Taking a Better History for Behavioral Issues Pre‐ and Post‐Deep Brain Stimulation: Issues Missed by Standardized Scales

Objectives: To screen for potentially underreported behavioral changes in patients with idiopathic Parkinson's disease (PD) pre‐ and post‐deep brain stimulation (DBS), a retrospective data base review was performed. Methods: In total, 113 patients who underwent unilateral or bilateral DBS at the University of Florida in either subthalamic nucleus or globus pallidus internus for PD were screened for behavioral issues by asking about the presence or absence of seven neuropsychiatric symptoms (panic, fear, paranoia, anger, suicidal flashes, crying, and laughing). Results: There was a high prevalence of fear (16.3%), panic (14.0%), and anger (11.6%) at baseline in this cohort. In the first six months following DBS implantation, anger (32.6%), fear (26.7%), and uncontrollable crying (26.7%) were the most frequent symptoms reported. Those symptoms also were present following six months of DBS surgery (30.2%, 29.1%, and 19.8%, respectively). New uncontrollable crying occurred more in the acute postoperative stage (less than or equal to six months) (p= 0.033), while new anger occurred more in the chronic postoperative stage (greater than six months) (p= 0.017). The frequency of uncontrollable laughing significantly increased with bilateral DBS (p= 0.033). Conclusions: Many of the neuropsychiatric issues were identified at preoperative baseline and their overall occurrence was more than expected. There was a potential for worsening of these issues post‐DBS. There were subtle differences in time course, and in unilateral vs. bilateral implantations. Clinicians should be aware of these potential behavioral issues that may emerge following DBS therapy, and should consider including screening questions in preoperative and postoperative interviews. Standardized scales may miss the presence or absence of these clinically relevant issues.     

Update and Mutational Analysis of SLC20A2: A Major Cause of Primary Familial Brain Calcification

Primary familial brain calcification (PFBC) is a heterogeneous neuropsychiatric disorder, with affected individuals presenting a wide variety of motor and cognitive impairments, such as migraine, parkinsonism, psychosis, dementia, and mood swings. Calcifications are usually symmetrical, bilateral, and found predominantly in the basal ganglia, thalamus, and cerebellum. So far, variants in three genes have been linked to PFBC: SLC20A2, PDGFRB, and PDGFB. Variants in SLC20A2 are responsible for most cases identified so far and, therefore, the present review is a comprehensive worldwide summary of all reported variants to date. SLC20A2 encodes an inorganic phosphate transporter, PiT‐2, widely expressed in various tissues, including brain, and is part of a major family of solute carrier membrane transporters. Fifty variants reported in 55 unrelated patients so far have been identified in families of diverse ethnicities and only few are recurrent. Various types of variants were detected (missense, nonsense, frameshift) including full or partial SLC20A2 deletions. The recently reported SLC20A2 knockout mouse will enhance our understanding of disease mechanism and allow for screening of therapeutic compounds. In the present review, we also discuss the implications of these recent exciting findings and consider the possibility of treatments based on manipulation of inorganic phosphate homeostasis.     

Multislice spiral computed tomography coronary angiography in patients with stable angina pectoris

OBJECTIVES: This study was designed to prospectively evaluate the diagnostic performance of multislice spiral computed tomography (MSCT) coronary angiography for the detection of significant lesions in all segments of the coronary tree potentially suitable for revascularization. BACKGROUND: Noninvasive MSCT coronary angiography is a promising coronary imaging technique. METHODS: Sixteen-row MSCT coronary angiography was performed in 128 patients (89% men, mean age 58.9 +/- 11.7 years) in sinus rhythm with stable angina pectoris scheduled for conventional coronary angiography. Sixty percent (77 of 128) of patients received pre-scan oral beta-blockers, resulting in a mean heart rate of 57.7 +/- 7.7 beats/min. The diagnostic performance of MSCT for detection of significant lesions (> or =50% diameter reduction) was compared with that of quantitative coronary angiography (QCA). RESULTS: The sensitivity of MSCT for detection of significant lesions was 92% (216 of 234, 95% confidence interval [CI]: 88 to 95). Specificity was 95% (1,092 of 1,150, 95% CI: 93 to 96), positive predictive value 79% (216 of 274, 95% CI: 73 to 88), and negative predictive value 98% (1,092 of 1,110, 95% CI: 97 to 99). Two > or =50% lesions were missed because of motion artifacts and two because of severe coronary calcifications. The rest (78%, 14 of 18) were detected but incorrectly classified as <50% obstructions. All patients with and 86% (18 of 21) of patients without significant lesions on QCA were correctly classified by MSCT. All patients with significant left main disease or total occlusions were correctly identified on MSCT. CONCLUSIONS: Sixteen-row MSCT coronary angiography permits reliable detection of significant obstructive coronary artery disease in patients with stable angina in sinus rhythm.     

