Etoricoxib-induced life-threatening hyperkalemia and acute kidney dysfunction against the background of telmisartan and a low sodium diet

Drug-induced hyperkalemia is not uncommon and may be life-threatening when presenting acutely in the emergency department. We present a case of severe hyperkalemia precipitated acutely by etoricoxib in a patient who was on telmisartan and a low sodium (potassium chloride-rich) diet. A 75-year-old male with a past medical history of well-controlled diabetes and hypertension was prescribed etoricoxib (90 mg daily) for 3 days for musculoskeletal backache. He had been taking his routine medications including telmisartan and a potassium-rich salt substitute for many years, without any recent change in dosage or quantity. There was evidence of microalbuminurea; however, the renal functions and electrolytes prior to starting etoricoxib were normal. He presented to the emergency department with signs and symptoms of life-threatening hyperkalemia (serum potassium 7.7 mEq/dl), accelerated hypertension, congestive heart failure, pulmonary edema and acute renal failure. Acute medical management and withholding all drugs that could cause hyperkalemia improved his serum potassium levels over 24 h and renal parameters within 5 days. All the other drugs except etoricoxib were restarted under observation over 8 weeks with no recurrence of the acute episode. Non-steroidal analgesics and other COX-2 inhibitors (rofecoxib and celecoxib) have been known to precipitate renal failure and hyperkalemia specially in patients at risk for the same; although not unexpected, this may be the first reported case of life-threatening hyperkalemia precipitated by etoricoxib in a previously stable patient having increased risk of renal failure and hyperkalemia

Identification of a plasma signature of psychotic disorder in children and adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort

The identification of an early biomarker of psychotic disorder is important as early treatment is associated with improved patient outcome. Metabolomic and lipidomic approaches in combination with multivariate statistical analysis were applied to identify plasma alterations in children (age 11) (38 cases vs 67 controls) and adolescents (age 18) (36 cases vs 117 controls) preceeding or coincident with the development of psychotic disorder (PD) at age 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC). Overall, 179 lipids were identified at age 11, with 32 found to be significantly altered between the control and PD groups. Following correction for multiple comparisons, 8 of these lipids remained significant (lysophosphatidlycholines (LPCs) LPC(18: 1), LPC(18: 2), LPC(20: 3); phosphatidlycholines (PCs) PC(32: 2; PC(34: 2), PC(36: 4), PC(0-34-3) and sphingomyelin (SM) SM(d18: 1/24: 0)), all of which were elevated in the PD group. At age 18, 23 lipids were significantly different between the control and PD groups, although none remained significant following correction for multiple comparisons. In conclusion, the findings indicate that the lipidome is altered in the blood during childhood, long before the development of psychotic disorder. LPCs in particular are elevated in those who develop PD, indicating inflammatory abnormalities and altered phospholipid metabolism. These findings were not found at age 18, suggesting there may be ongoing alterations in the pathophysiological processes from prodrome to onset of PD

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

<p>Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.</p> <p>Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10]).</p> <p>Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).</p&gt

Impact of on-site cardiac catheterization on resource utilization and fatal and non-fatal outcomes after acute myocardial infarction

