Prevention and Management of Cardiac Implantable Electronic Device Infections: State-of-the-Art and Future Directions.

Cardiac implantable electronic device (CIED) infection is an increasingly common complication of device therapy. CIED infection confers significant patient morbidity and health care expenditure, hence it is essential that clinicians recognise the contemporary strategies for predicting, reducing and treating these events. Recent technological advances-in particular, the development of antimicrobial envelopes, leadless devices and validated risk scores-present decision-makers with novel strategies for managing this expanding patient population. This review summarises the key issues facing CIED patients and their physicians, and explores the supporting evidence for the latest therapeutic developments in this field.

Initial experience with the convergent procedure for longstanding persistent atrial fibrillation: A 5 year dataset.

In patients with longstanding persistent atrial fibrillation (AF), outcomes from catheter ablation remain suboptimal. The convergent procedure combines minimally invasive surgical ablation with subsequent catheter ablation, and may contribute towards maintenance of sinus rhythm in this patient group. We performed the convergent procedure on 43 patients with longstanding persistent AF from 2013-2018. Patients underwent clinical review at 3, 6, and 12 months and thereafter as necessitated by their symptoms. Our dataset describes patients' baseline characteristics and rhythm control protocols, as well as outcomes including arrhythmia recurrence, the need for antiarrhythmic drugs, requirement for repeat rhythm control procedures, and complications. These data provide a real world insight into the risks and benefits of the convergent procedure in patients with longstanding persistent AF.

The convergent procedure versus catheter ablation alone in longstanding persistent atrial fibrillation: A single centre, propensity-matched cohort study.

BACKGROUND: Maintenance of sinus rhythm is challenging in patients with longstanding persistent atrial fibrillation (PeAF). Minimally invasive surgical AF ablation may improve outcomes when combined with catheter ablation (the 'convergent' procedure). This study evaluates the safety and efficacy of the convergent procedure versus catheter ablation alone in longstanding PeAF. METHODS: 43 consecutive patients with longstanding PeAF underwent subxiphoid endoscopic ablation of the posterior left atrium followed by catheter ablation from 2013 to 2018. The primary outcome was AF-free survival at 12 months; secondary outcomes included change in EHRA class, echocardiographic data, procedural complications, freedom from anti-arrhythmic drugs (AADs), and long term arrhythmia-free survival. Outcomes were compared with a matched group of 43 patients who underwent catheter ablation alone. Both groups underwent multiple catheter ablations as required. Baseline characteristics were similar between groups. RESULTS: After 12 months, the convergent procedure was associated with increased AF-free survival on AADs (60.5% versus 25.6%, p = .002) and off AADs (37.2% versus 13.9%, p = .025), versus catheter ablation. Allowing for multiple procedures, after 30.5 ±â€¯13.3 months' follow-up the convergent procedure was associated with increased arrhythmia-free survival on AADs (58.1% versus 30.2%, p = .016) and off AADs (32.5% versus 11.6%, p = .036) versus catheter ablation. There were more complications in the convergent procedure group (11.6% versus 2.3%, p = .2). Multivariate analysis identified only the convergent procedure (OR 3.06 (1.23-7.6), p = .017) as predictive of arrhythmia-free survival long term. CONCLUSIONS: In longstanding PeAF, the convergent procedure is associated with improved arrhythmia-free survival versus catheter ablation alone. Complication rates are significant but have been shown to depreciate with experience.

Identifying avoidable switchboard delays in England's NHS hospitals: phase one of the national SWITCH project.

BACKGROUND: Inter-hospital communication frequently requires mediation via a switchboard. Identifying and eliminating switchboard inefficiencies may improve patient care. METHODS: All 175 acute hospital switchboards in England were contacted six times. Call contents and duration were recorded. No clinician calls or bleeps were connected. RESULTS: The mean delay before contacting a switchboard operative was 55±46 seconds. 115 hospitals (66%) used automated switchboards; 34 of these (30%) had infection control messages. Robot operators introduced an additional 40 second delay versus humans (mean 70.3±28 versus 29.8±23 seconds, p<0.0001). Multivariate analysis identified robot operators (HR 5.1, p<0.0001) and infection control messages (HR 2.9, p=0.003) as predictors of delays over 60 seconds. CONCLUSIONS: There are significant avoidable delays in contacting switchboard operatives across England. Quality improvement is underway.

