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Heart failure with reduced ejection fraction (HFrEF) is associated with significant morbidity and mortality, particularly in patients with New York Heart Association (NYHA) functional class IV symptoms. Decades of discovery have heralded significant advancements in the pharmacologic management of HFrEF. However, patients with NYHA IV symptoms remain an under-represented population in almost every clinical trial to date, leaving clinicians with limited evidence with which to guide drug treatment decisions in this patient group with severe heart failure. Randomized controlled trials of adult patients with NYHA IV symptoms of HFrEF randomized to current guideline-recommended medical therapy were included in this systematic review and meta-analysis. The outcomes of interest included the rate of all-cause mortality, cardiovascular mortality, and heart failure hospitalization. A total of 39 randomized controlled trials were included. A total of 6 studies examined angiotensin converting enzyme inhibitors, with meta-analyses of 2 demonstrating a reduced risk of all-cause mortality (relative risk (RR) 0.76, 95% confidence interval 0.59 to 0.97, p = 0.03). A total of 11 studies examined β blockers, with meta-analysis of 6 demonstrating a reduced risk of all-cause mortality (risk ratio 0.74, 95% confidence interval 0.60 to 0.92, p = 0.008). A study examined the mineralocorticoid antagonist spironolactone, reporting a reduced risk of all-cause mortality in the NYHA IV subgroup. A total of 6 studies examined device therapy, demonstrating the benefit of cardiac resynchronization therapy with or without an implantable cardiac defibrillator in reducing hospitalization in the NYHA IV subgroup. Although trial evidence exists for angiotensin converting enzyme inhibitors, β-blockers, and mineralocorticoid antagonist therapy in the NYHA IV population, the role of angiotensin receptor blockers is unclear. Ivabradine, angiotensin receptor neprilysin inhibitors, and sodium-glucose transport protein 2 inhibitors remain underinvestigated and have not been proved to provide any benefit above standard heart failure therapy in patients with HFrEF and NYHA IV symptoms.

We sought to determine the association between heart failure (HF) and cognitive change and dementia.Systematic search of three electronic databases was performed and 29 eligible studies involving approximately 3 million participants were identified. Twelve studies examined dementia and 20 cognitive change, but only a subset of studies could be included in the meta-analysis. These findings indicated that HF was not significantly associated with dementia (n = 8, hazard ratio 1.18, 95% confidence interval 0.93-1.50), but increased the risk of cognitive impairment (n = 3, hazard ratio 1.80, 95% confidence interval 1.14-2.86) . Additionally, HF was associated with poorer mean cognitive performance in global cognition (Hedges' g -0.73, 95% confidence interval -1.12 to -0.35), memory (Hedges' g -0.57, 95% confidence interval -0.72 to -0.42), executive function (Hedges' g -0.58, 95% confidence interval -0.72 to -0.43), attention/speed (Hedges' g -0.50, 95% confidence interval -0.63 to -0.37) and language (Hedges' g -0.61, 95% confidence interval -1.05 to -0.17).Patients with HF perform worse on all cognitive tests and have an increased risk of cognitive impairment. These findings highlight the need for clinicians to consider cognition as part of routine care for patients with HF.

Observational studies have demonstrated that the pneumococcal polysaccharide vaccine (PPV) is associated with reduced risk of cardiovascular events. This may be mediated through IgM antibodies to OxLDL, which have previously been associated with cardioprotective effects. The Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE) is a double-blind, randomised controlled trial (RCT) of PPV in preventing ischaemic events. Participants received PPV or placebo once at baseline and are being followed-up for incident fatal and non-fatal myocardial infarction or stroke over 6 years.A subgroup of participants at one centre (Canberra; n = 1,001) were evaluated at 1 month and 2 years post immunisation for changes in surrogate markers of atherosclerosis, as pre-specified secondary outcomes: high-sensitive C-reactive protein (CRP), pulse wave velocity (PWV), and carotid intima-media thickness (CIMT). In addition, 100 participants were randomly selected in each of the intervention and control groups for measurement of anti-pneumococcal antibodies (IgG, IgG2, IgM) as well as anti-OxLDL antibodies (IgG and IgM to CuOxLDL, MDA-LDL, and PC-KLH).Concentrations of anti-pneumococcal IgG and IgG2 increased and remained high at 2 years in the PPV group compared to the placebo group, while IgM increased and then declined, but remained detectable, at 2 years. There were statistically significant increases in all anti-OxLDL IgM antibodies at 1 month, which were no longer detectable at 2 years; there was no increase in anti-OxLDL IgG antibodies. There were no significant changes in CRP, PWV or CIMT between the treatment groups at the 2-year follow-up.PPV engenders a long-lasting increase in anti-pneumococcal IgG, and to a lesser extent, IgM titres, as well as a transient increase in anti-OxLDL IgM antibodies. However, there were no detectable changes in surrogate markers of atherosclerosis at the 2-year follow-up. Long-term, prospective follow-up of clinical outcomes is continuing to assess if PPV reduces CVD events.

