Cost-Effectiveness of Transcatheter Aortic Valve Implantation in Intermediate and Low Risk Severe Aortic Stenosis Patients in Singapore.

INTRODUCTION: Singapore has the world's second most efficient healthcare system while costing less than 5% GDP. It remains unclear whether transcatheter aortic valve implantation (TAVI) is cost-effective for treating intermediate-low risk severe aortic stenosis (AS) patients in a highly efficient healthcare system. MATERIALS AND METHODS: A two-phase economic model combining decision tree and Markov model was developed to assess the costs, effectiveness, and the incremental cost-effectiveness ratio (ICER) of transfemoral (TF) TAVI versus surgical aortic valve replacement (SAVR) in intermediate-low risk patients over an 8-year time horizon. Mortality and complications rates were based on PARTNER 2 trial cohort A and Singapore life table. Costs were mainly retrieved from Singapore National University Health System database. Health utility data were obtained from Singapore population based on the EuroQol-5D (EQ-5D). A variety of sensitivity analyses were conducted. RESULTS: In base case scenario, the incremental effectiveness of TF-TAVI versus SAVR was 0.19 QALYs. The ICER of TF-TAVI was S$33,833/QALY. When time horizon was reduced to 5 years, the ICER was S$60,825/QALY; when event rates from the propensity analysis was used, the ICER was S$21,732/QALY and S$44,598/QALY over 8-year and 5-year time horizons, respectively. At a willingness to pay threshold of S$73,167/QALY, TF-TAVI had a 98.19% probability of being cost-effective after 100,000 simulations. The model was the most sensitive to the costs of TF-TAVI procedure. CONCLUSION: TF-TAVI is a highly cost-effective option compared to SAVR for intermediate-low risk severe AS patients from a Singapore healthcare system perspective. Increased procedure experience, reduction in device cost, and technology advance may have further increased the cost-effectiveness of TF-TAVI per scenario analysis.

Cephalopod-inspired robot capable of cyclic jet propulsion through shape change.

The compliance and conformability of soft robots provide inherent advantages when working around delicate objects or in unstructured environments. However, rapid locomotion in soft robotics is challenging due to the slow propagation of motion in compliant structures, particularly underwater. Cephalopods overcome this challenge using jet propulsion and the added mass effect to achieve rapid, efficient propulsion underwater without a skeleton. Taking inspiration from cephalopods, here we present an underwater robot with a compliant body that can achieve repeatable jet propulsion by changing its internal volume and cross-sectional area to take advantage of jet propulsion as well as the added mass effect. The robot achieves a maximum average thrust of 0.19 N and maximum average and peak swimming speeds of 18.4 cm/s (0.54 body lengths/s) and 32.1 cm/s (0.94 BL/s), respectively. We also demonstrate the use of an onboard camera as a sensor for ocean discovery and environmental monitoring applications.

Comparison of postoperative cognitive decline in patients undergoing conventional vs miniaturized cardiopulmonary bypass: A randomized, controlled trial.

Background: Neurocognitive dysfunction is a common complication of coronary artery bypass grafting (CABG) with incidence of 19-38%. The miniaturized cardiopulmonary bypass (MCPB) system was developed to reduce hemodilution and inflammation and provides better cerebral protection than conventional cardiopulmonary bypass (CCPB). In a meta-analysis, MCPB was associated with a 10-fold reduction in the incidence of strokes. However, its effect on postoperative cognitive decline (POCD) is unknown. We assessed if MCPB decreases POCD after CABG and compared the risk factors. Methods: A total of 71 Asian patients presenting for elective CABG at a tertiary center were enrolled. They were randomly assigned to MCPB (n = 36) or CCPB group (n = 35) and followed up in a single-blinded, prospective, randomized controlled trial. The primary outcome was POCD as measured by the repeatable battery of neuropsychological status (RBANS). Inflammatory markers (tumor necrosis factor-alpha and interleukin-6), hematocrit levels, and neutron-specific enolase (NSE) levels were studied. Results: Overall, the incidence of POCD at 3 months was 50%, and this was not significantly different between both groups (51.4 vs 50.0%, P = 0.90). Having <6 years of formal education [risk ratio (RR) = 3.014, 95% confidence interval (CI) = 1.054-8.618, P = 0.040] was significantly associated with POCD in the CCPB group, while the lowest hematocrit during cardiopulmonary bypass was independently associated with POCD in the MCPB group (RR = 0.931, 95% CI = 0.868-0.998, P = 0.044). The postoperative inflammatory markers and NSE levels were similar between the two groups. Conclusions: This study shows that the MCPB was not superior to CCPB with cell salvage and biocompatible tubing with regard to the neurocognitive outcomes measured by the RBANS.

