Frequency and predictors of hyperkalemia in patients ≥60 years of age with heart failure undergoing intense medical therapy

Hyperkalemia is a concern in heart failure (HF), especially in older patients with co-morbidities. Previous studies addressing this issue have focused mainly on younger patients. This study was aimed at determining the frequency and predictors of hyperkalemia in older patients with HF undergoing intense medical therapy. Frequency and predictors of hyperkalemia were defined in patients (n = 566) participating in the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure, in which patients ≥60 years of age were randomized to a standard versus an intensified N-terminal brain natriuretic peptide-guided HF therapy. During an 18-month follow-up 76 patients (13.4%) had hyperkalemia (≥5.5 mmol/L) and 28 (4.9%) had severe hyperkalemia (≥6.0 mmol/L). Higher baseline serum potassium (odds ratio [OR] 2.92 per mmol/L), baseline creatinine (OR 1.11 per 10 μmol/L), gout (OR 2.56), New York Heart Association (NYHA) class (compared to NYHA class II, IV OR 3.08), higher dosage of spironolactone at baseline (OR 1.20 per 12.5 mg/day), and higher dose changes of spironolactone (compared to no dose change: 12.5 mg, OR 1.45; 25 mg, OR 2.52; >25 mg, OR 3.24) were independent predictors for development of hyperkalemia (p <0.05 for all comparisons). In conclusion, hyperkalemia is common in patients ≥60 years of age with HF undergoing intense medical therapy. Risk is increased in patients treated with spironolactone, in addition to patient-specific risk factors such as chronic kidney disease, higher serum potassium, advanced NYHA class, and gout. Careful surveillance of serum potassium and cautious use of spironolactone in patients at risk may help to decrease the incidence of potentially hazardous complications caused by hyperkalemia.

Outcome in adult patients after arterial switch operation for transposition of the great arteries

BACKGROUND: The arterial switch operation (ASO) is currently the treatment of choice in neonates with transposition of the great arteries (TGA). The outcome in childhood is encouraging but only limited data for long-term outcome into adulthood exist. METHODS AND RESULTS: We studied 145 adult patients (age>16, median 25years) with ASO followed at our institution. Three patients died in adulthood (mortality 2.4/1000-patient-years). Most patients were asymptomatic and had normal left ventricular function. Coronary lesions requiring interventions were rare (3 patients) and in most patients related to previous surgery. There were no acute coronary syndromes. Aortic root dilatation was frequent (56% patients) but rarely significant (>45mm in 3 patients, maximal-diameter 49mm) and appeared not to be progressive. There were no acute aortic events and no patient required elective aortic root surgery. Progressive neo-aortic-valve dysfunction was not observed in our cohort and only 1 patient required neo-aortic-valve replacement. Many patients (42.1%), however, had significant residual lesions or required reintervention in adulthood. Right ventricular outflow tract lesions or dysfunction of the neo-pulmonary-valve were frequent and 8 patients (6%) required neo-pulmonary-valve replacement. Cardiac interventions during childhood (OR 3.0, 95% CI 1.7-5.4, P<0.0001) were strong predictors of outcome (cardiac intervention/significant residual lesion/death) in adulthood. CONCLUSIONS: Adult patients with previous ASO remain free of acute coronary or aortic complications and have low mortality. However, a large proportion of patients require re-interventions or present with significant right sided lesions. Life-long cardiac follow-up is, therefore, warranted. Periodic noninvasive surveillance for coronary complications appears to be safe in adult ASO patients.

