"But I didn't drink!": What to do with discordant phosphatidylethanol results.

Liver transplantation (LT) teams must be adept at detecting, evaluating, and treating patients' alcohol use, given its prominence among psychological and behavioral phenomena which cause and contribute to liver diseases. Phosphatidylethanol (PEth) is a highly useful alcohol biomarker increasingly recommended for routine use in hepatology and LT. PEth is unique among alcohol biomarkers because of its wide detection window, high sensitivity and specificity, and the correlation of its numerical value with different patterns of alcohol use. Alongside myriad clinical opportunities in hepatology and LT, PEth also confers numerous challenges: little guidance exists about its clinical use; fearing loss of LT access and the reactions of their clinicians and families, candidates and recipients are incentivized to conceal their alcohol use; and liver clinicians report lack of expertise diagnosing and treating substance-related challenges. Discordance between patient self-reported alcohol use and toxicology is yet another common and particularly difficult circumstance. This article discusses the general toxicological properties of PEth; explores possible scenarios of concordance and discordance among PEth results, patient history, and self-reported drinking; and provides detailed clinical communication strategies to explore discordance with liver patients, a key aspect of its use.

The possible clinical utility of the alcohol biomarker phosphatidylethanol for managing suspected alcohol withdrawal in hospitalized patients: A case report.

BACKGROUND AND OBJECTIVES: The decision to initiate pharmacotherapy for alcohol withdrawal is typically based on examining self-reported use of alcohol and symptoms of withdrawal. Phosphatidylethanol (PEth) is a biomarker that could aim in clinical decision-making in withdrawal management. METHODS: This report describes three cases highlighting the potential clinical utility of PEth in caring for individuals at risk for alcohol withdrawal. RESULTS: Two of the cases received phenobarbital when their PEth showed that the risk of withdrawal was low and one case where PEth could have shown this was needed. The results were only available in a delayed fashion, however, could have been useful in informing clinical care. DISCUSSION AND CONCLUSION: PEth can be a useful tool if available without delay. PEth can be used to quickly rule out alcohol withdrawal and avoid misdiagnoses and prolonged hospital stays. SCIENTIFIC SIGNIFICANCE: This is a clinical case study available looking at PEth and withdrawal in hospitalized patients. It proposes that PEth can be used as a way to quickly rule out alcohol withdrawal to avoid misdiagnoses and the possibility of a prolonged hospital stay.

Fiduciary assignment as a potential intervention for substance use disorder: a retrospective chart review.

Background: Assignment of fiduciaries to veterans with disability payments is an intervention thought to improve quality of life; however, in veterans who use substances, a proportion of these payments may be misspent on drugs and/or alcohol. While fiduciary assignment may reduce funds available to purchase substances, clinical efficacy of this intervention in the management of substance use disorders has not been rigorously demonstrated.Objectives: The purpose of this study is to evaluate changes in clinical status before and after fiduciary assignment.Methods: This was a retrospective chart review of 50 (44 male, 6 female) veterans who were assigned a fiduciary and determined to have a substance use disorder (SUD). SUD-related data including outpatient and inpatient treatment, toxicology testing, and measures of psychosocial functioning for the three years before and after fiduciary assignment were extracted and compared.Results: Veterans were found to have higher rates of any form of employment after fiduciary assignment (Wilcoxon, Signed Ranked S-statistic = 0.22, pr = 0.02). Two changes in measures of substance use were found after fiduciary assignment. There was a reduction in positive screens for heroin (tstatistic = -2.7, p = .01), but an increase in positive screens for fentanyl (t statistic = 2.53, p = .02). There were some potentially clinically but not statistically significant trends in increased adherence with mental health appointments, number of medical hospitalizations, and rates of employment post-fiduciary assignment.Conclusions: Understanding the clinical impact of fiduciary assignment for veteran's benefits is desirable but still pending at this time.

Patients' experiences with continuation or discontinuation of buprenorphine before painful procedures: A brief report.

