Search

Objective: Determine the cost-effectiveness of screening all pregnant women aged 16-25 years for chlamydia compared with selective screening or no screening.Design: Cost effectiveness based on a decision model.Setting: Antenatal clinics in Australia.Sample: Pregnant women, aged 16-25 years.Methods: Using clinical data from a previous study, and outcomes data from the literature, we modelled the short-term perinatal (12-month time horizon) incremental direct costs and outcomes from a government (as the primary third-party funder) perspective for chlamydia screening. Costs were derived from the Medicare Benefits Schedule, Pharmaceutical Benefits Scheme, and average cost-weights reported for hospitalisations classified according to the Australian refined diagnosis-related groups.Main Outcome Measures: Direct costs of screening and managing chlamydia complications, number of chlamydia cases detected and treated, and the incremental cost-effectiveness ratios were estimated and subjected to sensitivity analyses.Results: Assuming a chlamydia prevalence rate of 3%, screening all antenatal women aged 16-25 years at their first antenatal visit compared with no screening was $34,931 per quality-adjusted life-years gained. Screening all women could result in cost savings when chlamydia prevalence was higher than 11%. The incremental cost-effectiveness ratios were most sensitive to the assumed prevalence of chlamydia, the probability of pelvic inflammatory disease, the utility weight of a positive chlamydia test and the cost of the chlamydia test and doctor's appointment.Conclusion: From an Australian government perspective, chlamydia screening of all women aged 16-25 years old during one antenatal visit was likely to be cost-effective compared with no screening or selective screening, especially with increasing chlamydia prevalence.Tweetable Abstract: Chlamydia screening for all pregnant women aged 16-25 years during an antenatal visit is cost effective. [ABSTRACT FROM AUTHOR]

It is commonly believed that dispensed prices of medicines in Australia are substantially lower than those in other developed countries, particularly the US. This article reports the results of an analysis comparing dispensed prices for the most commonly prescribed and the highest cost items in Australia with dispensed prices in the US. Although a large majority of items are less expensive in Australia than in the US, Australian prices are higher for a substantial number of products, particularly generic drugs. This article examines various policies affecting the pricing of generics in Australia. It is postulated that the main cause for higher prices for a substantial number of generic products is the lack of price competition. This results from government policy which ensures that a price reduction by one company is communicated immediately to all competitors in that market along with an invitation to match the reduced price. The dominant strategy for all suppliers is to only reduce their price in response to a reduction in price by a competitor. The result is a lack of differentiation in pricing across brands of a medicine on the Schedule of Pharmaceutical Benefits. The government could improve the structure of the generics market and encourage greater competition by ceasing to disclose competitor firms' offers to other competitors. The government could conduct pricing reviews of each generic product relatively infrequently (eg, only once annually or every 18 months). At the time of the pricing review, the government would request confidential offers on price for a generic from all players in the market. Brands should then all be listed under the Pharmaceutical Benefits Scheme (PBS) at the offered price. Prices offered by the individual supplier would apply until the next pricing review. The PBS would continue to subsidise up to the price of the lowest priced brand, with brand premiums applying to all brands priced higher than the benchmark price. Such an approach would provide opportunity for players in the market to capture market share by being the lowest priced brand. [ABSTRACT FROM AUTHOR]

As of 2024, arterial hypertension is still considered the leading modifiable cardiovascular risk factor and, due to high rates of undertreatment and poor blood pressure control, the major contributor to human morbidity and mortality. Development of new treatment options and better interventions in lifestyle correction have become a priority of experimental and clinical research. In the last decades, dietary supplementation of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and generation of gut microbiota-derived short chain fatty acids (SCFAs) have surged as potential and promising interventions for hypertension and cardiovascular prevention. ω-3 PUFAs are considered "essential" fatty acids that can be obtained only from dietary sources. Although previous intervention trials were not consistent in reporting a significant benefit of ω-3 PUFAs, the recent REDUCE-IT trial has provided robust evidence in support of their role in cardiovascular prevention. Recent studies have also identified the intestinal microbiota as a potential player in the pathophysiology and progression of hypertension. Although this might occur through many pathways, generation of SCFAs that is highly dependent on dietary fiber intake is primarily involved, providing an additional target for the development of novel therapeutic strategies. For these reasons, some scientific societies currently recommend dietary supplementation of ω-3 PUFAs and fiber-containing foods in patients with hypertension. In this narrative review, we summarize the results of studies that examined the effects of ω-3 PUFAs and SCFAs on blood pressure, highlighting the mechanisms of action on the vascular system and their possible impact on hypertension, hypertension-related organ damage and, ultimately, cardiovascular outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: A prothrombotic state was demonstrated in patients with Cushing's syndrome and is involved in the development and progression of cardiovascular and renal damage in hypertensive patients. This study was designed to examine the relationships between cortisol secretion and the hemostatic and fibrinolytic systems in hypertension., Methods: In 149 middle-aged, nondiabetic, essential hypertensive patients free of cardiovascular and renal complications, we measured hemostatic markers that express the spontaneous activation of the coagulation and fibrinolytic systems and assessed daily cortisol levels (8 AM, 3 PM, 12 AM; area under the curve, AUC-cortisol) together with the cortisol response to dexamethasone overnight suppression (DST-cortisol)., Results: Plasma levels of D-dimer (D-dim), prothrombin fragment 1 + 2 (F1 + 2), and von Willebrand factor (vWF) were progressively and significantly higher across tertiles of AUC-cortisol and DST-cortisol, whereas no differences were observed in fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, protein C, and protein S. D-dim, F1 + 2, and vWF were significantly and directly correlated with age and both AUC-cortisol and DST-cortisol. Multivariate regression analysis showed that both AUC-cortisol and DST-cortisol were related to plasma D-dim, F1 + 2, and vWF independently of age, body mass index, blood pressure, and renal function., Conclusion: Greater daily cortisol profile and cortisol response to overnight suppression are independently associated with a prothrombotic state in hypertensive patients and might contribute to the development of organ damage and higher risk of cardiovascular complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Brosolo, Da Porto, Bulfone, Vacca, Bertin, Vivarelli, Catena and Sechi.)

