TILES-2019: A longitudinal physiologic and behavioral data set of medical residents in an intensive care unit.

The TILES-2019 data set consists of behavioral and physiological data gathered from 57 medical residents (i.e., trainees) working in an intensive care unit (ICU) in the United States. The data set allows for the exploration of longitudinal changes in well-being, teamwork, and job performance in a demanding environment, as residents worked in the ICU for three weeks. Residents wore a Fitbit, a Bluetooth-based proximity sensor, and an audio-feature recorder. They completed daily surveys and interviews at the beginning and end of their rotation. In addition, we collected data from environmental sensors (i.e., Internet-of-Things Bluetooth data hubs) and obtained hospital records (e.g., patient census) and residents' job evaluations. This data set may be may be of interest to researchers interested in workplace stress, group dynamics, social support, the physical and psychological effects of witnessing patient deaths, predicting survey data from sensors, and privacy-aware and privacy-preserving machine learning. Notably, a small subset of the data was collected during the first wave of the COVID-19 pandemic.

A Randomized First-in-Human Study With UB-312, a UBITh® α-Synuclein Peptide Vaccine.

BACKGROUND: α-Synuclein (αSyn) is believed to play a central role in Parkinson's disease (PD) neuropathology and is considered a target for disease modification. UB-312 is a synthetic αSyn peptide conjugated to a T helper peptide and is expected to induce antibodies specifically against oligomeric and fibrillar αSyn, making UB-312 a potential immunotherapeutic for synucleopathies. OBJECTIVE: To investigate the safety, tolerability, and immunogenicity of UB-312 vaccination in healthy participants and to determine a safe and immunologically optimal dose for the first-in-patient study. METHODS: Fifty eligible healthy participants were enrolled in a 44-week, randomized, placebo-controlled, double-blind study. Participants in seven cohorts were randomized to three intramuscular UB-312 or placebo injections at weeks 1, 5, and 13 (doses ranging between 40 and 2000 µg). Safety and tolerability were assessed by adverse events, clinical laboratory, vital signs, electrocardiograms, and neurological and physical examinations. Immunogenicity was assessed by measuring serum and cerebrospinal fluid (CSF) anti-αSyn antibody concentrations. RESULTS: Twenty-three participants received all three vaccinations of UB-312. Most adverse events were mild, transient, and self-resolving. Common treatment-emergent adverse events included headache, nasopharyngitis, vaccination-site pain, lumbar puncture-site pain, and fatigue. UB-312 induced dose- and time-dependent antibody production. Antibodies were detectable in serum and CSF of all participants receiving the 300/300/300 µg UB-312 dose regimen. The average CSF/serum ratio was 0.2%. CONCLUSIONS: UB-312 was generally safe, well tolerated, and induced anti-αSyn antibodies in serum and CSF of healthy participants. The 100 and 300 µg doses are selected for further evaluation in participants with PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Integrating Management of Hepatitis C Infection into Primary Care: the Key to Hepatitis C Elimination Efforts.

Elimination of hepatitis C virus (HCV), a leading cause of liver disease in the USA and globally, has been made possible with the advent of highly efficacious direct acting antivirals (DAAs). DAA regimens offer cure of HCV with 8-12 weeks of a well-tolerated once daily therapy. With increasingly straightforward diagnostic and treatment algorithms, HCV infection can be managed not only by specialists, but also by primary care providers. Engaging primary care providers greatly increases capacity to diagnose and treat chronic HCV and ultimately make HCV elimination a reality. However, barriers remain at each step in the HCV cascade of care from screening to evaluation and treatment. Since primary care is at the forefront of patient contact, it represents the ideal place to concentrate efforts to identify barriers and implement solutions to achieve universal HCV screening and increase curative treatment.

From prostate to the pons: The first reported case of multi-organ septic emboli and brain empyema from an untreated prostate abscess.

Prostate abscesses in developed countries are becoming increasingly less common. Left untreated these abscesses can lead to numerous complications, including some which are very rare.

Disseminated Mycobacterium bovis infection after deceased donor liver transplantation: A case report.

