Adverse Events and Complications Associated With Intrathecal Drug Delivery Systems: Insights From the Manufacturer and User Facility Device Experience (MAUDE) Database.

BACKGROUND: Modern intrathecal drug delivery systems (IDDS) are technologically advanced to deliver medication through various automated and patient-controlled programs. They also are associated with unique complications ranging from post-operative complications, medication-related adverse events (AE), device malfunction, to refill associated AE. OBJECTIVES: To systematically analyze real-world complications and AE reported on the Food and Drug Administration's Manufacturer and User Facility Device Experience database (MAUDE) associated with IDDS among patients predominantly with chronic pain disorders. MATERIALS AND METHODS: MAUDE database was sampled for a month four times a year during the study period, February 2018 to February 2019. The database was resampled every six months till August 2020 to evaluate for any additional reported cases during the index months. The two FDA approved IDDS, were included. AE were broadly classified into causes related to catheter malfunction, pump malfunction, biologic, and medication-related AE. RESULTS: A total of 1001 reports were included in the final analysis. The top three reasons for adverse report are infection/erosion (15.7%, n = 157), motor stall (12.4%, n = 125) and adverse medication reactions (11.8%, n = 119), respectively. There were five deaths among patients with IDDS. Epidural hematoma (n = 3) after IDDS surgery resulted in a death and residual neurological deficits after surgical evacuation. Programming errors, medication concentration discrepancy, and failure to turn on the pump after reprogramming are various preventable causes of medication-related IDDS AEs. CONCLUSIONS: Analysis of AE associated with IDDS from the MAUDE database provided a real-world perspective different from reported registry complications. Awareness and vigilance of preventable IDDS-related complications is the first step toward mitigating risks to provide safe and effective intrathecal drug delivery for chronic pain management.

Temporal Trends and Outcomes of Left Ventricular Aneurysm After Acute Myocardial Infarction.

There are limited data on the prevalence and an outcome of left ventricular (LV) aneurysms following acute myocardial infarction (AMI). Using the National Inpatient Sample during 2000 to 2017, a retrospective cohort of AMI admissions was evaluated for LV aneurysms. Complications included ventricular arrhythmias, mechanical, cardiac arrest, pump failure, LV thrombus, and stroke. Outcomes of interest included in-hospital mortality, temporal trends, complications, hospitalization costs, and length of stay. A total 11,622,528 AMI admissions, with 17,626 (0.2%) having LV aneurysms were included. The LV aneurysm cohort was more often female, with higher comorbidity, and admitted to large urban hospitals (all p < 0.001). In 2017, compared with 2000, there was a slight increase in LV aneurysms prevalence in those with (adjusted odds ratio [aOR] 1.57 [95% confidence interval {CI} 1.41 to 1.76]) and without (aOR 1.13 [95% CI 1.00 to .127]) ST-segment-elevation AMI (p < 0.001 for trend). LV aneurysms were more commonly noted with anterior ST-segment-elevation AMI (31%) compared with inferior (12.3%) and other (7.9%). Ventricular arrhythmias (17.6% vs 8.0%), mechanical complications (2.6% vs 0.2%), cardiac arrest (7.1% vs 5.0%), pump failure (26.3% vs 16.1%), cardiogenic shock (10.0% vs 4.8%) were more common in the LV aneurysm cohort (all p < 0.001). Those with LV aneurysms had comparable in-hospital mortality compared with those without (7.4% vs 6.2%; aOR 1.02 [95% CI 0.90 to 1.14]; p = 0.43). The LV aneurysm cohort had longer length of hospital stay, higher hospitalization costs, and fewer discharges to home. In conclusion, LV aneurysms were associated with higher morbidity, more frequent complications, and greater in-hospital resource utilization, without any differences in in-hospital mortality in AMI.

Complement activation in pauci-immune necrotizing and crescentic glomerulonephritis: results of a proteomic analysis.