Objective: Glycometabolic changes are associated with hypercortisolism in Cushing's syndrome. Because impaired glucose tolerance (IGT) and insulin resistance are frequently detected in patients with essential hypertension, we hypothesized that in these patients, early glycometabolic abnormalities might be related to differences in regulation of cortisol secretion., Methods: In a cross-sectional study, we included 155 nondiabetic, essential hypertensive patients who were free of organ complications. The homeostasis model assessment (HOMA) index and the area under the curve of plasma glucose (AUC-glucose) and insulin (AUC-insulin) concentration following an oral glucose tolerance test were measured, together with daily plasma cortisol (8 a.m., 3 p.m. and 12 a.m.; AUC-cortisol) and 8 a.m. cortisol after 1 mg overnight dexamethasone suppression test (DST)., Results: IGT was present in 27% of patients who were older and had higher BMI, plasma triglycerides and uric acid, AUC-cortisol and DST-cortisol, and lower HDL-cholesterol. Frequency of IGT increased progressively across tertiles of DST-cortisol, together with levels of glycated hemoglobin, fasting insulin and C-peptide, HOMA-index, AUC-glucose, and AUC-insulin. AUC-cortisol and DST-cortisol were directly correlated with insulin, C-peptide, HOMA-index, AUC-glucose, and AUC-insulin. Multivariate regression analysis showed that DST-cortisol was directly and independently correlated with HOMA index, AUC-glucose, and AUC-insulin. In a logistic regression model, both AUC-cortisol and DST-cortisol independently predicted IGT., Conclusion: Daily cortisol and cortisol response to DST are independent determinants of IGT and insulin resistance in nondiabetic patients with hypertension, suggesting that even subtle differences in regulation of cortisol secretion might increase the risk of these patients to develop diabetes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Elevated plasma lipoprotein(a) [Lp(a)] is a relatively common and highly heritable trait conferring individuals time-dependent risk of developing atherosclerotic cardiovascular disease (CVD). Following its first description, Lp(a) triggered enormous scientific interest in the late 1980s, subsequently dampened in the mid-1990s by controversial findings of some prospective studies. It was only in the last decade that a large body of evidence has provided strong arguments for a causal and independent association between elevated Lp(a) levels and CVD, causing renewed interest in this lipoprotein as an emerging risk factor with a likely contribution to cardiovascular residual risk. Accordingly, the 2022 consensus statement of the European Atherosclerosis Society has suggested inclusion of Lp(a) measurement in global risk estimation. The development of highly effective Lp(a)-lowering drugs (e.g., antisense oligonucleotides and small interfering RNA, both blocking LPA gene expression) which are still under assessment in phase 3 trials, will provide a unique opportunity to reduce "residual cardiovascular risk" in high-risk populations, including patients with arterial hypertension. The current evidence in support of a specific role of Lp(a) in hypertension is somehow controversial and this narrative review aims to overview the general mechanisms relating Lp(a) to blood pressure regulation and hypertension-related cardiovascular and renal damage.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), including alpha-linolenic acid (ALA) and its derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are "essential" fatty acids mainly obtained from diet sources comprising plant oils, marine blue fish, and commercially available fish oil supplements. Many epidemiological and retrospective studies suggested that ω-3 PUFA consumption decreases the risk of cardiovascular disease, but results of early intervention trials have not consistently confirmed this effect. In recent years, some large-scale randomized controlled trials have shed new light on the potential role of ω-3 PUFAs, particularly high-dose EPA-only formulations, in cardiovascular prevention, making them an attractive tool for the treatment of "residual" cardiovascular risk. ω-3 PUFAs' beneficial effects on cardiovascular outcomes go far beyond the reduction in triglyceride levels and are thought to be mediated by their broadly documented "pleiotropic" actions, most of which are directed to vascular protection. A considerable number of clinical studies and meta-analyses suggest the beneficial effects of ω-3 PUFAs in the regulation of blood pressure in hypertensive and normotensive subjects. These effects occur mostly through regulation of the vascular tone that could be mediated by both endothelium-dependent and independent mechanisms. In this narrative review, we summarize the results of both experimental and clinical studies that evaluated the effect of ω-3 PUFAs on blood pressure, highlighting the mechanisms of their action on the vascular system and their possible impact on hypertension, hypertension-related vascular damage, and, ultimately, cardiovascular outcomes.

