Comparison of the TONOVET Plus®, TonoVet®, and Tono-Pen Vet™ tonometers in normal cats and cats with glaucoma.

OBJECTIVES: To determine the accuracy, precision, and clinical applicability of the ICare® TONOVET Plus (TVP) in cats. ANIMALS AND PROCEDURES: IOP readings obtained with the TVP were compared to values obtained concurrently with the original TONOVET (TV01) and Tono-Pen Vet™ (TP) in 12 normal cats (24 eyes) and 8 glaucomatous LTBP2-mutant cats (13 eyes) in vivo. Reproducibility of TVP readings was also assessed for three observers in the above cats. The anterior chambers of five different normal cat eyes were cannulated ex vivo. IOP was measured with the TVP, TV01, and TP at manometric IOPs ranging from 5 to 70 mmHg. Data were analyzed by linear regression, ANOVA and Bland-Altman plots. ANOVA was used to assess reproducibility of TVP readings obtained by different observers and an ANCOVA model controlled for variation of individual cats. p < .05 was considered significant. RESULTS: TVP values strongly correlated with TV01 values (y = 1.045x + 1.443, R2 = .9667). The TP significantly underestimated IOP relative to the TVP and TV01, particularly at high IOP. IOP values obtained by 1 observer were significantly higher (~1 mmHg average) compared to the other 2 observers via ANCOVA analysis (p = .0006479 and p = .0203). Relative to manometry, the TVP and TV01 were significantly more accurate (p < .0001) and precise (p < .0070) than the TP in ex vivo eyes. CONCLUSIONS: IOP readings obtained with the TVP and TV01 are broadly interchangeable between models and between observers, but subtle differences may be important in a research context. TP readings vastly underestimate high IOP in feline glaucoma.

Does Physician Gender and Gender Composition of Clinical Teams Affect Guideline Concordance and Patient Outcomes in Out-of-Hospital Cardiac Arrest?

Objective: Prior literature has shown improved outcomes in morbidity and mortality for admitted patients cared for by female physicians. One theory is that female physicians adhere closely to guideline recommendations. We sought to determine whether patients who have out-of-hospital cardiac arrest (OHCA) experience more guideline-concordant postcardiac arrest care and potentially better outcomes based on the gender of their treating physician and gender distribution of the treatment teams. Methods: This study is a retrospective cohort study from the Colorado Cardiac Arrest Registry, local registry of OHCA patients treated at one academic urban tertiary care hospital. We analyzed adult OHCA patients who survived to hospital admission but were comatose. Patient demographic data and arrest characteristics were abstracted for subjects, and the gender of the provider was abstracted from the medical record. Results: Patients were admitted by a female attending in 28.5% of the cohort. The difference in guideline-concordant care between male and female providers was not significant. No statistical difference was found between all-male or mixed gender teams in adherence to guideline-concordant care. No patient was cared for by an all-female team. Neither gender of the admitting physician nor gender of the physician who led the family meeting to discuss prognosis was associated with a survival difference. Conclusions: Prior literature has described differences in outcome based on gender of the treating physician. Our analysis targeted a similar question in a cohort of OHCA patients with survival to hospital admission. We determined that there was no difference in postcardiac arrest guideline concordance and survival to hospital discharge based on treating physician gender. This finding differs from the prior literature and supports the importance of diverse clinical teams in medicine.

The effect of visually significant dermatochalasis and blepharoptosis on driving safety.

OBJECTIVE: To evaluate the impact of visually significant blepharoptosis and dermatochalasis on driving safety and performance. Patients with visually significant blepharoptosis often complain of difficulty with driving, but the impact of blepharoptosis on driving has not been evaluated in a real-world setting. METHODS: Retrospective cohort study of 610 consecutive adult patients undergoing bilateral functional blepharoplasty or ptosis repair surgery at a single, University-based practice between 2014 and 2017. This cohort had a median age of 65 and was predominantly female. Pre-operative rates of motor vehicle collisions (MVCs) and moving violations (MVs) extracted from state Department of Transportation (DOT) records were compared with post-operative rates, using each patient as their own control. Poisson models were used for analysis. RESULTS: Subjects were included in the study for a median of 730 days before eyelid surgery (IQR 346 - 730) and 783 days after surgery (IQR 449 - 1176). There were 30 total MVCs before surgery (0.024 per subject, per year) and 48 after surgery (0.036 per subject, per year) (p = 0.08). There were 81 MVs before surgery (0.065 per subject, per year) and 66 after (0.049 per subject, per year) (p = 0.11). The multivariable model comparing MVCs pre- versus post-surgery adjusting for age, ptosis severity, gender, and comorbidities yields a rate ratio of 0.63 (p = 0.05). The multivariable model comparing MVs pre- versus post-surgery demonstrates a rate-ratio of 1.2 (p = 0.20). Older age was associated with lower rates of moving violations (coefficient of -0.03, p < 0.01). None of the other variables included in the final models had a significant association with MVCs or MVs. CONCLUSIONS: In this cohort, visually significant blepharoptosis and dermatochalasis were not associated with rates of MVCs or MVs. Further work is needed to study the impact of these common conditions on driving, for example adjusting MVC and MV rates by miles driven, which may influence decisions about when to operate on ptotic eyelids.

