Randomized Controlled Trial of Self-Directed Care for Medically Uninsured Adults With Serious Mental Illness.

OBJECTIVE: Self-directed care (SDC) is a treatment model in which recipients self-manage funds designated for provision of services. The model is designed to cost no more than traditional services while achieving superior participant outcomes. The authors examined the model's impact on outcomes, service costs, and user satisfaction among medically uninsured, low-income individuals with serious mental illness. METHODS: Adults in the public mental health system (N=42) were randomly assigned (1:1) to receive SDC or services as usual and were assessed at baseline and 6- and 12-month follow-ups. Outcomes included perceived competence for mental health self-management, met and unmet needs, degree of autonomy support, self-perceived recovery, and employment. Mixed-effects random regression analysis tested for differences in longitudinal changes in outcomes between the two study conditions. Differences in service costs were analyzed with negative binomial regression models. RESULTS: Compared with individuals in the control condition, SDC participants reported greater improvement in perceived competence, met and unmet needs, autonomy support, recovery from symptom domination, and employment. No differences were found between the two groups in total per-person service costs or costs for individual services. The most frequent nontraditional purchases were for medical, dental, and vision services (33%) and health and wellness supports (33%). Satisfaction with SDC services was high. CONCLUSIONS: Mental health SDC services achieved participant outcomes superior to treatment as usual, with equivalent service use and costs and high user satisfaction. This model may be well suited to the needs of uninsured adults with low income who receive public behavioral health care.

A Case of Acute Pulmonary Embolus after mRNA SARS-CoV-2 Immunization.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a critical strategy to overcome the COVID-19 pandemic. Multiple SARS-CoV-2 vaccines have been developed in a rapid timeframe to combat the pandemic. While generally safe and effective, rare cases of venous thromboembolism (VTE) have been reported after two adenovirus-based vaccines, the AstraZeneca ChAdOx1 nCoV-19 vaccine and the Janssen Ad.26.COV2.S vaccine, as well as after the Pfizer-BioNTech BNT162b2 mRNA vaccine. Here, we present the case of a patient who developed acute pulmonary emboli (PE) shortly after his second dose of the Moderna mRNA-1273 SARS-CoV-2 vaccine. We report the results of an extensive thrombophilia workup that was normal except for the identification of positive lupus anticoagulant (LA) signals. It is our goal to contribute to the body of knowledge regarding SARS-CoV-2 vaccines and encourage vaccine adverse event reporting so that clinicians can have a full appreciation and awareness of the possible adverse events related to these critical vaccines.

Reducing Blood Loss by Changing to Small Volume Tubes for Laboratory Testing.

OBJECTIVE: To reduce diagnostic blood loss by using small volume tubes for routine laboratory testing throughout the hospital, as blood loss from laboratory testing can be substantial for patients and may lead to hospital-acquired anemia. PATIENTS AND METHODS: Diagnostic blood loss was evaluated in hospitalized patients between April 1, 2017, and June 1, 2018. The preintervention, during intervention, and postintervention mean diagnostic blood loss per hospitalized patient was compared across the floors and for each type of tube for hematology, basic metabolic panel, and coagulation tests. Mean hemoglobin levels, blood transfusions per hospitalized patient, and percent redraws were also compared. RESULTS: The total volume of blood drawn for all the 3 tests decreased across each implementation phase; however, only patients admitted to the transplant and critical care (T/CC) units had increased hemoglobin levels. In addition, there was a significant reduction in transfusions across implementation phases. The incidence risk ratio for transfusion reduced even more in patients admitted to the T/CC units. Finally, there was no significant difference in the overall percent redraws across all the units. CONCLUSION: The use of small volume tubes in exchange for standard sized tubes markedly decreased diagnostic blood loss by 25.7% in all the units and 22.9% in the T/CC units. Also, the number of transfusions decreased across units, with the greatest decrease in the T/CC units. An increase in mean hemoglobin levels was observed specifically in patients admitted to the T/CC units, with no corresponding change in percent redraws across all the units.

Platelet Function Analyzer 100 and Brain Natriuretic Peptide as Biomarkers in Obstructive Hypertrophic Cardiomyopathy.