Decomposing Blaschke Products And Polynomials

The goal of this paper is to contribute to the understanding of complex polynomials and Blaschke products, two very important function classes in mathematics. For a polynomial, $f,$ of degree $n,$ we study when it is possible to write $f$ as a composition $f=g\circ h$, where $g$ and $h$ are polynomials, each of degree less than $n.$ A polynomial is defined to be \emph{decomposable }if such an $h$ and $g$ exist, and a polynomial is said to be \emph{indecomposable} if no such $h$ and $g$ exist. We apply the results of Rickards in \cite{key-2}. We show that $$C_{n}=\{(z_{1},z_{2},...,z_{n})\in\mathbb{C}^{n}\,|\,(z-z_{1})(z-z_{2})...(z-z_{n})\,\mbox{is decomposable}\},$$ has measure $0$ when considered a subset of $\mathbb{R}^{2n}.$ Using this we prove the stronger result that $$D_{n}=\{(z_{1},z_{2},...,z_{n})\in\mathbb{C}^{n}\,|\,\mbox{There exists\,}a\in\mathbb{C}\,\,\mbox{with}\,\,(z-z_{1})(z-z_{2})...(z-z_{n})(z-a)\,\mbox{decomposable}\},$$ also has measure zero when considered a subset of $\mathbb{R}^{2n}.$ We show that for any polynomial $p$, there exists an $a\in\mathbb{C}$ such that $p(z)(z-a)$ is indecomposable, and we also examine the case of $D_{5}$ in detail. The main work of this paper studies finite Blaschke products, analytic functions on $\overline{\mathbb{D}}$ that map $\partial\mathbb{D}$ to $\partial\mathbb{D}.$ In analogy with polynomials, we discuss when a degree $n$ Blaschke product, $B,$ can be written as a composition $C\circ D$, where $C$ and $D$ are finite Blaschke products, each of degree less than $n.$ Decomposable and indecomposable are defined analogously. Our main results are divided into two sections. First, we equate a condition on the zeros of the Blaschke product with the existence of a decomposition where the right-hand factor, $D,$ has degree $2.$ We also equate decomposability of a Blaschke product, $B,$ with the existence of a Poncelet curve, whose foci are a subset of the zeros of $B,$ such that the Poncelet curve satisfies certain tangency conditions. This result is hard to apply in general, but has a very nice geometric interpretation when we desire a composition where the right-hand factor is degree 2 or 3. Our second section of finite Blaschke product results builds off of the work of Cowen in \cite{key-3}. For a finite Blaschke product $B,$ Cowen defines the so-called monodromy group, $G_{B},$ of the finite Blaschke product. He then equates the decomposability of a finite Blaschke product, $B,$ with the existence of a nontrivial partition, $\mathcal{P},$ of the branches of $B^{-1}(z),$ such that $G_{B}$ respects $\mathcal{P}$. We present an in-depth analysis of how to calculate $G_{B}$, extending Cowen's description. These methods allow us to equate the existence of a decomposition where the left-hand factor has degree 2, with a simple condition on the critical points of the Blaschke product. In addition we are able to put a condition of the structure of $G_{B}$ for any decomposable Blaschke product satisfying certain normalization conditions. The final section of this paper discusses how one can put the results of the paper into practice to determine, if a particular Blaschke product is decomposable. We compare three major algorithms. The first is a brute force technique where one searches through the zero set of $B$ for subsets which could be the zero set of $D$, exhaustively searching for a successful decomposition $B(z)=C(D(z)).$ The second algorithm involves simply examining the cardinality of the image, under $B,$ of the set of critical points of $B.$ For a degree $n$ Blaschke product, $B,$ if this cardinality is greater than $\frac{n}{2}$, the Blaschke product is indecomposable. The final algorithm attempts to apply the geometric interpretation of decomposability given by our theorem concerning the existence of a particular Poncelet curve. The final two algorithms can be implemented easily with the use of an HTML

