Effectiveness of out-patient based acute heart failure care: a pilot randomised controlled trial.

OBJECTIVES: Acute heart failure (AHF) hospitalisation is associated with 10% mortality. Outpatient based management (OPM) of AHF appeared effective in observational studies. We conducted a pilot randomised controlled trial (RCT) comparing OPM with standard inpatient care (IPM). METHODS: We randomised patients with AHF, considered to need IV diuretic treatment for ≥2 days, to IPM or OPM. We recorded all-cause mortality, and the number of days alive and out-of-hospital (DAOH). Quality of life, mental well-being and Hope scores were assessed. Mean NHS cost savings and 95% central range (CR) were calculated from bootstrap analysis. Follow-up: 60 days. RESULTS: Eleven patients were randomised to IPM and 13 to OPM. There was no statistically significant difference in all-cause mortality during the index episode (1/11 vs 0/13) and up to 60 days follow-up (2/11 vs 2/13) [p = .86]. The OPM group accrued more DAOH {47 [36,51] vs 59 [41,60], p = .13}. Two patients randomised to IPM (vs 6 OPM) were readmitted [p = .31]. Hope scores increased more with OPM within 30 days but dropped to lower levels than IPM by 60 days. More out-patients had increased total well-being scores by 60 days (p = .04). OPM was associated with mean cost savings of £2658 (95% CR 460-4857) per patient. CONCLUSIONS: Patients with acute HF randomised to OPM accrued more days alive out of hospital (albeit not statistically significantly in this small pilot study). OPM is favoured by patients and carers and is associated with improved mental well-being and cost savings.

Arrhythmogenic gene remodelling in elderly patients with type 2 diabetes with aortic stenosis and normal left ventricular ejection fraction.

NEW FINDINGS: What is the central question of this study? Type 2 diabetes is associated with a higher rate of ventricular arrhythmias compared with the non-diabetic population, but the associated myocardial gene expression changes are unknown; furthermore, it is also unknown whether any changes are attributable to chronic hyperglycaemia or are a consequence of structural changes. What is the main finding and its importance? We found downregulation of left ventricular ERG gene expression and increased NCX1 gene expression in humans with type 2 diabetes compared with control patients with comparable left ventricular hypertrophy and possible myocardial fibrosis. This was associated with QT interval prolongation. Diabetes and associated chronic hyperglycaemia may therefore promote ventricular arrhythmogenesis independently of structural changes. Type 2 diabetes is associated with a higher rate of ventricular arrhythmias, and this is hypothesized to be independent of coronary artery disease or hypertension. To investigate further, we compared changes in left ventricular myocardial gene expression in type 2 diabetes patients with patients in a control group with left ventricular hypertrophy. Nine control patients and seven patients with type 2 diabetes with aortic stenosis undergoing aortic valve replacement had standard ECGs, signal-averaged ECGs and echocardiograms before surgery. During surgery, a left ventricular biopsy was taken, and mRNA expressions for genes relevant to the cardiac action potential were estimated by RT-PCR. Mathematical modelling of the action potential and calcium transient was undertaken using the O'Hara-Rudy model using scaled changes in gene expression. Echocardiography revealed similar values for left ventricular size, filling pressures and ejection fraction between groups. No difference was seen in positive signal-averaged ECGs between groups, but the standard ECG demonstrated a prolonged QT interval in the diabetes group. Gene expression of KCNH2 and KCNJ3 were lower in the diabetes group, whereas KCNJ2, KCNJ5 and SLC8A1 expression were higher. Modelling suggested that these changes would lead to prolongation of the action potential duration with generation of early after-depolarizations secondary to a reduction in density of the rapid delayed rectifier K+ current and increased Na+ -Ca2+ exchange current. These data suggest that diabetes leads to pro-arrythmogenic changes in myocardial gene expression independently of left ventricular hypertrophy or fibrosis in an elderly population.

Plasma uric acid remains a marker of poor outcome in hypertensive pregnancy: a retrospective cohort study.