Alcoholic beverages are common components of diets worldwide and understanding their effects on humans' health is crucial. Because hypertension is the leading risk factor for cardiovascular diseases and all-cause mortality, the relationship of alcohol consumption with blood pressure (BP) has been the subject of extensive investigation. For the purpose of this review, we searched the terms "alcohol", "ethanol", and "arterial hypertension" on Pubmed MeSH and selected the most relevant studies. Short-term studies showed a biphasic BP response after ingestion of high doses of alcohol, and sustained alcohol consumption above 30 g/day, significantly, and dose-dependently, increased the risk for hypertension. These untoward effects of alcoholic beverages on BP can be mediated by a multiplicity of neurohormonal mechanisms. In addition to the effects on BP, excess alcohol intake might contribute to cardiac and renal hypertensive organ damage, although some studies suggest possible benefits of moderate alcohol consumption on additional cardiovascular risk factors, such as diabetes and lipoprotein(a). Some intervention studies and cumulative analyses support the evidence of a benefit of the reduction/withdrawal of alcohol consumption on BP and cardiovascular outcomes. This is why guidelines of scientific societies recommend avoidance or limitation of alcohol intake below one unit/day for women and two units/day for men. This narrative article overviews all these topics, providing an update of the current knowledge on the relationship between alcohol and BP.

The metabolic effects of insulin predominate in skeletal muscle, fat, and liver where the hormone binds to its receptor, thereby priming a series of cell-specific and biochemically diverse intracellular mechanisms. In the presence of a good secretory reserve in the pancreatic islets, a decrease in insulin sensitivity in the metabolic target tissues leads to compensatory hyperinsulinemia. A large body of evidence obtained in clinical and experimental studies indicates that insulin resistance and the related hyperinsulinemia are causally involved in some forms of arterial hypertension. Much of this involvement can be ascribed to the impact of insulin on renal sodium transport, although additional mechanisms might be involved. Solid evidence indicates that insulin causes sodium and water retention, and both endogenous and exogenous hyperinsulinemia have been correlated to increased blood pressure. Although important information was gathered on the cellular mechanisms that are triggered by insulin in metabolic tissues and on their abnormalities, knowledge of the insulin-related mechanisms possibly involved in blood pressure regulation is limited. In this review, we summarize the current understanding of the cellular mechanisms that are involved in the pro-hypertensive actions of insulin, focusing on the contribution of insulin to the renal regulation of sodium balance and body fluids.

Introduction: Stress hyperglycemia is a frequent finding in patients with COVID-19 infection and could affect the outcome of disease. Cytokines released in response to infection could have adverse effects on insulin sensitivity and pancreatic beta-cell function. The aim of the study was to examine the relationships of stress hyperglycemia with cytokines and clinical outcomes in hospitalized patients with COVID-19., Methods: In a cross-sectional analysis of 150 patients hospitalized for COVID-19 infection who were included in the GIRA-COVID database, we identified patients with stress hyperglycemia by calculation of the Stress Hyperglycemia Ratio (SHR) and use of a cut-off of 1.14. Plasma levels of cytokines principally involved in COVID-19 infection-related cytokine storm were measured. Outcome variables were use of mechanical ventilation and death within 60 days from hospital admission., Results: Patients with SHR > 1.14 had significantly higher plasma insulin, HOMA-index, and levels of interleukin-10 (IL-10), interleukin-10/tumor necrosis factor-a ratio (IL-10/TNF-α), and CXC motif chemokine ligand 10 (CXCL10) than patients with SHR ≤ 1.14. IL-10, IL-10/TNF-α ratio, CXCL10, and IFN-γ were significantly and directly related with SHR in univariate analysis and multivariate logistic regression models showed that IL-10, IL-10/TNF-α ratio, and CXCL10 were independently associated with SHR>1.14. In a multivariate logistic model, stress hyperglycemia predicted use of mechanical ventilation (OR 2.453; CI 1.078-6.012) and death (OR 2.281; CI 1.049-7.369) independently of diabetes and other major confounders., Conclusions: In patients hospitalized for COVID-19 infection, stress hyperglycemia is associated with worse clinical outcomes and is independently related to levels of cytokines that might impair glucose homeostasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Da Porto, Tascini, Colussi, Peghin, Graziano, De Carlo, Bulfone, Antonello, Sozio, Fabris, Curcio, Pucillo, Catena and Sechi.)

Background: Left ventricular (LV) abnormalities were reported in patients with overt and subclinical Cushing syndrome. The aim of this study was to investigate the relationships of daily plasma cortisol profile and cortisol response to an overnight suppression test with cardiac changes in patients with hypertension., Methods: In a cross-sectional study, we included 136 nondiabetic, patients with essential hypertension who were free of cardiovascular and renal complications. Plasma cortisol was measured at 8 am, 3 pm, and 12 am and at 8 am after overnight suppression with 1 mg dexamethasone (dexamethasone suppression test [DST]). Echocardiography was performed with standard B-mode and tissue-Doppler imaging., Results: LV hypertrophy was present in 30% and LV diastolic dysfunction in 51% of patients who were older and had significantly higher body mass index, systolic blood pressure, duration of hypertension, and 12 am and DST cortisol. LV mass index and relative wall thickness increased progressively across tertiles of DST cortisol, together with progressive worsening of diastolic function. LV mass index was directly related to age, systolic blood pressure, duration of hypertension, and 12 am and DST cortisol, and inversely to creatinine clearance. Multivariate regression analysis showed independent correlation of LV mass index with body mass index, systolic blood pressure, and 12 am and DST cortisol. Logistic regression showed that DST cortisol independently predicted LV hypertrophy., Conclusions: Midnight and DST plasma cortisol levels are independent determinants of LV mass and geometry in patients with essential hypertension suggesting that even minor changes in regulation of cortisol secretion could contribute to cardiac abnormalities in these patients.