Metabolomic profiling of metoprolol hypertension treatment reveals altered gut microbiota-derived urinary metabolites.

INTRODUCTION: Metoprolol succinate is a long-acting beta-blocker prescribed for the management of hypertension (HTN) and other cardiovascular diseases. Metabolomics, the study of end-stage metabolites of upstream biologic processes, yield insight into mechanisms of drug effectiveness and safety. Our aim was to determine metabolomic profiles associated with metoprolol effectiveness for the treatment of hypertension. METHODS: We performed a prospective pragmatic trial (NCT02293096) that enrolled patients between 30 and 80 years with uncontrolled HTN. Patients were started on metoprolol succinate at a dose based upon systolic blood pressure (SBP). Urine and blood pressure measurements were collected weekly. Individuals with a 10% decline in SBP or heart rate (HR) were considered responsive. Genotype for the CYP2D6 enzyme, the primary metabolic pathway for metoprolol, was evaluated for each subject. Unbiased metabolomic analyses were performed on urine samples using UPLC-QTOF mass spectrometry. RESULTS: Urinary metoprolol metabolite ratios are indicative of patient CYP2D6 genotypes. Patients taking metoprolol had significantly higher urinary levels of many gut microbiota-dependent metabolites including hydroxyhippuric acid, hippuric acid, and methyluric acid. Urinary metoprolol metabolite profiles of normal metabolizer (NM) patients more closely correlate to ultra-rapid metabolizer (UM) patients than NM patients. Metabolites did not predict either 10% SBP or HR decline. CONCLUSION: In summary, urinary metabolites predict CYP2D6 genotype in hypertensive patients taking metoprolol. Metoprolol succinate therapy affects the microbiome-derived metabolites.

Prevalence and Severity of Artifacts in Optical Coherence Tomographic Angiograms.

Importance: Artifacts can affect optical coherence tomographic angiography (OCTA) images and may be associated with misinterpretation of OCT scans in both clinical trials and clinical settings. Objectives: To identify the prevalence and type of artifacts in OCTA images associated with quantitative output and to analyze the role of proprietary quality indices in establishing image reliability. Design, Setting, and Participants: This cross-sectional study evaluated baseline OCTA images acquired in multicenter clinical trials and submitted to the Fundus Photograph Reading Center in Madison, Wisconsin, between January 1, 2016, and December 31, 2018. Images were captured using the 3 mm × 3 mm and/or 6 mm × 6 mm scan protocol with commercially available OCTA systems. Artifacts, including decentration, segmentation error, movement, blink, refraction shift, defocus, shadow, Z offset, tilt, and projection, were given a severity grade based on involvement of cross-sectional OCT and area of OCT grid affected. Main Outcomes and Measures: Prevalence and severity of OCTA artifacts and area under the receiver operating characteristic curve (AUC) of quality indices with image reliability. Results: A total of 406 OCTA images from 234 eyes were included in this study, of which 221 (54.4%) were 6 mm × 6 mm scans and 185 (45.6%) were 3 mm × 3 mm scans. At least 1 artifact was documented in 395 images (97.3%). Severe artifacts associated with the reliability of quantitative outputs were found in 217 images (53.5%). Shadow (26.9% [109 images]), defocus (20.9% [85 images]), and movement (16.0% [65 images]) were the 3 most prevalent artifacts. Prevalence of artifacts did not vary with the imaging system used or with the scan protocol; however, the type of artifacts varied. Commercially recommended quality index thresholds had an AUC of 0.80 to 0.83, sensitivity of 97% to 99%, and specificity of 37% to 41% for reliable images. Conclusions and Relevance: Findings from this study suggest that artifacts associated with quantitative outputs on commercially available OCTA devices are highly prevalent and that identifying common artifacts may require correlation with the angiogram and cross-sectional OCT scans. Knowledge of these artifacts and their implications for OCTA indices appears to be warranted for more accurate interpretation of OCTA images.

