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.

Comparing the use of cobalt chromium stents to stainless steel stents in primary percutaneous coronary intervention for acute myocardial infarction: a prospective registry.

OBJECTIVES: To determine clinical outcome and rates of target vessel revascularization (TVR) in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI who were treated with cobalt-chromium stents compared to stainless steel bare metal stents (BMS). BACKGROUND: The newer generation cobalt chromium stents were reported to achieve lower rates of TVR compared with conventional BMS. METHODS: Consecutive STEMI cases admitted within 12 h of symptom onset and undergoing primary angioplasty and bare metal stent implantation 1 January 2002 and 31 December 2008 were identified. Primary outcomes were rates of clinically-driven TVR at six months as well as occurrence of major adverse cardiovascular events (MACE) either of all-cause death, repeat myocardial infarction or TVR at six months. RESULTS: 1030 cases with 1175 lesions (84% males) and median age of 58 years underwent primary PCI for STEMI in our registry. Overall procedural success rate was 98%. Stainless steel stents were inserted in 65% of the culprit lesions (stainless steel, n = 766 versus cobalt chromium, n = 264). Primary outcomes of TVR (3.5% in the stainless steel group and 3.4% in the cobalt chromium group, P = 0.93) and MACE (8.4% in the stainless steel group and 5.3% in the cobalt chromium group, P = 0.11) after six months were no different between the two groups. However, there were more deaths at 30 days in the stainless steel group compared to the cobalt chromium group (3.5% versus 0.4%, HR 4.04 (1.03-3.88), P = 0.04). CONCLUSION: Both cobalt-chromium and stainless steel coronary stents were associated with similar and low risk of clinically-driven TVR.

Primary cutaneous cryptococcosis due to Cryptococcus gattii in Singapore.

Cryptococcosis is an invasive fungal infection that occurs worldwide. Infections caused by Cryptococcus (C.) neoformans are commonly associated with immunocompromised patients, while those caused by C. gattii predominantly affect immunocompetent hosts. However, the latter has also been increasingly reported in immunocompromised patients such as those with HIV. Cutaneous involvement by C. gattii in immunocompetent patients is a rare manifestation, with only a few cases reported worldwide. C. gattii infection has rarely been reported in Singapore, with all three reported cases presenting as meningitis in immunocompetent individuals. Its natural habitat is the Eucalyptus tree, which is common in Singapore. We report the case of a 37-year-old migrant worker who had primary cutaneous infection due to C. gattii after sustaining traumatic inoculation.

Isolation of the first three cases of Clostridium difficile polymerase chain reaction ribotype 027 in Singapore.

INTRODUCTION: The incidence of Clostridium (C.) difficile infection (CDI) was on the rise from 2001 to 2006 in Singapore. Recent unpublished data suggests that its incidence had remained stable or decreased in most local public hospitals between 2006 and 2010. It is, however, not known if the polymerase chain reaction (PCR) ribotype 027 strains have been circulating, although reports suggest that this strain is emerging in Asia, with the first cases reported from Japan in 2007, as well as in Hong Kong and Australia in 2009. We initiated a culture-based surveillance to detect this epidemic strain in Singapore. METHODS: From September 2008 to December 2009, all non-duplicate toxin-positive stool samples from the three largest public hospitals in Singapore were collected for culture and further analysis. RESULTS: Out of the 366 samples collected, 272 viable isolates were cultured. Of these, 240 tested toxin-positive and ten tested positive for the binary toxin gene; 35 different PCR ribotypes were found. Three isolates that tested positive for binary toxin contained the same PCR ribotyping pattern as the C. difficile 027 control strain. All three had the 18-bp deletion and single nucleotide tcdC deletion at position 117. Susceptibility testing was performed, demonstrating susceptibility to erythromycin and moxifloxacin. CONCLUSION: We report the first three isolates of C. difficile 027 from Singapore. However, their susceptibility patterns are more consistent with the historical 027 strains. Rising CDI incidence may not be associated with the emergence of the epidemic 027 strain at this time.

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.

Percutaneous transcatheter aortic valve replacement: first transapical implant in Asia.

Percutaneous transcatheter implantation of the aortic valve has been demonstrated as an alternative to open heart surgery in high-risk patients with symptomatic severe aortic stenosis (AS) who are not suitable for open surgery. The majority of these new devices are delivered via the transfemoral approach. However, due to the current size of delivery sheaths, the small and tortuous iliofemoral anatomy makes this approach challenging. The transapical approach provides a viable option for this patient subgroup. The first-in-Asia transcatheter aortic valve implantation via the transapical route is described. A 79-year-old Chinese woman with symptomatic severe AS and peripheral arterial disease, who was at high surgical risk, was successfully treated, and had good functional and haemodynamic results at the three-month follow-up.

Percutaneous transcatheter aortic valve replacement: first transfemoral implant in Asia.

Surgical aortic valve replacement (AVR) is the standard of care for patients with symptomatic severe aortic stenosis (AS), providing relief of symptoms and prolonging survival. However, many patients are either denied or not offered surgery due to high surgical risk or non-operability for open AVR. The technology of percutaneous aortic valve implantation emerged in 2002, and has since evolved rapidly with satisfactory results. Currently, almost all the procedures are performed predominantly in Europe and North America. The first-in-Asia percutaneous transcatheter aortic valve implantation via the transfemoral route is described. A 77-year-old man with symptomatic severe AS and at high surgical risk was successfully treated, with sustained clinical improvement and satisfactory haemodynamic results at 30-day follow-up.

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.

Streptococcal cellulitis following preparation of fresh raw seafood.

We describe three zoonotic streptococcal soft tissue infections resulting from fresh seafood contact. One was a localized thumb infection with Streptococcus iniae in an immunocompetent healthy young male resulting from a puncture wound from a crab pincer. The other two were cases of ascending upper limb cellulitis associated with bacteraemia in mastectomy patients. One of these infections was caused by S. iniae while the other was caused by Streptococcus dysgalactiae subsp. dysgalactiae, a species that has not been previously described as a cause of zoonotic infection. Hence when cleaning raw seafood, protective equipment should be used to minimize the risk of percutaneous injuries.

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.

Edwards syndrome with double trisomy.

Double trisomy is rare and the only case reported in the literature died soon after birth. We present another case of double trisomy (48XYY, +18) in a male neonate, who was born to a 28-year-old gravida three parity one mother at 35 weeks of gestation. The baby had features of trisomy 18. Karyotype of the patient showed 48, XYY, +18, Ish (DYZ3*2), (D18Z1*3), nuc ish (DYZ3*2), (D18Z1*3) . The patient had clinical features of trisomy 18. There was no family history of diabetes mellitus and no exposure to chemicals. It has been suggested that the rarity of Y-chromosome involvement in trisomy 18 may be due to discrepancy between the sexes.

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.