16 research outputs found
Reducing Intrathecal Baclofen Related Infections: Service Evaluation and Best Practice Guidelines
Objectives:
Intrathecal baclofen (ITB) pumps are an effective treatment for spasticity; however infection rates have been reported in 3â26% of patients in the literature. The multidisciplinary ITB service has been established at The National Hospital for Neurology and Neurosurgery, UCLH, Queen Square, London for over 20âyears. Our study was designed to clarify the rate of infection in our ITB patient cohort and secondly, to formulate and implement best practice guidelines and to determine prospectively, whether they effectively reduced infection rates. /
Methods:
Clinical record review of all patients receiving ITB preâintervention; January 2013âMay 2015, and following practice changes; June 2016âJune 2018. /
Results:
Four of 118 patients receiving ITB during the first time period (3.4%, annual incidence rate of infection 1.4%) developed an ITBârelated infection (three following ITB pump replacement surgery, one after initial implant). Infections were associated with 4.2% of ITBârelated surgical procedures. Three of four pumps required explantation.
Following change in practice (preâoperative chlorhexidine skin wash and intraoperative vancomycin wash of the fibrous pocket of the replacement site), only one of 160 ITB patients developed infection (pump not explanted) in the second time period (0.6%, annual incidence rate 0.3%). The infection rate related to ITB surgical procedures was 1.1%. In cases of ITB pump replacement, the infection rate was reduced to 3.3% from 17.6%. /
Conclusions:
This study suggests that a straightforward change in clinical practice may lower infection rates in patients undergoing ITB therapy
Mavacamten Treatment for Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results From the MAVA-LTE Study, EXPLORER-LTE Cohort.
This study was funded by Bristol Myers Squibb, Princeton, New Jersey, USA. Bristol Myers Squibbâs policy on data sharing is available
online at https://www.bms.com/researchers-and-partners/clinicaltrials-and-research/disclosure-commitment.html. Dr Rader has
received consulting fees from Medtronic, Bristol Myers Squibb, and
ReCor Medical. Dr OreËziak has received personal fees from Bristol
Myers Squibb. Dr Saberi has received personal fees from Bristol Myers
Squibb. Dr Fermin has received consulting fees from Alnylam, Eidos
Therapeutics, Bristol Myers Squibb, and Pfizer. Dr Wheeler has
received personal fees and research support from Bristol Myers
Squibb. Dr Garcia-Pavia has received consulting and speaking fees
from Bristol Myers Squibb, Rocket Pharmaceuticals, and Cytokinetics
and speaking fees from Bristol Myers Squibb and Cytokinetics. Dr
Zwas has received personal fees from Bristol Myers Squibb. Dr Masri
has received grants from Akcea, Pfizer, and Ultromics and consulting
fees from Alnylam, Cytokinetics, Eidos Therapeutics, Ionis, and
Pfizer. Dr Owens has received consulting fees from Bristol Myers
Squibb, Cytokinetics, and Pfizer. Dr Hegde serves on the faculty of the
Cardiovascular Imaging Core Laboratory at Brigham and Womenâs
Hospital, and her institution has received payments for her consulting work from Bristol Myers Squibb. Dr Seidler has received
consulting fees or honoraria for lectures from Bristol Myers Squibb
and Cytokinetics. Dr Balaratnam and Dr Sehnert are employees of
Bristol Myers Squibb and own stock of Bristol Myers Squibb. Shawna
Fox is an employee of IQVIA, a partner providing statistics services to
Bristol Myers Squibb. Dr Olivotto has received grants from Amicus,
Boston Scientific, Bristol Myers Squibb, Cytokinetics, Genzyme, and
Menarini International and consulting fees from Amicus, Cytokinetics, Genzyme, MS Pharma, Rocket Pharmaceuticals, and Tenaya
Therapeutics.BACKGROUND
Data assessing the long-term safety and efficacy of mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy are needed.
OBJECTIVES
The authors sought to evaluate interim results from the EXPLORER-Long Term Extension (LTE) cohort of MAVA-LTE (A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed EXPLORER-HCM; NCT03723655).
METHODS
After mavacamten or placebo withdrawal at the end of the parent EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545), patients could enroll in MAVA-LTE. Patients received mavacamten 5Â mg once daily; adjustments were made based on site-read echocardiograms.
RESULTS
Between April 9, 2019, and March 5, 2021, 231 of 244 eligible patients (94.7%) enrolled in MAVA-LTE (mean age: 60 years; 39% female). At data cutoff (August 31, 2021) 217 (93.9%) remained on treatment (median time in study: 62.3 weeks; range: 0.3-123.9 weeks). At 48 weeks, patients showed improvements in left ventricular outflow tract (LVOT) gradients (mean change ± SD from baseline: resting: -35.6 ± 32.6 mm Hg; Valsalva: -45.3 ± 35.9 mm Hg), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (median: -480 ng/L; Q1-Q3: -1,104 to -179 ng/L), and NYHA functional class (67.5% improved by â„1 class). LVOT gradients and NT-proBNP reductions were sustained through 84 weeks in patients who reached this timepoint. Over 315 patient-years of exposure, 8 patients experienced an adverse event of cardiac failure, and 21 patients had an adverse event of atrial fibrillation, including 11 with no prior history of atrial fibrillation. Twelve patients (5.2%) developed transient reductions in site-read echocardiogram left ventricular ejection fraction of <50%, resulting in temporary treatment interruption; all recovered. Ten patients discontinued treatment due to treatment-emergent adverse events.