BACKGROUND AND OBJECTIVES: Patients with opioid use disorder may be asked by their clinicians to discontinue maintenance buprenorphine treatment before surgical operations due to concerns that buprenorphine will interfere with acute pain management. However, discontinuation of buprenorphine may not be well tolerated or safe for all patients. We, therefore, administered a survey to better understand the experiences of patients on buprenorphine treatment who had previously undergone painful procedures and had their buprenorphine maintenance treatment either continued or discontinued before the procedure. METHODS: After this study received institutional review board approval, patients were invited to participate if they were being prescribed sublingual buprenorphine for treatment of opioid use disorder and had also previously undergone a painful procedure requiring treatment with full agonist opioids. Patients who were eligible and agreed to participate (n = 32) then completed a survey of basic demographics; medical, psychiatric, and substance use histories; and their experience and satisfaction with the treatment of pain and substance use in the perioperative period, including whether buprenorphine was continued or discontinued before their procedure. RESULTS: Compared with patients whose home dose of buprenorphine was continued (n = 15), patients whose buprenorphine was discontinued preoperatively (n = 17) reported less satisfaction with pain management and were more likely to be prescribed full agonist opioids upon discharge. DISCUSSION AND CONCLUSIONS: Consistent with prior studies, these survey findings suggest that discontinuation of buprenorphine before painful surgeries may be associated with poorer clinical outcomes. SCIENTIFIC SIGNIFICANCE: This survey study adds patients' perspective to a growing body of scientific literature suggesting that discontinuation of maintenance buprenorphine treatment before painful procedures may decrease patient satisfaction and increase clinical risk.

Clinical outcomes after implantation of a centrifugal flow left ventricular assist device and concurrent cardiac valve procedures.

BACKGROUND: Cardiac valve procedures are commonly performed concurrently during implantation of left ventricular assist devices, but the added procedural risk has not been studied in detail. METHODS AND RESULTS: Data from patients receiving the HeartWare Ventricular Assist Device in the ADVANCE bridge to transplant (BTT) trial and continued access protocol were reviewed. Of 382 consecutive patients who completed follow-up between August 2008 and June 2013 (mean time on support 389 days, median 271 days), 262 (68.6%) underwent isolated HeartWare Ventricular Assist Device implantation, 75 (19.6%) a concurrent valve procedure, and 45 (11.8%) concurrent nonvalvular procedures. Of the concurrent valve procedures, 56 were tricuspid, 13 aortic, and 6 mitral. Survival was similar between groups (79% for concurrent valve procedures and 85% for HeartWare Ventricular Assist Device only at 1 year; P=0.33). Concurrent valve procedures were also associated with increased unadjusted early right heart failure (RHF). A multivariable analysis for death and RHF (121 total events) identified female sex (odds ratio=2.0 [95% confidence interval, 1.2-3.3; P=0.0053]) and preimplant tricuspid regurgitation severity (odds ratio=2.9 [95% confidence interval, 1.8-4.8, P<0.0001]) as independent predictors while concurrent tricuspid valve procedures (TVP) were not predictors. Furthermore, patients with significant preimplant tricuspid regurgitation who did not receive a TVP experienced an increased rate of late RHF compared with those who received TVP (0.19 versus 0.05 events per patient-year, respectively; P=0.024). CONCLUSIONS: Compared with HeartWare Ventricular Assist Device alone, survival was equivalent for the concurrent valve procedure group. Tricuspid regurgitation severity was the most important predictor of increased postoperative RHF, and concurrent TVP was not an independent predictor of RHF overall. Concurrent TVP may reduce the rate of late RHF for patients with significant preimplant tricuspid insufficiency. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00751972.

Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide.