CYP2D6 Genotype Phenotype Discordance Due to Drug-Drug Interaction.

Drug-drug interactions have been demonstrated to alter cytochrome 2D6 (CYP2D6) enzyme phenotype due to inhibitor ingestion, although it is unclear how substrate interactions affect phenotype. This was a pragmatic clinical trial examining the kinetics of a CYP2D6 enzyme probe drug with and without CYP2D6-dependent substrates. Patients were enrolled into an inpatient study unit, and orally administered a 2 mg microdose of dextromethorphan (DM) to probe enzyme activity with and without CYP2D6-dependent drug-drug interactions. Thirty-nine subjects were enrolled in this trial. Twelve subjects were on no CYP2D6-dependent drugs and 27 were on one or more CYP2D6-dependent drugs. There were 1 poor metabolizer, 5 intermediate metabolizers, 31 normal metabolizers, and 2 ultra-rapid metabolizers. Those with co-ingestion of another CYP2D6-dependent drug were 9.49 (95% confidence interval (CI): 1.54-186.41; P = 0.01) times more likely to have genotype-phenotype discordance based upon the 3 hours dextrophan/dextromethorphan (DX/DM) ratio. CYP2D6 substrate co-ingestions can cause genotype-phenotype discordance.

Synthetic cannabinoid "Black Mamba" infidelity in patients presenting for emergency stabilization in Colorado: a P SCAN Cohort.

BACKGROUND: Use of new psychoactive substances (NPS) has increased over the last decade. During this period, variability of both clinical presentations and chemical compositions of these compounds has increased. Synthetic cannabinoids (SCs) are the most commonly used NPS and there are more than 100 documented unique molecules in this class. "Black Mamba", often associated to ADB-FUBINACA, is the most commonly used SC in Colorado. It has been linked to kidney injury, myocardial toxicity, seizures, and death. OBJECTIVES: We aim to identify the chemical constituents and quantification of eight cases of reported "Black Mamba" use in order to further understand the clinical variability in patients presenting for emergency stabilization. METHODS: We report data from eight cases of reported "Black Mamba" use prospectively captured through the Colorado site of the Psychoactive Surveilance Consortium and Analysis Network (P SCAN). P SCAN is a geographically representative group of academic hospitals that capture clinical presentation, outcome, and biologic samples from patients that present for emergency stabilization following NPS use. Serum and urine samples were analyzed and quantified by liquid chromatography-quadrupole time-of-flight mass spectrometry after a qualitative screen for over 600 unique NPS compounds. RESULTS: In the reported eight cases, the median age was 28 years old. There were four male and four females. Four patients had agitation/delirium and four patients had chest pain. Normal saline, benzodiazepines and ondansetron were the common treatment provided in the emergency department (ED). Two patients were discharged from the ED and six patients being admitted for emergency observation with a median length of stay (LOS) of six hours. No deaths were reported. Confirmatory testing revealed that only five patients (62.5%) had SCs found in blood or urine samples. Cocaine, NRG-3, 3-methoxyphencyclidine hydrochloride (MeO-PCP), and methamfetamine were identified in other presentations. CONCLUSIONS: The wide range of clinical presentations from "Black Mamba" use may be explained by the wide variability of chemical constituents found by laboratory analysis.

Electrostatic potential distribution of a soft spherical particle with a charged core and pH-dependent charge density.

In this paper we provide numerical results for the electrostatic potential profile of a soft charged particle with a charged core and pH-dependent charge density. The present study serves as a useful platform for better quantification of the electrostatic potential profile of the MS2 bacteriophage virus. In this context, this work improves the analysis of a similar recent study [Phan et al., J. Chem. Phys. 139 (2013) 244908] in two aspects. First, as compared to the previous study, we provide numerical rather than analytical results for the electrostatic potential profile. This is important because the analytical treatment forbids the investigation of cases with intermediate to large charge density, relative to the bulk charge density of the electrolyte, of the viral surface. Second, the consideration of pH-dependent charge density in the electrostatic potential profile is a more credible representation of the electrostatics of the virus, which is known to demonstrate pH-dependent variation in the electrophoretic mobility. In fact, we establish that the various predictions on the electrostatic potential profile made in the previous study are substantially modified when the effect of pH is considered, and the result must now be described in terms of the difference pH-pKa, where Ka refers to the ionization constant of the acid that produces the PEL ions.