The single nucleotide polymorphism CRTh2 rs533116 is associated with allergic asthma and increased expression of CRTh2.

BACKGROUND: CRTh2 (chemoattractant-receptor homologous molecule expressed on Th2 cells) is expressed by Th2 cells and other cells involved in allergic inflammation. Single nucleotide polymorphisms (SNPs) in CRTh2 (rs11571288, rs545659, rs634681) have been associated with various phenotypes of allergy in ethnically distinct populations. Here, we assessed the association between CRTh2 rs533116 and allergic asthma, expression of CRTh2 and Th2 cytokine production. METHODS: CRTh2 rs533116 was genotyped in an ethnically diverse population (n = 1282). The proportion of cells expressing CRTh2 was determined in peripheral blood from subjects with allergic airways disease and controls as well as with in vitro differentiated Th2 cells. Receptor function was assessed by stimulating Th2 cells with the CRTh2-specific agonist 13,14-dihydro-15-keto-PGD(2) (DK-PGD(2) ) and measuring IL-4 and IL-13 by intracellular staining and ELISA. RESULTS: CRTh2 rs533116 was associated with allergic asthma in White people (2.67 [1.09-6.55], P < 0.05), and expression of CRTh2 was higher in subjects with allergic airways disease compared to controls (P < 0.05). Among allergic individuals, the AA genotype was significantly associated with more eosinophils and higher expression of CRTh2 by both CD4(+) T cells and eosinophils (P < 0.05). In vitro, the AA genotype was associated with a higher proportion of CRTh2(+) cells during Th2 differentiation as well as more IL-4 and IL-13 expression following DK-PGD(2) stimulation (P < 0.05). CONCLUSIONS: These findings show an association between CRTh2 rs533116 and allergic asthma and suggest this may be mediated by elevated expression of CRTh2, leading to higher numbers of circulating eosinophils and Th2 cytokine production.

The effect of high-protein, low-carbohydrate diets in the treatment of type 2 diabetes: a 12 month randomised controlled trial.

AIMS/HYPOTHESIS: Short-term dietary studies suggest that high-protein diets can enhance weight loss and improve glycaemic control in people with type 2 diabetes. However, the long-term effects of such diets are unknown. The aim of this study was to determine whether high-protein diets are superior to high-carbohydrate diets for improving glycaemic control in individuals with type 2 diabetes. METHODS: Overweight/obese individuals (BMI 27-40 kg/m(2)) with type 2 diabetes (HbA(1c) 6.5-10%) were recruited for a 12 month, parallel design, dietary intervention trial conducted at a diabetes specialist clinic (Melbourne, VIC, Australia). Of the 108 initially randomised, 99 received advice to follow low-fat (30% total energy) diets that were either high in protein (30% total energy, n = 53) or high in carbohydrate (55% total energy, n = 46). Dietary assignment was done by a third party using computer-generated random numbers. The primary endpoint was change in HbA(1c). Secondary endpoints included changes in weight, lipids, blood pressure, renal function and calcium loss. Study endpoints were assessed blinded to the diet group, but the statistical analysis was performed unblinded. This study used an intention-to-treat model for all participants who received dietary advice. Follow-up visits were encouraged regardless of dietary adherence and last measurements were carried forward for study non-completers. RESULTS: Ninety-nine individuals were included in the analysis (53 in high protein group, 46 in high carbohydrate group). HbA(1c) decreased in both groups over time, with no significant difference between groups (mean difference of the change at 12 months; 0.04 [95% CI -0.37, 0.46]; p = 0.44). Both groups also demonstrated decreases over time in weight, serum triacylglycerol and total cholesterol, and increases in HDL-cholesterol. No differences in blood pressure, renal function or calcium loss were seen. CONCLUSIONS/INTERPRETATION: These results suggest that there is no superior long-term metabolic benefit of a high-protein diet over a high-carbohydrate in the management of type 2 diabetes. TRIAL REGISTRATION: ACTRN12605000063617 ( www.anzctr.org.au ). FUNDING: This study was funded by a nutritional research grant from Meat and Livestock Australia (MLA). J.E. Shaw is supported by NHMRC Fellowship 586623.