Importance: Anecdotal experience raised the possibility that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) with rapidly increasing use, is associated with nonarteritic anterior ischemic optic neuropathy (NAION). Objective: To investigate whether there is an association between semaglutide and risk of NAION. Design, Setting, and Participants: In a retrospective matched cohort study using data from a centralized data registry of patients evaluated by neuro-ophthalmologists at 1 academic institution from December 1, 2017, through November 30, 2023, a search for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code H47.01 (ischemic optic neuropathy) and text search yielded 16 827 patients with no history of NAION. Propensity matching was used to assess whether prescribed semaglutide was associated with NAION in patients with type 2 diabetes (T2D) or overweight/obesity, in each case accounting for covarying factors (sex, age, systemic hypertension, T2D, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease) and contraindications for use of semaglutide. The cumulative incidence of NAION was determined with the Kaplan-Meier method and a Cox proportional hazards regression model adjusted for potential confounding comorbidities. Data were analyzed from December 1, 2017, through November 30, 2023. Exposures: Prescriptions for semaglutide vs non-GLP-1 RA medications to manage either T2D or weight. Main Outcomes and Measures: Cumulative incidence and hazard ratio of NAION. Results: Among 16 827 patients, 710 had T2D (194 prescribed semaglutide; 516 prescribed non-GLP-1 RA antidiabetic medications; median [IQR] age, 59 [49-68] years; 369 [52%] female) and 979 were overweight or obese (361 prescribed semaglutide; 618 prescribed non-GLP-1 RA weight-loss medications; median [IQR] age, 47 [32-59] years; 708 [72%] female). In the population with T2D, 17 NAION events occurred in patients prescribed semaglutide vs 6 in the non-GLP-1 RA antidiabetes cohort. The cumulative incidence of NAION for the semaglutide and non-GLP-1 RA cohorts over 36 months was 8.9% (95% CI, 4.5%-13.1%) and 1.8% (95% CI, 0%-3.5%), respectively. A Cox proportional hazards regression model showed higher risk of NAION for patients receiving semaglutide (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29); P < .001). In the population of patients who were overweight or obese, 20 NAION events occurred in the prescribed semaglutide cohort vs 3 in the non-GLP-1 RA cohort. The cumulative incidence of NAION for the semaglutide vs non-GLP-1 RA cohorts over 36 months was 6.7% (95% CI, 3.6%-9.7%) and 0.8% (95% CI, 0%-1.8%), respectively. A Cox proportional hazards regression model showed a higher risk of NAION for patients prescribed semaglutide (HR, 7.64; 95% CI, 2.21-26.36; P < .001). Conclusions and Relevance: This study's findings suggest an association between semaglutide and NAION. As this was an observational study, future study is required to assess causality.

Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation.

BACKGROUND: Contemporary ventricular assist device therapy results in a high rate of successful heart transplantation but is associated with bleeding, infections, and other complications. Further reductions in pump size, centrifugal design, and intrapericardial positioning may reduce complications and improve outcomes. METHODS AND RESULTS: We studied a small, intrapericardially positioned, continuous-flow centrifugal pump in patients requiring an implanted ventricular assist device as a bridge to heart transplantation. The course of investigational pump recipients was compared with that of patients implanted contemporaneously with commercially available devices. The primary outcome, success, was defined as survival on the originally implanted device, transplantation, or explantation for ventricular recovery at 180 days and was evaluated for both noninferiority and superiority. Secondary outcomes included a comparison of survival between groups and functional and quality-of-life outcomes and adverse events in the investigational device group. A total of 140 patients received the investigational pump, and 499 patients received a commercially available pump implanted contemporaneously. Success occurred in 90.7% of investigational pump patients and 90.1% of controls, establishing the noninferiority of the investigational pump (P<0.001; 15% noninferiority margin). At 6 months, median 6-minute walk distance improved by 128.5 m, and both disease-specific and global quality-of-life scores improved significantly. CONCLUSIONS: A small, intrapericardially positioned, continuous-flow, centrifugal pump was noninferior to contemporaneously implanted, commercially available ventricular assist devices. Functional capacity and quality of life improved markedly, and the adverse event profile was favorable. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00751972.