Drug Interaction Between Clopidogrel and Ranitidine or Omeprazole in Stable Coronary Artery Disease: A Double-Blind,Double Dummy,Randomized Study

Background

Proton-pump inhibitors (PPIs) are often prescribed to patients receiving dual antiplatelet therapy (DAPT). However, this class of medication, especially omeprazole, has been associated with a reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine.

Objectives

Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine.

Methods

We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily (bid) or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12? (Accumetrics; San Diego, CA, USA), depicting aggregability as percent inhibition of platelet aggregation (IPA).

Results

We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel (from 26.3 ± 32.9 to 17.4 ± 33.1 %; p = 0.025), with no statistical significant changes observed in the ranitidine group (from 32.6 ± 28.9 to 30.1 ± 31.3 %; p = 0.310). The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance (p = 0.07, 95 % confidence interval [CI] ?1.19 to 26.59); after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance (32.7 ± 30.8 vs. 17.7 ± 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04).

Conclusions

Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel.

Clinical Trial Registration

NCT01896557.

     

Splinted and unsplinted overdenture attachment systems: A systematic review and meta‐analysis

Splinted and unsplinted overdenture attachment systems have unique advantages and disadvantages. The aim of the present systematic review was to determine the influence of splinted and unsplinted overdenture attachment systems on the marginal bone loss, prosthetic complications and implant survival rate. PubMed/MEDLINE , Scopus and Cochrane databases were searched for articles published up to October 2017, using the following search terms: “overdenture AND attachment OR overdenture AND bar OR overdenture splinted.” The PICO question “Do splinted overdenture attachment systems promote better clinical results in comparison to unsplinted systems?” was evaluated. Eligible studies included randomized controlled clinical trials, prospective studies with at least 10 participants and a minimum follow‐up of 6 months, and studies published in English that compared splinted and unsplinted attachment systems within the same study. The 95% confidence interval (CI ) was considered for all outcomes analysed. After completion of the different steps in the article selection process, nine articles were included in the qualitative and quantitative analyses. A total of 984 implants were placed in 380 patients (mean age: 62.8 years). The meta‐analysis demonstrated no statistically significant differences between splinted and unsplinted attachment systems with regard to marginal bone loss (P  = .39; MD : ?0.11; 95% CI : ?0.37 to 0.14), complications (P  = .31; RR : 1.26; CI : 0.80‐1.99) and implant survival rate (P  = .14; RR : 0.37% CI : 0.10‐1.36). In addition, splinted and unsplinted overdenture attachment systems achieved similar results with regard to marginal bone loss, prosthetic complications and implant survival rate.     

Comparison of B-type natriuretic peptide levels in patients with heart failure with versus without mitral regurgitation

Functional mitral regurgitation (MR) occurs most often in patients with heart failure (HF) and is associated with an adverse prognosis. Recently, B-type natriuretic peptide (BNP) has been validated as a marker of cardiac function and prognosis. We sought to assess the relation between functional MR and BNP levels in patients with HF, and hypothesized that MR is associated with higher BNP levels. In all, 201 patients admitted with the diagnosis of HF had a transthoracic echocardiogram and measurement of BNP levels within 48 hours. MR was graded as none/trace, mild, moderate, or severe using recently published guidelines of the American Society of Echocardiography. BNP was measured by a commercially available instrument (Biosite). The relation of MR to BNP was assessed using multivariable linear regression methods with a Tobin estimation to account for the truncation of BNP values at an upper limit of 1,300 pg/ml. Mean age of the patients was 67 +/- 11 years. The median BNP level was 826 pg/ml. The etiology of HF was predominantly diastolic in 64 patients (32%); 137 patients (68%) had significant left ventricular (LV) systolic dysfunction. Mean LV ejection fraction was 37 +/- 17%. MR was present in 112 patients (56%). After adjusting for clinical, hemodynamic, and echocardiographic variables, only LV ejection fraction (p = 0.016) and moderate or severe MR (p = 0.023) were significantly associated with BNP. When MR was grouped as any MR versus no MR, only LV ejection fraction (p = 0.017) and any degree of MR (p = 0.029) were significantly associated with BNP.