Background Patient-reported outcome measures (PROMs) are an important tool for evaluating outcomes following breast device procedures and are used by breast device registries. PROMs can assist with device monitoring through benchmarked outcomes but need to account for demographic and clinical factors that may affect PROM responses. Objectives This study aimed to develop appropriate risk-adjustment models for the benchmarking of PROM data to accurately track device outcomes and identify outliers in an equitable manner. Methods Data for this study were obtained from the Australian Breast Device Registry, which consists of a large prospective cohort of patients with primary breast implants. The 5-question BREAST-Q implant surveillance module was used to assess PROMs at 1 year following implant insertion. Logistic regression models were used to evaluate associations between demographic and clinical characteristics and PROMs separately by implant indication. Final multivariate risk-adjustment models were built sequentially, assessing the independent significant association of these variables. Results In total, 2221 reconstructive and 12,045 aesthetic primary breast implants with complete 1-year follow-up PROMs were included in the study. Indication for operation (post-cancer, risk reduction, or developmental deformity) was included in the final model for all reconstructive implant PROMs. Site type (private or public hospital) was included in the final breast reconstruction model for look, rippling, and tightness. Age at operation was included in the reconstruction models for rippling and tightness and in the aesthetic models for look, rippling, pain, and tightness. Conclusions These multivariate models will be useful for equitable benchmarking of breast devices by PROMs to help track device performance. Level of Evidence: 2

To assess the accuracy and precision of infrared cameras compared to traditional measures of temperature measurement in a temperature, humidity, and distance controlled intensive care unit (ICU) population. This was a prospective, observational methods comparison study in a single centre ICU in Metropolitan Melbourne, Australia. A convenience sample of 39 patients admitted to a single room equipped with two ceiling mounted thermal imaging cameras was assessed, comparing measured cutaneous facial temperature via thermal camera to clinical temperature standards. Uncorrected correlation of camera measurement to clinical standard in all cases was poor, with the maximum reported correlation 0.24 (Wide-angle Lens to Bladder temperature). Using the wide-angle lens, mean differences were − 11.1 °C (LoA − 14.68 to − 7.51), − 11.1 °C ( − 14.3 to − 7.9), and − 11.2 °C ( − 15.23 to − 7.19) for axillary, bladder, and oral comparisons respectively (Fig. 1a). With respect to the narrow-angle lens compared to the axillary, bladder and oral temperatures, mean differences were − 7.6 °C ( − 11.2 to − 4.0), − 7.5 °C ( − 12.1 to − 2.9), and − 7.9 °C ( − 11.6 to − 4.2) respectively. AUCs for the wide-angle lens and narrow-angle lens ranged from 0.53 to 0.70 and 0.59 to 0.79 respectively, with axillary temperature demonstrating the greatest values. Infrared thermography is a poor predictor of patient temperature as measured by existing clinical standards. It has a moderate ability to discriminate fever. It is unclear if this would be sensitive enough for infection screening purposes.Fig. 1Bland–Altman plots for temperatures measured using clinical standards to infrared camera. a Wide-angle camera versus bladder temperature. b Narrow-angle camera versus bladder temperature Supplementary Information The online version contains supplementary material available at 10.1007/s10877-021-00731-y.