CONCLUSIONS
Mavacamten treatment showed clinically important and durable improvements in LVOT gradients, NT-proBNP levels, and NYHA functional class, consistent with EXPLORER-HCM. Mavacamten treatment was well tolerated over a median 62-week follow-up.S
Fluorescence in situ hybridisation analysis of chromosomal aberrations in gastric tissue: the potential involvement of Helicobacter pylori
In this series of experiments, a novel protocol was developed whereby gastric cells were collected using endoscopic cytology brush techniques, and prepared, such that interphase fluorescence in situ hybridization (FISH) could be performed. In total, 80 distinct histological samples from 37 patients were studied using four chromosome probes (over 32â000 cells analysed). Studies have previously identified abnormalities of these four chromosomes in upper GI tumours. Using premalignant tissues, we aimed to determine how early in Correa's pathway to gastric cancer these chromosome abnormalities occurred. Aneuploidy of chromosomes 4, 8, 20 and 17(p53) was detected in histologically normal gastric mucosa, as well as in gastritis, intestinal metaplasia, dysplasia and cancer samples. The levels of aneuploidy increased as disease severity increased. Amplification of chromosome 4 and chromosome 20, and deletion of chromosome 17(p53) were the more common findings. Hence, a role for these abnormalities may exist in the initiation of, and the progression to, gastric cancer. Helicobactor pylori infection was determined in premalignant tissue using histological analysis and PCR technology. Detection rates were comparable. PCR was used to subtype H. pylori for CagA status. The amplification of chromosome 4 in gastric tissue was significantly more prevalent in H. pylori-positive patients (n=7) compared to H. pylori-negative patients (n=11), possibly reflecting a role for chromosome 4 amplification in H. pylori-induced gastric cancer. The more virulent CagA strain of H. pylori was associated with increased disease pathology and chromosomal abnormalities, although numbers were small (CagA+ n=3, CagAâ n=4). Finally, in vitro work demonstrated that the aneuploidy induced in a human cell line after exposure to the reactive oxygen species (ROS) hydrogen peroxide was similar to that already shown in the gastric cancer pathway, and may further strengthen the hypothesis that H. pylori causes gastric cancer progression via an ROS-mediated mechanism
Teaching NeuroImages: Acute bilateral hand weakness from anterior spinal artery territory cord ischemia
Efficacy and Safety of Treatment With an Anti-M2e Monoclonal Antibody in Experimental Human Influenza
Real-World Treatment Sequencing, Toxicities, Health Utilities, and Survival Outcomes in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer.
OBJECTIVES
This real-world analysis describes treatment patterns, sequencing and clinical effectiveness, toxicities, and health utility outcomes in advanced-stage, incurable ALK-positive NSCLC patients across five different ALK-TKIs.
MATERIALS AND METHODS
Clinicodemographic, treatment, and toxicity data were collected retrospectively in patients with advanced-stage ALK-positive NSCLC at Princess Margaret Cancer Centre. Patient-reported symptoms, toxicities, and health utilities were collected prospectively.
RESULTS
Of 148 ALK-positive NSCLC patients seen July 2009-May 2021, median age was 58.9 years; 84 (57%) were female; 112 (76%) never-smokers; 54 (47%) Asian and 40 (35%) white; 139 (94%) received at least one ALK-TKI: crizotinib (n = 74; 54%) and alectinib (n = 61; 44%) were administered mainly as first-line ALK-TKI, ceritinib, brigatinib and lorlatinib were administered primarily after previous ALK-TKI failure. Median overall survival (OS) was 54.0 months; 31 (21%) patients died within two years of advanced-stage diagnosis. Treatment modifications were observed in 35 (47%) patients with crizotinib, 19 (61%) with ceritinib, 41 (39%) with alectinib, 9 (41%) with brigatinib and 8 (30%) with lorlatinib. Prevalence of dose modifications and self-reported toxicities were higher with early versus later generation ALK-TKIs (P<.05). The presence of early treatment modification was not negatively associated with progression-free survival (PFS) and OS analyses.
CONCLUSION
Serial ALK-TKI sequencing approaches are viable therapeutic options that can extend quality of life and quantity-of-life, though a fifth of patients died within two years. No best single sequencing approach could be determined. Clinically relevant toxicities occurred across all ALK-TKIs. Treatment modifications due to toxicity may not necessarily compromise outcomes, allowing multiple approaches to deal with ALK-TKI toxicities