The Incidence and Disparities in Use of Stigmatizing Language in Clinical Notes for Patients With Substance Use Disorder.

OBJECTIVE: The language used to describe people with substance use disorder impacts stigma and influences clinical decision making. This study evaluates the presence of stigmatizing language (SL) in clinical notes and detects patient- and provider-level differences. METHODS: All free-text notes generated in a large health system for patients with substance-related diagnoses between December 2020 and November 2021 were included. A natural language processing algorithm using the National Institute on Drug Abuse's "Words Matter" list was developed to identify use of SL in context. RESULTS: There were 546,309 notes for 30,391 patients, of which 100,792 (18.4%) contained SL. A total of 18,727 patients (61.6%) had at least one note with SL. The most common SLs used were "abuse" and "substance abuse." Nurses were least likely to use SL (4.1%) while physician assistants were most likely (46.9%). Male patients were more likely than female patients to have SL in their notes (adjusted odds ratio [aOR], 1.17; 95% confidence internal [CI], 1.11-1.23), younger patients aged 18 to 24 were less likely to have SL than patients 45 to 54 years (aOR, 0.55; 95% CI, 0.50-0.61), Asian patients were less likely to have SL than White patients (aOR, 0.45; 95% CI, 0.36-0.56), and Hispanic patients were less likely to have SL than non-Hispanic patients (aOR, 0.88; 95% CI, 0.80-0.98). CONCLUSIONS: The majority of patients with substance-related diagnoses had at least one note containing SL. There were also several patient characteristic disparities associated with patients having SL in their notes. The work suggests that more clinician interventions about use of SL are needed.

Teaching Spiritual and Religious Competencies to Psychiatry Residents: A Scoping and Systematic Review.

PURPOSE: For many persons worldwide, mental health is inseparably linked with spirituality and religion (S&R), yet psychiatrists have repeatedly expressed doubts regarding their preparedness to address patients' spirituality or religion appropriately. In recent decades, medical educators have developed and implemented curricula for teaching S&R-related competencies to psychiatry residents. The authors reviewed the literature to understand the scope and effectiveness of these educational initiatives. METHOD: The authors searched 8 databases to identify studies for a scoping review and a systematic review. The scoping review explored educational approaches (topics, methods) used in psychiatry residency programs to teach S&R-related competencies. The systematic review examined changes in psychiatry trainees' competencies and/or in patient outcomes following exposure to these educational interventions. RESULTS: Twelve studies met criteria for inclusion in the scoping review. All reported providing residents with both (1) a general overview of the intersections between mental health and S&R and (2) training in relevant interviewing and assessment skills. Seven of these studies-representing an estimated 218 postgraduate psychiatry trainees and at least 84 patients-were included in the systematic review. Residents generally rated themselves as being more competent in addressing patients' S&R-related concerns following the trainings. One randomized controlled trial found that patients with severe mental illness who were treated by residents trained in S&R-related competencies attended more appointments than control patients. CONCLUSIONS: S&R-related educational interventions appeared generally well tolerated and appreciated by psychiatry trainees and their patients; however, some topics (e.g., Alcoholics Anonymous) received infrequent emphasis, and some experiential teaching methodologies (e.g., attending chaplaincy rounds) were less frequently used for psychiatry residents than for medical students. The positive association between teaching S&R-related competencies to psychiatry residents and patient appointment attendance merits further study. Future trainings should supplement classroom learning with experiential approaches and incorporate objective measures of resident competence.

Metabolic profiling of arginine and nitric oxide pathways predicts hemodynamic abnormalities and mortality in patients with cardiogenic shock after acute myocardial infarction.