Background Strict isolation of COVID-19 patients to prevent cross infection may inadvertently cause serious adverse outcomes including psychological harm, limitations to care, increased incidence of delirium, deconditioning and reduced quality of life. Previous research exploring the staff perspective of the effect of isolation on patients is limited. The aim of this study is to understand staff perceptions and interpretations of their experiences of the care and treatment of isolated patients and the impact of isolation on patients, families, and staff. Method This qualitative, exploratory study is set in a major metropolitan, quaternary hospital in Melbourne, Australia. Data was collected in focus groups with clinical and non-clinical staff and analysed using content analysis. The hospital ethics committee granted approval. Each participant gave informed verbal consent. Results Participants included 58 nursing, medical, allied health, and non-clinical staff. Six main themes were identified: 1) Communication challenges during COVID-19; 2) Impact of isolation on family; 3) Challenges to patients’ health and safety; 4) Impact on staff; 5) Challenging standards of care; 6) Contextual influences: policy, decision-makers and the environment. Conclusion Isolating patients and restricting visitors resulted in good pandemic management, but staff perceived it came at considerable cost to staff and consumers. Innovative communication technology may facilitate improved connection between all parties. Mental health support is needed for patients, families, and staff. Further research using a co-design model with input from patients, families and staff is recommended to determine appropriate interventions to improve care. Preventing the spread of infection is essential for good pandemic management, but the cost to consumers and staff must be mitigated. Preparation for future pandemics must consider workforce preparedness, adapted models of care and workflow.

IntroductionThe world is undergoing a demographic transition to an older population. Preventive healthcare has reduced the burden of chronic illness at younger ages but there is limited evidence that these advances can improve health at older ages. Statins are one class of drug with the potential to prevent or delay the onset of several causes of incapacity in older age, particularly major cardiovascular disease (CVD). This paper presents the protocol for the STAtins in Reducing Events in the Elderly (STAREE) trial, a randomised double-blind placebo-controlled trial examining the effects of statins in community dwelling older people without CVD, diabetes or dementia.Methods and analysisWe will conduct a double-blind, randomised placebo-controlled trial among people aged 70 years and over, recruited through Australian general practice and with no history of clinical CVD, diabetes or dementia. Participants will be randomly assigned to oral atorvastatin (40 mg daily) or matching placebo (1:1 ratio). The co-primary endpoints are disability-free survival defined as survival-free of dementia and persistent physical disability, and major cardiovascular events (cardiovascular death or non-fatal myocardial infarction or stroke). Secondary endpoints are all-cause death, dementia and other cognitive decline, persistent physical disability, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, heart failure, atrial fibrillation, fatal and non-fatal cancer, all-cause hospitalisation, need for permanent residential care and quality of life. Comparisons between assigned treatment arms will be on an intention-to-treat basis with each of the co-primary endpoints analysed separately in time-to-first-event analyses using Cox proportional hazards regression models.Ethics and disseminationSTAREE will address uncertainties about the preventive effects of statins on a range of clinical outcomes important to older people. Institutional ethics approval has been obtained. All research outputs will be disseminated to general practitioner co-investigators and participants, published in peer-reviewed journals and presented at national and international conferences.Trial registration numberNCT02099123.

Background The Australian Breast Device Registry (ABDR) is a clinical quality registry which utilizes both surgical data and patient-reported outcome measures (PROMs) to understand device performance. The ABDR is the first national breast device registry utilizing the BREAST-Q Implant Surveillance module to conduct PROMs via text messaging as the primary method of contact for most patients. ABDR PROMs are structured upon a successful acceptability and feasibility study and a pilot study. Objectives This aim of this paper was to examine the challenges we faced and consider how lessons learned in implementing PROMs might inform future registry studies and interventions. Methods We tracked the number of completed follow-ups and documented feedback between October 2017 and December 2018 from various stakeholders, including sites, surgeons, and patients. Results In total, 10,617 patients were contacted: 59% of breast augmentation and 77% breast reconstruction patients responded to our PROMs survey. We encountered challenges and developed solutions to overcome several key issues, including database setup; follow-up contact methods; ethics; education of surgeons and patients; associated costs; and ongoing evaluation and modification. The strategies we devised to address these challenges included drawing on experiences from previous studies, greater communication with sites and surgeons, and having the flexibility to improve and modify our PROMs. Conclusions The ABDR PROMs experience and lessons learned can inform a growing number of registries seeking to conduct PROMs. We describe our approach, obstacles encountered, and strategies to increase patient participation. As more breast device registries worldwide adopt PROMs, data harmonization is crucial to better understand patient outcomes and device performance.