Recent evidence indicates that mildly increased fasting and post-oral load blood glucose concentrations contribute to development of organ damage in nondiabetic patients with hypertension. In previous studies, vitamin D deficiency was associated with decreased glucose tolerance. The aim of this study was to examine the relationships between serum 25(OH)D levels and glucose tolerance and insulin sensitivity in hypertension. In 187 nondiabetic essential hypertensive patients free of cardiovascular or renal complications, we measured serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) and performed a standard oral glucose tolerance test (OGTT). Patients with 25(OH)D deficiency/insufficiency were older and had significantly higher blood pressure, fasting and post-OGTT (G-AUC) glucose levels, post-OGTT insulin (I-AUC), PTH levels, and prevalence of metabolic syndrome than patients with normal serum 25(OH)D. 25(OH)D levels were inversely correlated with age, blood pressure, fasting glucose, G-AUC, triglycerides, and serum calcium and PTH, while no significant relationships were found with body mass index (BMI), fasting insulin, I-AUC, HOMA index, and renal function. In a multivariate regression model, greater G-AUC was associated with lower 25(OH)D levels independently of BMI and seasonal vitamin D variations. Thus, in nondiabetic hypertensive patients, 25(OH)D deficiency/insufficiency could contribute to impaired glucose tolerance without directly affecting insulin sensitivity.

Background: Financial incentives and audit/feedback are widely used in primary care to influence clinician behaviour and increase quality of care. While observational data suggest a decline in quality when these interventions are stopped, their removal has not been evaluated in a randomised controlled trial (RCT), to our knowledge. This trial aimed to determine whether chlamydia testing in general practice is sustained when financial incentives and/or audit/feedback are removed., Methods and Findings: We undertook a 2 × 2 factorial cluster RCT in 60 general practices in 4 Australian states targeting 49,525 patients aged 16-29 years for annual chlamydia testing. Clinics were recruited between July 2014 and September 2015 and were followed for up to 2 years or until 31 December 2016. Clinics were eligible if they were in the intervention group of a previous cluster RCT where general practitioners (GPs) received financial incentives (AU$5-AU$8) for each chlamydia test and quarterly audit/feedback reports of their chlamydia testing rates. Clinics were randomised into 1 of 4 groups: incentives removed but audit/feedback retained (group A), audit/feedback removed but incentives retained (group B), both removed (group C), or both retained (group D). The primary outcome was the annual chlamydia testing rate among 16- to 29-year-old patients, where the numerator was the number who had at least 1 chlamydia test within 12 months and the denominator was the number who had at least 1 consultation during the same 12 months. We undertook a factorial analysis in which we investigated the effects of removal versus retention of incentives (groups A + C versus groups B + D) and the effects of removal versus retention of audit/feedback (group B + C versus groups A + D) separately. Of 60 clinics, 59 were randomised and 55 (91.7%) provided data (group A: 15 clinics, 11,196 patients; group B: 14, 11,944; group C: 13, 11,566; group D: 13, 14,819). Annual testing decreased from 20.2% to 11.7% (difference -8.8%; 95% CI -10.5% to -7.0%) in clinics with incentives removed and decreased from 20.6% to 14.3% (difference -7.1%; 95% CI -9.6% to -4.7%) where incentives were retained. The adjusted absolute difference in treatment effect was -0.9% (95% CI -3.5% to 1.7%; p = 0.2267). Annual testing decreased from 21.0% to 11.6% (difference -9.5%; 95% CI -11.7% to -7.4%) in clinics where audit/feedback was removed and decreased from 19.9% to 14.5% (difference -6.4%; 95% CI -8.6% to -4.2%) where audit/feedback was retained. The adjusted absolute difference in treatment effect was -2.6% (95% CI -5.4% to -0.1%; p = 0.0336). Study limitations included an unexpected reduction in testing across all groups impacting statistical power, loss of 4 clinics after randomisation, and inclusion of rural clinics only., Conclusions: Audit/feedback is more effective than financial incentives of AU$5-AU$8 per chlamydia test at sustaining GP chlamydia testing practices over time in Australian general practice., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12614000595617., Competing Interests: All authors have completed the ICMJE uniform disclosure form. I have read the journal’s policy and the authors have the following competing interests: ML has received research grants to his institution from Gilead Sciences, Janssen-Cilag and ViiV Healthcare; NL is a member of the Editorial Board of PLOS Medicine.

Type 2 diabetes currently accounts for more than 90% of all diabetic patients. Lifestyle interventions and notably dietary modifications are one of the mainstays for the prevention and treatment of type 2 diabetes. In this context, the Mediterranean diet with its elevated content of phytonutrients has been demonstrated to effectively improve glucose homeostasis. Oleuropein is the most abundant polyphenolic compound contained in extra-virgin olive oil and might account for some of the anti-diabetic actions of the Mediterranean diet. With the aim to provide an overview of the possible contributions of oleuropein to glucose metabolism, we conducted a PubMed/Medline search in order to provide an update to the available evidence regarding this interesting compound. This narrative review summarizes the data that was obtained in in vitro and animal studies and the results of clinical investigations. Preclinical studies indicate that oleuropein improves glucose transport, increases insulin sensitivity, and facilitates insulin secretion by pancreatic β-cells, thereby supporting the hypothesis of the possible benefits of the control of hyperglycemia. However, on the clinical side, the available evidence is still preliminary and requires more extensive investigations. Thus, many questions remain unanswered in regards to the potential benefits of oleuropein in diabetes prevention and treatment. These questions should be addressed in appropriately designed studies in the future.

