Computational Fluid Dynamic Assessment of Patients with Congenital Heart Disease from 3D Rotational Angiography.

For congenital heart disease patients, multiple imaging modalities are needed to discern anatomy and functional information such as differential blood flow. During cardiac catheterization, 3D rotational angiography (3DRA) can provide CTA-like images, enabling anatomical information and intraprocedural guidance. We seek to establish whether unique aspects of this technique can also generate quantitative functional blood flow information. We propose that systematic integration of 3DRA imaging, catheter hemodynamic information, and computational fluid dynamics (CFD), can provide quantitative information regarding blood flow dynamics and energetics, without additional imaging or procedures. We report a single center retrospective feasibility study comprising four patients with 3DRA imaging and a complete set of hemodynamic data. 3DRA was processed and segmented to reconstruct vascular regions of interest (ROI), and a computational grid for CFD modeling of blood flow through the ROI was generated. Blood flow was simulated by integrating catheter hemodynamic data to devise boundary conditions at vascular ROI inlets and outlets. The 3DRA-based workflow successfully generated key computational outputs commonly used for cardiovascular applications, including flow patterns, distribution fractions, wall shear stress. Computational outputs obtained were as detailed and resolved as those obtained from more commonly used CT or MR angiography. Accuracy was confirmed by comparing computed flow distributions with measurements for 2 cases, showing less than 2.0% error from the measured data. Systematic integration of catheter hemodynamic information, 3DRA imaging, and CFD modeling, provides an effective and feasible alternative to obtain important quantitative blood flow information and visualization, without additional imaging.

Hemodynamics Indicates Differences Between Patients With And Without A Stroke Outcome After Left Ventricular Assist Device Implantation.

Stroke remains a leading cause of complications and mortality in heart failure patients treated with LVAD circulatory support. Hemodynamics plays a central role in affecting risk and etiology of stroke during LVAD support. Yet, detailed quantitative assessment of hemodynamic variables and their relation to stroke outcomes in patients with an implanted LVAD remains a challenge. We present an in silico hemodynamics analysis in a set of 12 patients on LVAD support; 6 with reported stroke outcomes and 6 without. We conducted patient-specific hemodynamics simulations for models with the LVAD outflow graft reconstructed from cardiac-gated CT images. A pre-implantation baseline flow model was virtually generated for each case by removing the LVAD outflow graft and driving flow from the aortic root. Hemodynamics was characterized using quantitative descriptors for helical flow, vortex generation, and wall shear stress. Our analysis showed higher average values for descriptors of positive helical flow, vortex generation, and wall shear stress, across the 6 cases with stroke outcomes on LVAD support, when compared with cases without stroke. When the descriptors for LVAD-driven flow were compared against estimated baseline flow pre-implantation, extent of positive helicity was higher, and vorticity and wall shear were lower in cases with stroke compared to those without. The study suggests that quantitative analysis of hemodynamics after LVAD implantation; and hemodynamic alterations from a pre-implant flow scenario, can potentially reveal hidden information linked to stroke outcomes during LVAD support. This has broad implications on understanding stroke etiology, LVAD treatment planning, surgical optimization, and efficacy assessment.

The Relation Between Viscous Energy Dissipation and Pulsation for Aortic Hemodynamics Driven by a Left Ventricular Assist Device.

Left ventricular assist device (LVAD) provides mechanical circulatory support for patients with advanced heart failure. Treatment using LVAD is commonly associated with complications such as stroke and gastro-intestinal bleeding. These complications are intimately related to the state of hemodynamics in the aorta, driven by a jet flow from the LVAD outflow graft that impinges into the aorta wall. Here we conduct a systematic analyses of hemodynamics driven by an LVAD with a specific focus on viscous energy transport and dissipation. We conduct a complementary set of analysis using idealized cylindrical tubes with diameter equivalent to common carotid artery and aorta, and a patient-specific model of 27 different LVAD configurations. Results from our analysis demonstrate how energy dissipation is governed by key parameters such as frequency and pulsation, wall elasticity, and LVAD outflow graft surgical anastomosis. We find that frequency, pulsation, and surgical angles have a dominant effect, while wall elasticity has a weaker effect, in determining the state of energy dissipation. For the patient-specific scenario, we also find that energy dissipation is higher in the aortic arch and lower in the abdominal aorta, when compared to the baseline flow without an LVAD. This further illustrates the key hemodynamic role played by the LVAD outflow jet impingement, and subsequent aortic hemodynamics during LVAD operation.