To test dual blood biomarkers compared with electrocardiogram (ECG) for hypertrophic cardiomyopathy (HC) screening, we performed 3 analyses and cut-point assessments. First, we measured platelet function analyzer (PFA)-100 (n = 99) and normalized B-type natriuretic peptide (BNP) or NT-proBNP (BNP/upper limit of normal [ULN], n = 92) in 64 patients with HC and 29 normal controls (NCs). Second, from the regression equation between PFA and gradient (r = 0.77), we derived estimated PFA in a population of 189 patients with functional class I HC in whom measured BNP/ULN and ECG were available, and calculated single and dual biomarker sensitivity and specificity compared with ECG. Finally, we compared BNP/ULN in class I patients based on mutation and familial history status. In 42 patients with obstructive HC versus NCs, there was a slight overlap of PFA and BNP/ULN, but for the product of PFA × BNP/ULN, there was near-complete separation of values. Among patients with class I obstructive HC, estimated PFA × BNP/ULN had a sensitivity of 93% and a specificity of 100%; in latent and nonobstructive HC, sensitivity dropped to 61% and 72%; for ECG in obstructive, latent, and nonobstructive HC, sensitivity was 71%, 34%, and 67%. Functional class I patients with positive (n = 28) and negative (n = 36) sarcomere mutations and a positive (n = 71) or a negative (n = 109) family history had significant elevations of BNP/ULN versus NC, with no between-group differences. In conclusion, PFA and BNP were highly associated with obstructive HC and could potentially be used for screening; BNP was not uniquely elevated in patients with familial versus nonfamilial or mutation-positive versus mutation-negative HC.

Safety and Efficacy of Intensified Antiplatelet Therapy in Patients Undergoing Neuroendovascular Procedures.

INTRODUCTION: The purpose of this study was to evaluate safety and efficacy of intensified antiplatelet therapy guided by VerifyNow assay P2Y12 reaction unit (PRU) reported values in patients undergoing neuroendovascular procedures. METHODS: An observational, retrospective review was conducted at a single academic tertiary referral center and comprehensive stroke center from December 1, 2012, to August 31, 2014. The primary objective was to determine the prevalence of thromboembolic complications stratified by preprocedural PRU values. Secondary outcomes were assessed by investigating whether the goal PRU value of 190 or less is sufficient to reduce thromboembolic complications on the day of the procedure, and 30- and 90-day postprocedure. RESULTS: There was no statistically significant difference in the overall rate of complications in the two groups (two events in the group with preprocedural PRU values of 190 or more versus seven events in the group with preprocedural PRU values of less than 190, p = 0.668). Furthermore, the rates of thromboembolic events by 90 days were not significantly different in the two groups (one event in the group with preprocedural PRU ≥ 190 versus four events in patients with preprocedural PRU < 190, p = 1). Similarly, there was no statistically significant difference in the rate of hemorrhagic events in the two groups by 90-day postprocedure (one versus three events, p = 0.558). CONCLUSION: The observed rate of thromboembolic and hemorrhagic complications in patients with preprocedural PRU values of less than 190 was not significantly different from the rate observed in patients with preprocedural PRU values of greater than 190. Sources of funding: No external funding used.

Correction of factor XI deficiency by liver transplantation.

Orthotopic liver transplantation for other diseases typically results in a coincidental cure for hemophilia A and B; however, long-term outcomes of liver transplant in hemophilia C are not very well described. Herein, the authors report a patient of severe congenital factor XI (FXI) deficiency who received an orthotopic liver transplant. The authors discuss the perioperative management and long-term outcomes. The normalization of his FXI levels confirms that the liver is the most clinically relevant site of synthesis of FXI.

Safety and efficacy of ticagrelor for neuroendovascular procedures. A single center initial experience.

INTRODUCTION: Although platelet response testing is controversial, up to one-third of neuroendovascular patients are 'resistant' to clopidogrel and are at risk for in stent thrombotic complications and may require alternative antiplatelet therapy. Ticagrelor is a new reversible ADP P2Y12 platelet receptor inhibitor with no known resistance. We describe the clinical experience with ticagrelor for neuroendovascular procedures as an alternative in clopidogrel P2Y12 platelet resistant patients. METHODS: We reviewed our cerebrovascular database for all patients who were non-responders to clopidogrel, defined as P2Y12% inhibition <30%, despite repeat clopidogrel loading dose of at least 600 mg, and who were then administered ticagrelor. RESULTS: 18 patients were non-responders to clopidogrel; 10 (56%) were men, eight (44%) were women, with a median age of 61 years (range 38-84). All patients received loading doses of at least 600 mg of clopidogrel and showed P2Y12 levels below 20% prior to ticagrelor administration. Patients were loaded with 180 mg of ticagrelor, and all but one patient showed an initial P2Y12 response above 60%. 11 patients underwent stenting, two underwent coiling, and five underwent treatment by pipeline embolization device. No patient experienced any adverse effects in the postoperative period related to the use of ticagrelor. CONCLUSIONS: Ticagrelor offers an effective alternative to clopidogrel non-responders. All of our patients showed immediate platelet inhibition after a loading dose of 180 mg of ticagrelor, with no adverse effects. The cost of medication, patient compliance (twice a day doses), and reversible inhibition should be taken into consideration when using ticagrelor.