Background: Little is known on the clinical relevance of the nutritional status and body composition of patients hospitalized with SARS-CoV-2 infection. The aim of our study was to assess the prevalence of malnutrition in patients with COVID-19 pneumonia using bioelectrical impedance vector analysis (BIVA), and to evaluate the relationship of their nutritional status with the severity and outcome of disease., Methods: Among 150 consecutive patients who were hospitalized with COVID-19 pneumonia, 37 (24.3%) were classified as malnourished by BIVA, and were followed-up for 60 days from admission. Outcome measures were differences in the need for invasive mechanical ventilation, in-hospital mortality, and the duration of hospital stay in survivors., Results: During 60 days of follow-up, 10 (27%) malnourished patients and 13 (12%) non-malnourished patients required invasive mechanical ventilation ( p = 0.023), and 13 (35%) malnourished patients and 9 (8%) non-malnourished patients died ( p < 0.001). The average duration of the hospital stay in survivors was longer in patients with malnutrition (18.2 ± 15.7 vs. 13.2 ± 14.8 days, p < 0.001). In survival analyses, mechanical ventilation free (log-rank 7.887, p = 0.050) and overall (log-rank 17.886, p < 0.001) survival were significantly longer in non-malnourished than malnourished patients. The Cox proportional ratio showed that malnutrition was associated with an increased risk of mechanical ventilation (HR 4.375, p = 0.004) and death (HR 4.478, p = 0.004) after adjusting for major confounders such as age, sex, and BMI., Conclusions: Malnutrition diagnosed with BIVA was associated with worse outcomes in hospitalized patients with COVID-19 pneumonia.

Previous studies have shown that plasma lipoprotein(a) (Lp(a)) plays an important role in the development of hypertensive organ damage. The aim of the present study was to investigate the relationship of Lp(a) with markers of arterial stiffening in hypertension. In 138 essential hypertensive patients free of diabetes, renal failure and cardiovascular complications, we measured plasma lipids and assessed vascular stiffness through the use of pulse wave analysis and calculation of the brachial augmentation index (AIx), and measured the pulse wave velocity (PWV). Plasma Lp(a) levels were significantly and directly related to both AIx ( r = 0.490; p < 0.001) and PWV ( r = 0.212; p = 0.013). Multiple regression analysis showed that AIx was independently correlated with age, C-reactive protein, and plasma Lp(a) (beta 0.326; p < 0.001), while PWV was independently and directly correlated with age, and inversely with HDL, but not with plasma Lp(a). Logistic regression indicated that plasma Lp(a) could predict an AIx value above the median for the distribution ( p = 0.026). Thus, in a highly selective group of patients with hypertension, plasma Lp(a) levels were significantly and directly related to markers of vascular stiffening. Because of the relevance of vascular stiffening to cardiovascular risk, the reduction of Lp(a) levels might be beneficial for cardiovascular protection in patients with hypertension.

Background: COVID-19 has caused considerable morbidity and mortality worldwide and cardiac involvement has been reported during infection. The short-term cardiac outcome in survivors of COVID-19 is not known., Objective: To examine the heart of patients who survived COVID-19 and to compare the cardiac outcome between patients who recovered from mild-to-moderate or severe illness., Methods: With use of ECG and echocardiography, we examined the heart of 105 patients who had been hospitalized with COVID-19 and were consecutively recruited after hospital discharge while attending follow-up visits. Survivors of COVID-19 were compared with 105 matched controls. We also compared the cardiac outcome and lung ultrasound scan between COVID-19 patients who had mild-to-moderate or severe illness., Results: Cardiac data were collected a median of 41 days from the first detection of COVID-19. Symptoms were present in a low percentage of patients. In comparison with matched controls, no considerable structural or functional differences were observed in the heart of survivors of COVID-19. Lung ultrasound scan detected significantly greater residual pulmonary involvement in COVID-19 patients who had recovered from severe than mild-to-moderate illness. No significant differences were detected in ECG tracings nor were found in the left and right ventricular function of patients who had recovered from mild-to-moderate or severe illness., Conclusions: In a short-term follow-up, no abnormalities were identified in the heart of survivors of COVID-19, nor cardiac differences were detected between patients who had different severity of illness. With the limitations of a cross-sectional study, these findings suggest that patients who recover from COVID-19 do not have considerable cardiac sequelae.