OBJECTIVE: To examine the relationship between hyperuricaemia, haemoconcentration and maternal and fetal outcomes in hypertensive pregnancies. DESIGN: Retrospective analysis of a database of hypertensive pregnancies. SETTING: St George Hospital, a major obstetric unit in Australia. POPULATION: A cohort of 1880 pregnant women without underlying hypertension or renal disease, referred for management of pre-eclampsia or gestational hypertension. METHODS: Demographic, clinical and biochemical data at time of referral and delivery were collected for each pregnancy. Women were grouped according to diagnosis (pre-eclampsia or gestational hypertension) and logistic regression analysis was used to determine the relationship between uric acid, haemoglobin, haematocrit and adverse outcomes; an α level of P < 0.01 was used for statistical significance. MAIN OUTCOME MEASURES: Composites of adverse maternal and fetal outcomes. RESULTS: In women with 'benign' GH (without proteinuria or any other maternal clinical feature of pre-eclampsia) gestation-corrected hyperuricaemia was associated with increased risk of a small-for-gestational-age infant (OR 2.5; 95% CI 1.3-4.8) and prematurity (OR 3.2; 95% CI 1.4-7.2), but not with adverse maternal outcome. In the whole cohort of hypertensive pregnant women (those with pre-eclampsia or gestational hypertension) the risk of adverse maternal outcome (OR 2.0; 95% CI 1.6-2.4) and adverse fetal outcome (OR 1.8; 95% CI 1.5-2.1) increased with increasing concentration of uric acid. Hyperuricaemia corrected for gestation provided additional strength to these associations. Haemoglobin and haematocrit were not associated with adverse pregnancy outcome. CONCLUSIONS: Hyperuricaemia in hypertensive pregnancy remains an important finding because it identifies women at increased risk of adverse maternal and particularly fetal outcome; the latter, even in women with gestational hypertension without any other feature of pre-eclampsia.

Comprehensive survey of developmental genes in the pea aphid, Acyrthosiphon pisum: frequent lineage-specific duplications and losses of developmental genes.

Aphids exhibit unique attributes, such as polyphenisms and specialized cells to house endosymbionts, that make them an interesting system for studies at the interface of ecology, evolution and development. Here we present a comprehensive characterization of the developmental genes in the pea aphid, Acyrthosiphon pisum, and compare our results to other sequenced insects. We investigated genes involved in fundamental developmental processes such as establishment of the body plan and organogenesis, focusing on transcription factors and components of signalling pathways. We found that most developmental genes were well conserved in the pea aphid, although many lineage-specific gene duplications and gene losses have occurred in several gene families. In particular, genetic components of transforming growth factor beta (TGFbeta) Wnt, JAK/STAT (Janus kinase/signal transducer and activator of transcription) and EGF (Epidermal Growth Factor) pathways appear to have been significantly modified in the pea aphid.

Anterior development in the parthenogenetic and viviparous form of the pea aphid, Acyrthosiphon pisum: hunchback and orthodenticle expression.

In the dipteran Drosophila, the genes bicoid and hunchback work synergistically to pattern the anterior blastoderm during embryogenesis. bicoid, however, appears to be an innovation of the higher Diptera. Hence, in some non-dipteran insects, anterior specification instead relies on a synergistic interaction between maternally transcribed hunchback and orthodenticle. Here we describe how orthologues of hunchback and orthodenticle are expressed during oogenesis and embryogenesis in the parthenogenetic and viviparous form of the pea aphid, Acyrthosiphon pisum. A. pisum hunchback (Aphb) mRNA is localized to the anterior pole in developing oocytes and early embryos prior to blastoderm formation - a pattern strongly reminiscent of bicoid localization in Drosophila. A. pisum orthodenticle (Apotd), on the other hand, is not expressed prior to gastrulation, suggesting that it is the asymmetric localization of Aphb, rather than synergy between Aphb and Apotd, that regulates anterior specification in asexual pea aphids.

Role of angiotensin receptor blockers in the prevention and management of ischaemic stroke.

Angiotensin receptor blockers (ARB's) are an important class of antihypertensive agents and appear to have a role in the prevention and management of ischaemic stroke. We present a discussion of the data on ARB's in this important condition.

A comparison of antimicrobial susceptibility profile of urinary pathogens for the years, 1999 and 2003.

