Cost-effectiveness of MRI targeted biopsy strategies for diagnosing prostate cancer in Singapore.

BACKGROUND: To evaluate the cost-effectiveness of six diagnostic strategies involving magnetic resonance imaging (MRI) targeted biopsy for diagnosing prostate cancer in initial and repeat biopsy settings from the Singapore healthcare system perspective. METHODS: A combined decision tree and Markov model was developed. The starting model population was men with mean age of 65 years referred for a first prostate biopsy due to clinical suspicion of prostate cancer. The six diagnostic strategies were selected for their relevance to local clinical practice. They comprised MRI targeted biopsy following a positive pre-biopsy multiparametric MRI (mpMRI) [Prostate Imaging - Reporting and Data System (PI-RADS) score ≥ 3], systematic biopsy, or saturation biopsy employed in different testing combinations and sequences. Deterministic base case analyses with sensitivity analyses were performed using costs from the healthcare system perspective and quality-adjusted life years (QALY) gained as the outcome measure to yield incremental cost-effectiveness ratios (ICERs). RESULTS: Deterministic base case analyses showed that Strategy 1 (MRI targeted biopsy alone), Strategy 2 (MRI targeted biopsy ➔ systematic biopsy), and Strategy 4 (MRI targeted biopsy ➔ systematic biopsy ➔ saturation biopsy) were cost-effective options at a willingness-to-pay (WTP) threshold of US$20,000, with ICERs ranging from US$18,975 to US$19,458. Strategies involving MRI targeted biopsy in the repeat biopsy setting were dominated. Sensitivity analyses found the ICERs were affected mostly by changes to the annual discounting rate and prevalence of prostate cancer in men referred for first biopsy, ranging between US$15,755 to US$23,022. Probabilistic sensitivity analyses confirmed Strategy 1 to be the least costly, and Strategies 2 and 4 being the preferred strategies when WTP thresholds were US$20,000 and US$30,000, respectively. LIMITATIONS AND CONCLUSIONS: This study found MRI targeted biopsy to be cost-effective in diagnosing prostate cancer in the biopsy-naïve setting in Singapore.

De novo aortopathy and cardiovascular outcomes in paediatric liver transplant recipients.

With the increase in long-term survival of post-transplant children, there is a paradigm shift in the emphasis of post-transplant care. We describe de novo cardiovascular abnormalities, which occurred in otherwise asymptomatic paediatric liver transplant recipients, who received liver allografts between 1991 and 2014 at the National University Hospital, Singapore, detected during routine post-transplant monitoring. A total of 96 paediatric liver transplants were performed in 90 children. After transplant, 7/90 (7.8%) recipients were identified with new-onset aortopathy. Glycogen storage disease type I (42.9% versus 2.4%; p<0.001) and recipient Epstein-Barr virus seropositivity (85.7 versus 31.0%, p=0.004) were significant risk factors for aortopathy on univariate analysis. On multivariate analysis, only glycogen storage disease type I remained as the significant risk factor (odds ratio 51.3 [95% confidence intervals: 1.1-2498.1, p=0.047]). Liver transplant is a double-edged sword that reverses certain cardiopulmonary complications of end-stage liver disease but may induce de novo structural cardiac injury in the form of aortic dilation.

Radiation Dose and Image Quality in Pediatric Cardiac Computed Tomography: A Comparison Between Sequential and Third-Generation Dual-Source High-Pitch Spiral Techniques.

The aim of this study was to investigate whether there is a reduction in radiation dose and improvement in image quality of pediatric cardiac computed tomography scans performed using the high-pitch spiral technique on a new third-generation dual-source 2 × 192-slice scanner (group B) compared with scans performed using the sequential technique on a single-source 256-slice scanner (group A). We performed a retrospective observational study on 40 patients aged ≤18 years who underwent prospectively electrocardiogram-triggered cardiac computed tomography. Image quality was assessed by pre-defined objective indices and a four-point subjective score. Apart from a higher mean heart rate in group A (P = 0.016), there were otherwise no significant inter-group differences in patient characteristics. The median effective dose was 4.41 mSv (interquartile range 2.58-5.90 mSv) in group A and 0.52 mSv (interquartile range 0.39-0.59 mSv) in group B (P < 0.001), representing a 88 % reduction. Subjective image quality score was significantly better in group B (4 = excellent with no artifact, mode 57.1 %) than in group A (3 = good with mild artifact, mode 57.9 %) (P < 0.001). Noise index, signal-to-noise ratio and contrast-to-noise ratio between both groups were not statistically significant. New third-generation dual-source high-pitch spiral scan technique can deliver excellent image quality with low radiation dose. Our results suggest that it should be considered as a first-choice technique for performing cardiac computed tomography in the pediatric population.

