Introduction of an interdisciplinary heart team-based transcatheter aortic valve implantation programme: short and mid-term outcomes.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been developed to treat symptomatic aortic stenosis in patients deemed too high risk for open-heart surgery. To address this complex population, an interdisciplinary heart team approach was proposed. AIM: Present the short- and mid-term outcomes of the first 100 patients in the Royal Prince Alfred Hospital multidisciplinary TAVI programme. METHODS: Single-centre registry. Baseline and procedural data were prospectively recorded. Outcomes were recorded according to Valve Academic Research Consortium - version 2 guidelines. RESULTS: All patients underwent a comprehensive interdisciplinary pre-procedural evaluation. Sixty-eight transfemoral and 32 transapical implantations were performed. Mean age was 82 (±8.9) years old with an average logistic EuroSCORE of 33. Although 13 procedures had major complications, there was no intraprocedural mortality. During the first month, 9% of patients were re-admitted due to heart failure and 13% had a permanent pacemaker implanted. A 3% 30-day and 8% follow-up (mean 17 months) mortalities were recorded. While no significant differences in the rate of complications were found between the first and second half of the experience, all cases of mortality within 30 days (n = 3) occurred in the initial half. Sustained haemodynamic results were obtained with TAVI (immediate mean aortic valve gradient reduction from 47 to 9 mmHg; 1-year echocardiographic gradient 9.9 mmHg, with no moderate or severe aortic regurgitation). CONCLUSION: Excellent results can be achieved with TAVI in very high-risk patients at an Australian institution. A comprehensive evaluation based on a heart team can overcome most of the difficulties imposed by this challenging population.

Plasma total bilirubin levels predict amputation events in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS/HYPOTHESIS: Bilirubin has antioxidant and anti-inflammatory activities. Previous studies demonstrated that higher bilirubin levels were associated with reduced prevalence of peripheral arterial disease (PAD). However, the relationship between bilirubin and lower-limb amputation, a consequence of PAD, is currently unknown. We hypothesised that, in patients with type 2 diabetes, bilirubin concentrations may inversely associate with lower-limb amputation. METHODS: The relationship between baseline plasma total bilirubin levels and amputation events was analysed in 9,795 type 2 diabetic patients from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. The analysis plan was pre-specified. Lower-limb amputation was adjudicated blinded to treatment allocation. Relevant clinical and biochemical data were available for analyses. Amputation was a pre-specified tertiary endpoint. RESULTS: Bilirubin concentrations were significantly inversely associated with lower-limb amputation, with a greater than threefold risk gradient across levels. Individuals with lower bilirubin concentrations had a higher risk for first amputation (HR 1.38 per 5 µmol/l decrease in bilirubin concentration, 95% CI 1.07, 1.79, p = 0.013). The same association persisted after adjustment for baseline variables, including age, height, smoking status, γ-glutamyltransferase level, HbA1c, trial treatment allocation (placebo vs fenofibrate), as well as previous PAD, non-PAD cardiovascular disease, amputation or diabetic skin ulcer, neuropathy, nephropathy and diabetic retinopathy (HR 1.38 per 5 µmol/l decrease in bilirubin concentration, 95% CI 1.05, 1.81, p = 0.019). CONCLUSIONS/INTERPRETATION: Our results identify a significant inverse relationship between bilirubin levels and total lower-limb amputation, driven by major amputation. Our data raise the hypothesis that bilirubin may protect against amputation in type 2 diabetes.

Combining functional and linkage disequilibrium information in the selection of tag SNPs.

UNLABELLED: We have developed an online program, WCLUSTAG, for tag SNP selection that allows the user to specify variable tagging thresholds for different SNPs. Tag SNPs are selected such that a SNP with user-specified tagging threshold C will have a minimum R2 of C with at least one tag SNP. This flexible feature is useful for researchers who wish to prioritize genomic regions or SNPs in an association study. AVAILABILITY: The online WCLUSTAG program is available at http://bioinfo.hku.hk/wclustag/

Politics and the management of public health disasters: reflections on the SARS epidemic in greater China.

This paper examines the problems of coordination between and within six jurisdictional players, namely the Hong Kong SAR Government, the Guangdong Province, the Central Authority (PRC), the Taiwanese Government, the Taipei Government and the World Health Organization during the SARS episode from November 2002 until August 2003. We found that the diverging political interests and entrenched administrative practices accounted for the poor coordination between and within these players. The obsession with "political correctness" has severely hampered "rational" decision making among the jurisdictional players. The highly fragmented and compartmentalised intra-jurisdictional public health system means that marshalling resources from health and non-health sectors is difficult.

Levomepromazine versus chlorpromazine in treatment-resistant schizophrenia: a double-blind randomized trial.