BACKGROUND: It is unclear whether abnormalities of arginine and nitric oxide metabolism are related to hemodynamic dysfunction and mortality in patients with cardiogenic shock (CS) after acute myocardial infarction. METHODS AND RESULTS: Plasma metabolites reflecting arginine bioavailability, nitric oxide metabolism, and protein oxidation were analyzed by mass spectrometry in patients with CS (n=79) and age- and gender-matched patients with coronary artery disease and normal left ventricular function (n=79). CS patients had higher levels of asymmetric dimethylarginine (ADMA; P<0.0001), symmetric dimethylarginine (P<0.0001), monomethylarginine (P=0.0003), nitrotyrosine (P<0.0001), and bromotyrosine (P<0.0001) and lower levels of arginine (P<0.0001), ratio of arginine to ornithine (P=0.03), and ratio of arginine to ornithine plus citrulline) (P=0.0003). CS patients with elevated ADMA levels were 3.5-fold (95% confidence interval, 1.4 to 11.3; P=0.02) more likely to die in 30 days than patients with low ADMA levels. ADMA remained the only independent predictor of mortality on multiple logistic regression analysis. In patients with normal renal function, symmetric dimethylarginine levels inversely correlated with mean arterial pressure and systemic vascular resistance, whereas levels of ADMA correlated with pulmonary capillary wedge pressure and both systolic and diastolic pulmonary artery pressures. Despite dramatic elevations, levels of protein oxidation products did not predict hemodynamic dysfunction or mortality in CS patients. CONCLUSIONS: CS is characterized by an arginine-deficient and highly specific pro-oxidant state, with elevated levels of methylated arginine derivatives, including endogenous nitric oxide synthase inhibitors. Levels of methylated arginine derivatives strongly correlate with hemodynamic dysfunction. Among all clinical and laboratory parameters monitored, ADMA levels were the strongest independent predictor of 30-day mortality.

The Solar Cycle.

The solar cycle is reviewed. The 11-year cycle of solar activity is characterized by the rise and fall in the numbers and surface area of sunspots. A number of other solar activity indicators also vary in association with the sunspots including; the 10.7 cm radio flux, the total solar irradiance, the magnetic field, flares and coronal mass ejections, geomagnetic activity, galactic cosmic ray fluxes, and radioisotopes in tree rings and ice cores. Individual solar cycles are characterized by their maxima and minima, cycle periods and amplitudes, cycle shape, the equatorward drift of the active latitudes, hemispheric asymmetries, and active longitudes. Cycle-to-cycle variability includes the Maunder Minimum, the Gleissberg Cycle, and the Gnevyshev-Ohl (even-odd) Rule. Short-term variability includes the 154-day periodicity, quasi-biennial variations, and double-peaked maxima. We conclude with an examination of prediction techniques for the solar cycle and a closer look at cycles 23 and 24. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/lrsp-2015-4.

Gastrointestinal bleeding in recipients of the HeartWare Ventricular Assist System.

OBJECTIVES: This study evaluated gastrointestinal bleeding (GIB) in patients receiving the HeartWare HVAD System (HeartWare Inc., Framingham, Massachusetts) in the pivotal BTT (Bridge to Transplant) trial and under the continued access protocol (CAP). BACKGROUND: GIB has become a significant problem for recipients of continuous flow device left ventricular assist devices (CF-LVAD). The need for anticoagulation and antiplatelet therapies complicates the management of GIB. METHODS: Bleeding events from 382 patients with advanced heart failure (140 patients enrolled in the BTT trial, and an additional 242 CAP patients) were analyzed. Post-implant anticoagulation consisted of heparin followed by warfarin at a target international normalized ratio of 2 to 3. Acetylsalicylic acid was recommended at 81 to 325 mg. RESULTS: Overall, 59 of 382 (15.4%) patients experienced 108 GIB events (0.27 events per patient year). Mean time to first bleed was 273.1 days and 86.1% of events occurred beyond 30 days. Freedom from GIB was 84.1% at 1 year. Median international normalized ratio at the time of first bleed was 2.4 ± 1.4. The most common etiology of bleeding identified was arteriovenous malformation and the most common site was the small intestine. Repeat bleeding was infrequent, though GIB patients required more readmissions and developed nondevice infections more frequently. No patients required surgical intervention and no deaths directly related to GIB occurred. CONCLUSIONS: Recipients of the HeartWare Ventricular Assist Device System had an incidence of 0.27 GIB/patient year with a freedom from GIB of 84.1% at 1 year. All patients with GIB events were managed with medical and endoscopic therapies, although 31% of patients experienced a recurrence of GIB. No surgical intervention was required. GIB did not impact survival. (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure [ADVANCE]; NCT00751972).

