Jul 172014
 

Intermittent facial flushing and diarrhea.

N Engl J Med. 2014 Jul 17;371(3):260

Authors: Mc Cormack O, Reynolds JV

Abstract
A 67-year-old man presented with a history of vague abdominal discomfort on the right side, intermittent diarrhea, and episodes of facial flushing every 2 to 3 days. He reported no history of ingestion of alcohol or other precipitants of flushing.

PMID: 25014690 [PubMed - in process]

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Jul 162014
 
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Etamicastat, a novel dopamine β-hydroxylase inhibitor: tolerability, pharmacokinetics, and pharmacodynamics in patients with hypertension.

Clin Ther. 2013 Dec;35(12):1983-96

Authors: Almeida L, Nunes T, Costa R, Rocha JF, Vaz-da-Silva M, Soares-da-Silva P

Abstract
BACKGROUND: Etamicastat is a dopamine β-hydroxylase (DβH) inhibitor currently in clinical development for the treatment of hypertension and heart failure.
OBJECTIVE: This study assessed the tolerability, pharmacokinetics, and pharmacodynamics of etamicastat in patients with arterial hypertension.
METHODS: This randomized, double-blind, placebo-controlled study was conducted in male patients aged between 18 and 65 years with mild to moderate hypertension. Participants received once-daily doses of etamicastat 50, 100, or 200 mg or placebo for 10 days. Antihypertensive effect was assessed by 24-hour ambulatory blood pressure monitoring (ABPM).
RESULTS: The study enrolled 23 male volunteers, with ages between 49 and 64 years. There were no serious adverse events reported. All adverse events were mild to moderate in intensity and resolved without sequelae. Etamicastat Tmax was 1 hour postdose, and mean t½ was 19 to 28 hours following repeated administration. Etamicastat underwent N-acetylation by N-acetyltransferase 2 (NAT2), forming the metabolite BIA 5-961. Following repeated administration, mean etamicastat AUC was 2- to 3-fold greater in poor acetylators than in rapid acetylators. Approximately 50% of the etamicastat dose was recovered in urine-30% as unchanged etamicastat and 20% as BIA 5-961. Dose-dependent decreases in systolic and diastolic blood pressure were observed after 10 days of treatment. The mean (95% CI) decreases versus placebo in nighttime SBP were statistically significant with all 3 etamicastat doses (50 mg, -11.66 mm Hg [-21.57 to -1.76; P < 0.05]; 100 mg, -14.92 mm Hg [-24.98 to -4.87; P < 0.01]; and 200 mg, -13.62 mm Hg [-22.29 to -3.95; P < 0.01]).
CONCLUSIONS: Etamicastat was well tolerated and showed a pharmacokinetic profile consistent with a once-daily regimen. NAT2 phenotype markedly affected the pharmacokinetics. The antihypertensive effect of etamicastat, assessed by 24-hour ABPM, was dose dependent up to 100 mg. The assessment of etamicastat as a novel antihypertensive therapy requires further study in broader populations. EudraCT trial registration 2008-002789-09.

PMID: 24296323 [PubMed - indexed for MEDLINE]

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Jul 162014
 
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The measurement of the QT interval.

Curr Cardiol Rev. 2014 Aug;10(3):287-94

Authors: Postema PG, Wilde AA

Abstract
The evaluation of every electrocardiogram should also include an effort to interpret the QT interval to assess the risk of malignant arrhythmias and sudden death associated with an aberrant QT interval. The QT interval is measured from the beginning of the QRS complex to the end of the T-wave, and should be corrected for heart rate to enable comparison with reference values. However, the correct determination of the QT interval, and its value, appears to be a daunting task. Although computerized analysis and interpretation of the QT interval are widely available, these might well over- or underestimate the QT interval and may thus either result in unnecessary treatment or preclude appropriate measures to be taken. This is particularly evident with difficult T-wave morphologies and technically suboptimal ECGs. Similarly, also accurate manual assessment of the QT interval appears to be difficult for many physicians worldwide. In this review we delineate the history of the measurement of the QT interval, its underlying pathophysiological mechanisms and the current standards of the measurement of the QT interval, we provide a glimpse into the future and we discuss several issues troubling accurate measurement of the QT interval. These issues include the lead choice, U-waves, determination of the end of the T-wave, different heart rate correction formulas, arrhythmias and the definition of normal and aberrant QT intervals. Furthermore, we provide recommendations that may serve as guidance to address these complexities and which support accurate assessment of the QT interval and its interpretation.

PMID: 24827793 [PubMed - indexed for MEDLINE]

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Jul 142014
 
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In-Hospital Worsening Heart Failure and Associations With Mortality, Readmission, and Healthcare Utilization.

