Gender differences with short-term vs 12 months dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO dual therapy stent: 2-years follow-up results of the REDUCE trial.

BACKGROUND: Gender differences in the thrombotic and bleeding risk have been suggested to condition the benefits of antithrombotic therapies in Acute Coronary Syndrome (ACS) patients, and mainly among those undergoing percutaneous coronary interventions with drug eluting stents (DES). The impact of gender on the optimal duration of dual antiplatelet therapy (DAPT) in ACS patients is still unexplored and was, therefore, the aim of the present sub-study. METHODS: REDUCE was a prospective, multicenter, randomized investigator-initiated study designed to enroll 1500 ACS patients after treatment with the COMBO Dual Stent Therapy, based on a noninferiority design. Patients were randomized in a 1:1 fashion to either 3 or 12 months of DAPT. Primary study endpoint was a composite of all-cause mortality, myocardial infarction, definite/probable stent thrombosis (ST), stroke, target-vessel revascularization (TVR) and bleedings (BARC II, III, V) at 12 months. Secondary endpoints were cardiovascular mortality and the individual components of the primary endpoint within 24 months. RESULTS: From June 2014 to May 2016 300 women and 1196 men were included in the study. Among them, 43.7% of females and 51.9% of males were assigned to the 3 months DAPT treatment. Baseline characteristics were well matched between the two arms, with the exception of a lower rate of TIMI flow < 3 (p = 0.04), lower systolic blood pressure (p = 0.05) and use of spironolactone (p = 0.006) among women and a more advanced age (p = 0.05) among men receiving a short-term DAPT. At a mean follow-up of 525 (± 198) days, no difference in the primary endpoint was observed according to DAPT duration in both females [6.9% vs 5.9%, HR (95% CI) = 1.19 (0.48-2.9), p = 0.71] and males [8.2% vs 9%, HR (95% CI) = 0.92 (0.63-1.35), p = 0.67; p INT = 0.20]. Results were confirmed after correction for baseline differences [females: adjusted HR (95% CI) = 1.12 (0.45-2.78), p = 0.81; males: adjusted HR (95% CI) = 0.90 (0.61-1.32), p = 0.60]. Comparable rates of survival, thrombotic (MI, stent thrombosis, TVR, stroke) and bleeding events were observed with the two DAPT strategies, with no impact of gender. CONCLUSIONS: The present study shows that among ACS patients randomized in the REDUCE trial, a 3 months DAPT strategy offers comparable results as compared to a standard 12 months DAPT at 2-years follow-up in both male and female gender.

ST22 and ST239 MRSA duopoly in Singaporean hospitals: 2006-2010.

Surveillance is integral for the monitoring and control of infectious diseases. We conducted prospective laboratory surveillance of methicillin-resistant Staphylococcus aureus (MRSA) in five Singaporean public-sector hospitals from 2006 to 2010, using WHONET 5.6 for data compilation and analysis. Molecular profiling using multilocus variable-number tandem-repeat analysis, staphylococcal cassette chromosome mec classification and multilocus sequence typing was performed for a random selection of isolates. Our results showed overall stable rates of infection and bacteraemia, although there was significant variance among the individual hospitals, with MRSA rates increasing in two smaller hospitals and showing a trend towards decreasing in the two largest hospitals. The proportion of blood isolates that are EMRSA-15 (ST22-IV) continued to increase over time, slowly replacing the multi-resistant ST239-III. A new MRSA clone - ST45-IV - is now responsible for a small subset of hospital infections locally. More effort is required in Singaporean hospitals in order to reduce the rates of MRSA infection significantly.

Acinetobacter calcoaceticus-Acinetobacter baumannii complex species in clinical specimens in Singapore.

