Embolization of percutaneous left atrial appendage closure devices: Timing, management and clinical outcomes.

BACKGROUND: Left atrial appendage (LAA) occluder embolization is an infrequent but serious complication. OBJECTIVES: We aim to describe timing, management and clinical outcomes of device embolization in a multi-center registry. METHODS: Patient characteristics, imaging findings and procedure and follow-up data were collected retrospectively. Device embolizations were categorized according to 1) timing 2) management and 3) clinical outcomes. RESULTS: Sixty-seven centers contributed data. Device embolization occurred in 108 patients. In 70.4 % of cases, it happened within the first 24 h of the procedure. The device was purposefully left in the LA and the aorta in two (1.9 %) patients, an initial percutaneous retrieval was attempted in 81 (75.0 %) and surgery without prior percutaneous retrieval attempt was performed in 23 (21.3 %) patients. Two patients died before a retrieval attempt could be made. In 28/81 (34.6 %) patients with an initial percutaneous retrieval attempt a second, additional attempt was performed, which was associated with a high mortality (death in patients with one attempt: 2.9 % vs. second attempt: 21.4 %, p < 0.001). The primary outcome (bailout surgery, cardiogenic shock, stroke, TIA, and/or death) occurred in 47 (43.5 %) patients. Other major complications related to device embolization occurred in 21 (19.4 %) patients. CONCLUSIONS: The majority of device embolizations after LAA closure occurs early. A percutaneous approach is often the preferred method for a first rescue attempt. Major adverse event rates, including death, are high particularly if the first retrieval attempt was unsuccessful. CONDENSED ABSTRACT: This dedicated multicenter registry examined timing, management, and clinical outcome of device embolization. Early embolization (70.4 %) was most frequent. As a first rescue attempt, percutaneous retrieval was preferred in 75.0 %, followed by surgical removal (21.3 %). In patients with a second retrieval attempt a higher mortality (death first attempt: 2.9 % vs. death second attempt: 24.1 %, p < 0.001) was observed. Mortality (10.2 %) and the major complication rate after device embolization were high.

Antisense oligonucleotide targeting DMPK in patients with myotonic dystrophy type 1: a multicentre, randomised, dose-escalation, placebo-controlled, phase 1/2a trial.

BACKGROUND: Myotonic dystrophy type 1 results from an RNA gain-of-function mutation, in which DM1 protein kinase (DMPK) transcripts carrying expanded trinucleotide repeats exert deleterious effects. Antisense oligonucleotides (ASOs) provide a promising approach to treatment of myotonic dystrophy type 1 because they reduce toxic RNA levels. We aimed to investigate the safety of baliforsen (ISIS 598769), an ASO targeting DMPK mRNA. METHODS: In this dose-escalation phase 1/2a trial, adults aged 20-55 years with myotonic dystrophy type 1 were enrolled at seven tertiary referral centres in the USA and randomly assigned via an interactive web or phone response system to subcutaneous injections of baliforsen 100 mg, 200 mg, or 300 mg, or placebo (6:2 randomisation at each dose level), or to baliforsen 400 mg or 600 mg, or placebo (10:2 randomisation at each dose level), on days 1, 3, 5, 8, 15, 22, 29, and 36. Sponsor personnel directly involved with the trial, participants, and all study personnel were masked to treatment assignments. The primary outcome measure was safety in all participants who received at least one dose of study drug up to day 134. This trial is registered with ClinicalTrials.gov (NCT02312011), and is complete. FINDINGS: Between Dec 12, 2014, and Feb 22, 2016, 49 participants were enrolled and randomly assigned to baliforsen 100 mg (n=7, one patient not dosed), 200 mg (n=6), 300 mg (n=6), 400 mg (n=10), 600 mg (n=10), or placebo (n=10). The safety population comprised 48 participants who received at least one dose of study drug. Treatment-emergent adverse events were reported for 36 (95%) of 38 participants assigned to baliforsen and nine (90%) of ten participants assigned to placebo. Aside from injection-site reactions, common treatment-emergent adverse events were headache (baliforsen: ten [26%] of 38 participants; placebo: four [40%] of ten participants), contusion (baliforsen: seven [18%] of 38; placebo: one [10%] of ten), and nausea (baliforsen: six [16%] of 38; placebo: two [20%] of ten). Most adverse events (baliforsen: 425 [86%] of 494; placebo: 62 [85%] of 73) were mild in severity. One participant (baliforsen 600 mg) developed transient thrombocytopenia considered potentially treatment related. Baliforsen concentrations in skeletal muscle increased with dose. INTERPRETATION: Baliforsen was generally well tolerated. However, skeletal muscle drug concentrations were below levels predicted to achieve substantial target reduction. These results support the further investigation of ASOs as a therapeutic approach for myotonic dystrophy type 1, but suggest improved drug delivery to muscle is needed. FUNDING: Ionis Pharmaceuticals, Biogen.