Serious Skin Injuries Following Exposure to Unapproved Mole and Skin Tag Removers.

Objective: We sought to describe skin injuries associated with unapproved topical mole and skin tag removers containing concentrated salicylic acid, Sanguinaria canadensis, or other caustic agents. Methods: We identified skin injuries associated with unapproved non-device topical mole and skin tag removers reported to the US Food and Drug Administration (FDA) through October 30, 2021 or described in Amazon consumer product reviews between 2019 and 2021. Results: We identified 38 cases, including 30 from Amazon consumer product reviews and eight reported to the FDA. Twenty-eight were from 2021. The most common reason for use was for mole and/or skin tag removal. Listed ingredients included salicylic acid, Sanguinaria canadensis, botanicals (includes homeopathic products), and calcium oxide. Seven cases involved products without ingredients listed. Adverse events included burns, pain, and ulceration, some resulting in permanent scarring and disfigurement. There were 14 facial injuries, including four adjacent to the eye. Reported treatments included antibiotics, hospital care, wound care, and dermatology advice to have a skin graft. Limitations: Limitations include underreporting of adverse events to the FDA, limited clinical details and potential bias in consumer reviews, and poor replicability of review searches due to the dynamic nature of the Amazon website. Conclusion: Unapproved, non-device topical mole and skin tag removers are associated with serious skin injuries. We found Amazon consumer reviews to be a novel and useful data source for safety surveillance of these types of skin products. When dermatologists are consulted about skin injuries, exposure to these products should be considered in the differential diagnosis.

Dosing Recommendations for Quetiapine When Coadministered With HIV Protease Inhibitors.

Although current quetiapine labeling recommends that its dosage should be lowered 6-fold when coadministered with strong cytochrome P450 (CYP)3A inhibitors, a reported case of coma in a patient receiving quetiapine with lopinavir and ritonavir prompted the reevaluation of labeling recommendations for the dosing of quetiapine when coadministered with human immunodeficiency virus (HIV) protease inhibitors. Literature and database (FDA Adverse Event Reporting System and United States Symphony Health Solutions' Integrated Dataverse Database) searches allowed us to identify cases of coma and related adverse events involving the coadministration of quetiapine and HIV protease inhibitors and to estimate the frequency of concomitant use. Literature review and physiologically based pharmacokinetic modeling allowed us to estimate the potential for CYP3A inhibition to contribute to adverse events related to HIV protease inhibitor-quetiapine coadministration. We identified excess sedation following coadministration of quetiapine and an HIV protease inhibitor in 3 reports without obvious confounders. In prescription claims data, 0.4% of quetiapine patients were dispensed a concurrent ritonavir prescription. The quetiapine dose was not reduced on ritonavir initiation in 90% of therapy episodes. Available data indicate to us that all HIV protease inhibitors combined with ritonavir are likely to be strong CYP3A inhibitors. We predicted that ritonavir would increase quetiapine exposure comparable to the strong CYP3A inhibitor ketoconazole. The current dosing recommendations for use of quetiapine with strong CYP3A inhibitors (ie, 6-fold lower quetiapine dose) are appropriate and should be followed when quetiapine is coadministered with HIV protease inhibitors.

Hepatitis B Virus Reactivation Associated With Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus: A Review of Cases Reported to the U.S. Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Direct-acting antiviral agents (DAAs) are used increasingly to treat hepatitis C virus (HCV) infection. Reports were published recently on hepatitis B virus (HBV) reactivation (HBV-R) in patients with HBV-HCV co-infection. Hepatitis B virus reactivation, defined as an abrupt increase in HBV replication in patients with inactive or resolved HBV infection, may result in clinically significant hepatitis. OBJECTIVE: To assess whether HBV-R is a safety concern in patients receiving HCV DAAs. DESIGN: Descriptive case series. SETTING: U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). PATIENTS: 29 patients with HBV-R receiving HCV DAAs. MEASUREMENTS: Clinical and laboratory data. RESULTS: The FDA identified 29 unique reports of HBV-R in patients receiving DAAs from 22 November 2013 to 15 October 2016. Two cases resulted in death and 1 case in liver transplantation. Patients in whom HBV-R developed were heterogeneous regarding HCV genotype, DAAs received, and baseline HBV characteristics. At baseline, 9 patients had a detectable HBV viral load, 7 had positive results on hepatitis B surface antigen (HBsAg) testing and had an undetectable HBV viral load, and 3 had negative results on HBsAg testing and had an undetectable HBV viral load. For the remaining 10 patients, data points were not reported or the data were uninterpretable. Despite provider knowledge of baseline HBV, HBV-R diagnosis and treatment were delayed in 7 cases and possibly 7 others. LIMITATIONS: The quality of information varied among reports. Because reporting is voluntary, HBV-R associated with DAAs likely is underreported. CONCLUSION: Hepatitis B virus reactivation is a newly identified safety concern in patients with HBV-HCV co-infection treated with DAAs. Patients with a history of HBV require clinical monitoring while receiving DAA therapy. Studies would help determine the risk factors for HBV-R, define monitoring frequency, and identify patients who may benefit from HBV prophylaxis and treatment. DAAs remain a safe and highly effective treatment for the management of HCV infection. PRIMARY FUNDING SOURCE: None.