This study was performed to determine the prevalence, distribution of specimen sources, and antimicrobial susceptibility of the Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) species complex in Singapore. One hundred and ninety-three non-replicate Acb species complex clinical isolates were collected from six hospitals over a 1-month period in 2006. Of these, 152 (78·7%) were identified as A. baumannii, 18 (9·3%) as 'Acinetobacter pittii' [genomic species (gen. sp.) 3], and 23 (11·9%) as 'Acinetobacter nosocomialis' (gen. sp. 13TU). Carbapenem resistance was highest in A. baumannii (72·4%), followed by A. pittii (38·9%), and A. nosocomialis (34·8%). Most carbapenem-resistant A. baumannii and A. nosocomialis possessed the bla(OXA-23-like) gene whereas carbapenem-resistant A. pittii possessed the bla(OXA-58-like) gene. Two imipenem-resistant strains (A. baumannii and A. pittii) had the bla(IMP-like) gene. Representatives of carbapenem-resistant A. baumannii were related to European clones I and II.

Nox2 and Nox4 mediate tumour necrosis factor-α-induced ventricular remodelling in mice.

Reactive oxygen species (ROS) and pro-inflammatory cytokines are crucial in ventricular remodelling, such as inflammation-associated myocarditis. We previously reported that tumour necrosis factor-α (TNF-α)-induced ROS in human aortic smooth muscle cells is mediated by NADPH oxidase subunit Nox4. In this study, we investigated whether TNF-α-induced ventricular remodelling was mediated by Nox2 and/or Nox4. An intravenous injection of murine TNF-α was administered to a group of mice and saline injection was administered to controls. Echocardiography was performed on days 1, 7 and 28 post-injection. Ventricular tissue was used to determine gene and protein expression of Nox2, Nox4, ANP, interleukin (IL)-1ß, IL-2, IL-6, TNF-α and to measure ROS. Nox2 and Nox4 siRNA were used to determine whether or not Nox2 and Nox4 mediated TNF-α-induced ROS and upregulation of IL-1ß and IL-6 in adult human cardiomyocytes. Echocardiography showed a significant increase in left ventricular end-diastolic and left ventricular end-systolic diameters, and a significant decrease in the ejection fraction and fractional shortening in mice 7 and 28 days after TNF-α injection. These two groups of mice showed a significant increase in ventricular ROS, ANP, IL-1ß, IL-2, IL-6 and TNF-α proteins. Nox2 and Nox4 mRNA and protein levels were also sequentially increased. ROS was significantly decreased by inhibitors of NADPH oxidase, but not by inhibitors of other ROS production systems. Nox2 and Nox4 siRNA significantly attenuated TNF-α-induced ROS and upregulation of IL-1ß and IL-6 in cardiomyocytes. Our study highlights a novel TNF-α-induced chronic ventricular remodelling mechanism mediated by sequential regulation of Nox2 and Nox4 subunits.

Clinical services and professional support: a review of mobile telepaediatric services in Queensland.

In Queensland, the majority of rural hospitals and some regional hospitals lack paediatricians or paediatric sub-specialists. Many specialist referrals result in a transfer to a tertiary paediatric hospital in Brisbane--up to 3000 km away. Travel is difficult, time-consuming and expensive, especially from rural and remote areas in Queensland. The telepaediatric service managed by the Centre for Online Health (COH) at the Royal Children's Hospital (RCH) in Brisbane, delivers general and specialist paediatric support directly into selected neonatal and paediatric wards in a convenient and child-friendly manner. We conducted a review of telepaediatric service records to determine which clinical and educational services had been delivered through the mobile videoconference systems. Telepaediatric service activity records for all consultations conducted between January 2005 and July 2010 were summarised.Since 2005, seven mobile telepaediatric systems have been established in selected regional hospitals throughout Queensland. For some hospitals, the service was used mainly for consultations with specialists based at the RCH or at The Townsville Hospital (TTH) in north Queensland. During a 67 month period, a total of 966 consultations were conducted during 465 videoconference sessions, totaling about 228 hours of activity. In addition, 39 education sessions were delivered to regional staff through the mobile robot systems by specialists based at the RCH in Brisbane. The telepaediatric robots have proven useful for general paediatric support for hospitals without a local paediatrician; sub-specialist paediatric support and professional education and support for regional clinicians. Our service model provided a streamlined method of delivering specialist health services to children and families living in rural and remote regions of Queensland.

Scaling of musical preferences by the mentally retarded.