The oft-applied assumption in the use of Quality Adjusted Life Years (QALYs) in economic evaluation, that all QALYs are valued equally, has been questioned from the outset. The literature has focused on differential values of a QALY based on equity considerations such as the characteristics of the beneficiaries of the QALYs. However, a key characteristic which may affect the value of a QALY is the type of QALY itself. QALY gains can be generated purely by gains in survival, purely by improvements in quality of life, or by changes in both. Using a discrete choice experiment and a new methodological approach to the derivation of relative weights, we undertake the first direct and systematic exploration of the relative weight accorded different QALY types and do so in the presence of equity considerations; age and severity. Results provide new evidence against the normative starting point that all QALYs are valued equally., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The aim of this study was to simulate and compare the healthcare and economic outcomes associated with routine use of intraoperative transoesophageal echocardiography (TOE) in patients undergoing cardiac surgery with those associated with a scenario where TOE is not routinely used., Methods: The impact of TOE on surgical decision-making was estimated through a systematic literature review. Individual short-term morbidity and mortality estimates were generated by application of the Society of Thoracic Surgeons risk calculator. Long-term event rates, unit costs, and utility weights were sourced from published literature and expert opinion. A discrete-event simulation model was then constructed to simulate both the in-hospital and post-discharge outcomes for patients undergoing cardiac surgery. Robustness of the base case results was examined through deterministic and probabilistic sensitivity analyses. An incremental cost-effectiveness ratio of €30 000 per quality-adjusted life-year gained was assumed to represent acceptable cost-effectiveness., Results: Routine use of intraoperative TOE was associated with lower costs and higher benefits per patient, which indicates that use of TOE is a dominant strategy. The intervention resulted in the avoidance of 299 cardiac complications, 20 strokes, and 11 all-cause deaths per 10 000 patients. Routine intraoperative TOE was associated with an increased occurrence of bleeding owing to more valvular surgery and subsequent long-term anticoagulation., Conclusions: Routine intraoperative TOE is a cost-effective procedure for patients undergoing cardiac surgery, leading to lower overall costs. It was associated with a decrease in long-term complications including stroke, cardiac complications, and death, although there was a slight increase in extracranial bleeding events., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Screening young adults who are sexually active for genital Chlamydia trachomatis infection is promoted in several high-income countries, but its effectiveness at the population level is highly debated. We aimed to investigate the effects of opportunistic chlamydia testing in primary care on the estimated chlamydia prevalence in the population aged 16-29 years in Australia., Methods: We did a cluster-randomised controlled trial. Clusters were rural towns with a minimum of 500 women and men aged 16-29 years and no more than six primary care clinics. We randomly allocated each cluster using a computer-generated minimisation algorithm to receive a multifaceted, clinic-based chlamydia testing intervention or to continue usual care. The intervention included computerised reminders to test patients, an education package, payments for chlamydia testing, and feedback on testing rates. The primary outcome was chlamydia prevalence, estimated before randomisation (survey 1) and at the end of the trial (survey 2) in patients aged 16-29 years who attended the clinics. Analyses were done by intention to treat. General practitioners and clinic staff were aware of group allocation, whereas patients and laboratory staff who performed the chlamydia tests were not. This trial was completed on Dec 31, 2015, and is registered (ACTRN12610000297022)., Findings: Between Dec 14, 2010, and Sept 14, 2015, 26 clusters (63 clinics) received the chlamydia testing intervention and 26 (67 clinics) continued usual care. Over a mean duration of 3·1 years (SD 0·3), 93 828 young adults attended intervention clinics and 86 527 attended control clinics. The estimated chlamydia prevalence decreased from 5·0% (95% CI 3·8 to 6·2) at survey 1 to 3·4% (2·7 to 4·1) at survey 2 in the intervention clusters (difference -1·6%, 95% CI -2·9 to -0·3) and from 4·6% (95% CI 3·5 to 5·7) at survey 1 to 3·4% (2·4 to 4·5) at survey 2 in the control clusters (difference -1·1%, -2·7 to 0·5). The unadjusted odds ratio for the difference between intervention and control clusters was 0·9 (95% CI 0·5 to 1·5)., Interpretation: These findings, in conjunction with evidence about the feasibility of sustained uptake of opportunistic testing in primary care, indicate that sizeable reductions in chlamydia prevalence might not be achievable., Funding: Australian Government Department of Health, National Health and Medical Research Council, Victorian Department of Health and Human Services, and New South Wales Ministry of Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Financial incentives and audit plus feedback on performance are two strategies commonly used by governments to motivate general practitioners (GP) to undertake specific healthcare activities. However, in recent years, governments have reduced or removed incentive payments without evidence of the potential impact on GP behaviour and patient outcomes. This trial (known as ACCEPt-able) aims to determine whether preventive care activities in general practice are sustained when financial incentives and/or external audit plus feedback on preventive care activities are removed. The activity investigated is annual chlamydia testing for 16- to 29-year-old adults, a key preventive health strategy within this age group., Methods/design: ACCEPt-able builds on a large cluster randomised controlled trial (RCT) that evaluated a 3-year chlamydia testing intervention in general practice. GPs were provided with a support package to facilitate annual chlamydia testing of all sexually active 16- to 29-year-old patients. This package included financial incentive payments to the GP for each chlamydia test conducted and external audit plus feedback on each GP's chlamydia testing rates. ACCEPt-able is a factorial cluster RCT in which general practices are randomised to one of four groups: (i) removal of audit plus feedback-continue to receive financial incentive payments for each chlamydia test; (ii) removal of financial incentive payments-continue to receive audit plus feedback; (iii) removal of financial incentive payments and audit plus feedback; and (iv) continue financial incentive payments and audit plus feedback. The primary outcome is chlamydia testing rate measured as the proportion of sexually active 16- to 29-year-olds who have a GP consultation within a 12-month period and at least one chlamydia test., Discussion: This will be the first RCT to examine the impact of removal of financial incentive payments and audit plus feedback on the chlamydia testing behaviour of GPs. This trial is particularly timely and will increase our understanding about the impact of financial incentives and audit plus feedback on GP behaviour when governments are looking for opportunities to control healthcare budgets and maximise clinical outcomes for money spent. The results of this trial will have implications for supporting preventive health measures beyond the content area of chlamydia., Trial Registration: The trial has been registered on the Australian and New Zealand Clinical Trials Registry ( ACTRN12614000595617 ).

