Background: Alemtuzumab is a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS), and immune thrombocytopenia (ITP) has been identified as a risk. Objective: To examine ITP incidence, treatment, and outcomes during the clinical development of alemtuzumab for RRMS and discuss postmarketing experience outside clinical trials. Methods: CAMMS223 and Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) I and II investigated two annual courses of alemtuzumab 12 mg (or 24 mg in CAMMS223/CARE-MS II) versus subcutaneous interferon beta-1a three times per week. Patients completing core studies could enroll in an extension. Monthly monitoring for ITP continued until 48 months after the last alemtuzumab infusion. Results: Of 1485 alemtuzumab-treated MS patients in the clinical development program, 33 (2.2%) developed ITP (alemtuzumab 12 mg, 24 [2.0%]; alemtuzumab 24 mg, 9 [3.3%]) over median 6.1 years of follow-up after the first infusion; most had a sustained response to first-line ITP therapy with corticosteroids, platelets, and/or intravenous immunoglobulin. All cases occurred within 48 months of the last alemtuzumab infusion. Postmarketing surveillance data suggest that the ITP incidence is not higher in clinical practice than in clinical trials. Conclusion: Alemtuzumab-associated ITP occurs in approximately 2% of patients and is responsive to therapy. Careful monitoring is key for detection and favorable outcomes.
ImportanceIn patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited.ObjectiveTo report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial.Design, Setting, and ParticipantsSURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021.InterventionPatients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis.Main Outcomes and MeasuresThe prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years.ResultsA total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm2 vs 1.8 [0.6] cm2; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention.Conclusions and RelevanceAmong intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.
Patients are not undergoing evaluation at the onset of the dementia process. Diagnosis is delayed. Home-based, patient-centered care may improve early screening and detection of dementia.
We report the case of a patient with selective topographic orientation deficits in both familiar and novel environments after bilateral medial occipital infarctions. Extensive neuropsychological assessment revealed intact functioning in all other cognitive domains. The findings are interpreted in terms of a dissociation between the retrosplenial posterior cingulate and the superior parietal lobule in the right hemisphere.
Background and Purpose Upon referral from the primary care provider (PCP), dementia is diagnosed either by a neuropsychological evaluation (NPE) or at a multidisciplinary neurocognitive clinic (MNC). Following the NPE, patients continue receiving care from their PCP. In contrast, patients at the MNC are followed by a multidisciplinary care team that provides expertise across specialties in dementia care and education for the patient, family members, and care providers. The purpose of the study was to determine the utilization of acute healthcare services during the 2 years following a diagnosis of dementia in patients from the MNC and NPE. Methods A retrospective review was performed of 581 electronic medical records from January 2010 through December 2014 for 2 cohorts of patients diagnosed with dementia 1) by a neuropsychologist or 2) in a MNC. Acute-care hospital admissions, emergency room (ER) visits, and nonroutine PCP visits were identified. Categorical demographics and utilization variables were summarized by frequency. Chi-square analysis was used to analyze demographic characteristics and overall utilization between MNCs and NPE. Utilization in comparison with various demographic characteristics was analyzed using Spearman correlation coefficients and negative binomial regressions. Results Patients evaluated in the MNC were older, more severely impaired, and lived alone more often compared with NPE patients, but there was no increase in hospital admissions and ER visits. Patients who underwent NPE were 1.58 times more likely to have a nonroutine PCP office visit than patients evaluated in the MNC (p=0.0093). Conclusions Performing follow-up in multidisciplinary clinics provides patients with more education and may help to reduce the utilization of healthcare services.
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