronic care outcomes related to aging. Limited evidence was available across geographic settings and key populations. As re-design of care delivery in the US continues to evolve, better understanding of patient-level HIV-related and primary care health outcomes, especially across different staffing models and among different patient populations and geographic locations, is urgently needed to improve HIV disease management.

The video head impulse test during post-rotatory nystagmus: physiology and clinical implications.

The aim of this study was to test the effects of a sustained nystagmus on the head impulse response of the vestibulo-ocular reflex (VOR) in healthy subjects. VOR gain (slow-phase eye velocity/head velocity) was measured using video head impulse test goggles. Acting as a surrogate for a spontaneous nystagmus (SN), a post-rotatory nystagmus (PRN) was elicited after a sustained, constant-velocity rotation, and then head impulses were applied. 'Raw' VOR gain, uncorrected for PRN, in healthy subjects in response to head impulses with peak velocities in the range of 150°/s-250°/s was significantly increased (as reflected in an increase in the slope of the gain versus head velocity relationship) after inducing PRN with slow phases of nystagmus of high intensity (>30°/s) in the same but not in the opposite direction as the slow-phase response induced by the head impulses. The values of VOR gain themselves, however, remained in the normal range with slow-phase velocities of PRN < 30°/s. Finally, quick phases of PRN were suppressed during the first 20-160 ms of a head impulse; the time frame of suppression depended on the direction of PRN but not on the duration of the head impulse. Our results in normal subjects suggest that VOR gains measured using head impulses may have to be corrected for any superimposed SN when the slow-phase velocity of nystagmus is relatively high and the peak velocity of the head movements is relatively low. The suppression of quick phases during head impulses may help to improve steady fixation during rapid head movements.

Visual, Ocular Motor, and Cochleo-Vestibular Loss in Patients With Heteroplasmic, Maternally-Inherited Diabetes Mellitus and Deafness (MIDD), 3243 Transfer RNA Mutation.

BACKGROUND: Mitochondrial encephalopathy, lactic acidosis, and stroke-like symptoms (MELAS) and MIDD (maternally-inherited diabetes mellitus and deafness) are caused by A3243G transfer RNA mutations that affect mitochondrial function. Hearing loss and early onset diabetes mellitus constitute the main MIDD phenotype. Regarding the ophthalmologic manifestations of MIDD, we hypothesized that decreased vestibulo-ocular reflex (VOR) gain in patients with MIDD may contribute to impaired dynamic visual acuity. METHODS: Neuro-ophthalmologic, neuroimaging, and neuro-otologic evaluations were performed in 2 nonrelated patients with MIDD who complained of oscillopsia with head movement. We obtained quantitative recording of the horizontal and the vertical VOR, using the video head impulse test device. RESULTS: In the 2 patients, we detected visual, ocular motor, and vestibular abnormalities. Decreased VOR gain in the planes of all 3 semicircular canals and impaired dynamic visual acuity was demonstrated in both cases. CONCLUSIONS: MIDD patients are primarily recognized by their advanced hearing loss or deafness, early onset diabetes mellitus, and lactic acidosis. Decreased vision in these patients relates primarily to peri-macular retinal atrophy. In addition, loss of vestibular function causes poor dynamic visual acuity. Both patients, in their late fifties, had evidence of progressive central and peripheral nervous system dysfunction.

Compensatory saccades benefit from prediction during head impulse testing in early recovery from vestibular deafferentation.