This case demonstrates the significance, and ongoing relevance of mycobacterial infections, especially in patients who have recently been started on immunosuppression.

Systemic lupus erythematosus presenting as Evans syndrome.

Hematologic abnormalities are an important part of the diagnostic criteria for systemic lupus erythematosus (SLE). This case presents a patient diagnosed with Evans Syndrome with underlying SLE on initial presentation.

Short-term use of oral amiodarone causing torsades de pointes.

Amiodarone is one of the most commonly used antiarrhythmic drugs. Despite its well-known side effects, amiodarone is considered to be a relatively safe drug, especially in short-term usage to prevent life-threatening ventricular arrhythmias. Our case demonstrates an instance where short-term usage can yield drug side effect.

An Exploration of Residents' Implicit Biases Towards Depression-a Pilot Study.

BACKGROUND: Implicit attitudes are outside of conscious awareness and are thought to affect automatic responses outside of one's deliberate control, with the potential to impact physician-patient relationships. OBJECTIVE: To measure the nature and extent of implicit biases towards depression in internal medicine and psychiatry residents. DESIGN: Descriptive and comparative study. PARTICIPANTS: Fifty-one residents from three internal medicine programs and 35 residents from three psychiatry programs located in two states. INTERVENTIONS: Participants were sent a link to voluntarily participate in four online implicit association tests. Residents' identities were anonymous. MAIN MEASURES: Four implicit association tests to measure the association of (1) attitude (good/bad), (2) permanence, (3) controllability, and (4) etiology with depression/physical illness. KEY RESULTS: Internal medicine residents demonstrated a significant association between depression and negative attitudes (t(38) = 6.01, p < .001, Cohen's d = .95), uncontrollability (t(35) = 4.80, p < .001, Cohen's d = .79), temporariness (t(37) = 2.94, p = .006, Cohen's d = .48), and a psychologic etiology (t(1) = 6.91, p < .001, Cohen's d = 1.24). Psychiatry residents only demonstrated an association between depression and a psychologic etiology (t(2) = 4.79, p < .001, Cohen's d = 4.5). When comparing the two specialties, internal medicine and psychiatry differed on two of the IATs. Internal medicine residents were more likely to associate negative attitudes with depression than psychiatry residents (t(63) = 4.66, p < .001, Cohen's d = 1.18) and to associate depression with being uncontrollable (t(57) = 3.17, p = .002, Cohen's d = .81). CONCLUSIONS: Internal medicine residents demonstrated biases in their attitudes towards depression and significantly differed in some areas from psychiatry residents. This pilot study needs to be replicated to confirm our findings and further work needs to be done to determine the effect of these attitudes on the provision of clinical care.

Internal Medicine Residents' Attitudes Toward Simulated Depressed Cardiac Patients During an Objective Structured Clinical Examination: A Randomized Study.

BACKGROUND: Physician biases toward mental conditions such as depression have been shown to adversely affect medical outcomes. OBJECTIVE: To explore the relationship between residents' explicit bias toward depressed patients and their clinical skills on a cardiac case during an objective structured clinical exam (OSCE). DESIGN: Prospective parallel randomized controlled study. PARTICIPANTS: One hundred eighty-five internal medicine residents from three residency programs in two states. INTERVENTION: During October-November 2015, residents were randomized to either a depressed or non-depressed standardized patient (SP) presenting with acute chest pain. MAIN MEASURES: The Medical Condition Regard Scale (MCRS) assessed residents' explicit bias toward patients with depression. Their clinical skills (history-taking, physical examination, patient counseling, patient-physician interaction (PPI), differential diagnosis, and workup plan) and facial expressions were rated during an OSCE. KEY RESULTS: No significant relationships were found between resident explicit bias and clinical skill measurements. Residents who examined the depressed SP scored lower, on average, on history-taking (t [183] = -2.77, p < 0.01, Cohen's d = 0.41) and higher on PPI (t [183] = 2.24, p < 0.05, Cohen's d = 0.33) than residents examining the non-depressed SP. There were no differences, on average, between stations on physical examination, counseling, correct diagnosis, workup plan, or overall SP satisfaction. Facial recognition software demonstrated that residents with a non-depressed SP had more neutral expressions than depressed-SP residents (t [133] = -2.46, p < 0.05, Cohen's d = 0.46), and residents with a depressed SP had more disgusted expressions than non-depressed-SP residents (t [83.52] = 2.10, p < 0.05, Cohen's d = 0.28). CONCLUSIONS: Extrinsic bias did not predict OSCE performance in this study. Some differences were noted in the OSCE performance between the two stations. Further study is needed to examine the effects of patient mental health conditions on physician examination procedures, diagnostic behaviors, and patient outcomes.