Objective: Determine the cost-effectiveness of screening all pregnant women aged 16-25 years for chlamydia compared with selective screening or no screening., Design: Cost effectiveness based on a decision model., Setting: Antenatal clinics in Australia., Sample: Pregnant women, aged 16-25 years., Methods: Using clinical data from a previous study, and outcomes data from the literature, we modelled the short-term perinatal (12-month time horizon) incremental direct costs and outcomes from a government (as the primary third-party funder) perspective for chlamydia screening. Costs were derived from the Medicare Benefits Schedule, Pharmaceutical Benefits Scheme, and average cost-weights reported for hospitalisations classified according to the Australian refined diagnosis-related groups., Main Outcome Measures: Direct costs of screening and managing chlamydia complications, number of chlamydia cases detected and treated, and the incremental cost-effectiveness ratios were estimated and subjected to sensitivity analyses., Results: Assuming a chlamydia prevalence rate of 3%, screening all antenatal women aged 16-25 years at their first antenatal visit compared with no screening was $34,931 per quality-adjusted life-years gained. Screening all women could result in cost savings when chlamydia prevalence was higher than 11%. The incremental cost-effectiveness ratios were most sensitive to the assumed prevalence of chlamydia, the probability of pelvic inflammatory disease, the utility weight of a positive chlamydia test and the cost of the chlamydia test and doctor's appointment., Conclusion: From an Australian government perspective, chlamydia screening of all women aged 16-25 years old during one antenatal visit was likely to be cost-effective compared with no screening or selective screening, especially with increasing chlamydia prevalence., Tweetable Abstract: Chlamydia screening for all pregnant women aged 16-25 years during an antenatal visit is cost effective., (© 2015 Royal College of Obstetricians and Gynaecologists.)

This study examined healthcare utilization and associated costs for a severely obese population before receiving bariatric surgery relative to an age- and sex-matched sample from the Australian general population. Severely obese subjects receiving laparoscopic adjustable gastric banding (LAGB) surgery in 2009 (n = 11,769) were identified. Utilization of medical services and pharmaceuticals in the 3.5 years before surgery were ascertained for each severely obese subject through linkage with Medicare, Australia's universal health insurance scheme. Equivalent data were retrieved for each subject from the matched general population sample (n = 140,000). Severely obese subjects utilized significantly more medical services annually compared to the general population (mean: 22.8 vs. 12.1/person, standardized incidence ratio (SIR): 1.89 (95% confidence interval (CI) 1.88-1.89)), translating to twofold higher mean annual costs (Australian $1,140 vs. $567/person). The greatest excess costs in the obese related to consultations with general practitioners, psychiatrists/psychologists and other specialists, investigations for obstructive sleep apnea, and in vitro fertilization. Severely obese subjects also utilized significantly more pharmaceutical prescriptions annually (mean: 11.4 vs. 5.3/person, SIR 2.18 (95% CI: 2.17-2.19)), translating to 2.2-fold higher mean annual costs ($595/person vs. $270/person). The greatest excess costs in the obese related to diabetes drugs, lipid-modifying agents, psychoanaleptics, acid-related disorder drugs, agents acting on the rennin-angiotensin system, immunosuppressants, and obstructive airway disease drugs. Overall, healthcare costs in the severely obese population were more than double those incurred by the general population.

Background: Since the mid-1990s, early dialysis initiation has dramatically increased in many countries. The Initiating Dialysis Early and Late (IDEAL) study demonstrated that, compared with late initiation, planned early initiation of dialysis was associated with comparable clinical outcomes and increased health care costs. Because residual renal function is a key determinant of outcome and is better preserved with peritoneal dialysis (PD), the present pre-specified subgroup analysis of the IDEAL trial examined the effects of early-compared with late-start dialysis on clinical outcomes in patients whose planned therapy at the time of randomization was PD., Methods: Adults with an estimated glomerular filtration rate (eGFR) of 10 - 15 mL/min/1.73 m(2) who planned to be treated with PD were randomly allocated to commence dialysis at an eGFR of 10 - 14 mL/min/1.73 m(2) (early start) or 5 - 7 mL/min/1.73 m(2) (late start). The primary outcome was all-cause mortality., Results: Of the 828 IDEAL trial participants, 466 (56%) planned to commence PD and were randomized to early start (n = 233) or late start (n = 233). The median times from randomization to dialysis initiation were, respectively, 2.03 months [interquartile range (IQR):1.67 - 2.30 months] and 7.83 months (IQR: 5.83 - 8.83 months). Death occurred in 102 early-start patients and 96 late-start patients [hazard ratio: 1.04; 95% confidence interval (CI): 0.79 - 1.37]. No differences in composite cardiovascular events, composite infectious deaths, or dialysis-associated complications were observed between the groups. Peritonitis rates were 0.73 episodes (95% CI: 0.65 - 0.82 episodes) per patient-year in the early-start group and 0.69 episodes (95% CI: 0.61 - 0.78 episodes) per patient-year in the late-start group (incidence rate ratio: 1.19; 95% CI: 0.86 - 1.65; p = 0.29). The proportion of patients planning to commence PD who actually initiated dialysis with PD was higher in the early-start group (80% vs 70%, p = 0.01)., Conclusion: Early initiation of dialysis in patients with stage 5 chronic kidney disease who planned to be treated with PD was associated with clinical outcomes comparable to those seen with late dialysis initiation. Compared with early-start patients, late-start patients who had chosen PD as their planned dialysis modality were less likely to commence on PD.