The ability of institutionalized retardates in scaling musical preferences was compared with that of normals. The retardates' scale values and scale forms obtained by two kinds of scaling procedures are very similar to those of normals. Deficits, however, are observed in their lower internal consistency and relative uncertainty and in higher response polarization and perseveration.

Clinical features and treatment outcomes of vancomycin-intermediate Staphylococcus aureus (VISA) and heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) in a tertiary care institution in Singapore.

This retrospective case-control study was undertaken to review the clinical features associated with heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) and vancomycin-intermediate S. aureus (VISA) infections and the local impact they have on clinical outcome. Compared with vancomycin-susceptible S. aureus (n = 30), hVISA and VISA infections (n = 10) are found to be associated with a longer period of prior glycopeptide use (P = 0.01), bone/joint (P < 0.01) and prosthetic infections (P = 0.04), as well as treatment failure, as evidenced by longer bacteremic (P < 0.01) and culture positivity (P < 0.01) periods. This was observed to have resulted in longer hospital length of stay (P < 0.01) and total antibiotic therapy duration (P = 0.01). There was, however, no significant difference in the overall patient mortality or the hospitalization cost (P = 0.12) in both groups. Clinicians should be cognizant of the association between hVISA/VISA with high bacterial load deep-seated infections. We recommend targeted and even universal screening for hVISA/VISA in methicillin-resistant S. aureus (MRSA) infections.

Association of acute ischemic stroke with the MTHFR C677T polymorphism but not with NOS3 gene polymorphisms in a Singapore population.

BACKGROUND AND PURPOSE: The association of polymorphisms in the nitric oxide synthase 3 (NOS3) gene (T-786C, variable number tandem repeats 4A/B/C, and G894T) and in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T) with acute ischemic stroke have been reported. METHODS: First-time onset acute ischemic stroke patients (n = 120) and controls (n = 207) with no past history of stroke were compared. Allele specific gene amplification and restriction fragment length polymorphism (RFLP) analysis were used to determine the genotype and allelic frequencies in both groups. Plasma homocysteine (Hcy) and nitrite levels were measured. RESULTS: No significant association of NOS3 polymorphisms with ischemic stroke was noted. The TT genotype of the MTHFR C677T polymorphism was significantly associated with ischemic stroke (P = 0.004). Elevated plasma Hcy levels were also significantly associated with ischemic stroke (P = 0.001). CONCLUSIONS: The TT genotype of C677T polymorphism in the MTHFR gene contributes to genetic susceptibility of acute ischemic stroke in a Singapore population.

Arterial stiffness, metabolic syndrome and inflammation amongst Asian ischaemic stroke patients.

BACKGROUND AND PURPOSE: Arterial stiffness and metabolic syndrome (MetS) are risk factors for ischaemic stroke. We studied the association of arterial stiffness, measured by carotid-femoral pulse wave velocity (PWV) and MetS amongst ischaemic stroke patients. We also investigated the role of inflammation measured by serum erythrocyte sedimentation rate (ESR) in the metabolic syndrome-arterial stiffness relationship. METHODS: Amongst the 229 prospectively recruited acute ischaemic stroke patients, we measured carotid-femoral PWV using applanation tonometry and the inflammatory marker serum ESR. RESULTS: Carotid-femoral PWV was significantly higher amongst patients with MetS (P = 0.002), increased waist circumference (P = 0.010), raised blood pressure (P < 0.001) and abnormal glycemia (P = 0.002); and increased with the number of MetS components (P = 0.002). In a sub-group of 199 patients, carotid-femoral PWV was significantly correlated with serum ESR (P < 0.001). In multivariate regression analysis including serum ESR and MetS as variables, carotid-femoral PWV was independently associated with higher ESR (P = 0.002) but not with MetS (P = 0.139). CONCLUSIONS: Arterial stiffness is significantly associated with MetS amongst ischaemic stroke patients, and inflammation appears to be involved in this relationship.

Extraction of microsporidial DNA from modified trichrome-stained clinical slides and subsequent species identification using PCR sequencing.