BACKGROUND: Complement activation plays an important role in the pathophysiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), although it remains unclear which pathway is activated. Whether pauci-immune necrotizing crescentic glomerulonephritis (pauci-immune GN) with negative ANCA serology is part of the spectrum of AAV or a different disease entity is essentially unknown. METHODS: We used proteomic analysis to delineate the complement profile in a series of 13 kidney biopsies of patients with pauci-immune GN, with either proteinase 3 (PR3) (five patients) or myeloperoxidase (MPO) antibodies (four patients) or with consistently negative ANCA serology (four patients). Immunofluorescence staining of glomeruli was essentially negative in the PR3-ANCA and MPO-ANCA groups, while a mild staining for C3 was seen in the ANCA-negative cases. No electron-dense deposits were found in the PR3-ANCA and MPO-ANCA groups, but mesangial and few subepithelial deposits were clearly present in the ANCA-negative specimens. RESULTS: Mass spectrometry revealed low spectra numbers for C3 and immunoglobulins in both PR3-positive and MPO-positive patients with minimal or no C4 and C9. In contrast, larger spectra numbers for C3, moderate spectra numbers for C9, complement factor H-related protein-1 and low spectra numbers for C4, C5 and immunoglobulins were found in the ANCA-negative cases. CONCLUSION: While complement activation is noted in AAV, the complement activation appears to be more prominent in the ANCA-negative glomerulonephritis. The larger amount of C3 and moderate amount of C9 in the ANCA-negative glomerulonephritis implies activation of the alternate and terminal pathway of complement, suggesting that this entity may be caused or promoted by a genetic or acquired defect in the alternative pathway.

Coincidental Impact of Transcatheter Patent Foramen Ovale Closure on Migraine with and without Aura - A Comprehensive Meta-Analysis.

BACKGROUND: We analyzed the literature to assess the coincidental impact on migraines of transcatheter patent foramen ovale (PFO) closure performed for secondary stroke prevention. METHODS: We searched Medline, EMBASE, and the Cochrane database for studies published up until August 2013. We included English-language studies that provided information on complete resolution or improvement in migraine headaches following PFO closure. Two study authors identified 375 original articles and both independently reviewed 32 relevant manuscripts. Data including study methodology, inclusion criteria, PFO closure and migraine outcomes were extracted manually from all eligible studies. Pooled odds (and probability) of resolution or improvement of migraine headaches were calculated using random-effects models. RESULTS: Twenty studies were analyzed. Most were uncontrolled studies that included a small number of patients with cryptogenic stroke who had undergone PFO closure and had variable time of followup. The probability of complete resolution of migraine with PFO closure (18 studies, 917 patients) was 0.46 (95% confidence interval 0.39, 0.53) and of any improvement in migraine (17 studies, 881 patients) was 0.78 (0.74, 0.82). There was evidence for publication bias in studies reporting on improvement in migraines (Begg's p=0.002), but not for studies on complete resolution of migraine (p=0.3). In patients with aura, the probability of complete resolution of migraine post-PFO closure was 0.54 (0.43, 0.65), and in those without aura, complete resolution occurred in 0.39 (0.29, 0.51). CONCLUSIONS: Among patients with unexplained stroke and migraine undergoing transcatheter PFO closure, resolution of headaches occurred in a majority of patients with aura and for a smaller proportion of patients without aura.

Acute coronary syndromes without coronary plaque rupture.

The latest advances in plaque imaging have provided clinicians with opportunities to treat acute coronary syndrome (ACS) and provide individualized treatment recommendations based not only on clinical manifestations, angiographic characteristics, and biomarker data, but also on the findings of plaque morphology. Although a substantial proportion of ACS events originate from plaques with an intact fibrous cap (IFC), clinicians predominantly equate ACS with plaque rupture arising from thin-cap fibroatheromas. In this Review, we discuss the recent advances in our understanding of plaque morphology in ACS with IFC, reviewing contemporary data from intravascular imaging. We also explore whether use of such imaging might provide a roadmap for more effective management of patients with ACS.