J Am Heart Assoc. 2014;3(4)

Authors: DeVore AD, Hammill BG, Sharma PP, Qualls LG, Mentz RJ, Waltman Johnson K, Fonarow GC, Curtis LH, Hernandez AF

Abstract
BACKGROUND: A subset of patients hospitalized with acute heart failure experiences worsening clinical status and requires escalation of therapy. Worsening heart failure is an end point in many clinical trials, but little is known about its prevalence in clinical practice and its associated outcomes.
METHODS AND RESULTS: We analyzed inpatient data from the Acute Decompensated Heart Failure National Registry linked to Medicare claims to examine the prevalence and outcomes of patients with worsening heart failure, defined as the need for escalation of therapy at least 12 hours after hospital presentation. We compared patients with worsening heart failure to patients with an uncomplicated hospital course and patients with a complicated presentation. Of 63 727 patients hospitalized with acute heart failure, 11% developed worsening heart failure. These patients had the highest observed rates of mortality, all-cause readmission, and Medicare payments at 30 days and 1 year after hospitalization (P < 0.001 for all comparisons). The adjusted hazards of 30-day mortality were 2.56 (99% CI, 2.34 to 2.80) compared with an uncomplicated course and 1.29 (99% CI, 1.17 to 1.42) compared with a complicated presentation. The adjusted cost ratios for postdischarge Medicare payments at 30 days were 1.35 (99% CI, 1.24 to 1.46) compared with an uncomplicated course and 1.11 (99% CI, 1.02 to 1.22) compared with a complicated presentation.
CONCLUSIONS: In-hospital worsening heart failure was common and was associated with higher rates of mortality, all-cause readmission, and postdischarge Medicare payments. Prevention and treatment of in-hospital worsening heart failure represents an important goal for patients hospitalized with acute heart failure.

PMID: 25015076 [PubMed - as supplied by publisher]

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Jul 132014
 
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Hospital Discharge Instructions: Comprehension and Compliance Among Older Adults.

J Gen Intern Med. 2014 Jul 12;

Authors: Albrecht JS, Gruber-Baldini AL, Hirshon JM, Brown CH, Goldberg R, Rosenberg JH, Comer AC, Furuno JP

Abstract
BACKGROUND: Little is known regarding the prevalence or risk factors for non-comprehension and non-compliance with discharge instructions among older adults.
OBJECTIVE: To quantify the prevalence of non-comprehension and non-compliance with discharge instructions and to identify associated patient characteristics.
RESEARCH DESIGN: Prospective cohort study.
SUBJECTS: Four hundred and fifty adults aged ≥ 65 admitted to medical and surgical units of a tertiary care facility and meeting inclusion criteria.
MEASURES: We collected information on demographics, psycho-social factors, discharge diagnoses, and medications using surveys and patient medical records. Domains within discharge instructions included medications, follow-up appointments, diet, and exercise. At 5 days post-discharge, we assessed comprehension by asking patients about their discharge instructions, and compared responses to written instructions from medical charts. We assessed compliance among patients who understood their instructions.
RESULTS: Prevalence of non-comprehension was 5 % for follow-up appointments, 27 % for medications, 48 % for exercise and 50 % for diet recommendations. Age was associated with non-comprehension of medication [odds ratio (OR) 1.07; 95 % confidence interval (CI) 1.04, 1.12] and follow-up appointment (OR 1.08; 95 % CI 1.00, 1.17) instructions. Male sex was associated with non-comprehension of diet instructions (OR 1.91; 95 % CI 1.10, 3.31). Social isolation was associated with non-comprehension of exercise instructions (OR 9.42; 95 % CI 1.50, 59.11) Depression was associated with non-compliance with medication (OR 2.29; 95 % CI 1.02, 5.10) and diet instructions (OR 3.30; 95 % CI 1.24, 8.83).
CONCLUSIONS: Non-comprehension of discharge instructions among older adults is prevalent, multi-factorial, and varies by domain.

PMID: 25015430 [PubMed - as supplied by publisher]

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Jul 122014
 
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Direct oral anticoagulants: integration into clinical practice.

Postgrad Med J. 2014 Jul 10;

Authors: Cowell RP

Abstract
The introduction of direct oral anticoagulants (OACs) for the treatment and prevention of thromboembolic disease represents a shift from the traditional vitamin K antagonist-based therapies, which have been the mainstay of treatment for almost 60 years. A challenge for hospital formularies will be to manage the use of direct OACs from hospital to outpatient settings. Three direct OACs-apixaban, dabigatran and rivaroxaban-are widely approved across different indications, with rivaroxaban approved across the widest breadth of indications. A fourth direct OAC, edoxaban, has also completed phase III trials. Implementation of these agents by physicians will require an understanding of the efficacy and safety profile of these drugs, as well as an awareness of renal function, comedication use, patient adherence and compliance. Optimal implementation of direct OACs in the hospital setting will provide improved patient outcomes when compared with traditional anticoagulants and will simplify the treatment and prevention of thromboembolic diseases.

PMID: 25012514 [PubMed - as supplied by publisher]

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