Molecular techniques involving polymerase chain reaction (PCR) and sequencing provide a relatively simple and objective means of identifying microsporidia to species level. We modified previously described methods of DNA extraction and PCR conditions for identification of microsporidia from museum slides, clinical specimens and environmental samples and successfully identified Vittaforma corneae in 11 out of 13 cases of microsporidial infection from used trichrome-stained slides of corneal scrapings from HIV-negative patients with keratoconjunctivitis.

Pyloric stenosis in a newborn baby with polycystic kidneys.

Patients with infantile hypertrophic pyloric stenosis (IHPS) have an increased incidence of renal anomalies. Association of IHPS and polycystic kidney disease (PKD) has been reported in three case histories. It is uncertain whether the association of PKD and IHPS is due to genetics, a pathophysiological link or a chance phenomenon. One hypothesis linking the two conditions is nitric oxide synthetase (NOS) deficiency. NOS deficiency leads to lack of locally available nitric oxide causing a failure of smooth muscle relaxation. It is therefore plausible that NOS deficiency plays a part in the pathogenesis of pyloric stenosis, hypertension and cyst development in autosomal-dominant PKD.

Association analysis of endothelial nitric oxide synthase gene polymorphism with primary hypertension in a Singapore population.

Vascular endothelial cells produce nitric oxide (NO), which contributes to the regulation of blood pressure and regional blood flow. Endothelial nitric oxide synthase (eNOS) gene polymorphisms are associated with coronary artery disease, but their linkage with primary hypertension is controversial. A total of 103 individuals with primary hypertension and 104 normotensive control subjects were studied in Singapore. The specific genotypes for G894T missense variant in exon 7, variable number tandem repeats (VNTR) in intron 4 (eNOS 4A/B/C) and T-786C in the promoter were isolated using allele-specific gene amplification and restriction fragment length polymorphism to examine the association of genotype and allelic frequency in both groups. Logistic regression analysis was also used to detect the association between genotypes and hypertension. Five genotypes of intron 4 VNTR (AA, AB, BB, AC and BC) were observed. Intron 4 B/B genotype was significantly associated with the hypertension group (P = 0.035), but disequilibrium of G894T and T-786C was absent between the two groups (P = 0.419 and P = 0.227), respectively. The overall distribution of allelic frequency differed significantly between the two groups, with four-repeat allele (4A) of intron 4 more frequent in the normotensive group than the hypertensive group (P = 0.019). Logistic regression analysis showed that intron 4 B/B genotype was significantly associated with systolic blood pressure of individuals with body mass index greater than 25 kg/m2 (P = 0.04). In conclusion, the eNOS 4 B/B genotype is a genetic susceptibility factor for primary hypertension in a Singapore population.

Lenticulostriate vasculopathy in twin-to-twin transfusion syndrome.

Intracranial pathology is a common and important complication in extremely low birth weight babies. Lenticulostriate vasculopathy (LSV) is an abnormal finding on cranial ultrasounds of sick babies and has been associated with congenital infection, chromosomal aberration and twin-to-twin transfusion. We describe a previously unreported situation of LSV being detected in both donor and recipient twin. This pair of monochorionic, diamniotic twins was admitted to the Neonatal Intensive Care Unit at 28 weeks of gestation. The mother underwent an emergency caesarean section because ultrasound and Doppler studies showed stage III twin-to-twin transfusion syndrome. The first twin weighed 998 g and second twin weighed 600 g. The first twin had an uneventful stay, whereas the second twin needed prolonged continuous positive airway pressure and indomethacin for patent ductus arteriosus. Both of them developed LSV. The clinical significance of this condition on the neuro-developmental outcome of a neonate has not yet been fully determined.

Emergence of community-associated methicillin-resistant Staphylococcus aureus in Singapore: a further six cases.