Background: Planned early initiation of dialysis therapy based on estimated kidney function does not influence mortality and major comorbid conditions, but amelioration of symptoms may improve quality of life and decrease costs., Study Design: Patients with progressive chronic kidney disease and a Cockcroft-Gault estimated glomerular filtration rate of 10-15 mL/min/1.73 m(2) were randomly assigned to start dialysis therapy at a glomerular filtration rate of either 10-14 (early start) or 5-7 mL/min/1.73 m(2) (late start)., Setting & Population: Of the original 828 patients in the IDEAL (Initiation of Dialysis Early or Late) Trial in renal units in Australia and New Zealand, 642 agreed to participate in this cost-effectiveness study. STUDY PERSPECTIVE & TIMEFRAME: A societal perspective was taken for costs. Patients were enrolled between July 1, 2000, and November 14, 2008, and followed up until November 14, 2009., Intervention: Planned earlier start of maintenance dialysis therapy., Outcomes: Difference in quality of life and costs., Results: Median follow-up of patients (307 early start, 335 late start) was 4.15 years, with a 6-month difference in median duration of dialysis therapy. Mean direct dialysis costs were significantly higher in the early-start group ($10,777; 95% CI, $313 to $22,801). Total costs, including costs for resources used to manage adverse events, were higher in the early-start group ($18,715; 95% CI, -$3,162 to $43,021), although not statistically different. Adjusted for differences in baseline quality of life, the difference in quality-adjusted survival between groups over the time horizon of the trial was not statistically different (0.02 full health equivalent years; 95% CI, -0.09 to 0.14)., Limitations: Missing quality-of-life questionnaires and skewed cost data, although similar in each group, decrease the precision of results., Conclusion: Planned early initiation of dialysis therapy in patients with progressive chronic kidney disease has higher dialysis costs and is not associated with improved quality of life., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: In clinical practice there is considerable variation in the timing of initiation of dialysis. The IDEAL trial (Initiating Dialysis Early and Late study) showed that planned early initiation of dialysis in patients with stage 5 chronic kidney disease (CKD) was not associated with an improvement in clinical outcome, but was associated with increased costs. The predominant dialysis modality worldwide is hemodialysis (HD). This subanalysis of the IDEAL trial examined whether the timing of the initiation of dialysis in those who had chosen HD influenced survival and the occurrence of complications., Methods: Patients on the IDEAL trial were older than 18 years and had progressive advanced CKD. They were randomly assigned to commence dialysis at an estimated glomerular filtration rate (eGFR) of 10-14 ml/min (early start) or when the eGFR was 5-7 ml/min (late start). The primary outcome was death from any cause., Results: Between 2000 and 2008, 362 of the 828 patients (43.7%) randomized in the trial planned to commence HD. 322 (88.9%) of these subsequently commenced HD and 17 (4.7%) commenced peritoneal dialysis, with a median time to the initiation of dialysis of 1.63 months in the early-start group and 6.93 months in the late- start group. During a median follow-up time of 3.81 years, 50 of 171 patients in the early-start group (29.2%) and 59 in the late-start group (30.1%) died (hazard ratio with early initiation=0.97: 95% CI: 0.66-1.41; p=0.86). There was no significant difference in the frequency of cardiovascular events, infections, or access-related events, but there was a significantly higher frequency of fluid and electrolyte events in the late-start group (p=0.02)., Conclusion: In this subanalysis of the IDEAL trial, patients commencing dialysis early with stage 5 CKD for whom the planned dialysis modality was HD did not have an improvement in survival or any reduction in most clinical outcomes apart from fluid and electrolyte events., (Copyright © 2011 S. Karger AG, Basel.)

Background: In clinical practice, there is considerable variation in the timing of the initiation of maintenance dialysis for patients with stage V chronic kidney disease, with a worldwide trend toward early initiation. In this study, conducted at 32 centers in Australia and New Zealand, we examined whether the timing of the initiation of maintenance dialysis influenced survival among patients with chronic kidney disease., Methods: We randomly assigned patients 18 years of age or older with progressive chronic kidney disease and an estimated glomerular filtration rate (GFR) between 10.0 and 15.0 ml per minute per 1.73 m2 of body-surface area (calculated with the use of the Cockcroft-Gault equation) to planned initiation of dialysis when the estimated GFR was 10.0 to 14.0 ml per minute (early start) or when the estimated GFR was 5.0 to 7.0 ml per minute (late start). The primary outcome was death from any cause., Results: Between July 2000 and November 2008, a total of 828 adults (mean age, 60.4 years; 542 men and 286 women; 355 with diabetes) underwent randomization, with a median time to the initiation of dialysis of 1.80 months (95% confidence interval [CI], 1.60 to 2.23) in the early-start group and 7.40 months (95% CI, 6.23 to 8.27) in the late-start group. A total of 75.9% of the patients in the late-start group initiated dialysis when the estimated GFR was above the target of 7.0 ml per minute, owing to the development of symptoms. During a median follow-up period of 3.59 years, 152 of 404 patients in the early-start group (37.6%) and 155 of 424 in the late-start group (36.6%) died (hazard ratio with early initiation, 1.04; 95% CI, 0.83 to 1.30; P=0.75). There was no significant difference between the groups in the frequency of adverse events (cardiovascular events, infections, or complications of dialysis)., Conclusions: In this study, planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes. (Funded by the National Health and Medical Research Council of Australia and others; Australian New Zealand Clinical Trials Registry number, 12609000266268.)