β-Arrestin2 influences the response to methadone in opioid-dependent patients

β-Arrestin2 (ARRB2) is a component of the G-protein-coupled receptor complex and is involved in μ-opioid and dopamine D(2) receptor signaling, two central processes in methadone signal transduction. We analyzed 238 patients in methadone maintenance treatment (MMT) and identified a haplotype block (rs34230287, rs3786047, rs1045280 and rs2036657) spanning almost the entire ARRB2 locus. Although none of these single nucleotide polymorphisms (SNPs) leads to a change in amino-acid sequence, we found that for all the SNPs analyzed, with exception of rs34230287, homozygosity for the variant allele confers a nonresponding phenotype (n=73; rs1045280C and rs2036657G: OR=3.1, 95% CI=1.5-6.3, P=0.004; rs3786047A: OR=2.5, 95% CI=1.2-5.1, P=0.02) also illustrated by a 12-fold shorter period of negative urine screening (P=0.01). The ARRB2 genotype may thus contribute to the interindividual variability in the response to MMT and help to predict response to treatment.

Morbidity in 201 patients with small sized meningioma treated by microsurgery

The management of patients with small, often asymptomatic meningiomas is controversial and includes observation, microsurgery (MS) and stereotactic radiosurgery (SRS). The purpose of this retrospective study was to analyze the morbidity and the extent of removal after MS for small (< or =3 cm) intracranial meningiomas and compare these results to those of SRS reported in the literature.

Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies

Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m(-2) (continuous infusion for 5 days), doxorubicin 30 mg m(-2) day(-1) x 3 (total dose 90 mg m(-2)), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1-6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33-63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade > or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

Parental understanding of wheeze and its impact on asthma prevalence estimates

The epidemiology of wheeze in children, when assessed by questionnaires, is dependent on parents' understanding of the term "wheeze". In a questionnaire survey of a random population sample of 4,236 children aged 6-10 yrs, parents' definition of wheeze was assessed. Predictors of a correct definition were determined and the potential impact of incorrect answers on prevalence estimates from the survey was assessed. Current wheeze was reported by 13.2% of children. Overall, 83.5% of parents correctly identified "whistling or squeaking" as the definition of wheeze; the proportion was higher for parents reporting wheezy children (90.4%). Frequent attacks of reported wheeze (adjusted odds ratio (OR) 3.0), maternal history of asthma (OR 1.5) and maternal education (OR 1.5) were significantly associated with a correct answer, while the converse was found for South Asian ethnicity (OR 0.6), first language not English (OR 0.6) and living in a deprived neighbourhood (OR 0.6). In summary, the present study showed that misunderstanding could lead to an important bias in assessing the prevalence of wheeze, resulting in an underestimation in children from South Asian and deprived family backgrounds. Prevalence estimates for the most severe categories of wheeze might be less affected by this bias and questionnaire surveys on wheeze should incorporate measures of parents' understanding of the term wheeze.

The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic risk factor for atopic asthma. The SAPALDIA Cohort Study

BACKGROUND: IL-18 is a pleiotrophic cytokine involved in both, T-helper type 1 (Th1) and Th2 differentiation. Recently genetic variants in the IL-18 gene have been associated with increased risk of atopy and asthma. OBJECTIVE: To examine the relationship of a genetic, haplotype-tagging promotor variant -137G/C in the IL-18 gene with atopic asthma in a large, well-characterized and population-based study of adults. METHODS: Prospective cohort study design was used to collect interview and biological measurement data at two examination time-points 11 years apart. Multivariate logistic regression analysis was used to assess the association of genotype with asthma and atopy. RESULTS: The G-allele of the IL-18 promotor variant (-137G/C) was associated with a markedly increased risk for the prevalence of physician-diagnosed asthma with concomitant skin reactivity to common allergens. Stratification of the asthma cases by skin reactivity to common allergens revealed an exclusive association of IL-18 -137 G-allele with an increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95% confidence interval: (1.64-8.02) for GC or GG carriers vs. CC carriers), and no according association with asthma and concomitant negative skin reactivity (adjusted OR: 1.13; 0.66-1.94). The interaction between IL-18 -137G/C genotype and positive skin prick test was statistically significant (P=0.029). None of 74 incident asthma cases with atopy at baseline exhibited the CC genotype. CONCLUSION: Our results strongly suggest that this variant of the IL-18 gene is an important genetic determinant involved in the development of atopic asthma.

CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis

OBJECTIVE: To determine whether pharmacogenetic tests such as N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1) genotyping are useful in identifying patients prone to antituberculosis drug-induced hepatotoxicity in a cosmopolite population. METHODS: In a prospective study we genotyped 89 patients treated with isoniazid (INH) for latent tuberculosis. INH-induced hepatitis (INH-H) or elevated liver enzymes including hepatitis (INH-ELE) was diagnosed based on the clinical diagnostic scale (CDS) designed for routine clinical practice. NAT2 genotypes were assessed by fluorescence resonance energy transfer probe after PCR analysis, and CYP2E1 genotypes were determined by PCR with restriction fragment length polymorphism analysis. RESULTS: Twenty-six patients (29%) had INH-ELE, while eight (9%) presented with INH-H leading to INH treatment interruption. We report no significant influence of NAT2 polymorphism, but we did find a significant association between the CYP2E1 *1A/*1A genotype and INH-ELE (OR: 3.4; 95% CI:1.1-12; p = 0.02) and a non significant trend for INH-H (OR: 5.9; 95% CI: 0.69-270; p = 0.13) compared with other CYP2E1 genotypes. This test for predicting INH-ELE had a positive predictive value (PPV) of 39% (95% CI: 26-54%) and a negative predictive value (NPV) of 84% (95% CI: 69-94%). CONCLUSION: The genotyping of CYP2E1 polymorphisms may be a useful predictive tool in the common setting of a highly heterogeneous population for predicting isoniazid-induced hepatic toxicity. Larger prospective randomized trials are needed to confirm these results.

Unexplained syncope--is screening for carotid sinus hypersensitivity indicated in all patients aged >40 years?

OBJECTIVE: To determine the frequency, age distribution and clinical presentation of carotid sinus hypersensitivity (CSH) among 373 patients (age range 15-92 years) referred to two autonomic referral centres during a 10-year period. METHODS: Carotid sinus massage (CSM) was performed both supine and during 60 degree head-up tilt. Beat-to-beat blood pressure, heart rate and a three-lead electrocardiography were recorded continuously. CSH was classified as cardioinhibitory (asystole > or = 3 s), vasodepressor (systolic blood pressure fall > or = 50 mm Hg) or mixed. All patients additionally underwent autonomic screening tests for orthostatic hypotension and autonomic failure. RESULTS: CSH was observed in 13.7% of all patients. The diagnostic yield of CSM was nil in patients aged < 50 years (n = 65), 2.4% in those aged 50-59 years (n = 82), 9.1% in those aged 60-69 years (n = 77), 20.7% in those aged 70-79 years (n = 92) and reached 40.4% in those > 80 years (n = 57). Syncope was the leading clinical symptom in 62.8%. In 27.4% of patients falls without definite loss of consciousness was the main clinical symptom. Mild and mainly systolic orthostatic hypotension was recorded in 17.6%; evidence of sympathetic or parasympathetic dysfunction was found in none. CONCLUSIONS: CSH was confirmed in patients > 50 years, the incidence steeply increasing with age. The current European Society of Cardiology guidelines that recommend testing for CSH in all patients > 40 years with syncope of unknown aetiology may need reconsideration. Orthostatic hypotension was noted in some patients with CSH, but evidence of sympathetic or parasympathetic failure was not found in any of them.

Labor induction in preeclampsia: is misoprostol more effective than dinoprostone?