An investigation into the health-related quality of life of individuals living with HIV who are receiving HAART.

The health authorities have recently accepted the routine provision of highly active antiretroviral therapy to persons living with AIDS in South Africa. There is a need to investigate the impact of HAART on the health-related quality of life of people living with HIV/AIDS (PLWHA) in a resource-poor environment, as this will have an influence on compliance and treatment outcome. The aim of this study was to explore whether HAART is efficacious in improving the self-reported health-related quality of life (HRQoL) in a group of PWLA in WHO Stages 3 and 4 living in a resource-poor community. A quasi-experimental, prospective repeated measures design was used to monitor the HRQoL over time in participants recruited to an existing HAART programme. The HRQoL of 117 participants was determined through the use of the Xhosa version of the EQ-5D and measurements were taken at baseline, one, six and 12 months. At the time of the 12-month questionnaire, 95 participants had been on HAART for 12 months. Not all participants attended all follow-up visits, but only two participants had withdrawn from the HAART programme, after two or three months. At baseline, the rank order of problems reported in all domains of the EQ-5D was significantly greater than at 12 months. The mean score on the global rating of health status increased significantly (p < 0.001) from a mean of 61.7 (SD = 22.7) at baseline to 76.1 at 12 months (SD = 18.5) It is concluded that, even in a resource-poor environment, HRQoL can be greatly improved by HAART, and that the possible side effects of the drugs seem to have a negligible impact on the wellbeing of the subjects. This bodes well for the anticipated roll-out of HAART within the public health sector in South Africa.

Fat oxidation, body composition and insulin sensitivity in diabetic and normoglycaemic obese adults 5 years after weight loss.

OBJECTIVE: To investigate whether normal glucose-tolerant and type II diabetic overweight adults differ in response to weight regain with regard to substrate oxidation and metabolic parameters. METHODS: A total of 15 overweight-obese subjects: seven normal glucose tolerant (NGT) and eight with type II diabetes (DM) were restudied 5 y after significant weight loss. Prediet, after 28 days calorie restriction and at 5 y, subjects were characterised for weight, height, waist-to-hip ratio (WHR) and body composition by dual-energy X-ray absorptiometry. Fasting glucose, insulin, leptin and lipid levels were measured and subjects underwent euglycaemic-hyperinsulinaemic clamp (insulin 0.25 U/kg/h for 150 min). Indirect calorimetry was performed resting and in the final 30 min of the clamp. Dietary assessment was by 4-day diet-diary. RESULTS: Both NGT and DM groups regained weight at 5 y and were not different to prediet. Total body fat (%) and WHR were higher at 5 y compared to prediet in both groups. Fasting glucose was increased in NGT subjects at 5 y, and fasting insulin was higher in both groups at 5 y compared to prediet. Insulin sensitivity (GIR) was similar at 5 y compared to prediet, but at 5 y DM subjects were more insulin resistant than NGT subjects. At 5 y, both DM and NGT groups had significantly reduced basal fat oxidation and no significant suppression of fat oxidation with insulin. Clamp respiratory quotient levels at 5 y were significantly higher in NGT compared to DM subjects. CONCLUSION: Reduced basal fat oxidation, and reduced variation in substrate oxidation in response to insulin develop with fat regain and fasting hyperinsulinaemia in both NGT and DM obese adults.

