Full sequencing and haplotype analysis of MAPT in Parkinson's disease and rapid eye movement sleep behavior disorder

Background: MAPT haplotypes are associated with PD, but their association with rapid eye movement sleep behavior disorder is unclear. Objective: To study the role of MAPT variants in rapid eye movement sleep behavior disorder. Methods: Two cohorts were included: (A) PD (n = 600), rapid eye movement sleep behavior disorder (n = 613) patients, and controls (n = 981); (B) dementia with Lewy bodies patients with rapid eye movement sleep behavior disorder (n = 271) and controls (n = 950). MAPT‐associated variants and the entire coding sequence of MAPT were analyzed. Age‐, sex‐, and ethnicity‐adjusted analyses were performed to examine the association between MAPT, PD, and rapid eye movement sleep behavior disorder. Results: MAPT‐H2 variants were associated with PD (odds ratios: 0.62‐0.65; P = 0.010‐0.019), but not with rapid eye movement sleep behavior disorder. In PD, the H1 haplotype odds ratio was 1.60 (95% confidence interval: 1.12‐2.28; P = 0.009), and the H2 odds ratio was 0.68 (95% confidence interval: 0.48‐0.96; P = 0.03). The H2/H1 haplotypes were not associated with rapid eye movement sleep behavior disorder. Conclusions: Our results confirm the protective effect of the MAPT‐H2 haplotype in PD, and define its components. Furthermore, our results suggest that MAPT does not play a major role in rapid eye movement sleep behavior disorder, emphasizing different genetic background than in PD in this locus.</p

Differences in Generalist and Specialist Physicians’ Knowledge and Use of Angiotensin-Converting Enzyme Inhibitors for Congestive Heart Failure

OBJECTIVE: To quantify the extent and determinants of underutilization of angiotensin-converting enzyme (ACE) inhibitors for patients with congestive heart failure, especially with respect to physician specialty and clinical indication. DESIGN: Survey of a national systematic sample of physicians. PARTICIPANTS: Five hundred family practitioners, 500 general internists, and 500 cardiologists. MEASUREMENTS AND MAIN RESULTS: Physicians’ choice of medications were determined for four hypothetical patients with left ventricular systolic dysfunction: (1) new-onset, symptomatic; (2) asymptomatic; (3) chronic heart failure, on digitalis and diuretic; and (4) asymptomatic, post–myocardial infarction. For each patient, randomized controlled trials have demonstrated that ACE inhibitors decrease mortality or the progression of symptoms. Among the 727 eligible physicians returning surveys (adjusted response rate 58%), approximately 90% used ACE inhibitors for patients with chronic heart failure who were already taking digitalis and a diuretic. However, family practitioners and general internists chose ACE inhibitors less frequently ( p ≤ .01) than cardiologists for the other indications. Respective rates of ACE inhibitor use for each simulated patient were new-onset, symptomatic (family practitioners 72%, general internists 76%, cardiologists 86%); asymptomatic (family practitioners 68%, general internists 78%, cardiologists 93%); and asymptomatic, post–myocardial infarction (family practitioners 58%, general internists 70%, cardiologists 94%). Compared with generalists, cardiologists were more likely ( p ≤ .05) to increase ACE inhibitors to a target dosage (45% vs 26%) and to tolerate systolic blood pressures of 90 mm Hg or less (43% vs 15%). CONCLUSIONS: Compared with cardiologists, family practitioners and general internists probably underutilize ACE inhibitors, particularly among patients with decreased ejection fraction who are either asymptomatic or post–myocardial infarction. Educational efforts should focus on these indications and emphasize the dosages demonstrated to lower mortality and morbidity in the trials