An examination of survival by sex and race in the HeartWare Ventricular Assist Device for the Treatment of Advanced Heart Failure (ADVANCE) Bridge to Transplant (BTT) and continued access protocol trials.

BACKGROUND: The Ventricular Assist Device for the Treatment of Advanced Heart Failure (ADVANCE) Bridge to Transplant (BTT) trial was a multicenter, prospective trial of the HeartWare Ventricular Assist Device (HVAD). The performance of the HVAD in various demographic sub-groups was evaluated. METHODS: Baseline characteristics, adverse events, and survival were compared for men vs. women and whites vs. non-whites in the combined ADVANCE BTT and continued access protocol trial. Of 332 patients enrolled in these trials, 236 were men and 96 women, with 228 whites and 104 non-whites. RESULTS: At baseline, women had a smaller body surface area (1.8 ± 0.2 vs. 2.1 ± 0.3 m2, p < 0.0001), less hypertension (50.0% vs. 61.9%, p = 0.05), and less ischemic cardiomyopathy (15.6% vs. 45.3%, p < 0.0001). Differences in Kaplan-Meier survival were not significant at 180 days (men, 91.8%; women, 91.7%) and 1 year (men, 85.3%; women, 85.1%) despite adjustment for baseline differences. Men had a lower incidence of early right heart failure and renal and respiratory dysfunction, and a shorter length of stay. In the analysis by race, non-whites were younger than whites and had less ischemic heart failure, more hypertension, and lower creatinine levels at baseline. Non-whites had lower rates of arrhythmia, bleeding requiring rehospitalization, and device malfunctions than whites. Survival was high in non-whites and whites, at 94.1% vs. 90.4% at 180 days and 89.2% vs. 82.8% at 1 year, respectively, despite adjustment for baseline differences. CONCLUSIONS: Although heart failure etiology differed between men and women and between whites and non-whites, sex and race were not factors that affected survival in patients receiving the HVAD as BTT, which was high in all sub-groups.

The HVAD Left Ventricular Assist Device: Risk Factors for Neurological Events and Risk Mitigation Strategies.

OBJECTIVES: The purpose of this study was to determine the risk factors for ischemic in hemorrhage cerebrovascular events in patients supported by the HeartWare ventricular assist device (HVAD). BACKGROUND: Patients supported with left ventricular assist devices are at risk for both ischemic and hemorrhagic cerebrovascular events. METHODS: Patients undergoing implantation with a HVAD as part of the bridge-to-transplant trial and subsequent continued access protocol were included. Neurological events (ischemic cerebrovascular accidents [ICVAs] and hemorrhagic cerebrovascular accidents [HCVAs]) were assessed, and the risk factors for these events were evaluated in a multivariable model. RESULTS: A total of 382 patients were included: 140 bridge-to-transplant patients from the ADVANCE (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure) clinical trial and 242 patients from the continued access protocol. Patients had a mean age of 53.2 years; 71.2% were male, and 68.1% were white. Thirty-eight percent had ischemic heart disease, and the mean duration of support was 422.7 days. The overall prevalence of ICVA was 6.8% (26 of 382); for HCVA, it was 8.4% (32 of 382). Pump design modifications and a protocol-driven change in the antiplatelet therapy reduced the prevalence of ICVA from 6.3% (17 of 272) to 2.7% (3 of 110; p = 0.21) but had a negligible effect on the prevalence of HVCA (8.8% [24 of 272] vs. 6.4% [7 of 110]; p = 0.69). Multivariable predictors of ICVA were aspirin ≤81 mg and atrial fibrillation; predictors of HCVA were mean arterial pressure >90 mm Hg, aspirin ≤81 mg, and an international normalized ratio >3.0. Eight of the 30 participating sites had established improved blood pressure management (IBPM) protocols. Although the prevalence of ICVA for those with and without IBPM protocols was similar (5.3% [6 of 114] vs. 5.2% [14 of 268]; p = 0.99), those with IBPM protocols had a significantly lower prevalence of HCVA (1.8% [2 of 114] vs. 10.8% [29 of 268]; p = 0.0078). CONCLUSIONS: Anticoagulation, antiplatelet therapy, and blood pressure management affected the prevalence of cerebrovascular events after implantation of the HVAD. Attention to these clinical parameters can have a substantial impact on the occurrence of serious neurological events. (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure [ADVANCE]; NCT00751972).