Postprandial triglycerides in response to high fat: role of dietary carbohydrate.

BACKGROUND: The postprandial triglyceride response following a meal high in fat (HFM) has been related to atherogenesis and insulin resistance. We examined the influence of dietary carbohydrate and the accompanying insulin secretory response on the postprandial triglyceride response following a HFM. MATERIALS AND DESIGN: High-fat meals of equal fat content (fat 80 g) containing either 20 g (low) or 100 g (high) of carbohydrate (HFM-LC and HFM-HC, respectively), and therefore not isocaloric (4250 kJ of HFM-LC and 5450 kJ of HFM-HC), were consumed by seven (four male, three female) normolipidaemic subjects (aged 32.9 +/- 3.7 years, BMI 24.7 +/- 1.8 kg m-2). Blood and indirect calorimetry data were collected at 0-4 h. RESULTS: HFM-HC produced a significant rise in plasma glucose (Delta0.54 +/- 0.23 mmol L-1, P = 0.05) at 2 h, while a HFM-LC elicited no mean change from baseline. Following a HFM-LC, the plasma insulin incremental area under the curve (AUC) was significantly lower (31.3 +/- 6.7 vs. 83.2 +/- 11.9 mU l-1 h-1, P < 0.0003) and the postprandial triglyceride response AUC was significantly greater (1.66 +/- 0.36 vs. 1.24 +/- 0.31 mmol L-1 h-1, P < 0.006) compared with a HFM-HC. Plasma free fatty acids were suppressed by 44% (P = 0.04) and 66% (P < 0.0001) at 1 h following HFM-LC and HFM-HC, respectively, compared with baseline. There were no significant differences between the meals in energy expenditure, substrate oxidation rates, or respiratory quotient responses. CONCLUSIONS: By design, the HFMs were not isocaloric but the presence of carbohydrate in a HFM invoked an insulin response that significantly reduced the 4 h postprandial triglyceride response even in healthy, normolipidaemic subjects. This phenomenon may have clinical implications, particularly in relation to insulin sensitivity.

Independent influences of central fat and skeletal muscle lipids on insulin sensitivity.

OBJECTIVE: Insulin resistance is closely associated with two disparate aspects of lipid storage: the intracellular lipid content of skeletal muscle and the magnitude of central adipose beds. Our aim was to determine their relative contribution to impaired insulin action. RESEARCH METHODS AND PROCEDURES: Eighteen older (56 to 75 years of age) men were studied before elective knee surgery. Insulin sensitivity (M/Delta I) was determined by hyperinsulinemic-euglycemic clamp. Central abdominal fat (CF) was assessed by DXA. Skeletal muscle was excised at surgery and assayed for content of metabolically active long-chain acyl-CoA esters (LCAC). RESULTS: Significant inverse relationships were observed between LCAC and M/Delta I (R(2) = 0.34, p = 0.01) and between CF and M/Delta I (R(2) = 0.38, p = 0.006), but not between CF and LCAC (R(2) = 0.0005, p = 0.93). In a multiple regression model (R(2) = 0.71, p < 0.0001), both CF (p = 0.0006) and LCAC (p = 0.0009) were independent statistical predictors of M/Delta I. Leptin levels correlated inversely with M/Delta I (R(2) = 0.60, p = 0.0002) and positively with central (R(2) = 0.41, p = 0.006) and total body fat (R(2) = 0.63, p = 0.0001). DISCUSSION: The mechanisms by which altered lipid metabolism in skeletal muscle influences insulin action may not be related directly to those linking central fat and insulin sensitivity. In particular, it is unlikely that muscle accumulation of lipids directly derived from labile central fat depots is a principal contributor to peripheral insulin resistance. Instead, our results imply that circulating factors, other than nonesterified fatty acids or triglyceride, mediate between central fat depots and skeletal muscle tissue. Leptin was not exclusively associated with central fat, but other factors, secreted specifically from central fat cells, could modulate muscle insulin sensitivity.