OBJECTIVE: To compare the efficacy of vaginal misoprostol versus dinoprostone for induction of labor (IOL) in patients with preeclampsia according to the WHO criteria. STUDY DESIGN: Ninety-eight patients were retrospectively analyzed. A total of 47 patients received 3 mg dinoprostone suppositories every 6 h (max. 6 mg/24 h) whereas 51 patients in the misoprostol group received either 50 mug misoprostol vaginally every 12 h, or 25 mug every 6 h (max. 100 mug/24 h). Primary outcomes were vaginal delivery within 24 and 48 h, respectively. RESULTS: The probability of delivering within 48 h was more than three-fold higher in the misoprostol than in the dinoprostone group: odds ratio (OR)=3.48; 95% confidence interval (CI) 1.24, 10.30, whereas no significant difference was observed within 24 h (P=0.34). No correlation was seen between a ripe cervix prior to IOL and delivery within 24/48 h (P=0.33 and P=1.0, respectively). More cesarean sections were performed in the dinoprostone group due to failed IOL (P=0.0009). No significant differences in adverse maternal outcome were observed between both study groups, whereas more neonates (12 vs. 6) of the dinoprostone group were admitted to the NICU (P=0.068). CONCLUSION: This study suggests that misoprostol may have some advantages compared to dinoprostone, including improved efficacy and lower cost of the drug, even in cases of preeclampsia.

Mast fruiting of large ectomycorrhizal African rain forest trees: importance of dry season intensity, and the resource limitation hypothesis

Mast fruiting is a distinctive reproductive trait in trees. This rain forest study, at a nutrient-poor site with a seasonal climate in tropical Africa, provides new insights into the causes of this mode of phenological patterning. •  At Korup, Cameroon, 150 trees of the large, ectomycorrhizal caesalp, Microberlinia bisulcata, were recorded almost monthly for leafing, flowering and fruiting during 1995–2000. The series was extended to 1988–2004 with less detailed data. Individual transitions in phenology were analysed. •  Masting occurred when the dry season before fruiting was drier, and the one before that was wetter, than average. Intervals between events were usually 2 or 3 yr. Masting was associated with early leaf exchange, followed by mass flowering, and was highly synchronous in the population. Trees at higher elevation showed more fruiting. Output declined between 1995 and 2000. •  Mast fruiting in M. bisulcata appears to be driven by climate variation and is regulated by internal tree processes. The resource-limitation hypothesis was supported. An ‘alternative bearing’ system seems to underlie masting. That ectomycorrhizal habit facilitates masting in trees is strongly implied.

Safety of ondansetron loading doses in children with cancer

INTRODUCTION: In highly emetogenic chemotherapy, the recommended dose of the serotonin-receptor antagonist ondansetron (5 mg/m(2) q8h) may be insufficient to prevent chemotherapy-induced nausea and vomiting. In adults, ondansetron-loading doses (OLD) of 32 mg are safe. We aimed to evaluate in children the safety of an OLD of 16 mg/m(2) (top, 24 mg) i.v., followed by two doses of 5 mg/m(2) q8h. MATERIALS AND METHODS: This retrospective single-center study included all pediatric oncology patients having received >/=1 OLD between 2002 and 2005. Adverse events (AE) definitely, probably, or possibly related to OLD were studied, excluding AE not or unlikely related to the OLD. Associations between potential predictors and at least moderate AE were analyzed by mixed logistic regression. RESULTS: Of 167 patients treated with chemotherapy, 37 (22%) received 543 OLD. The most common AE were hypotension, fatigue, injection site reaction, headache, hot flashes/flushes, and dizziness. At least mild AE were described in 139 OLD (26%), at least moderate AE in 23 (4.2%), and severe AE in 5 (0.9%; exact 95% confidence interval [CI], 0.4-2.1). Life-threatening or lethal AE were not observed (0.0%; 0.0-0.6). At least moderate AE were significantly more frequent in female patients (odds ratio [OR] 3.5; 95% CI 1.4-8.8; p = 0.010), after erroneously given second OLD (17.0; 1.9-154; p = 0.012) and higher 24 h cumulative surface corrected dose (1.26 per mg/m(2); 1.06-1.51; p = 0.009). OLD given to infants below 2 years were not associated with more frequent AE. CONCLUSIONS: Ondansetron-loading doses of 16 mg/m(2) (top, 24 mg) i.v. seem to be safe in infants, children, and adolescents.