Drive-line infections and sepsis in patients receiving the HVAD system as a left ventricular assist device.

BACKGROUND: Drive-line infections and sepsis lead to significant morbidity and even mortality in patients with ventricular assist devices (VADs). The HeartWare HVAD system is unique compared with other VAD systems in that it has a thin, flexible drive-line and is implanted directly into the pericardial space without the need for a pump pocket. We reviewed 332 patients receiving the HVAD in the pivotal ADVANCE Bridge to Transplant (BTT) trial and Continued Access Protocol (CAP) to determine the incidence of drive-line infections and sepsis. METHODS: Summary statistics of outcomes and Kaplan-Meier freedom-from-event analyses were performed. The Cochran-Mantel-Haenszel test for homogeneity was used to determine whether there was any site effect on rates of either drive-line exit-site or sepsis infections. RESULTS: Drive-line exit-site infections occurred in 16.9% (56 of 332) of patients (0.25 event per patient-year [EPPY]). These infections were primarily treated with antibiotics and most occurred >30 days post-implant (88%, or 66 of 75 drive-line infections). Sepsis occurred in 17.2% (57 of 332) of patients (0.23 EPPY), and sepsis events occurred more frequently >30 days post-implant (86%, or 60 of 70 sepsis events). Of patients with sepsis, 17.5% (10 of 57) died due to sepsis-related neurologic events (7 of 10) and multisystem organ failure (2 of 10) and cardiopulmonary failure (1 of 10), whereas there were no deaths related to drive-line infections. In addition, 17.5% (10 of 57) of patients had a stroke event while under treatment for sepsis (7 hemorrhagic and 3 ischemic strokes), and 3.5% (2 of 57 patients with sepsis) had a device exchange for VAD thrombus (4 days before and 1 day after sepsis diagnosis). Patients with drive-line infections or sepsis had a larger body mass index compared to those without infection (29.4 vs 27.6 kg/m(2), p = 0.015), and were more frequently diabetic (43.7% vs 31.2%, p = 0.034). Although there was no negative impact on survival in patients with drive-line exit-site infections, there was a trend for reduced survival in patients with sepsis events when compared to those patients without sepsis. CONCLUSIONS: The incidence of drive-line infection and sepsis was low in patients receiving the HVAD pump. Despite a trend toward reduced survival in patients with sepsis events, the overall survival of patients with either drive-line infections or sepsis was excellent.

An analysis of pump thrombus events in patients in the HeartWare ADVANCE bridge to transplant and continued access protocol trial.