Demographic profile and extent of healthcare resource utilisation of patients with severe traumatic brain injury: still a major public health problem.

INTRODUCTION: Trauma is the fifth principal cause of death in Singapore, with traumatic brain injury (TBI) being the leading specific subordinate cause. METHODS: This study was an eight-year retrospective review of the demographic profiles of patients with severe TBI who were admitted to the neurointensive care unit (NICU) of the National Neuroscience Institute at Tan Tock Seng Hospital, Singapore, between 2004 and 2011. RESULTS: A total of 780 TBI patients were admitted during the study period; 365 (46.8%) patients sustained severe TBI (i.e. Glasgow Coma Scale score ≤ 8), with the majority (75.3%) being male. The ages of patients with severe TBI ranged from 14-93 years, with a bimodal preponderance in young adults (i.e. 21-40 years) and elderly persons (i.e. > 60 years). Motor vehicle accidents (48.8%) and falls (42.5%) were the main mechanisms of injury. Invasive line monitoring was frequently employed; invasive arterial blood pressure monitoring and central venous pressure monitoring were used in 81.6% and 60.0% of the patients, respectively, while intracranial pressure (ICP) measurement was required in 47.4% of the patients. The use of tiered therapy to control ICP (e.g. sedation, osmotherapy, cerebrospinal fluid drainage, moderate hyperventilation and barbiturate-induced coma) converged with international practices. CONCLUSION: The high-risk groups for severe TBI were young adults and elderly persons involved in motor vehicle accidents and falls, respectively. In the NICU, the care of patients with severe TBI requires heavy utilisation of resources. The healthcare burden of these patients extends beyond the acute critical care phase.

Use of an active surveillance system by the FDA to observe patterns of quinine sulfate use and adverse hematologic outcomes in CMS Medicare data.

PURPOSE: In 2005, the Food and Drug Administration approved Qualaquin (quinine) for treatment of malaria and later ordered unapproved quinine formulations off the market. In 2009, labeling for Qualaquin added a warning for use for leg cramps, as serious hematologic reactions could occur. We examined quinine use trends among Medicare beneficiaries focusing on indications for use and associations with adverse hematologic outcomes. METHODS: Medicare beneficiaries, aged 65 years and older, in 2006-2012, were included in incident quinine or comparator, diltiazem, cohorts if 183 days prior to dispensing, they were enrolled in Medicare, had no dispensing of quinine, diltiazem, ticlodipine, clopidogrel, and sulfonamide drugs, and had no diagnoses of thrombocytopenia, immune thrombocytopenic purpura (ITP), thrombotic microangiopathy (TMA), or hemolytic-uremic syndrome (HUS). Diagnoses of malaria or leg cramps were observed during 183 days prior to index dispensing. Outcomes of ITP, TMA, or HUS in inpatient or emergency room settings were then observed during drug use. RESULTS: Prevalent use of quinine decreased by 99%, from 419 675 to 6036 users during 2006-2012. Of 88 066 quinine users, 9 had diagnoses of malaria and 36 218 had leg cramps. Incidence rates (per 1000 person-years) for ITP were quinine 1.67 and diltiazem 0.40 [incidence rate ratio 4.2 (95% confidence interval 2.5, 6.5)], for TMA were quinine 0.23 and diltiazem 0.03 [incidence rate ratio 6.9 (95% confidence interval 1.3, 24.0)], and for HUS were quinine 0 and diltiazem 0.01. CONCLUSIONS: Use of quinine decreased substantially, although diagnoses of leg cramps persist. To our knowledge, this is the first demonstration of an association for quinine and ITP and TMA in claims data.