BACKGROUND: Patterns of care for acute myocardial infarction (AMI) strongly depend on the availability of on-site cardiac catheterization facilities. Although the management found at hospitals without on-site catheterization does not lead to increased mortality, little it known about its impact on resource utilization and non-fatal outcomes. METHODS: We identified all patients (n = 35,289) admitted with a first AMI in the province of Quebec between January 1, 1996 and March 31, 1999 using population-based administrative databases. Medical resource utilization and non-fatal and fatal outcomes were compared among patients admitted to hospitals with and without on-site cardiac catheterization facilities. RESULTS: Cardiac catheterization and PCI were more frequently performed among patients admitted to hospitals with catheterization facilities. However, non-invasive procedures were not used more frequently at hospitals without catheterization facilities. To the contrary, echocardiography [odds ratio (OR), 2.04; 95% confidence interval (CI), 1.93–2.16] and multi-gated acquisition imaging (OR, 1.24; 95% CI, 1.17–1.32) were used more frequently at hospitals with catheterization, and exercise treadmill testing (OR, 1.02; 95% CI, 0.91–1.15) and Sestamibi/Thallium imaging (OR, 0.93; 95% CI, 0.88–0.98) were used similarly at hospitals with and without catheterization. Use of anti-ischemic medications and frequency of emergency room and physician visits, were similar at both types of institutions. Readmission rates for AMI-related cardiac complications and mortality were also similar [adjusted hazard ratio, recurrent AMI: 1.02, 95% CI, 0.89–1.16; congestive heart failure: 1.02; 95% CI, 0.90–1.15; unstable angina: 0.93; 95% CI, 0.85–1.02; mortality: 0.99; 95% CI, 0.93–1.05)]. CONCLUSION: Although on-site availability of cardiac catheterization facilities is associated with greater use of invasive cardiac procedures, non-availability of catheterization did not translate into a higher use of non-invasive tests or have an impact on the fatal and non-fatal outcomes available for study in our administrative database

Efficacy and Safety of Alirocumab in Individuals with Diabetes Mellitus:Pooled Analyses from Five Placebo-Controlled Phase 3 Studies

Introduction: Diabetes mellitus (DM) carries an elevated risk for cardiovascular disease. Here, we assessed alirocumab efficacy and safety in people with/without DM from five placebo-controlled phase 3 studies. Methods: Data from up to 78 weeks were analyzed in individuals on maximally tolerated background statin. In three studies, alirocumab 75 mg every 2 weeks (Q2W) was increased to 150 mg Q2W at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥ 70 mg/dL; two studies used alirocumab 150 mg Q2W throughout. The primary endpoint was percentage change in LDL-C from baseline to week 24. Results: In the alirocumab 150 mg pool (n = 2416), baseline LDL-C levels were 117.4 mg/dL (DM) and 130.6 mg/dL (without DM), and in the 75/150 mg pool (n = 1043) 112.8 mg/dL (DM) and 133.0 mg/dL (without DM). In the 150 mg Q2W group, week 24 LDL-C reductions from baseline were observed in persons with DM (− 59.9%; placebo, − 1.4%) and without DM (− 60.6%; placebo, + 1.5%); 77.7% (DM) and 76.8% (without DM) of subjects achieved LDL-C < 70 mg/dL. In the alirocumab 75/150 mg group, 26% (DM) and 36% (without DM) of subjects received dose increase. In this group, week 24 LDL-C levels changed from baseline by − 43.8% (DM; placebo, + 0.3%) and − 49.7% (without DM; placebo, + 5.1%); LDL-C < 70 mg/dL was achieved by 68.3% and 65.8% of individuals, respectively. At week 24, alirocumab was also associated with improved levels of other lipids. Adverse event rates were generally comparable in all groups (79.8–82.0%). Conclusions: Regardless of DM status, alirocumab significantly reduced LDL-C levels; safety was generally similar. Funding Sanofi and Regeneron Pharmaceuticals, Inc. Plain Language Summary Plain language summary available for this article. Electronic supplementary material The online version of this article (10.1007/s13300-018-0439-8) contains supplementary material, which is available to authorized users