Background Patient-reported outcome measures (PROMs) are increasingly employed in healthcare to assess outcomes. The BREAST-Q Implant Surveillance module (BREAST-Q IS) is a 5-question PROM utilized by the Australian Breast Device Registry to monitor the performance of breast devices. Validation of this tool is needed to assess its utility in this setting. Objectives The objective of this study was to assess the test-retest reliability of the BREAST-Q IS among breast implant recipients within a registry setting. Methods A test-retest reliability study was undertaken. Patients who underwent breast augmentation or breast reconstruction and registered with the Australian Breast Device Registry were eligible to participate. A total of 250 surveys were distributed. The BREAST-Q IS was administered to the same group of participants on 2 separate occasions with a 2-week test interval. Participants were divided into 2 groups: breast augmentation and breast reconstruction. A weighted kappa coefficient was calculated to assess the degree of test-retest reliability of the BREAST-Q IS. Results A total of 207 participants completed both tests. The response rate was 82% (n = 113) for the breast augmentation group and 94% (n = 94) for the breast reconstruction group. All 5 questions on the BREAST-Q IS obtained weighted kappa scores above 0.74 among both groups. Conclusions The BREAST-Q IS has good to excellent test-retest reliability for utilization among breast implant recipients in a registry setting. Further validation of the BREAST-Q IS will be required to establish the BREAST-Q IS as a valid and reliable PROM tool for breast implant recipients following breast device surgery.

Background Current pharmacologic therapies for patients with osteoarthritis are suboptimal. Objective To determine the efficacy of Curcuma longa extract (CL) for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee osteoarthritis and knee effusion-synovitis. Design Randomized, double-blind, placebo-controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000080224). Setting Single-center study with patients from southern Tasmania, Australia. Participants 70 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis. Intervention 2 capsules of CL (n = 36) or matched placebo (n = 34) per day for 12 weeks. Measurements The 2 primary outcomes were changes in knee pain on a visual analogue scale (VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. Outcomes were assessed over 12 weeks. Results CL improved VAS pain compared with placebo by -9.1 mm (95% CI, -17.8 to -0.4 mm [P = 0.039]) but did not change effusion-synovitis volume (3.2 mL [CI, -0.3 to 6.8 mL]). CL also improved WOMAC knee pain (-47.2 mm [CI, -81.2 to -13.2 mm]; P = 0.006) but not lateral femoral cartilage T2 relaxation time (-0.4 ms [CI, -1.1 to 0.3 ms]). The incidence of adverse events was similar in the CL (n = 14 [39%]) and placebo (n = 18 [53%]) groups (P = 0.16); 2 events in the CL group and 5 in the placebo group may have been treatment related. Limitation Modest sample size and short duration. Conclusion CL was more effective than placebo for knee pain but did not affect knee effusion-synovitis or cartilage composition. Multicenter trials with larger sample sizes are needed to assess the clinical significance of these findings. Primary funding source University of Tasmania and Natural Remedies Private Limited.

Background Multiple co-morbidities complicate initiation of medical therapy in patients with heart failure with reduced ejection fraction (HFrEF). Adherence to guidelines based on individual patient profiles is not well described. This paper examines the effect of individual patient profiles on guideline recommended therapies for HFrEF. Methods This was a prospective, observational, non-randomised study of hospitalised HFrEF patients over 30 days, from 2014 to 2017 in 16 hospitals. A previously developed algorithm-based guideline adherence score was used to determine adherence to key performance indicators: prescribing of beta blockers, angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), mineralocorticoid-receptor antagonist (MRAs) for HFrEF patients and early outpatient and heart failure (HF) disease management program review. Patients were classified as low, moderate and excellent adherence to medical therapy. Results Of the 696 HFrEF patients, 69.1% (n=481) were male with an average age of 73.15 years (SD±14.5 years). At discharge, 64.6% (n=427) were prescribed an ACEI/ARB, 78.7% (n=525) a beta blocker and 45.3% (n=302) prescribed MRA. Based on individual patient profiles, 18.2% (n=107) of eligible patients received an outpatient clinic and HF disease management program review within 30 days and 41.5% (n=71) were prescribed triple therapy. Based on individual profiles, 13% (n=21) of patients received an excellent guideline adherence score. Conclusion Individual patient profiles impact on adherence to guideline recommendations. Review in transitional care and prescribing of triple pharmacotherapy is suboptimal. Translational strategies to facilitate the implementation of guideline recommended therapies is warranted.