INTRODUCTION: The clinical features and molecular epidemiology of further cases of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection in Singapore are described. METHODS: Six cases of CA-MRSA infection that occurred between April and October 2004 are described. The bacterial isolates were tested for the presence of Panton-Valentine leukocidin (PVL) genes and typed via pulsedfield gel electrophoresis, staphylococcal chromosomal cassette mec (SCCmec) and multi-locus sequence typing. The results were compared with that of previously-reported local and international CA-MRSA isolates. RESULTS: There were four cases of cutaneous abscesses and one each of chronic osteomyelitis and endocarditis. CA-MRSA isolates from the last two cases tested negative for PVL genes. Three isolates were identical and related to the Oceanian clone, and one isolate to the predominant Taiwanese clone. The isolate causing osteomyelitis had a novel sequence type. CONCLUSION: CA-MRSA, though uncommon, is being isolated with increasing frequency in Singapore. A predominant clone (ST30- MRSA-IV) seems to be emerging locally.

Audio recordings of consultations with doctors for parents of critically sick babies.

BACKGROUND: Family centred care is an important part of neonatal intensive care. Ensuring effective communication in the neonatal intensive care unit (NICU) is a challenge but is crucial to the implementation of family centred care. Providing parents in NICU with audiotape recordings of their conversations with neonatologists could promote effective communication. OBJECTIVES: The objective of this review was to assess the usefulness of providing parents of sick babies with audiotape recordings of their consultations with neonatologists. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of electronic databases: Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 3, 2004), and MEDLINE (1966 - February 2004); and previous reviews including cross references and expert informants. There were no language restrictions applied to the electronic searches. Hand searching of conference and symposia proceedings was restricted to the English language. SELECTION CRITERIA: Randomised or quasi-randomised trials of any form of providing parents of babies in NICU with audiotape recordings of their conversation with doctors in the NICU. DATA COLLECTION AND ANALYSIS: Four reviewers independently assessed the eligibility of the trials. MAIN RESULTS: Our searches did not identify any trials which met the eligibility criteria. AUTHORS' CONCLUSIONS: There is no information available from randomised or quasi-randomised trials to demonstrate any benefits from providing parents in NICU with audiotape recordings of their conversations with neonatologists.

Intracoronary stenting in the treatment of acute or threatened closure in angiographically small coronary arteries (< 3.0 mm) complicating percutaneous transluminal coronary angioplasty.

The effect of the Flex-Stent on immediate and long-term angiographic and clinical results for acute and threatened closure was evaluated in 42 consecutive patients with coronary arterial segments < 3.0 mm in diameter after percutaneous transluminal coronary angioplasty (PTCA). Forty-two consecutive patients were treated with Flex-Stent (2.0 or 2.5 mm) for acute or threatened closure complicating PTCA. Ten patients (24%) had acute closure and 32 (76%) had threatened closure with a residual luminal stenosis of > 50%. Successful stent deployment was achieved in 40 patients (95%) with a primary clinical success rate of 90% (freedom from myocardial infarction, coronary artery surgery, and death). In-hospital complications occurred in 5 patients (some patients fell into more than one category): 3 (7.1%) had coronary bypass surgery, 1 (2.4%) had acute stent thrombosis, 1 (2.4%) had subacute stent thrombosis, 2 (4.8%) had myocardial infarction, and 1 (2.4%) had dextran allergy. There was no hospital death. Clinical follow-up was complete at a mean of 14.8 +/- 7.6 months, and recurrence of angina was noted in 20 of 38 eligible patients (53%). Angiographic restenosis was found in 19 of 29 patients (66%) (76.3% of eligible patients) on follow-up angiography (mean 5.9 +/- 4.6 months). Fourteen patients (74%) underwent successful repeat PTCA at the stented site, 4 of 38 patients (11%) had bypass surgery. Intracoronary stenting in the treatment of acute or threatened closure in arteries < 3.0 mm is effective in improving the acute clinical outcome and is a viable nonsurgical alternative for this subset of patients.

Molecular typing of multiresistant Streptococcus pneumoniae serogroup 19 in Singapore.