Coronary artery bypass grafting in patients with low ejection fraction: what are the risk factors?

BACKGROUND: Left ventricular (LV) dysfunction alone is insufficient as an independent predictor of postoperative complications and mortality in coronary artery bypass graft (CABG) surgery. Our objective was to identify additional independent risk factors in patients with low left ventricle ejection fraction (EF) who underwent CABG. METHODS: We retrospectively analyzed CABG results of 346 consecutive patients with low EF (≤30%) in a single institution between 2009 and 2015. The primary study endpoint was 30-day all-cause mortality. The secondary endpoints were the development of major adverse cardiac events (MACE) and renal complications after operation. A subgroup of patients underwent additional analyses of the interaction between extents of viable myocardium and postoperative endpoints. RESULTS: The analysis showed that preoperative hemodynamic instability (AOR=4.57; 95% CI: 1.53-13.7, P=0.007) and serum creatinine >166 µmol/L (AOR=3.46; 95% CI: 1.12-10.7, P=0.031) were independent predictors of 30-day death. Both urgent and emergency operations were predictors for MACE (P=0.038; P=0.005) and renal complications (P=0.004; P=0.007). Pre-existing diabetes mellitus increased the likelihood of renal complications (P=0.020). In the sub-analysis of patients with viable myocardium, the mortality was significantly lower with predicted mortality (P=0.014). CONCLUSIONS: Patients with significant LV dysfunction undergoing isolated CABG have fair short-term survival even with EF less than 30%. Hemodynamic instability prior to operation and preoperative kidney dysfunction are strong predictors of mortality in patients with low EF. Favorable coronary targets, meticulous operative techniques, and optimal surgical timing before hemodynamic deterioration occurs are essential to minimize the risk of revascularization complications and early postoperative mortality.

Time needed to resolve patient complaints and factors influencing it: a cohort study.

OBJECTIVE: There has been an increase in the number and complexity of patient complaints against healthcare institutions. An understanding of the resources needed in this area is important for proper planning. DESIGN: Cohort study. SETTING: A 1250-bed tertiary-care teaching hospital. PARTICIPANTS: All patient complaints received between 1 February 2014 and 31 January 2015 were prospectively included in this cohort study. MAIN OUTCOME MEASURES: The amount of time spent on the investigation and liaising with the complainant for each case was recorded. The complainant's personal details and characteristics were recorded anonymously. RESULTS: In total, 908 patient complaints were recorded from 801 individuals during the study period. Longer median person-hours were spent on managing complaints that were brought forward by men (1.48 h), those who were distant relatives of the patients (2.08 h), foreigners (1.58 h) and non-subsidised patients (1.83 h). Patient complaints falling into the categories of clinical domain (3.00 h) and patient rights (2.54 h), quality (3.00 h) and safety (2.83 h) required the longest median time to manage. Multiple logistic regression analysis revealed that the total amount of time spent on the complaints was predicted by the gender of the complainant, the relationship of the complainant with the patient, the subsidy status of the patient, the severity and the domain of the complaint. CONCLUSIONS: This study reported the time required to manage patient complaints in a larger tertiary-care academic medical centre. Predictors of the time spent on resolving patient complaints can be used as parameters for resource planning.

Resolution of ascending aortic dissection in a Stanford type A patient.

We observed an unusual natural course of a Stanford type A aortic dissection. The patient presented to the emergency department with an acute aortic dissection involving an ascending aorta and left-sided hemiparesis. The patient declined surgery and was managed conservatively. A follow-up scan after 1 month revealed that the patient had a complete spontaneous resolution of the dissection in the ascending aorta. Such a development is very rare and unexpected in patients with Stanford type A aortic dissection.

Endovascular management of traumatic thoracic aortic transection.

The conventional treatment of traumatic thoracic aortic transection is open surgical repair but it is associated with high rates of morbidity and mortality, particularly in patients with multiple injuries. We reviewed our experience of endovascular repair of traumatic thoracic aortic transection. Between March 2002 and December 2007, 7 patients (male 6, female 1; mean age 40 years) with multiple injuries secondary to blunt trauma underwent endovascular stenting. One patient required adjunctive surgery to facilitate endovascular stenting. Mean intensive care unit stay was 8.6 days (range, 3-16 days). Arterial access in all patients was obtained by femoral cut-down. The mean operating time was 122 min. Technical success was achieved in all cases. There was no mortality. One patient suffered a right parietal stroke, but none developed procedure-related paralysis. The mean follow-up period was 18.6 months (range, 6-48 months). There was no evidence of endoleak, stent migration, or late pseudoaneurysm formation on follow-up computed tomography. Endovascular stents can be used to treat traumatic thoracic aortic transection, with low rates of morbidity and mortality. Although early and midterm results are promising, the long-term durability of endovascular stenting for traumatic thoracic aortic transection remains unknown.

Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC).

BACKGROUND: Progression of non-small cell lung cancer (NSCLC) from early- to late-stage may signify the accumulation of gene mutations. An advanced-stage tumor's mutation profile may also have prognostic value, guiding treatment decisions. Mutation detection of multiple genes is limited by the low amount of deoxyribonucleic acid extracted from low-volume diagnostic lung biopsies. We explored whole genome amplification (WGA) to enable multiple molecular analyses. METHODS: Eighty-eight advanced-stage NSCLC patients were enrolled. Their low-volume lung biopsies underwent WGA before direct sequencing for epidermal growth factor receptor (EGFR), KRAS (rat sarcoma virus), p53, and CMET (mesenchymal-epithelial transition factor) mutations. Overall survival impact was examined. Surgically-resected tumors from 133 early-stage NSCLC patients were sequenced for EGFR, KRAS and p53 mutations. We compared the mutation frequencies of both groups. RESULTS: It is feasible for low-volume lung biopsies to undergo WGA for mutational analysis. KRAS and CMET mutations have a deleterious effect on overall survival, hazard ratios 5.05 (p = 0.009) and 23.65 (p = 0.005), respectively. EGFR and p53 mutations, however, do not have a survival impact. There also does not seem to be significant differences in the frequency of mutations in EGFR, KRAS, and p53 between early- and advanced-stage disease: 20% versus 24% (p = 0.48), 29% versus 27% (p = 0.75), 10% versus 6% (p = 0.27), respectively. CONCLUSIONS: In advanced-stage NSCLC, KRAS, and CMET mutations suggest poor prognosis, whereas EGFR and p53 mutations do not seem to have survival impact. Mutations in EGFR, KRAS and p53 are unlikely to be responsible for the progression of NSCLC from early- to late-stage disease. WGA may be used to expand starting deoxyribonucleic acid from low-volume lung biopsies for further analysis of advanced-stage NSCLC.

Contractile and vasorelaxant effects of hydrogen sulfide and its biosynthesis in the human internal mammary artery.

This study aimed to test these hypotheses: cystathionine gamma-lyase (CSE) is expressed in a human artery, it generates hydrogen sulfide (H(2)S), and H(2)S relaxes a human artery. H(2)S is produced endogenously in rat arteries from cysteine by CSE. Endogenously produced H(2)S dilates rat resistance arteries. Although CSE is expressed in rat arteries, its presence in human blood vessels has not been described. In this study, we showed that both CSE mRNA, determined by reverse transcription-polymerase chain reaction, and CSE protein, determined by Western blotting, apparently occur in the human internal mammary artery (internal thoracic artery). Artery homogenates converted cysteine to H(2)S, and the H(2)S production was inhibited by dl-propargylglycine, an inhibitor of CSE. We also showed that H(2)S relaxes phenylephrine-precontracted human internal mammary artery at higher concentrations but produces contraction at low concentrations. The latter contractions are stronger in acetylcholine-prerelaxed arteries, suggesting inhibition of nitric oxide action. The relaxation is partially blocked by glibenclamide, an inhibitor of K(ATP) channels. The present results indicate that CSE protein is expressed in human arteries, that human arteries synthesize H(2)S, and that higher concentrations of H(2)S relax human arteries, in part by opening K(ATP) channels. Low concentrations of H(2)S contract the human internal mammary artery, possibly by reacting with nitric oxide to form an inactive nitrosothiol. The possibility that CSE, and the H(2)S it generates, together play a physiological role in regulating the diameter of arteries in humans, as has been demonstrated in rats, should be considered.

Stent-graft for recurrent melioidosis mycotic aortic aneurysm.

Melioidosis is a tropical disease caused by Burkholderia pseudomallei and is prevalent in South East Asia and Northern Australia. It can infect any organ system and is potentially deadly. Melioidosis causing a mycotic aneurysm of the aorta is rare. We present a patient with a melioidosis mycotic aneurysm of the descending aorta presenting with fever and right pleural effusion, managed successfully with initial Dacron graft repair with staged omental reinforcement, and subsequent endovascular stent grafting of a late anastomotic leak.

Transcontinental transport of a patient with an AbioMed BVS 5000 BVAD.

In patients with severe cardiogenic shock requiring implantation of a short-term assist device transportation to a specialized heart center for further therapy may be necessary. We report the first successful transcontinental air transport (from Singapore to Berlin, Germany) of a patient with fulminating myocarditis requiring implantation of a biventricular assist device.