OBJECTIVE: We compared the effect of levomepromazine (LMP) with chlorpromazine (CPZ) in treatment-resistant schizophrenia (TRS). METHODS: We carried out a double-blind, parallel group study (n = 19/arm) with balanced randomization in blocks of 4 and stratification by sex. Subjects entered a 30-week trial, of which phases I-III were open: phase I (wk 0-6) baseline; phase II (wk 7-9) stepwise transition to haloperidol (HAL), 30 mg/d, plus benztropine (BT), 4 mg/d; phase III (wk 10-15) HAL, 40-60 mg/d, plus BT, 4-6 mg/d; phase IV (wk 16-20) stepwise transition to LMP or CPZ (500 mg/d) following randomization; phase V (wk 21-28) stepwise increase of LMP or CPZ (600-1000 mg/d, dose reduction permitted) to establish optimum dose; and phase VI (wk 29-30) optimized dose maintained. Criteria for TRS were based on those established by Kane et al in 1988. The criterion for a response to treatment was a reduction of 25% or more in total Brief Psychiatric Rating Scale score. RESULTS: Both LMP (p = 0.007) and CPZ (p = 0.030) improved TRS relative to baseline. Although there was no significant difference between the 2 groups in treatment response at study end point, hierarchical linear modelling of longitudinal outcome revealed a significant (p = 0.006) advantage of LMP over CPZ for the BPRS total score. Ten of 19 participants on LMP and 8 of 19 on CPZ met the criterion for treatment response, and 9 of the 18 responders did so on 200-700 mg/d phenothiazine. The mean dose of responders was 710 (standard deviation [SD] 265) mg/d (LMP) and 722 (SD 272) mg/d (CPZ). Akathisia was associated with a nonresponse to phenothiazines (p = 0.010). BPRS scores increased significantly on HAL (p = 0.006). Two of 19 participants on LMP and 5 of 19 on CPZ withdrew early from the study. CONCLUSION: LMP and CPZ may be useful in the management of TRS. A modest advantage of LMP compared with CPZ was seen in longitudinal analysis. High doses of neuroleptics may contribute to TRS; reduction of neuroleptics to modest or moderate doses should be considered before categorizing a patient as treatment resistant.

Parotid-sparing radiotherapy: does it really reduce xerostomia?

AIMS: Parotid-sparing radiotherapy (PSRT) was introduced for patients with selected head and neck cancer requiring bilateral upper-neck irradiation at our centre in 2000. The aim of this study was to compare the subjective degree of xerostomia in patients treated with PSRT between January 2000 and June 2003 with patients treated using conventional techniques (radiotherapy) over the same period. MATERIALS AND METHODS: Eligible patients were required to have completed treatment 6 months previously and be recurrence-free at the time of interview. PSRT was defined as conformal radiotherapy, in which the mean dose to at least one parotid gland was 33 Gy or less, as determined by the dose-volume histogram. Patients receiving radiotherapy were treated with standard parallel-opposed fields, such that both parotids received a minimum of 40 Gy. Xerostomia was assessed using a validated questionnaire containing six questions with a rating between 0 and 10. Lower scores indicated less difficulty with xerostomia. RESULTS: Thirty-eight eligible patients treated with PSRT were identified: 25 with oropharyngeal cancer and 13 with nasopharyngeal cancer (NPC). The mean overall questionnaire score (Q1-5) for this group was 4.20 (standard error = 0.33). Forty-four patients (24 oropharyngeal, 21 NPC) treated with radiotherapy over the same period were eligible. The mean overall questionnaire score (Q1-5) for this group was 5.86 (standard error = 0.35). The difference in mean overall scores between the two groups of patients was statistically significant (P < 0.001), as were the scores for four of the six individual questions. CONCLUSION: These results suggest that PSRT offers improved long-term xerostomia-related quality of life compared with conventional radiotherapy.

Glucocorticoid treatment and cardiovascular disease.

The propensity of glucocorticoids to produce hyperglycaemia, hypertension, dyslipidaemia, and central obesity has long been a cause for concern among physicians regarding possible adverse cardiovascular events. Should heart failure be added to this list of concerns?

Sex-related differences in the regulation of macrophage cholesterol metabolism.

Men have an earlier onset and higher incidence of coronary heart disease than women, independent of environmental risk factor exposure. As a consequence, there has been considerable interest in the potential role of sex hormones in atherogenesis. An emerging body of evidence suggests that sex-specific tissue and cellular characteristics may mediate sex-specific responses to a variety of stimuli. Recent studies have shown that oestrogen, progesterone and androgens all regulate processes integral to human macrophage foam cell formation, a key event in atherogenesis, in a sex-specific manner; findings that may have important implications for understanding the sex gap in atherosclerosis. Physiological levels of 17beta-estradiol and progesterone are both associated with a female-specific reduction in cholesteryl ester accumulation in human macrophages. By contrast, androgens increase cholesteryl ester formation in male but not in female donor human macrophages. This review summarizes current data concerning the sex-specific effects of sex hormones on processes important to macrophage foam cell formation and the basic mechanisms responsible for the sex specificity of such effects. Future research in this promising field may eventually lead to the novel concept of 'sex-specific' treatments directed at inhibiting atherogenesis.

Regularization of RIF blind image deconvolution.