Urinary tract infection is a common condition worldwide; responsible for significant morbidity in both hospitalized and community patients. The laboratory records, for microbial isolates of infected urine and their susceptibility profiles for the years 1999 and 2003 were retrospectively reviewed and compared. In 2003, there was a significant decline in recovery ofCitrobacter spp compared to 1999. Conversely, the proportion of K pneumoniae, E coli and Enterococci increased dramatically in 2003, in both practices. For Proteus vulgaris and Proteus mirabilis, rates of isolation were increased in 2003, in hospital practice and community practice, respectively. Significant changes in antimicrobial susceptibility were also evident. A greater proportion of isolates from both practices were resistant to ampicillin, amoxicillin-clavulanic acid, cefuroxime, ceftazidime and cotrimoxazole in 2003 when compared to 1999. With respect to E coli, there were significant increases in prevalence of resistance to cefuroxime and amoxicillin-clavulanic acid. The overall resistance rate for norfloxacin remained relatively low and was unchanged for E coli. Continued surveillance of uropathogen resistance trends is important and this information should be communicated to clinicians. The feasibility of using the fluoroquinolones as a first line of therapy in urinary tract infection should be considered.

Wing dimorphism in aphids.

Many species of insects display dispersing and nondispersing morphs. Among these, aphids are one of the best examples of taxa that have evolved specialized morphs for dispersal versus reproduction. The dispersing morphs typically possess a full set of wings as well as a sensory and reproductive physiology that is adapted to flight and reproducing in a new location. In contrast, the nondispersing morphs are wingless and show adaptations to maximize fecundity. In this review, we provide an overview of the major features of the aphid wing dimorphism. We first provide a description of the dimorphism and an overview of its phylogenetic distribution. We then review what is known about the mechanisms underlying the dimorphism and end by discussing its evolutionary aspects.

A comparison of antimicrobial susceptibility profile of urinary pathogens for the years, 1999 and 2003 / Una comparación del perfil de susceptibilidad antimicrobiana de los patógenos urinarios en los Años 1999 y 2003

Urinary tract infection is a common condition worldwide; responsible for significant morbidity in both hospitalized and community patients. The laboratory records, for microbial isolates of infected urine and their susceptibility profiles for the years 1999 and 2003 were retrospectively reviewed and compared. In 2003, there was a significant decline in recovery ofCitrobacter spp compared to 1999. Conversely, the proportion of K pneumoniae, E coli and Enterococci increased dramatically in 2003, in both practices. For Proteus vulgaris and Proteus mirabilis, rates of isolation were increased in 2003, in hospital practice and community practice, respectively. Significant changes in antimicrobial susceptibility were also evident. A greater proportion of isolates from both practices were resistant to ampicillin, amoxicillin-clavulanic acid, cefuroxime, ceftazidime and cotrimoxazole in 2003 when compared to 1999. With respect to E coli, there were significant increases in prevalence of resistance to cefuroxime and amoxicillin-clavulanic acid. The overall resistance rate for norfloxacin remained relatively low and was unchanged for E coli. Continued surveillance of uropathogen resistance trends is important and this information should be communicated to clinicians. The feasibility of using the fluoroquinolones as a first line of therapy in urinary tract infection should be considered.

La infección del tracto urinario es una condición común a nivel mundial. Esa condición es significativamente responsable de la morbilidad, tanto en los pacientes hospitalizados como en los no hospitalizados. Los datos de laboratorio en relación con los aislados microbianos de la orina infectada y sus perfiles de susceptibilidad en los años 1999 y 2003, fueron revisados y comparados de manera retrospectiva. En 2003, se produjo un descenso significativo de la recuperación de infecciones por Citrobacter spp, en comparación con 1999. En contraste con ello, la proporción de K pneumoniae, E coli y Enterococci en ambas prácticas, aumentó dramáticamente en 2003. En el caso de Proteus vulgaris y Proteus mirabilis, las tasas de aislamiento aumentaron en el año 2003 en la práctica médica hospitalaria y comunitaria respectivamente. También aquí se hicieron evidentes cambios significativos en la susceptibilidad antimicrobiana. Una proporción mayor de aislados de ambas prácticas resultó ser resistente a la ampicilina, la combinación amoxicilina/ácido clavulánico, la ceftazidima y el cotrimoxazol en 2003, en comparación con 1999. Con respecto al E coli, hubo aumentos significativos en la prevalencia de la resistencia a la cefuroxima y la asociación amoxicilina/ácido clavulánico La tasa de resistencia general frente a la norfloxacina permaneció relativamente baja y no presentó variaciones frente al E coli. La vigilancia permanente de las tendencias de la resistencia a los patógenos es importante, y la investigación así obtenida, debe ser comunicada a los clínicos. Debe considerarse la factibilidad de usar fluoroquinolonas como terapia de primera línea.