Correlation of falls in patients with Amyotrophic Lateral Sclerosis with objective measures of balance, strength, and spasticity.

BACKGROUND: Persons diagnosed with Amyotrophic Lateral Sclerosis (ALS) often demonstrate neurological deficits that predispose them to repeated falls and associated adverse consequences. Determining contributing factors to falls in this population is critical to improve safety and patient outcomes. OBJECTIVE: The purpose of this study was to correlate clinical measures of gait speed, balance, strength, spasticity, and a self-reported rating scale of function with fall incidence in individuals with ALS. METHODS: Thirty-one participants with a confirmed ALS diagnosis were recruited from an outpatient clinic. Each participant performed the following tests: timed gait speed, Berg Balance Scale (BBS), manual muscle testing (MMT) for lower extremity (LE) strength, Modified Ashworth Scale (MAS) for LE spasticity, and the ALS Functional Rating Scale-Revised (ALSFRS-R). Each participant reported number of falls that occurred in the past three months. Pearson correlation coefficients were calculated to determine correlations between variables. RESULTS: Significant correlation was found between fall incidence and composite LE strength score (rp = 0.385, p = 0.032). CONCLUSIONS: There is a relationship between LE weakness and number of falls in the ALS population. Preventing disuse-related LE muscle weakness and education of need for external support may decrease the number of falls experienced by individuals with ALS.

Prenatal HIV testing in Wisconsin: results of a survey among women who gave birth in 2003.

Since 1995 the United States Public Health Service has recommended voluntary prenatal human immunodeficiency virus (HIV) testing for all pregnant women in the United States. To better understand how well this goal is being met in Wisconsin, the Wisconsin Division of Public Health facilitated a review of hospital medical records for a random sample of women who gave birth in Wisconsin in 2003. Of the 968 maternal medical records reviewed, 68% (95% CI: 65%-71%) showed evidence that the mother had a completed HIV antibody test during pregnancy. Rates of prenatal HIV testing were higher in Milwaukee County. After controlling for residence, prenatal HIV testing rates were higher among Hispanic mothers compared to white mothers; African American and white mothers had similar testing rates. These data suggest that the goal of voluntary HIV testing for all pregnant women is not currently being met in Wisconsin.

The Wisconsin Cardiovascular Health Program: a partnership effort to improve the health of Wisconsin residents.

The CHP is actively engaging citizens, health professionals, and organizations as partners to help change community and patient behaviors and risk factors that may lead to heart disease and stroke and to develop environmental strategies and cardiovascular policy initiatives. We welcome additional physician involvement throughout the state in this important initiative.

A review: discharge navigation and its effect on heart failure readmissions.

PURPOSE AND OBJECTIVES: The purpose of this literature review is to investigate the potential benefit of the discharge navigator, patient education, and discharge planning in prevention of hospital readmissions for heart failure as it relates to case management. PRIMARY SETTING: Applicable to all health care sectors where case management is practiced. FINDINGS/CONCLUSIONS: In the United States, over 50% of hospitalized patients older than 65 years with congestive heart failure are readmitted within 6 months of their hospital discharge. The Patient Protection and Affordable Care Act, commonly called Obamacare, was signed into law in 2010 and effective 2012 the Centers for Medicare and Medicaid Services (CMS) began the Readmissions Reduction Program, which requires the CMS to reduce payments to inpatient prospective payment system hospitals with excess readmissions. An estimated total of 2,217 hospitals across the nation will be penalized a percentage of their base Medicare reimbursements. Provisions of the Affordable Care Act that increase hospital's financial accountability for preventable readmissions have made it imperative to identify interventions that reduce hospital readmissions for patients with heart failure. Current evidence suggests that improving transition of care through intense repetitive education reduces hospital readmissions for heart failure by: IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: : Case managers are faced with an ever-changing health care climate, including the demands of hospital readmission prevention. Because of this, case managers are in a unique position to ensure that the patient has a good understanding of their disease, medications, and follow-up instructions. One of the most effective ways to accomplish this is to be sure that every patient is assessed for discharge planning purposes and receives specific and consistent education throughout the care continuum, including follow-up care.