Caregiver workload in the ICU setting is difficult to numerically quantify. Ambient Intelligence utilises computer vision-guided neural networks to continuously monitor multiple datapoints in video feeds, has become increasingly efficient at automatically tracking various aspects of human movement.To assess the feasibility of using Ambient Intelligence to track and quantify allpatient and caregiver activity within a bedspace over the course of an ICU admission and also to establish patient specific factors, and environmental factors such as time ofday, that might contribute to an increased workload in ICU workers.5000 images were manually annotated and then used to train You Only LookOnce (YOLOv4), an open-source computer vision algorithm. Comparison of patientmotion and caregiver activity was then performed between these patients.The algorithm was deployed on 14 patients comprising 1762800 framesof new, untrained data. There was a strong correlation between the number ofcaregivers in the room and the standardized movement of the patient (p0.0001) withmore caregivers associated with more movement. There was a significant difference incaregiver activity throughout the day (p0.05), HDU vs. ICU status (p0.05), delirious vs. non delirious patients (p0.05), and intubated vs. not intubated patients(p0.05). Caregiver activity was lowest between 0400 and 0800 (average .71 ± .026caregivers per hour) with statistically significant differences in activity compared to 0800-2400 (p0.05). Caregiver activity was highest between 1200 and 1600 (1.02 ± .031 caregivers per hour) with a statistically significant difference in activity comparedto activity from 1600 to 0800 (p0.05). The three most dominant predictors of workeractivity were patient motion (Standardized Dominance 78.6%), Mechanical Ventilation(Standardized Dominance 7.9%) and Delirium (Standardized Dominance 6.2%).Ambient Intelligence could potentially be used to derive a single standardized metricthat could be applied to patients to illustrate their overall workload. This could be usedto predict workflow demands for better staff deployment, monitoring of caregiver workload, and potentially as a tool to predict burnout.

Current cardiovascular pharmacotherapy targets maladaptive overactivation of the renin-angiotensin-aldosterone system (RAAS), which occurs throughout the continuum of cardiovascular disease spanning from hypertension to heart failure with reduced ejection fraction. Over the past 16 years, 4 prospective, randomized, placebo-controlled clinical trials using candesartan, perindopril, irbesartan, and spironolactone in patients with heart failure with preserved ejection fraction (HFpEF) failed to demonstrate increased efficacy of RAAS blockade added to guideline-directed medical therapy. We reappraise these trials and their weaknesses, which precluded statistically significant findings. Recently, dual-acting RAAS blockade with sacubitril-valsartan relative to stand-alone valsartan failed to improve outcome in the PARAGON-HF trial (Efficacy and Safety of LCZ696 Compared with Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction). The majority of patients with HFpEF experience hypertension, frequently with subclinical left ventricular dysfunction, contributed to by comorbidities such as coronary disease, diabetes mellitus, overweight, and atrial fibrillation. Contrasting the findings in HFpEF, trials evaluating RAAS blockade on either side of HFpEF on the cardiovascular continuum in patients with high-risk hypertension and heart failure with reduced ejection fraction, respectively, showed positive outcomes. We do not have a biologically plausible explanation for such divergent efficacy of RAAS blockade. Based on considerations of well-established clinical efficacy in hypertension and heart failure with reduced ejection fraction and the shortcomings of aforementioned clinical trials in HFpEF, we argue that RAAS blockers including MRAs (mineralocorticoid receptor antagonists; aldosterone antagonists) should be used in the treatment of patients with HFpEF.

Background: The Poly Implant Prothese incident and breast implant-associated anaplastic large cell lymphoma have pointed to the need for uniform registries for breast implants as key features to monitoring the outcomes of breast implant surgeries internationally. The purpose of this study was to identify and harmonize common data elements collected by breast implant registries across the International Collaboration of Breast Registry Activities (ICOBRA) global consortium. Methods: The authors convened an international group of surgeons, consumers, nurses, registry experts, and regulators to review the data points. A modified Delphi approach was applied, to rate the importance of each point on a six-point Likert scale. Results: Data points from six national breast implant registries were divided into categories: clinical, implant-related, patient-reported findings; operation details and implanting technique details; patient characteristics; unique device identifiers; unique patient identifiers; and clinical demographics. A total of 52 data points collected by over 33 percent of national registries were identified. After five rounds, 34 data points formed the final set with agreed definitions. The group recognized the critical importance of additional elements that are currently not uniformly collected (e.g., patient-reported outcomes and longterm data) and set out the process for the dynamic global set updates driven by evidence gaps. Conclusions: The authors defined internationally agreed on common data elements and definitions used in breast implant registries. This collaboration will allow data sets to be combined, enabling an effective global early warning system of implant-related problems and further work on data sets.