Myocardial infarction in young adults.

Although myocardial infarction (MI) mainly occurs in patients older than 45, young men or women can suffer MI. Fortunately, its incidence is not common in patients younger than 45 years. However, the disease carries a significant morbidity, psychological effects, and financial constraints for the person and the family when it occurs at a young age. The causes of MI among patients aged less than 45 can be divided into four groups: (1) atheromatous coronary artery disease; (2) non-atheromatous coronary artery disease; (2) hyper-coagulable states; (4) MI related to substance misuse. There is a considerable overlap between all the groups. This article reviews the literature and highlights the practical issues involved in the management of young adults with MI.

Cocaine and the heart.

Cocaine is the second commonest illicit drug used and the most frequent cause of drug related deaths. Its use is associated with both acute and chronic complications that may involve any system, the most common being the cardiovascular system. Cocaine misuse has a major effect in young adult drug users with resulting loss of productivity and undue morbidity with cocaine related cardiac and cerebrovascular effects. Many cocaine users have little or no idea of the risks associated with its use. Patients, health care professionals, and the public should be educated about the dangers and the considerable risks of cocaine use. This review concentrates on the cardiovascular effects of cocaine and their management.

Role of cardiac troponin testing in percutaneous transluminal coronary angioplasty.

Percutaneous transluminal coronary angioplasty (PTCA) is a common invasive procedure for myocardial revascularization. This article reviews the role of monitoring cardiac troponins in identifying procedural myocardial damage as a result of PTCA, its associations with balloon inflation time, stenting, side-branch occlusion and the prognostic implications of elevated levels of cardiac troponins. A review of several studies demonstrates that cardiac troponins are more sensitive than creatine kinase MB, CK-MB (mass) in detecting minor myocardial damage during PTCA. Increases in post-procedural cardiac troponin T and cardiac troponin I are associated with a greater degree of morbidity and mortality. Increases are more common and more pronounced following a longer duration of balloon inflation time, stenting and side-branch occlusion. Elevated cardiac troponins pre-procedure are a poor prognostic indicator.

Twenty-four-hour automated blood pressure monitoring as a predictor of preeclampsia.

OBJECTIVE: The purpose of this study was to determine the predictive ability of parameters of 24-hour ambulatory blood pressure monitoring for the development of preeclampsia or gestational hypertension in women who are already considered at risk for these disorders. STUDY DESIGN: One hundred twenty-two pregnant women who were considered high risk for the development of preeclampsia underwent 24-hour ambulatory blood pressure monitoring between 18 and 30 weeks gestation, while their condition was normotensive according to routine mercury sphygmomanometry. One hundred sixty-four healthy primigravid women who were considered at usual risk for preeclampsia underwent the same tests as a parallel study. Routine blood pressure, awake and sleep average blood pressure, and 24-hour mean average blood pressure were entered into multiple logistic regression as predictors of either preeclampsia or gestational hypertension; significant variables were then tested by a series of receiver operator curves. RESULTS: Eight percent of usual risk and 45% of high risk women experienced the development of preeclampsia or gestational hypertension. In both groups, the average routine mercury blood pressure and awake, sleeping, and 24-hour ambulatory blood pressure monitoring-derived blood pressure were significantly higher in women who later experienced the development of preeclampsia or gestational hypertension. In usual risk women, 24-hour systolic blood pressure of >or=115 mm Hg and sleeping systolic blood pressure of >or=106 mm Hg were predictive of later preeclampsia or gestational hypertension, but sensitivities were low (77% and 54%, respectively). In high risk women, sleeping diastolic blood pressure of >or=62 mm Hg and sleeping mean arterial pressure of >or=79 mm Hg were predictive of preeclampsia or gestational hypertension, but again sensitivities were low (70% and 65%, respectively). CONCLUSION: Awake and sleeping blood pressure are higher in midpregnancy in women who later experience the development of preeclampsia or gestational hypertension. Twenty-four-hour ambulatory blood pressure monitoring provides a noninvasive method of selecting some of these women, but this test has a sensitivity no better than that of other predictive tests, even in women at high risk for preeclampsia.

Pax group III genes and the evolution of insect pair-rule patterning.