BACKGROUND: The HeartWare left ventricular assist device (HVAD, HeartWare Inc, Framingham, MA) is the first implantable centrifugal continuous-flow pump approved for use as a bridge to transplantation. An infrequent but serious adverse event of LVAD support is thrombus ingestion or formation in the pump. In this study, we analyze the incidence of pump thrombus, evaluate the comparative effectiveness of various treatment strategies, and examine factors pre-disposing to the development of pump thrombus. METHODS: The analysis included 382 patients who underwent implantation of the HVAD as part of the HeartWare Bridge to Transplant (BTT) and subsequent Continued Access Protocol (CAP) trial. Descriptive statistics and group comparisons were generated to analyze baseline characteristics, incidence of pump thrombus, and treatment outcomes. A multivariate analysis was performed to assess significant risk factors for developing pump thrombus. RESULTS: There were 34 pump thrombus events observed in 31 patients (8.1% of the cohort) for a rate of 0.08 events per patient-year. The incidence of pump thrombus did not differ between BTT and CAP. Medical management of pump thrombus was attempted in 30 cases, and was successful in 15 (50%). A total of 16 patients underwent pump exchange, and 2 underwent urgent transplantation. Five patients with a pump thrombus died after medical therapy failed, 4 of whom also underwent a pump exchange. Survival at 1 year in patients with and without a pump thrombus was 69.4% and 85.5%, respectively (p = 0.21). A multivariable analysis revealed that significant risk factors for pump thrombus included a mean arterial pressure > 90 mm Hg, aspirin dose ≤ 81 mg, international normalized ratio ≤ 2, and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile level of ≥ 3 at implant. CONCLUSIONS: Pump thrombus is a clinically important adverse event in patients receiving an HVAD, occurring at a rate of 0.08 events per patient-year. Significant risk factors for pump thrombosis include elevated blood pressure and sub-optimal anti-coagulation and anti-platelet therapies. This suggests that pump thrombus event rates could be reduced through careful adherence to patient management guidelines.

Giant convection cells found on the Sun.

Heat is transported through the outermost 30% of the Sun's interior by overturning convective motions. These motions are evident at the Sun's surface in the form of two characteristic cellular structures: granules and supergranules (~1000 and ~30,000 kilometers across, respectively). The existence of much larger cells has been suggested by both theory and observation for more than 45 years. We found evidence for giant cellular flows that persist for months by tracking the motions of supergranules. As expected from the effects of the Sun's rotation, the flows in these cells are clockwise around high pressure in the north and counterclockwise in the south and transport angular momentum toward the equator, maintaining the Sun's rapid equatorial rotation.

HeartWare ventricular assist system for bridge to transplant: combined results of the bridge to transplant and continued access protocol trial.

BACKGROUND: The HeartWare Ventricular Assist System (HeartWare Inc, Framingmam, MA) is a miniaturized implantable, centrifugal design, continuous-flow blood pump. The pivotal bridge to transplant and continued access protocols trials have enrolled patients with advanced heart failure in a bridge-to-transplant indication. METHODS: The primary outcome, success, was defined as survival on the originally implanted device, transplant, or explant for ventricular recovery at 180 days. Secondary outcomes included an evaluation of survival, functional and quality of life outcomes, and adverse events. RESULTS: A total of 332 patients in the pivotal bridge to transplant and continued access protocols trial have completed their 180-day primary end-point assessment. Survival in patients receiving the HeartWare pump was 91% at 180 days and 84% at 360 days. Quality of life scores improved significantly, and adverse event rates remain low. CONCLUSIONS: The use of the HeartWare pump as a bridge to transplant continues to demonstrate a high 180-day survival rate despite a low rate of transplant. Adverse event rates are similar or better than those observed in historical bridge-to-transplant trials, despite longer exposure times due to longer survival and lower transplant rates.

Variations in the Sun's meridional flow over a solar cycle.

The Sun's meridional flow is an axisymmetric flow that is generally directed from its equator toward its poles at the surface. The structure and strength of the meridional flow determine both the strength of the Sun's polar magnetic field and the intensity of sunspot cycles. We determine the meridional flow speed of magnetic features on the Sun using data from the Solar and Heliospheric Observatory. The average flow is poleward at all latitudes up to 75 degrees, which suggests that it extends to the poles. It was faster at sunspot cycle minimum than at maximum and substantially faster on the approach to the current minimum than it was at the last solar minimum. This result may help to explain why this solar activity minimum is so peculiar.