The head impulse test (HIT) can identify a deficient vestibulo-ocular reflex (VOR) by the compensatory saccade (CS) generated once the head stops moving. The inward HIT is considered safer than the outward HIT, yet might have an oculomotor advantage given that the subject would presumably know the direction of head rotation. Here, we compare CS latencies following inward (presumed predictable) and outward (more unpredictable) HITs after acute unilateral vestibular nerve deafferentation. Seven patients received inward and outward HITs delivered at six consecutive postoperative days (POD) and again at POD 30. All head impulses were recorded by portable video-oculography. CS included those occurring during (covert) or after (overt) head rotation. Inward HITs included mean CS latencies (183.48 ms ± 4.47 SE) that were consistently shorter than those generated during outward HITs in the first 6 POD (p = 0.0033). Inward HITs induced more covert saccades compared to outward HITs, acutely. However, by POD 30 there were no longer any differences in latencies or proportions of CS and direction of head rotation. Patients with acute unilateral vestibular loss likely use predictive cues of head direction to elicit early CS to keep the image centered on the fovea. In acute vestibular hypofunction, inwardly applied HITs may risk a preponderance of covert saccades, yet this difference largely disappears within 30 days. Advantages of inwardly applied HITs are discussed and must be balanced against the risk of a false-negative HIT interpretation.

Quantifying the vestibulo-ocular reflex with video-oculography: nature and frequency of artifacts.

Video-oculography devices are now used to quantify the vestibulo-ocular reflex (VOR) at the bedside using the head impulse test (HIT). Little is known about the impact of disruptive phenomena (e.g. corrective saccades, nystagmus, fixation losses, eye-blink artifacts) on quantitative VOR assessment in acute vertigo. This study systematically characterized the frequency, nature, and impact of artifacts on HIT VOR measures. From a prospective study of 26 patients with acute vestibular syndrome (16 vestibular neuritis, 10 stroke), we classified findings using a structured coding manual. Of 1,358 individual HIT traces, 72% had abnormal disruptive saccades, 44% had at least one artifact, and 42% were uninterpretable. Physicians using quantitative recording devices to measure head impulse VOR responses for clinical diagnosis should be aware of the potential impact of disruptive eye movements and measurement artifacts.

SCANED: Siamese collateral assessment network for evaluation of collaterals from ischemic damage.

This study conducts collateral evaluation from ischemic damage using a deep learning-based Siamese network, addressing the challenges associated with a small and imbalanced dataset. The collateral network provides an alternative oxygen and nutrient supply pathway in ischemic stroke cases, influencing treatment decisions. Research in this area focuses on automated collateral assessment using deep learning (DL) methods to expedite decision-making processes and enhance accuracy. Our study employed a 3D ResNet-based Siamese network, referred to as SCANED, to classify collaterals as good/intermediate or poor. Utilizing non-contrast computed tomography (NCCT) images, the network automates collateral identification and assessment by analyzing tissue degeneration around the ischemic site. Relevant features from the left/right hemispheres were extracted, and Euclidean Distance (ED) was employed for similarity measurement. Finally, dichotomized classification of good/intermediate or poor collateral is performed by SCANED using an optimal threshold derived from ROC analysis. SCANED provides a sensitivity of 0.88, a specificity of 0.63, and a weighted F1 score of 0.86 in the dichotomized classification.

Homodyned K-Distribution Parameter Estimation in Quantitative Ultrasound: Autoencoder and Bayesian Neural Network Approaches.

Quantitative ultrasound (QUS) analyzes the ultrasound (US) backscattered data to find the properties of scatterers that correlate with the tissue microstructure. Statistics of the envelope of the backscattered radio frequency (RF) data can be utilized to estimate several QUS parameters. Different distributions have been proposed to model envelope data. The homodyned K-distribution (HK-distribution) is one of the most comprehensive distributions that can model US backscattered envelope data under diverse scattering conditions (varying scatterer number density and coherent scattering). The scatterer clustering parameter ( α ) and the ratio of the coherent to diffuse scattering power ( k ) are the parameters of this distribution that have been used extensively for tissue characterization in diagnostic US. The estimation of these two parameters (which we refer to as HK parameters) is done using optimization algorithms in which statistical features such as the envelope point-wise signal-to-noise ratio (SNR), skewness, kurtosis, and the log-based moments have been utilized as input to such algorithms. The optimization methods minimize the difference between features and their theoretical value from the HK model. We propose that the true value of these statistical features is a hyperplane that covers a small portion of the feature space. In this article, we follow two approaches to reduce the effect of sample features' error. We propose a model projection neural network based on denoising autoencoders to project the noisy features into this space based on this assumption. We also investigate if the noise distribution can be learned by the deep estimators. We compare the proposed methods with conventional methods using simulations, an experimental phantom, and data from an in vivo animal model of hepatic steatosis. The network weight and a demo code are available online at ht.tp://code.sonography.ai.