Clopidogrel Resistance by P2Y12 Platelet Function Testing in Patients Undergoing Neuroendovascular Procedures: Incidence of Ischemic and Hemorrhagic Complications.

PURPOSE: The purpose of the study was to assess clopidogrel resistance and whether "intensified" antiplatelet therapy guided by platelet inhibition tests during neuroendovascular procedures would reduce ischemic complications. METHODS: We conducted a retrospective review of patients at Mayo Clinic in Jacksonville, Florida, who underwent neuroendovascular (NV) procedures and had P2Y12 platelet function testing from October 1, 2009, to September 30, 2010. The primary end-point was to determine P2Y12 resistance to antiplatelet therapy in patients who underwent NV procedures. Secondary objectives included incidence of hemorrhagic and ischemic events and a correlation between resistance and genetic CYP2C19 testing. RESULTS: 160 patients underwent P2Y12 platelet function tests. Eighty-one patients (81/160, 50.6%) met inclusion criteria. Platelet function tests identified 64 patients (79%) as non-resistant (≥20% P2Y12 inhibition) and 17 (21%) as resistant (<20% inhibition) after initial clopidogrel loading. There was an increased rate of death when a complication occurred in the resistant group by 30 day (17% versus 3%; p=0.059) and 90 day follow-up (23% versus 4%; p=0.032). There was no significant association found between complication and loading dose (p=0.0721). CONCLUSIONS: 21% of patients undergoing NV procedures were resistant to clopidogrel. Intensifying antiplatelet therapy to achieve ≥20% inhibition on platelet function testing did not result in higher numbers of ischemic or hemorrhagic events, but there was a trend toward more death in the resistant group by 30 and 90 days of those experiencing complication(s). AUTHOR JUSTIFICATIONS: Jerah D. Nordeen, Pharm.D.: Primary author Alden V. Patel, Pharm.D.: Contributor of professional content, study design Robert M. Darracott, Pharm.D.: Contributor of professional content, study design Gretchen S. Johns, M.D.: Contributor of professional content, study design Philipp Taussky, M.D.: Contributor of professional content, study design Rabih G. Tawk, M.D.: Contributor of professional content, study design David A. Miller, M.D.: Contributor of professional content, study design William D. Freeman, M.D.: Contributor of professional content, study design Ricardo A. Hanel, MD, PhD: Contributor of professional content, study design. LIST OF ABBREVIATIONS: (NV)neuroendovascular(CYP)cytochrome P-450(PPI)proton pump inhibitors(PCI)percutaneous coronary intervention. LIST OF COMMERCIAL PRODUCTS: Aspirin (Acetylsalicylic Acid) (Bayer Corp, Morristown, NJ, USA) Clopidogrel (Plavix®) (Bristol Myers Squibb/Sanofi Pharmaceuticals, Princeton, NJ, USA) VerifyNow® (Accumetrics Inc., San Diego, CA, USA) Ticlopidine (Ticlid®) (Roche Laboratories, Basel, Switzerland) Prasugrel (Effient®) (Eli Lilly & Co., Indianapolis, IN, USA) Eptifibatide (Integrilin®) (Merck & Co., Inc., Whitehouse Station, NJ, USA) Abciximab (Reopro®) (Janssen Pharmaceuticals, Inc., Titusville, NJ, USA) Tirofiban (Aggrastat®) (MGI Pharma, Inc., Bloomington, MN, USA) Pantoprazole (Protonix®) (Pfizer Inc., New York, NY, USA) Omeprazole (Prilosec®) (Procter and Gamble Pharmaceuticals, Mason, OH, USA) Famotidine (Pepcid®) (McNeil Consumer & Specialty Pharmaceuticals, Fort Washington, PA, USA) Ticagrelor (Brilinta®) (AstraZeneca Pharmaceuticals, Wilmington, NC, USA).

Indexes of von Willebrand factor as biomarkers of aortic stenosis severity (from the Biomarkers of Aortic Stenosis Severity [BASS] study).