Pair-rule genes were identified and named for their role in segmentation in embryos of the long germ insect Drosophila. Among short germ insects these genes exhibit variable expression patterns during segmentation and thus are likely to play divergent roles in this process. Understanding the details of this variation should shed light on the evolution of the genetic hierarchy responsible for segmentation in Drosophila and other insects. We have investigated the expression of homologs of the Drosophila Pax group III genes paired, gooseberry and gooseberry-neuro in short germ flour beetles and grasshoppers. During Drosophila embryogenesis, paired acts as one of several pair-rule genes that define the boundaries of future parasegments and segments, via the regulation of segment polarity genes such as gooseberry, which in turn regulates gooseberry-neuro, a gene expressed later in the developing nervous system. Using a crossreactive antibody, we show that the embryonic expression of Pax group III genes in both the flour beetle Tribolium and the grasshopper Schistocerca is remarkably similar to the pattern in Drosophila. We also show that two Pax group III genes, pairberry1 and pairberry2, are responsible for the observed protein pattern in grasshopper embryos. Both pairberry1 and pairberry2 are expressed in coincident stripes of a one-segment periodicity, in a manner reminiscent of Drosophila gooseberry and gooseberry-neuro. pairberry1, however, is also expressed in stripes of a two-segment periodicity before maturing into its segmental pattern. This early expression of pairberry1 is reminiscent of Drosophila paired and represents the first evidence for pair-rule patterning in short germ grasshoppers or any hemimetabolous insect.

The prevalence and clinical significance of nocturnal hypertension in pregnancy.

OBJECTIVE: To determine (a) the prevalence of hypertension during sleep in pre-eclampsia and gestational hypertension, and (b) whether women with hypertension during sleep have worse pregnancy outcomes than hypertensive pregnant women with controlled (normal) blood pressure (BP) during sleep. DESIGN: Prospective double-blind cohort study. SETTING: Inpatients and outpatients managed in a day assessment unit (DAU) at St George Hospital, Sydney, Australia. PARTICIPANTS: A total of 186 hypertensive pregnant women, 158 of whom had successful 24 h BP monitoring; 40% had proteinuric pre-eclampsia (PE), 43% gestational hypertension (GH) and 17% essential hypertension (EH). INTERVENTIONS: Blood pressure, 24 h non-invasive, monitoring (Spacelabs 90207) was undertaken successfully in 158 women with PE, GH or EH, whether or not they were receiving antihypertensives. Women and clinicians were blinded to results of these BP monitors. Sleep hypertension was defined as BP > 117/68 mmHg at 26-30 weeks or > 123/72 mmHg after 30 weeks gestation. MAIN OUTCOME MEASURES: Maternal and fetal outcomes were compared between women with and without sleep hypertension and the prevalence of sleep hypertension was determined. RESULTS: Sleep hypertension was present in 59%, more commonly in PE (79%) than GH/EH (45%), P < 0.0001. Sleep hypertensives also had higher routine sphygmomanometer BPs [137(10)/91(7) mmHg; mean(SD)] than women with normal sleep BP [130(12)/ 87(8) mmHg] P = 0.007, and higher awake ambulatory blood pressure monitoring (ABPM) BPs [137(8)/88(7) versus 127(7)/79(6) mmHg], P < 0.0001. Awake, but not sleep, average heart rate was lower in sleep hypertensives [85(11) versus 91 (10) beats per minute, bpm], P = 0.002. Sleep hypertensives had a significantly greater frequency of renal insufficiency, liver dysfunction, thrombocytopenia and episodes of (awake) severe hypertension (P < 0.05), as well as lower birth weight babies [2715 (808) versus 3224(598) g, P < 0.0001]. CONCLUSIONS: Hypertension during sleep is a common finding in women with hypertensive disorders of pregnancy, particularly pre-eclampsia. These women also have higher awake BPs and a greater frequency of adverse maternal and fetal outcomes. These findings are largely explained by the greater likelihood of pre-eclamptics having sleep hypertension.

Community-based continuity of midwifery care versus standard hospital care: a cost analysis.

This paper reports the costs of providing a new model of maternity care compared to standard care in an Australian public hospital. The mean cost of providing care per woman was lower in the group who had the new model of care compared with standard care ($2,579 versus $3,483). Cost savings associated with new model of care were maintained even after costs associated with admission to special care nursery were excluded. The cost saving was also sustained even when the caesarean section rate in the new model of care increased to beyond that of the standard care group.