Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension

BACKGROUND: Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in patients with Alzheimer disease. METHODS AND RESULTS: Four hundred seventy‐seven patients with mild‐to‐moderate Alzheimer disease were randomized to the calcium‐channel blocker nilvadipine 8 mg/day or placebo for 78 weeks. Presence of OH (blood pressure drop ≥20/≥10 mm Hg after 1 minute of standing) and OH‐related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow‐up visits. Mean age of the study population was 72.2±8.2 years and mean Mini‐Mental State Examination score was 20.4±3.8. Baseline blood pressure was 137.8±14.0/77.0±8.6 mm Hg. Grade I hypertension was present in 53.4% (n=255). After 13 weeks, blood pressure had fallen by −7.8/−3.9 mm Hg for nilvadipine and by −0.4/−0.8 mm Hg for placebo (P<0.001). Across the 78‐week intervention period, there was no difference between groups in the proportion of patients with OH at a study visit (odds ratio [95% CI]=1.1 [0.8–1.5], P=0.62), nor in the proportion of visits where a patient met criteria for OH, corrected for number of visits (7.7±13.8% versus 7.3±11.6%). OH‐related adverse events were not more often reported in the intervention group compared with placebo. Results were similar for those with baseline hypertension. CONCLUSIONS: This study suggests that initiation of a low dose of antihypertensive treatment does not significantly increase the risk of OH in patients with mild‐to‐moderate Alzheimer disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02017340

J Thromb Haemost

Essentials The c.1544+1G>A mutation was identified in Gypsy Glanzmann thrombasthenia (GT) patients. Gypsy GT patients express normal α β carrying HPA-1b epitopes. To demonstrate HPA-1a alloimmunization by modified antigen capture assays. Gypsy GT patients could develop anti-HPA-1a alloantibodies against β and α β . ABSTRACT: Background Glanzmann thrombasthenia (GT) is a rare bleeding disorder caused by the absence or the dysfunction of the platelet α β integrin. A founder mutation in the ITGA2B gene was previously identified in French Gypsy patients. Interestingly, this mutation was strongly linked to the human platelet antigen-1b (HPA-1b). The HPA-1bb Gypsy patients are at risk of isoimmunization against α β , as this complex is not expressed at their platelet surface. Tentatively, they would, however, not have an increased risk of developing anti-HPA-1a alloantibodies by exposure of α β on platelets from random platelet transfusions. However, the β chain can also associate with the α subunit expressed at the platelet surface. Because Gypsy GT patients express normal α β carrying HPA-1b epitopes, these patients might develop anti-HPA-1a alloantibodies reacting with α β and/or β . Objectives/Patients/Methods To demonstrate this hypothesis, sera from HPA-1bb (n = 5) and HPA-1ab (n = 1) Gypsy GT patients were investigated by modified antigen capture assay using platelets or stable transfected cells. Furthermore, stable transfected cells expressing either α β or α β3 together with soluble monomeric chimeric β (as absorbent) were used to differentiate anti-β and anti-α β reactivity. Results Only HPA-1bb patients developed alloantibodies reacting with HPA-1a cells. Further analysis showed that HPA-1bb patients developed anti-HPA-1a alloantibodies reacting with β and/or α β . Conclusion In this study, we found that HPA-1bb patients who failed to express α β on the platelet surface can develop alloantibodies against HPA-1a reacting with β as well as α β . This is of particular importance as anti-HPA-1a alloantibodies might cause fetal neonatal alloimmune thrombocytopenia and/or platelet transfusion refractoriness

Sleep quality trajectories from head and neck cancer diagnosis to six months after treatment

Objectives: Patients with head and neck cancer (HNC) often report disturbances in their sleep quality, impairing their quality of life. This study aims to examine the trajectories of sleep quality from diagnosis up to 6-month after treatment, as well as the pre-treatment risk factors for poor sleep trajectories. Materials and Methods: Sleep quality (Pittsburgh sleep quality index) was measured shortly after diagnosis (pre-treatment), and at 3 and 6 months after finishing treatment. Patients were categorized into 5 trajectory groups. We examined the association of sleep quality trajectories with sociodemographic and clinical characteristics, coping style, HNC symptoms, and psychological distress. Results: Among 412 included patients, about a half either had a persistent good sleep (37.6%) or an improving (16.5%) trajectory. About a third had a persistent poor sleep (21.8%) or worsening (10.9%) sleep trajectory. The remaining patients (13.1%), alternated between good and poor sleep. Using persistent good sleep as a reference outcome, persistent poor sleepers were more likely to be woman (odds ratio [OR] = 1.98, 95% confidence interval [CI] 1.01–3.90), use painkillers prior to treatment (OR = 2.52, 95% CI 1.33–4.77), and have more pre-treatment anxiety symptoms (OR = 1.26, 95% CI 1.15–1.38). Conclusion: Unfavorable sleep quality trajectories are prevalent among HNC patients from pre-treatment to 6-month after treatment. A periodic sleep evaluation starting shortly after HNC diagnosis is necessary to identify persistent sleep problems, especially among high-risk group