A Comparative Computer Simulation of Dendritic Morphology

Computational modeling of neuronal morphology is a powerful tool for understanding developmental processes and structure-function relationships. We present a multifaceted approach based on stochastic sampling of morphological measures from digital reconstructions of real cells. We examined how dendritic elongation, branching, and taper are controlled by three morphometric determinants: Branch Order, Radius, and Path Distance from the soma. Virtual dendrites were simulated starting from 3,715 neuronal trees reconstructed in 16 different laboratories, including morphological classes as diverse as spinal motoneurons and dentate granule cells. Several emergent morphometrics were used to compare real and virtual trees. Relating model parameters to Branch Order best constrained the number of terminations for most morphological classes, except pyramidal cell apical trees, which were better described by a dependence on Path Distance. In contrast, bifurcation asymmetry was best constrained by Radius for apical, but Path Distance for basal trees. All determinants showed similar performance in capturing total surface area, while surface area asymmetry was best determined by Path Distance. Grouping by other characteristics, such as size, asymmetry, arborizations, or animal species, showed smaller differences than observed between apical and basal, pointing to the biological importance of this separation. Hybrid models using combinations of the determinants confirmed these trends and allowed a detailed characterization of morphological relations. The differential findings between morphological groups suggest different underlying developmental mechanisms. By comparing the effects of several morphometric determinants on the simulation of different neuronal classes, this approach sheds light on possible growth mechanism variations responsible for the observed neuronal diversity

Inactivation of murine norovirus by chemical biocides on stainless steel

<p>Abstract</p> <p>Background</p> <p>Human norovirus (NoV) causes more than 80% of nonbacterial gastroenteritis in Europe and the United States. NoV transmission via contaminated surfaces may be significant for the spread of viruses. Therefore, measures for prevention and control, such as surface disinfection, are necessary to interrupt the dissemination of human NoV. Murine norovirus (MNV) as a surrogate for human NoV was used to study the efficacy of active ingredients of chemical disinfectants for virus inactivation on inanimate surfaces.</p> <p>Methods</p> <p>The inactivating properties of different chemical biocides were tested in a quantitative carrier test with stainless steel discs without mechanical action. Vacuum-dried MNV was exposed to different concentrations of alcohols, peracetic acid (PAA) or glutaraldehyde (GDA) for 5 minutes exposure time. Detection of residual virus was determined by endpoint-titration on RAW 264.7 cells.</p> <p>Results</p> <p>PAA [1000 ppm], GDA [2500 ppm], ethanol [50% (v/v)] and 1-propanol [30% (v/v)] were able to inactivate MNV under clean conditions (0.03% BSA) on the carriers by ≥ 4 log₁₀within 5 minutes exposure time, whereas 2-propanol showed a reduced effectiveness even at 60% (v/v). Furthermore, there were no significant differences in virus reduction whatever interfering substances were used. When testing with ethanol, 1- and 2-propanol, results under clean conditions were nearly the same as in the presence of dirty conditions (0.3% BSA plus 0.3% erythrocytes).</p> <p>Conclusion</p> <p>Products based upon PAA, GDA, ethanol and 1-propanol should be used for NoV inactivation on inanimate surfaces. Our data provide valuable information for the development of strategies to control NoV transmission via surfaces.</p

Self-esteem is associated with premorbid adjustment and positive psychotic symptoms in early psychosis

<p>Abstract</p> <p>Background</p> <p>Low levels of self-esteem have been implicated as both a cause and a consequence of severe mental disorders. The main aims of the study were to examine whether premorbid adjustment has an impact on the subject's self-esteem, and whether lowered self-esteem contributes to the development of delusions and hallucinations.</p> <p>Method</p> <p>A total of 113 patients from the Thematically Organized Psychosis research study (TOP) were included at first treatment. The Positive and Negative Syndrome Scale (PANSS) was used to assess present symptoms. Premorbid adjustment was measured with the Premorbid Adjustment Scale (PAS) and self-esteem by the Rosenberg Self-Esteem Scale (RSES).</p> <p>Results</p> <p>Premorbid social adjustment was significantly related to lower self-esteem and explained a significant proportion of the variance in self-esteem. Self-esteem was significantly associated with the levels of persecutory delusions and hallucinations experienced by the patient and explained a significant proportion of the variance even after adjusting for premorbid functioning and depression.</p> <p>Conclusion</p> <p>There are reasons to suspect that premorbid functioning is an important aspect in the development of self- esteem, and, furthermore, that self-esteem is associated with the development of delusions and hallucinations.</p