The prevalence of penicillin-resistant Streptococcus pneumoniae in clinical isolates from the Pathology Department of the Singapore General Hospital, in 1995, was 25%. Most of the resistant isolates belonged to serogroup 19 and were resistant to multiple antibiotics. Field-inversion gel electrophoresis (FIGE), after chromosomal digestion with the restriction enzymes Apal and Smal, was performed on all isolates of multiresistant serogroup 19 S. pneumoniae so as to determine whether they were of clonal origin. Twenty-six isolates, including six controls, were studied. Analysis of the FIGE patterns revealed three distinct clusters of closely related strains. The predominant clone comprised ten isolates of multiresistant serogroup 19 S. pneumoniae and also included two controls of a different serogroup. The presence of multiresistant serogroup 19 S. pneumoniae in Singapore, appears to be due to the spread of a small number of clones.

Postnatal changes in maternal and neonatal plasma antioxidant vitamins and the influence of smoking.

OBJECTIVE: To study the postnatal changes in the plasma concentrations of fat soluble antioxidant vitamins and malondialdehyde (MDA) in mothers and their newborns and their relation to smoking. DESIGN: Prospective cohort study. SETTING: Tertiary perinatal centre. SUBJECTS: Eighteen non-smoking and 14 smoking mothers and 33 infants. MAIN OUTCOME MEASURES: Plasma concentrations of vitamins E, A, and beta-carotene and MDA were measured in mothers and infants at delivery and on day 4 post partum. RESULTS: Neonatal plasma levels of vitamins E, A, and beta-carotene were significantly lower than maternal levels both at delivery and on day 4 in both groups. There was a significant postnatal increase in plasma vitamin E levels in smoking mothers and neonates of both groups. A significant postnatal increase in maternal, but not neonatal, plasma vitamin A was noted in both groups. Cord plasma vitamin E levels were significantly lower in infants of smoking mothers (mean 4.7 v 6.5 micromol/l, p = 0.041). Plasma MDA was paradoxically lower in smoking mothers at delivery (3.19 v 4.01 micromol/l, p = 0.03) and on day 4 (1.37 v 3.29 micromol/l, p = 0.005) and in infants of the smoking group on day 4 (2.18 v 3.12 micromol/l, p = 0.014). Also, there was a significant postnatal fall in plasma MDA levels on day 4 in mothers and infants in the smoking group. CONCLUSIONS: The postnatal changes in plasma vitamin E were more pronounced in the smoking group. The postnatal changes in plasma vitamins A and beta-carotene were similar in both groups. The rapid decline in plasma MDA in smoking mothers and their infants suggests withdrawal of oxidative stress from smoking around delivery. This coincided with the increase in plasma vitamin E.

Antenatal supplementation of antioxidant vitamins to reduce the oxidative stress at delivery--a pilot study.

BACKGROUND: Preterm infants are at increased risk of oxidative stress and free-radical mediated diseases partly related to deficient antioxidant state. The purpose of this study was to investigate if maternal supplementation of antioxidant vitamins prior to delivery would reduce the oxidative stress in the mothers and their infants. STUDY DESIGN: A pilot case-control study. PATIENTS AND METHODS: Five mothers at risk of preterm delivery between 30 and 36 weeks were given a daily oral dose of betacarotene 20 mg, vitamin E 167.8 mg and vitamin C 1000 mg until delivery. Plasma levels of MDA and vitamins A, E and beta-carotene were measured prior to treatment in mothers and at delivery in both mothers and neonates. Seven mother-infant pairs comparable in gestation and birthweight acted as controls. RESULTS: In the supplemented group, median maternal plasma MDA at delivery was significantly lower compared to the pretreatment level (1.9 vs. 3.2 micromol/l, p=0.04) and it was also lower than the control group (1.9 vs. 3.65 micromol/l, p<0.001). In the supplemented group, median maternal plasma vitamin E at delivery was significantly higher than the levels prior to treatment (46 vs. 31 micromol/l, p=0.007) in the same group and those at delivery in the control group (46 vs. 30 micromol/l, p=0.03). There was a trend of lower plasma MDA and higher vitamin E at birth in infants born to supplemented mothers, but it did not reach statistical significance. CONCLUSION: A short supplementation of multiple antioxidant vitamins to a small sample of preterm pregnant women reduced the oxidative stress at delivery in mothers and probably in their neonates. Larger studies probably using larger doses are needed to evaluate the efficacy of this strategy.