Huntington's Disease In a Coloured Family

A South African Coloured (of mixed descent) family with Huntington's disease in which all four members of one sibship, ranging in age from 16 to 23 years, are affected, is described. One generation back, definitely two, and possibly three, members of a sibship of six were affected with the adult form. The offspring of the one affected male all show some evidence of this condition, the age of onset being between 13 and 16 years. The offspring of the one female carrier who was definitely affected do not at this time appear to have been affected. The literature concerning juvenile Huntington's disease, especially with regard to its clinical presentation, EEG, and air encephalographic findings, is reviewed and compared with the family described. The predominance of rigidity and akinesia in the juvenile form, as opposed to chorea, which is the main adult extrapyramidal manifestation, is stressed. This is, to our knowledge, the first report of a Coloured (mixed descent) family's manifesting the clinical features of juvenile Huntington's disease

2020 Heart Failure Society of South Africa perspective on the 2016 European Society of Cardiology Chronic Heart Failure Guidelines

Heart failure with a reduced ejection fraction (HFrEF) is a condition frequently encountered by healthcare professionals and, in order to achieve the best outcomes for patients, needs to be managed optimally. This guideline document is based on the European Society of Cardiology Guidelines for the treatment of acute and chronic heart failure published in 2016, and summarises what is considered the best current management of patients with the condition. It provides information on the definition, diagnosis and epidemiology of HFrEF in the African context. The best evidence-based treatments for HFrEF are discussed, including established therapies (beta-blockers, ACE-i/ARBs, mineralocorticoid receptor antagonists (MRAs), diuretics) that form the cornerstone of heart failure management as well as therapies that have only recently entered clinical use (angiotensin receptor-neprilysin inhibitor (ARNI), sodium/glucose cotransporter-2 (SGLT2) inhibitors). Guidance is offered in terms of more invasive therapies (revascularisation, implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation therapy (CRT) by implantation of a biventricular pacemaker with (CRT-D) or without (CRT-P) an ICD, left ventricular assist device (LVAD) use and heart transplantation) in order to ensure efficient use of these expensive treatment modalities in a resource-limited environment. Furthermore, additional therapies (digoxin, hydralazine and nitrates, ivabradine, iron supplementation) are discussed and advice is provided on general preventive strategies (vaccinations). Sections to discuss conditions that are particularly prevalent in sub-Saharan Africa (HIV-associated cardiomyopathy (CMO), peripartum CMO, rheumatic heart disease, atrial fibrillation) have been added to further improve clinical care for these commonly encountered disease processes. You are encouraged to read the complete 2016 ESC Heart Failure guideline: Ponikowski P, Voors AA, Anker SD, et al.; on behalf of the European Society of Cardiology. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2016,37:2129-2200

Efficacy of alemtuzumab over 6 years in relapsing–remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies

Background: Alemtuzumab is administered as two annual courses for relapsing–remitting multiple sclerosis (MS). Patients may relapse before completing the two-course regimen. Objective: The objective was to evaluate 6-year outcomes in patients who relapsed between alemtuzumab Courses 1 and 2 (early relapsers). Methods: Post hoc analysis of patients from the Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) studies who enrolled in the extension. Results: Early relapsers (CARE-MS I: 15%; CARE-MS II: 24%) had more relapses in 1–2 years pre-alemtuzumab and higher mean baseline Expanded Disability Status Scale score than patients without relapse. Their annualized relapse rate declined from Year 1 (CARE-MS I: 1.3; CARE-MS II: 1.2) to Year 2 following Course 2 (0.3; 0.5) and remained low thereafter. Over 6 years, 60% remained free of 6-month confirmed disability worsening; 24% (CARE-MS I) and 34% (CARE-MS II) achieved 6-month confirmed disability improvement. During Year 6, 69% (CARE-MS I) and 68% (CARE-MS II) were free of magnetic resonance imaging (MRI) disease activity. Median percent yearly brain volume loss (Year 1: −0.67% (CARE-MS I); −0.47% (CARE-MS II)) declined after Course 2 (Year 6: −0.24%; −0.13%). Conclusion: Early relapsers’ outcomes improved after completing the second alemtuzumab course. These findings support administering the approved two-course regimen to maximize clinical benefit. ClinicalTrials.gov registration numbers: CARE-MS I, II, extension: NCT00530348, NCT00548405, NCT00930553

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Supported by F. Hoffmann–La Roche

Long-term efficacy and safety of alemtuzumab in patients with RRMS: 12-year follow-up of CAMMS223

Background: In the phase 2 CAMMS223 trial (NCT00050778), alemtuzumab significantly improved clinical and MRI outcomes versus subcutaneous interferon beta-1a over 3 years in treatment-naive patients with relapsing–remitting MS. Here, we assess efficacy and safety of alemtuzumab over 12 years in CAMMS223 patients who enrolled in the CAMMS03409 extension (NCT00930553), with available follow-up through the subsequent TOPAZ extension (NCT02255656). Methods: In CAMMS223, patients received 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days); 22% received a third course. In the open-label, nonrandomized extensions, patients could receive as-needed additional alemtuzumab or other disease-modifying therapies. Results: Of 108 alemtuzumab-treated patients in CAMMS223, 60 entered the CAMMS03409 extension; 33% received a total of 2 alemtuzumab courses, and 73% received no more than 3 courses through Year 12. Over 12 years, annualized relapse rate was 0.09, 71% of patients had stable or improved Expanded Disability Status Scale scores, and 69% were free of 6-month confirmed disability worsening. In Year 12, 73% of patients were free of MRI disease activity. Cumulatively throughout the extensions (Years 7–12), 34% of patients had no evidence of disease activity. Adverse event (AE) incidence declined through Year 12. Infusion-associated reactions peaked at first course and declined thereafter. Cumulative thyroid AE incidence was 50%; one immune thrombocytopenia event occurred, and there were no autoimmune nephropathy cases. Conclusions: Alemtuzumab efficacy was maintained over 12 years in CAMMS223 patients, with 73% receiving no more than three courses. The safety profile in this cohort was consistent with other alemtuzumab clinical trials. © 2020, The Author(s)