Hospitalized children with respiratory syncytial virus infection and neuromuscular impairment face an increased risk of a complicated course

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of viral respiratory tract infection in children. In contrast to other confirmed risk factors that predispose to a higher morbidity and mortality, the particular risk of a preexisting neuromuscular impairment (NMI) in hospitalized children with RSV infection has not been prospectively studied in a multicenter trial. METHODS: The DMS RSV Paed database was designed for the prospective multicenter documentation and analysis of all clinically relevant aspects of the management of inpatients with RSV infection. Patients with clinically relevant NMI were identified according to the specific comments of the attending physicians and compared with those without NMI. RESULTS: This study covers 6 consecutive seasons; the surveillance took place in 14 pediatric hospitals in Germany from 1999 to 2005. In total, 1568 RSV infections were prospectively documented in 1541 pediatric patients. Of these, 73 (4.7%) patients displayed a clinically relevant NMI; 41 (56%) NMI patients had at least 1 additional risk factor for a severe course of the infection (multiple risk factors in some patients; prematurity in 30, congenital heart disease in 19, chronic lung disease 6 and immunodeficiency in 8). Median age at diagnosis was higher in NMI patients (14 vs. 5 months); NMI patients had a greater risk of seizures (15.1% vs. 1.6%), and a higher proportion in the NMI group had to be mechanically ventilated (9.6% vs. 1.9%). Eventually, the attributable mortality was significantly higher in the NMI group (5.5% vs. 0.2%; P < 0.001 for all). Multivariate logistic regression confirmed that NMI was independently associated with pediatric intensive care unit (PICU) admission (OR, 4.94; 95% CI, 2.69-8.94; P < 0.001] and mechanical ventilation (OR, 3.85; 95% CI, 1.28-10.22; P = 0.017). CONCLUSION: This is the first prospective multicenter study confirming the hypothesis that children with clinically relevant NMI face an increased risk for severe RSV-disease. It seems reasonable to include NMI as a cofactor into the decision algorithm of passive immunization.

Recanalization and outcome after intra-arterial thrombolysis in middle cerebral artery and internal carotid artery occlusion: does sex matter?

BACKGROUND AND PURPOSE: Recent studies have reported sex differences in recanalization and outcome after intravenous thrombolysis (IVT) in acute ischemic stroke. METHODS: We analyzed sex differences in outcome in consecutive patients with middle cerebral artery (MCA) M1 or M2 and internal carotid artery (ICA) occlusion treated with intra-arterial thrombolysis (IAT). Recanalization immediately after thrombolysis and outcome after 3 months were assessed. RESULTS: Two hundred five patients (111 men) with MCA and 43 (22 men) with ICA occlusion were identified. Baseline variables did not differ between the sexes except for a higher prevalence of smokers among men in the MCA group (31% vs 12%; P=0.001). Partial or complete recanalization (TIMI flow 2 or 3) of the MCA was observed in 71 (75%) women and 80 (72%) men (P=0.488). In the ICA group, 14 (67%) women and 11 men (50%) showed TIMI 2 or 3 recanalization (P=0.425). Favorable outcome (modified Rankin Scale score 0 to 2) was seen in 57 women (61%) and 63 men (57%) with MCA occlusion (P=0.512) and in 6 women (28%) and 4 men (18%) with ICA occlusion (P=0.656). After multiple-regression analyses, there was still no association between sex and outcome (P=0.763 for MCA and P=0.813 for ICA occlusion) or recanalization (P=0.488 for MCA and P=0.104 for ICA occlusion). CONCLUSIONS: There was no association between sex and recanalization or outcome after IAT. These findings are in contrast to previous studies reporting better recanalization and outcome after IVT in women and might have implications in the selection of patients for IAT or IVT.