Case Report: Oxaliplatin-Induced Immune-Mediated Thrombocytopenia.

Thrombocytopenia is a frequent complication of cancer may be due to a variety of causes including malignancy itself, acute disease processes, or cancer therapy. Systemic cancer therapy is the most common cause of thrombocytopenia in cancer patients observed nearly two-thirds of patients with solid tumors. Thrombocytopenia with traditional chemotherapy agents is most frequently the result of megakaryocyte cytotoxicity. Oxaliplatin is a platinum derivative commonly used in gastrointestinal malignancies and is associated with drug-induced immune thrombocytopenia.

Real-time evaluation of an image analysis system for monitoring surgical hemoglobin loss.

Monitoring blood loss is important for management of surgical patients. This study reviews a device (Triton) that uses computer analysis of a photograph to estimate hemoglobin (Hb) mass present on surgical sponges. The device essentially does what a clinician does when trying to make a visual estimation of blood loss by looking at a sponge, albeit with less subjective variation. The performance of the Triton system is reported upon in during real-time use in surgical procedures. The cumulative Hb losses estimated using the Triton system for 50 enrolled patients were compared with reference Hb measurements during the first quarter, half, three-quarters and full duration of the surgery. Additionally, the estimated blood loss (EBL) was calculated using the Triton measured Hb loss and compared with values obtained from both visual estimation and gravimetric measurements. Hb loss measured by Triton correlated with the reference method across the four measurement intervals. Bias remained low and increased from 0.1 g in the first quarter to 3.7 g at case completion. The limits of agreement remained narrow and increased proportionally from the beginning to the end of the cases, reaching a maximum range of -15.3 to 22.7 g. The median (IQR) difference of EBL derived from the Triton system, gravimetric method and visual estimation versus the reference value were 13 (74), 389 (287), and 4 (230) mL, respectively. Use of the Triton system to measure Hb loss in real-time during surgery is feasible and accurate.

In Vitro Evaluation of a Novel Image Processing Device to Estimate Surgical Blood Loss in Suction Canisters.

BACKGROUND: Clinicians are tasked with monitoring surgical blood loss. Unfortunately, there is no reliable method available to assure an accurate result. Most blood lost during surgery ends up on surgical sponges and within suction canisters. A novel Food and Drug Administration-cleared device (Triton system; Gauss Surgical, Inc, Los Altos, CA) to measure the amount of blood present on sponges using computer image analysis has been previously described. This study reports on performance of a complementary Food and Drug Administration-cleared device (Triton Canister System; Gauss Surgical, Inc, Los Altos, CA) that uses similar image analysis to measure the amount of blood in suction canisters. METHODS: Known quantities of expired donated whole blood, packed red blood cells, and plasma, in conjunction with various amounts of normal saline, were used to create 207 samples representing a wide range of blood dilutions commonly seen in suction canisters. Each sample was measured by the Triton device under 3 operating room lighting conditions (bright, medium, and dark) meant to represent a reasonable range, resulting in a total of 621 measurements. Using the Bland-Altman method, the measured hemoglobin (Hb) mass in each sample was compared to the results obtained using a standard laboratory assay as a reference value. The analysis was performed separately for samples measured under each lighting condition. It was expected that under each separate lighting condition, the device would measure the various samples within a prespecified clinically significant Hb mass range (±30 g per canister). RESULTS: The limits of agreement (LOA) between the device and the reference method for dark (bias: 4.7 g [95% confidence interval {CI}, 3.8-5.6 g]; LOA: -8.1 g [95% CI, -9.7 to -6.6 g] to 17.6 g [95% CI, 16.0-19.1 g]), medium (bias: 3.4 g [95% CI, 2.6-4.1 g]; LOA: -7.4 g [95% CI, -8.7 to -6.1 g] to 14.2 g [95% CI, 12.9-15.5 g]), and bright lighting conditions (bias: 4.1 g [95% CI, 3.2-4.9 g]; LOA: -7.6 g [95% CI, -9.0 to -6.2 g] to 15.7 g [95% CI, 14.3-17.1 g]) fell well within the predetermined clinically significant limits of ±30 g. Repeated measurements of the samples under the various lighting conditions were highly correlated with intraclass correlation coefficient of 0.995 (95% CI, 0.993-0.996; P < .001), showing that lighting conditions did not have a significant impact on measurements. Hb mass bias was significantly associated with hemolysis level (Spearman ρ correlation coefficient, -0.137; P = .001) and total canister volume (Spearman ρ correlation coefficient, 0.135; P = .001), but not ambient illuminance. CONCLUSIONS: The Triton Canister System was able to measure the Hb mass reliably with clinically acceptable accuracy in reconstituted blood samples representing a wide range of Hb concentrations, dilutions, hemolysis, and ambient lighting settings.