Bioinspired bi-phasic 3D nanoflowers of MgO/Mg(OH)2 coated melamine sponge as a novel bactericidal agent.

By roughly mimicking the surface architectural design of dragonfly wings, novel bi-phasic 3D nanoflowers of MgO/Mg(OH)2 were successfully synthesized via the electrospinning technique. The 3D nanoflowers were coated over a commercial melamine sponge and extensively characterized by SEM, XRD, FTIR, and EDS. The formation of distinct dense 3D nano petals was revealed by SEM images whereby the mean petal thickness and mean distance between the adjacent petals were found to be 36 nm and 121 nm, respectively. The bactericidal activities of synthesized 3D nano-flowers coated melamine sponges were assessed against five different bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa). This study demonstrated significant bactericidal activity of MgO/Mg(OH)2 3D nanoflowers coated MS against Gram-positive and Gram-negative bacteria. Plausible bactericidal mechanisms include envelope deformation, penetration, and induction of oxidative stress. This study introduces novel bioinspired biomaterial with the capacity to reduce the risk associated with pathogenic bacterial infections, especially in medical devices.

Isolated left-ventricular apical hypoplasia presenting as a left-ventricular mass on echocardiography.

Left-ventricular apical hypoplasia is a rare entity. Although it has typical imaging features on cardiovascular magnetic resonance, recognizing this condition on echocardiography can be challenging. This report describes an asymptomatic pediatric patient who initially presented with a left-ventricular mass on echocardiography.

EpCAM nuclear localization identifies aggressive thyroid cancer and is a marker for poor prognosis.

BACKGROUND: Proteolytic cleavage of the extracellular domain (EpEx) of Epithelial cell adhesion molecule (EpCAM) and nuclear signaling by its intracellular oncogenic domain Ep-ICD has recently been implicated in increased proliferation of cancer cells. The clinical significance of Ep-ICD in human tumors remains an enigma. METHODS: EpEx, Ep-ICD and beta-catenin immunohistochemistry using specific antibodies was conducted on 58 archived thyroid cancer (TC) tissue blocks from 34 patients and correlated with survival analysis of these patients for up to 17 years. RESULTS: The anaplastic (ATC) and aggressive thyroid cancers showed loss of EpEx and increased nuclear and cytoplasmic accumulation of Ep-ICD. In contrast, the low grade papillary thyroid cancers (PTC) showed membranous EpEx and no detectable nuclear Ep-ICD. The ATC also showed concomitant nuclear expression of Ep-ICD and beta-catenin. Kaplan-Meier Survival analysis revealed reduced overall survival (OS) for TC patients showing nuclear Ep-ICD expression or loss of membranous EpEx (p < 0.0004), median OS = 5 months as compared to 198 months for patients who did not show nuclear Ep-ICD or demonstrated only membranous EpE. CONCLUSION: We report reciprocal loss of membrane EpEx but increased nuclear and cytoplasmic accumulation of Ep-ICD in aggressive TC; nuclear Ep-ICD correlated with poor OS of TC patients. Thus nuclear Ep-ICD localization may serve as a useful biomarker for aggressive TC and may represent a novel diagnostic, prognostic and therapeutic target for aggressive TC.

Pneumococcal Pneumonia Resembling Acute Myocardial Infarction in an Adolescent Male.

Myocarditis is commonly associated with viruses. However, we present a novel case of a teenager with pneumococcal pneumonia and bacteremia complicated by myocarditis and rhabdomyolysis, presenting with features of acute ST-elevation myocardial infarction and cardiogenic shock. Physicians should be aware that Streptococcus pneumoniae infection, like Group A Streptococcus, can mimic acute myocardial infarction in young males without cardiovascular risk factors.