We correlated von Willebrand factor (VWF) activity indexes and brain natriuretic peptide (BNP) with measures of aortic stenosis (AS) severity, bleeding, symptoms, and freedom from death or aortic valve replacement. Patients with AS (n = 66 [16 mild, 20 moderate, and 30 severe]) and aortic valve replacement (n = 21) were assessed with VWF antigen, VWF latex agglutination immunoturbidic activity, platelet function analyzer collagen plus adenosine diphosphate (PFA-CADP), VWF multimer ratio, and BNP level after echocardiography. In patients with AS, the mean gradient correlated with BNP (Spearman r = 0.29, p = 0.02), VWF latex agglutination immunoturbidic activity/VWF antigen ratio (r = -0.41, p <0.001), PFA-CADP (r = 0.49, p <0.001), and VWF multimer ratio (r = -0.76, p <0.001). The area under the curve for detection of severe AS was 0.62 (95% confidence interval [CI] 0.48 to 0.77) by elevated BNP, 0.81 (95% CI 0.69 to 0.92) by PFA-CADP closure time, 0.69 (95% CI 0.55 to 0.82) by VWF latex agglutination immunoturbidic activity/VWF antigen ratio, and 0.86 (95% CI 0.76 to 0.95) by VWF multimer ratio. For the VWF multimer ratio, a threshold of 0.15 yielded a sensitivity and specificity for severe AS of 77% and positive predictive value of 74%. Bleeding (in 14%) was associated with a prolonged PFA-CADP time and reduced VWF latex agglutination immunoturbidic activity/VWF antigen ratio. Symptoms were associated with elevated BNP and low Duke Activity Status Index score. In 66 patients with AS, freedom from death (n = 4) or aortic valve replacement (n = 22) was associated with PFA-CADP (p = 0.003), VWF high-molecular-weight multimers (p = 0.009), and VWF latex agglutination immunoturbidic activity/VWF antigen ratio (p <0.001) but not BNP (p = 0.32). In severe AS versus aortic valve replacement, the PFA-CADP and VWF multimer ratio differed (p <0.001), but BNP and the VWF latex agglutination immunoturbidic activity/VWF antigen ratio did not. In conclusion, the VWF activity indexes were associated with AS severity and bleeding and were predictive of cardiovascular outcomes.

A comparison of bleeding complications post-ablation between warfarin and dabigatran.

INTRODUCTION: Although warfarin has traditionally been used for reducing risk of stroke in patients with atrial fibrillation, over the past year, the direct thrombin inhibitor dabigatran has become an accepted alternative. No study has conclusively investigated bleeding risks of patients treated with dabigatran immediately following radiofrequency catheter ablation (RFCA) procedures. METHODS: We evaluated 156 consecutive patients referred for RFCA of atrial arrhythmias: 31 patients were on dabigatran and 125 patients were on warfarin. The incidence of bleeding complications during the first 48 h and the first week following ablation were recorded and comparisons made using Fisher's exact test. Major complications were defined as hemorrhage requiring blood products or the need for vascular intervention. Minor complications were defined as prolonged bleeding from the catheter insertion site, hematoma formation, or development of ecchymosis. Our study also took into account the intraprocedure activated clotting time (ACT) levels in an effort to describe any differences between both patient groups. RESULTS: There were no differences in age, gender, procedure type, or level of intraprocedural anticoagulation between the warfarin and dabigatran groups. No major bleeding complications were observed in either patient group at either 48 h or 1 week postprocedure. Six of the 31 dabigatran patients and 21 of the 125 warfarin patients had minor bleeding complications. There was no statistically significant difference between the incidence of minor bleeding complications between the two groups (p = 0.7384), although rebleeding was more commonly observed in patients on dabigatran. In regard to the intraprocedure ACT levels, there was more variability in the dabigatran patient group, and it was more difficult to achieve the goal ACT level, yet these results did not affect overall bleeding complications. CONCLUSION: In our cohort, bleeding-related complications 48 h and 1 week post-ablation were similar for warfarin and dabigatran. Dabigatran is associated with more intraprocedural variability in ACT than warfarin.

Serum free light chains in the diagnosis and monitoring of patients with plasma cell dyscrasias.

Serum free light chain assay is a recently available test for diagnosis and monitoring of patients with plasma cell dyscrasias. In particular, this test is especially useful in patients that were previously difficult to follow with traditional laboratory methods. These patients include non-secretory multiple myeloma, amyloidosis and light chain deposition disease. In addition other uses for the test include monitoring response to treatment and earlier detection of relapse in all patients with plasma cell dyscrasias. Potential uses include assessing progression of patients with monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, solitary bone plasmacytoma and extramedullary plasmacytoma to multiple meyloma. Analytical considerations for the assay are also discussed.

Infantile Alexander's disease: serial neuroradiologic findings.

Serial neuroimaging studies in Alexander's disease were obtained on an African-American girl who died at 4z\x years of age. She presented with macrocephaly, psychomotor retardation, spasticity, a seizure disorder, and hydrocephalus. A thorough metabolic evaluation of defined leukodystrophies, including Krabbe's disease, adrenoleukodystrophy, metachromatic leukodystrophy, Canavan's disease, and Leigh disease, was negative. A diagnosis of Alexander's disease was made based on the clinical features and ruling out all other possible causes. It was confirmed by pathologic findings of numerous subpial, subependymal, and perivascular Rosenthal fibers throughout the entire cerebrum. Interestingly, autopsy also identified the stenotic sylvian aqueduct owing to Rosenthal fiber accumulation, explaining the origin of hydrocephalus. The evolution of magnetic resonance imaging findings appears to be unique in this disease.