Accuracy of Blood Loss Measurement during Cesarean Delivery.

Objective This study aims to compare the accuracy of visual, quantitative gravimetric, and colorimetric methods used to determine blood loss during cesarean delivery procedures employing a hemoglobin extraction assay as the reference standard. Study Design In 50 patients having cesarean deliveries blood loss determined by assays of hemoglobin content on surgical sponges and in suction canisters was compared with obstetricians' visual estimates, a quantitative gravimetric method, and the blood loss determined by a novel colorimetric system. Agreement between the reference assay and other measures was evaluated by the Bland-Altman method. Results Compared with the blood loss measured by the reference assay (470 ± 296 mL), the colorimetric system (572 ± 334 mL) was more accurate than either visual estimation (928 ± 261 mL) or gravimetric measurement (822 ± 489 mL). The correlation between the assay method and the colorimetric system was more predictive (standardized coefficient = 0.951, adjusted R2 = 0.902) than either visual estimation (standardized coefficient = 0.700, adjusted R2 = 00.479) or the gravimetric determination (standardized coefficient = 0.564, adjusted R2 = 0.304). Conclusion During cesarean delivery, measuring blood loss using colorimetric image analysis is superior to visual estimation and a gravimetric method. Implementation of colorimetric analysis may enhance the ability of management protocols to improve clinical outcomes.

Patient-centered medical home intervention at an internal medicine resident safety-net clinic.

IMPORTANCE: The patient-centered medical home (PCMH) model holds promise for improving primary care delivery, but it has not been adequately tested in teaching settings. DESIGN, SETTING, AND PARTICIPANTS: We implemented an intervention guided by PCMH principles at a safety-net teaching clinic with resident physician providers. Two similar clinics served as controls. MAIN OUTCOMES AND MEASURES: Using a cross-sectional design, we measured the effect on patient and resident satisfaction using the Consumer Assessment of Healthcare Providers and Systems survey and a validated teaching clinic survey, respectively. Both surveys were conducted at baseline and 1 year after the intervention. We also measured the effect on emergency department and hospital utilization. RESULTS: Following implementation of our intervention, the clinic's score on the National Committee for Quality Assurance's PCMH certification tool improved from 35 to 53 of 100 possible points, although our clinic did not achieve all must-pass elements to qualify as a PCMH. During the 1-year study period, 4676 patients were exposed to the intervention; 39.9% of these used at least 1 program component. Compared with baseline, patient-reported access and overall satisfaction improved to a greater extent in the intervention clinic, and the composite satisfaction rating increased from 48% to 65% in the intervention clinic vs from 50% to 59% in the control sites (P = .04). The improvements were particularly notable for questions relating to access. For example, satisfaction with urgent appointment scheduling increased from 12% to 53% in the intervention clinic vs from 14% to 18% in the control clinics (P < .001). Resident satisfaction also improved in the intervention clinic: the composite satisfaction score increased from 39% to 51% in the intervention clinic vs a decrease from 46% to 42% in the control clinics (P = .01). Emergency department utilization did not differ significantly between the intervention and control clinics, and hospitalizations increased from 26 to 27 visits per 1000 patients per month in the intervention clinic vs a decrease from 28 to 25 in the control clinics (P = .02). CONCLUSIONS AND RELEVANCE: Our PCMH-guided intervention, which represented a modest but substantive step toward the PCMH vision, had favorable effects on patient and resident satisfaction at a safety-net teaching clinic but did not reduce emergency department or hospital utilization in the first year. Our experience may provide lessons for other teaching clinics in safety-net settings hoping to implement PCMH-guided reforms.

Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration.

Metabolites in the kynurenine pathway, generated by tryptophan degradation, are thought to play an important role in neurodegenerative disorders, including Alzheimer's and Huntington's diseases. In these disorders, glutamate receptor-mediated excitotoxicity and free radical formation have been correlated with decreased levels of the neuroprotective metabolite kynurenic acid. Here, we describe the synthesis and characterization of JM6, a small-molecule prodrug inhibitor of kynurenine 3-monooxygenase (KMO). Chronic oral administration of JM6 inhibits KMO in the blood, increasing kynurenic acid levels and reducing extracellular glutamate in the brain. In a transgenic mouse model of Alzheimer's disease, JM6 prevents spatial memory deficits, anxiety-related behavior, and synaptic loss. JM6 also extends life span, prevents synaptic loss, and decreases microglial activation in a mouse model of Huntington's disease. These findings support a critical link between tryptophan metabolism in the blood and neurodegeneration, and they provide a foundation for treatment of neurodegenerative diseases.

On statistical evaluation of the linearity in assay validation.

Linearity is one of the most important characteristics for evaluation of the accuracy in assay validation. The current statistical method for evaluation of the linearity recommended by the Clinical Laboratory Standard Institute (CLSI) guideline EP6-A is reviewed. The method directly compares the point estimates with the pre-specified allowable limit and completely ignores the sampling error of the point estimates. An alternative method for evaluation of linearity, proposed by Kroll et al. (2000), considers the statistical test procedure based on the average deviation from linearity (ADL). However this procedure is based on an inappropriate formulation of hypotheses for the evaluation of linearity. Consequently, the type I error rates of both current methods may be inflated for inference of linearity. To claim the linearity of analytical methods, we propose that the hypothesis of proving the linearity should be formulated as the alternative hypothesis. Furthermore, any procedures for assessment of linearity should be based on the sampling distributions of the proposed test statistics. Therefore, we propose a two one-sided test (TOST) procedure and a corrected Kroll's procedure. The simulation studies were conducted to empirically compare the size and power between current and proposed methods. The simulation results show that the proposed methods not only adequately control size but also provide sufficient power. A numeric example illustrates the proposed methods.

Tests for equivalence or non-inferiority for paired binary data.

Assessment of therapeutic equivalence or non-inferiority between two medical diagnostic procedures often involves comparisons of the response rates between paired binary endpoints. The commonly used and accepted approach to assessing equivalence is by comparing the asymptotic confidence interval on the difference of two response rates with some clinical meaningful equivalence limits. This paper investigates two asymptotic test statistics, a Wald-type (sample-based) test statistic and a restricted maximum likelihood estimation (RMLE-based) test statistic, to assess equivalence or non-inferiority based on paired binary endpoints. The sample size and power functions of the two tests are derived. The actual type I error and power of the two tests are computed by enumerating the exact probabilities in the rejection region. The results show that the RMLE-based test controls type I error better than the sample-based test. To establish an equivalence between two treatments with a symmetric equivalence limit of 0.15, a minimal sample size of 120 is needed. The RMLE-based test without the continuity correction performs well at the boundary point 0. A numerical example illustrates the proposed procedures.