Building a Longitudinal National Integrated Cardiovascular Database　- Lessons Learnt From SingCLOUD.

Background: Real world data on clinical outcomes and quality of care for patients with coronary artery disease (CAD) are fragmented. We describe the rationale and design of the Singapore Cardiovascular Longitudinal Outcomes Database (SingCLOUD). Methods and Results: We designed a health data grid to integrate clinical, administrative, laboratory, procedural, prescription and financial data from all public-funded hospitals and primary care clinics, which provide 80% of health care in Singapore. Here, we explain our approach to harmonize real-world data from diverse electronic medical and non-medical platforms to develop a robust and longitudinal dataset. We present pilot data on patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) between 2012 and 2014. The initial data set had 53,395 patients. Of these, 35,203 had CAD confirmed on coronary angiography, of whom 21,521 had PCI. Eventually, limiting to 2012-2014, 3,819 patients had MI with PCI, while 5,989 had MI. Compared with the quality improvement registry, Singapore Cardiac Data Bank, which had 189 fields for analysis, the SingCLOUD platform generated an additional 313 additional data fields, and was able to identify an additional 250 heart failure events, 664 major adverse cardiovascular events at 2 years, and low-density lipoprotein levels to 1 year for 3,747 patients. Conclusions: By integrating multiple incongruent data sources, SINGCLOUD enables in-depth analysis of real-world cardiovascular "big data".

Evidence of Microvascular Changes in the Retina following Kawasaki Disease.

It is unclear whether all children with Kawasaki disease (KD) have increased later cardiovascular risk. The retinal microvasculature reflects changes in the microcirculation and is associated with traditional cardiovascular risk factors and events. The aim of this study was to investigate retinal microvascular parameters in two populations of patients with previous KD and control participants. We performed case-control studies of 116 (57 patients and 59 control participants) Australian and 156 (78 patients and 78 control participants) Singaporean individuals, at least two years since their acute illness. Standardised retinal photographs were graded by trained technicians using a semi-automated software, which quantifies the retinal microvasculature (calibre, branching angle, fractal dimensions, and tortuosity). Retinal venules of Singaporean KD patients were 9.67 µm (95% CI 4.87 to 14.51, p < 0.001) larger than control participants following correction for traditional cardiovascular risk factors. An incremental increase in the size of retinal venules in those with coronary artery abnormalities was observed. There was limited evidence that retinal venules were larger in Australian KD patients with coronary artery abnormalities compared to control participants (7.34 µm, 95% CI 1.30 to 15.99, p = 0.10). Differences in retinal microvasculature were particularly evident in Singaporean KD patients. Larger retinal venules may reflect chronic inflammation and endothelial dysfunction, and are associated with coronary artery disease in adults.

Application of post-surgical stimulated thyroglobulin for radioiodine remnant ablation selection in low-risk papillary thyroid carcinoma.

BACKGROUND: We present our ongoing experience in the use of postsurgical stimulated serum thyroglobulin (Stim-Tg) to assist in radioiodine remnant ablation (RRA) decision-making. METHODS: Patients with low-risk well-differentiated thyroid carcinoma (WDTC) with undetectable anti-Tg antibodies were prospectively followed after total thyroidectomy and therapeutic central compartment neck dissection, when indicated.Stim-Tg was performed 3 months postoperatively and used to base RRA selection. RESULTS: Of 104 patients, 59 patients (56.7%) had an undetectable Stim-Tg after thyroidectomy, 35 (33.7%) had Stim-Tg values of 1-5 microg/L, and 10 (9.6%) had Stim-Tg values >5 microg/L. RRA was administered to 1 patient (1.7%) with undetectable Stim-Tg, 6 patients (17.1%) with Stim-Tg1-5 microg/L, and 9 patients (90%) with Stim-Tg >5 microg/L, for a total of 16 patients (15.4%) receiving RRA. When compared to current RRA selection guidelines, the proposed protocol achieved a significantly lower RRA administration rate. CONCLUSION: Stim-Tg measurement performed several months after total thyroidectomy is a useful objective parameter in assisting RRA decision-making for patients with low-risk WDTC. (