Blind image restoration is the process of estimating both the true image and the blur from the degraded image, using only partial information about degradation sources and the imaging system. Our main interest concerns optical image enhancement, where the degradation often involves a convolution process. We provide a method to incorporate truncated eigenvalue and total variation regularization into a nonlinear recursive inverse filter (RIF) blind deconvolution scheme first proposed by Kundar, and by Kundur and Hatzinakos. Tests are reported on simulated and optical imaging problems.

A novel source of wheat fiber and protein: effects on fecal bulk and serum lipids.

BACKGROUND: Wheat fiber is a laxative and wheat protein may affect blood lipids. OBJECTIVE: We therefore tested the effects on laxation and serum lipid metabolism of a novel source of wheat fiber and protein produced by the amylolytic digestion of starch from wheat. DESIGN: Twenty-four healthy men and women consumed 3 different test cereals in random order, each for 2 wk. The test supplement and the positive control, American Association of Cereal Chemists wheat bran supplement, both provided the same amount of fiber (21 g/d) and the negative control supplement provided 1.7 g fiber/d. RESULTS: The test supplement and the positive control supplement increased fecal bulk similarly (239.5+/-19 and 216.7+/-19 g/d, respectively) and significantly more than did the negative control supplement (165.6+/-16 g/d, P < 0.010). Compared with the negative and positive control supplements, the week 2 value of the test supplement for the ratio of total to HDL cholesterol was significantly reduced (P = 0.046). CONCLUSION: We conclude that the product of amylolytic digestion of starch from wheat flakes, which is high in wheat fiber and protein, has a fecal bulking effect similar to that of wheat bran and may have a beneficial effect on serum lipids.

Pacing experience with the atrial screw-in leads at the Singapore General Hospital.

This is a retrospective study of atrial screw-in leads implanted at the Singapore General Hospital from January 1988 to August 1990. There were 21 (13 female and 8 male) consecutive patients, with age ranging from 17 to 79 years (mean 55 years). Thirteen patients had sick sinus syndrome and the remaining eight patients had high grade AV block. Eleven patients had AAI, six had DDD and four had DDDR pacing modes respectively. Three different models of unipolar screw-in leads were used. Eight patients had Medtronic Model 6957, seven had Medtronic Model 4057 and six had Siemens-Pacesetter Model 1007 pacing leads implanted. At the time of implant, the measured P wave amplitudes ranged from 1 to 4.8 mV (2.5 +/- 1.1 mV) and the pacing thresholds ranged from 0.5 to 2.3 volts (1.21 +/- 0.51 volts). There were no acute complications at the time of implant. On follow-up ranging from one month to two years, two patients had inadequate sensing in the atrium and one patient had high pacing threshold. There were no lead dislodgement. In conclusion, these screw-in leads can be safely used in the atrium with acceptable pacing characteristics.

Simulation of tsunamis from great earthquakes on the cascadia subduction zone.

Large earthquakes occur episodically in the Cascadia subduction zone. A numerical model has been used to simulate and assess the hazards of a tsunami generated by a hypothetical earthquake of magnitude 8.5 associated with rupture of the northern sections of the subduction zone. Wave amplitudes on the outer coast are closely related to the magnitude of sea-bottom displacement (5.0 meters). Some amplification, up to a factor of 3, may occur in some coastal embayments. Wave amplitudes in the protected waters of Puget Sound and the Strait of Georgia are predicted to be only about one fifth of those estmated on the outer coast.

Permanent pacemaker trends in Singapore General Hospital in the eighties.

This is a ten year survey of all the pacemakers implanted in the Department of Cardiology, Singapore General Hospital, from January 1980 to July 1989. There were 331 (164 male and 167 female) patients with pulse generators and leads implanted. The ages of the subjects ranged from 8 to 91 years (mean 63 years). Two-thirds of the patients were greater than 60 years. The indications for pacemaker implants were high grade atrioventricular block in 199 (60%) patients, sick sinus syndrome in 112 (34%) patients and in the remaining 20 (6%) of patients, no data was available, 298 (90%) patients had VVI pacing (133 were non-programmable and 165 were programmable pacemakers), 8 (2%) had AAI, 16 (5%) had DDD and the remaining 9 (3%) had VVIR mode of pacing. 282 (85%) of the patients had new pacemakers implanted while the remaining 49 (15%) patients had pacemaker replacements. At the time of replacement of pacemakers, 23 patients had upgrade of their non-programmable to programmable VVI pacemakers and 4 to DDD and VVIR pacing modes respectively. Furthermore, 293 (88%) patients had endocardial leads as compared to 38 (12%) with epicardial leads. In conclusion, most of the patients who require pacemaker implants will continue to have single chamber system. However, to improve longevity of the pacemakers, one should consider using low pacing threshold leads and programmable pacemakers.

A micromethod for measuring swine fever antibody by neutralisation and immunofluorescence.

A micromethod employing the neutralisation and direct immunofluorescence technique for the detection of antibodies against swine fever in pig serum samples is described. The micromethod is simple and reproducible when compared with the macromethod. A total of 80 blood samples were randomly collected for comparison. The results are promising and reveal a 100 per cent correlation with the macrotechnique.