Quantifying Induced Nystagmus Using a Smartphone Eye Tracking Application (EyePhone).

BACKGROUND: There are ≈5 million annual dizziness visits to US emergency departments, of which vestibular strokes account for over 250 000. The head impulse, nystagmus, and test of skew eye examination can accurately distinguish vestibular strokes from peripheral dizziness. However, the eye-movement signs are subtle, and lack of familiarity and difficulty with recognition of abnormal eye movements are significant barriers to widespread emergency department use. To break this barrier, we sought to assess the accuracy of EyePhone, our smartphone eye-tracking application, for quantifying nystagmus. METHODS AND RESULTS: We prospectively enrolled healthy volunteers and recorded the velocity of induced nystagmus using a smartphone eye-tracking application (EyePhone) and then compared the results with video oculography (VOG). Following a calibration protocol, the participants viewed optokinetic stimuli with incremental velocities (2-12 degrees/s) in 4 directions. We extracted slow phase velocities from EyePhone data in each direction and compared them with the corresponding slow phase velocities obtained by the VOG. Furthermore, we calculated the area under the receiver operating characteristic curve for nystagmus detection by EyePhone. We enrolled 10 volunteers (90% men) with an average age of 30.2±6 years. EyePhone-recorded slow phase velocities highly correlated with the VOG recordings (r=0.98 for horizontal and r=0.94 for vertical). The calibration significantly increased the slope of linear regression for horizontal and vertical slow phase velocities. Evaluating the EyePhone's performance using VOG data with a 2 degrees/s threshold showed an area under the receiver operating characteristic curve of 0.87 for horizontal and vertical nystagmus detection. CONCLUSIONS: We demonstrated that EyePhone could accurately detect and quantify optokinetic nystagmus, similar to the VOG goggles.

Burden of serious harms from diagnostic error in the USA.

BACKGROUND: Diagnostic errors cause substantial preventable harms worldwide, but rigorous estimates for total burden are lacking. We previously estimated diagnostic error and serious harm rates for key dangerous diseases in major disease categories and validated plausible ranges using clinical experts. OBJECTIVE: We sought to estimate the annual US burden of serious misdiagnosis-related harms (permanent morbidity, mortality) by combining prior results with rigorous estimates of disease incidence. METHODS: Cross-sectional analysis of US-based nationally representative observational data. We estimated annual incident vascular events and infections from 21.5 million (M) sampled US hospital discharges (2012-2014). Annual new cancers were taken from US-based registries (2014). Years were selected for coding consistency with prior literature. Disease-specific incidences for 15 major vascular events, infections and cancers ('Big Three' categories) were multiplied by literature-based rates to derive diagnostic errors and serious harms. We calculated uncertainty estimates using Monte Carlo simulations. Validity checks included sensitivity analyses and comparison with prior published estimates. RESULTS: Annual US incidence was 6.0 M vascular events, 6.2 M infections and 1.5 M cancers. Per 'Big Three' dangerous disease case, weighted mean error and serious harm rates were 11.1% and 4.4%, respectively. Extrapolating to all diseases (including non-'Big Three' dangerous disease categories), we estimated total serious harms annually in the USA to be 795 000 (plausible range 598 000-1 023 000). Sensitivity analyses using more conservative assumptions estimated 549 000 serious harms. Results were compatible with setting-specific serious harm estimates from inpatient, emergency department and ambulatory care. The 15 dangerous diseases accounted for 50.7% of total serious harms and the top 5 (stroke, sepsis, pneumonia, venous thromboembolism and lung cancer) accounted for 38.7%. CONCLUSION: An estimated 795 000 Americans become permanently disabled or die annually across care settings because dangerous diseases are misdiagnosed. Just 15 diseases account for about half of all serious harms, so the problem may be more tractable than previously imagined.