Should patients with complex febrile seizure be admitted for further management?

Background and aims

Children with first complex febrile seizure (CFS) are often admitted for observation. The goals of this study were 1) to assess the risk of seizure recurrence during admission, 2) to determine whether early EEG affects acute management.

Rates of hospitalization among patients with deep vein thrombosis before and after the introduction of rivaroxaban

Background. Compared to warfarin, the non-vitamin K antagonist oral anticoagulant rivaroxaban may have advantages in treating patients with venous thromboembolism, because injectable bridging therapy and routine laboratory monitoring are not required. The objective of this study was to compare the rate of hospitalization in patients treated with rivaroxaban after its introduction with what it would have been before the introduction of rivaroxaban. Methods. A retrospective claims analysis was conducted using the MarketScan Hospital Drug Database from January 2011 to December 2013. Adult patients with a primary diagnosis of deep vein thrombosis (DVT) treated with rivaroxaban or low-molecular-weight heparin (LMWH) bridged to warfarin during the first day of an evaluation at a hospital were identified. Based on propensity-score methods, historical LMWH/warfarin patients (i.e., patients who received LMWH/warfarin before the approval of rivaroxaban) were matched 4:1 to rivaroxaban patients, and the rates of hospitalization were compared. Results. All rivaroxaban-treated patients (n = 134) in the database were well matched with four historical LMWH/warfarin-treated patients (n = 536). Among the rivaroxaban cohort, 60% of the patients were admitted to the hospital, compared to 82% of the historical patients treated with LMWH/warfarin in the matched cohort. The difference was statistically significant and corresponded to a 27% reduction in hospital admissions (rate ratio [95% confidence interval]: 0.73 [0.62–0.84]). Hospital admission rates adjusted for time-trend analyses also led to similar results. Conclusion. The availability of rivaroxaban significantly reduced the hospitalization rate in patients with DVT treated with rivaroxaban compared to what it would have been if only LMWH/warfarin were available.     

C-type natriuretic peptide of rainbow trout (Oncorhynchus mykiss): primary structure and vasorelaxant activities

Natriuretic peptides (NPs) play important roles in osmoregulatory and cardiovascular systems of vertebrates. For functional studies of NPs, rainbow trout (Oncorhynchus mykiss), a euryhaline fish, is an interesting model. The information on homologous NPs of salmonid fish is, however, still incomplete with respect to C-type NP (CNP). In this study, we isolated cDNAs encoding the precursor of CNP from the brain of trout. Predicted mature CNP (CNP-22) sequence was identical to that of killifish Fundulus heteroclitus, and only one amino acid was different from that of the eel Anguilla japonica, demonstrating a greater conservation among different teleost species than is found with atrial NP (ANP) and ventricular NP (VNP). While the preprosegment of trout CNP retained 57% similarity to the eel sequence, similarities were low to those of sharks and tetrapods. The major site of expression identified by RT-PCR was the brain with minor expression in the atrium. The putative mature CNP-22 was synthesized and its biological activity was compared with other trout NPs (ANP and VNP) using trout ventral aorta, efferent branchial and celiacomesenteric arteries and anterior cardinal vein in vitro. Synthetic trout CNP-22 relaxed all pre-contracted vessels with potencies comparable to trout ANP and VNP.     

Pump dysfunction after myocardial infarction: Importance of location,extent and pattern of abnormal left ventricular segmental contraction

To delineate the relative effects on left ventricular function of the site, extent and nature of abnormal left ventricular segmental contraction (dyssynergy) and thereby determine the mechanism by which anterior myocardial infarction results in greater depression of left ventricular performance than does inferior infarction, 43 patients with remote myocardial infarction of similar extent (average 38 percent of left ventricular systolic perimeter) and associated hypokinesia or dyskinesia confined to either the anterior or inferior wall were compared; 10 additional patients were evaluated who exhibited generalized dyssynergy (72 percent of left ventricular perimeter). When the pattern of dyssynergy and extent of infarction were similar, the location alone of dyssynergy did not influence variables of left ventricular function. However, paradoxical outward systolic movement (dyskinesia) of the anterior or inferior wall resulted in greater depression (P < 0.05) of measures of left ventricular performance than did diminished inward systolic motion (hypokinesia) associated with infarction of similar extent and location. All measures of left ventricular performance were considerably more depressed (P < 0.05) in the 10 patients with generalized dyssynergy than in the 43 patients with localized dyssynergy. Thus, the location of infarction is not a unique determinant of left ventricular performance. Instead, the size of infarction is the principal characteristic of dyssynergy that impairs left ventricular function; the severity of the pattern of dyssynergy is significant but of lesser importance. It is therefore concluded that the greater reduction of left ventricular function in anterior than in inferior myocardial infarction is largely the result of the more extensive area of necrosis rather than of the location of the infarction.     

A novel small molecule approach for the treatment of propionic and methylmalonic acidemias

Propionic Acidemia (PA) and Methylmalonic Acidemia (MMA) are inborn errors of metabolism affecting the catabolism of valine, isoleucine, methionine, threonine and odd-chain fatty acids. These are multi-organ disorders caused by the enzymatic deficiency of propionyl-CoA carboxylase (PCC) or methylmalonyl-CoA mutase (MUT), resulting in the accumulation of propionyl-coenzyme A (P-CoA) and methylmalonyl-CoA (M-CoA in MMA only). Primary metabolites of these CoA esters include 2-methylcitric acid (MCA), propionyl-carnitine (C3), and 3-hydroxypropionic acid, which are detectable in both PA and MMA, and methylmalonic acid, which is detectable in MMA patients only (Chapman et al., 2012). We deployed liver cell-based models that utilized PA and MMA patient-derived primary hepatocytes to validate a small molecule therapy for PA and MMA patients. The small molecule, HST5040, resulted in a dose-dependent reduction in the levels of P-CoA, M-CoA (in MMA) and the disease-relevant biomarkers C3, MCA, and methylmalonic acid (in MMA). A putative working model of how HST5040 reduces the P-CoA and its derived metabolites involves the conversion of HST5040 to HST5040-CoA driving the redistribution of free and conjugated CoA pools, resulting in the differential reduction of the aberrantly high P-CoA and M-CoA. The reduction of P-CoA and M-CoA, either by slowing production (due to increased demands on the free CoA (CoASH) pool) or enhancing clearance (to replenish the CoASH pool), results in a net decrease in the CoA-derived metabolites (C3, MCA and MMA (MMA only)). A Phase 2 study in PA and MMA patients will be initiated in the United States.     

Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria

Primary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data. PH1 (68.4% of families) was the most severe PH type, whereas PH3 (11.0% of families) showed the slowest decline in renal function but the earliest symptoms. A group of patients with disease progression similar to that of PH3, but for whom no mutation was detected (11.3% of families), suggested further genetic heterogeneity. We confirmed that the AGXT p.G170R mistargeting allele resulted in a milder PH1 phenotype; however, other potential AGXT mistargeting alleles caused more severe (fully penetrant) disease. We identified the first PH3 patient with ESRD; a homozygote for two linked, novel missense mutations. Population analysis suggested that PH is an order of magnitude more common than determined from clinical cohorts (prevalence, approximately 1:58,000; carrier frequency, approximately 1:70). We estimated PH to be approximately three times less prevalent among African Americans than among European Americans because of a limited number of common European origin alleles. PH3 was predicted to be as prevalent as PH1 and twice as common as PH2, indicating that PH3 (and PH2) cases are underdiagnosed and/or incompletely penetrant. These results highlight a role for molecular analyses in PH diagnostics and prognostics and suggest that wider analysis of the idiopathic stone-forming population may be beneficial.