Renal denervation has been shown to lower blood pressure in the presence of antihypertensive medications; however, long-term safety and efficacy data from randomised trials of renal denervation are lacking. In this pre-specified analysis of the SPYRAL HTN-ON MED study, we compared changes in blood pressure, antihypertensive drug use, and safety up to 36 months in renal denervation versus a sham control group.This randomised, single-blind, sham-controlled trial enrolled patients from 25 clinical centres in the USA, Germany, Japan, the UK, Australia, Austria, and Greece, with uncontrolled hypertension and office systolic blood pressure between 150 mm Hg and 180 mm Hg and diastolic blood pressure of 90 mm Hg or higher. Eligible patients had to have 24-h ambulatory systolic blood pressure between 140 mm Hg and less than 170 mm Hg, while taking one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned (1:1) to radiofrequency renal denervation or a sham control procedure. Patients and physicians were unmasked after 12-month follow-up and sham control patients could cross over after 12-month follow-up completion. The primary endpoint was the treatment difference in mean 24-h systolic blood pressure at 6 months between the renal denervation group and the sham control group. Statistical analyses were done on the intention-to-treat population. Long-term efficacy was assessed using ambulatory and office blood pressure measurements up to 36 months. Drug surveillance was used to assess medication use. Safety events were assessed up to 36 months. This trial is registered with ClinicalTrials.gov, NCT02439775; prospectively, an additional 260 patients are currently being randomly assigned as part of the SPYRAL HTN-ON MED Expansion trial.Between July 22, 2015, and June 14, 2017, among 467 enrolled patients, 80 patients fulfilled the qualifying criteria and were randomly assigned to undergo renal denervation (n=38) or a sham control procedure (n=42). Mean ambulatory systolic and diastolic blood pressure were significantly reduced from baseline in the renal denervation group, and were significantly lower than the sham control group at 24 and 36 months, despite a similar treatment intensity of antihypertensive drugs. The medication burden at 36 months was 2·13 medications (SD 1·15) in the renal denervation group and 2·55 medications (2·19) in the sham control group (p=0·26). 24 (77%) of 31 patients in the renal denervation group and 25 (93%) of 27 patients in the sham control group adhered to medication at 36 months. At 36 months, the ambulatory systolic blood pressure reduction was -18·7 mm Hg (SD 12·4) for the renal denervation group (n=30) and -8·6 mm Hg (14·6) for the sham control group (n=32; adjusted treatment difference -10·0 mm Hg, 95% CI -16·6 to -3·3; p=0·0039). Treatment differences between the renal denervation group and sham control group at 36 months were -5·9 mm Hg (95% CI -10·1 to -1·8; p=0·0055) for mean ambulatory diastolic blood pressure, -11·0 mm Hg (-19·8 to -2·1; p=0·016) for morning systolic blood pressure, and -11·8 mm Hg (-19·0 to -4·7; p=0·0017) for night-time systolic blood pressure. There were no short-term or long-term safety issues associated with renal denervation.Radiofrequency renal denervation compared with sham control produced a clinically meaningful and lasting blood pressure reduction up to 36 months of follow-up, independent of concomitant antihypertensive medications and without major safety events. Renal denervation could provide an adjunctive treatment modality in the management of patients with hypertension.Medtronic.

Late referral for heart transplantation (HTx) is associated with worse patient outcomes. There are no universally accepted definitions of what constitutes a timely referral for HTx assessment.To evaluate the impact of late referral (LR) on HTx outcomes.This single-centre retrospective observational study included 80 patients undergoing HTx between 2016-2019. We applied a simple clinical tool, derived from markers of advanced heart failure (HF), to classify LR in HTx patients and assess the impact of LR on HTx outcomes. Outcome measures included duration of intensive care unit (ICU) stay, total hospitalisation stay, cost of transplant admission and one-year mortality.Based upon the clinical profile, LR was defined by the presence of four or more out of 10 criteria for more than 6 months in HTx patients. In this model, 34 patients were timely referrals and 46 were LR. Patients who were LR had: a longer median time between initial diagnosis and referral (3 vs 7 ys; p=0.03); more features of advanced HF, including inotrope requirements (p=0.004); more comorbidities (p=0.014); and hospitalisations (p0.0001). Late referral was not associated with longer ICU (p=0.14) or hospital stay (p=0.051), however LR incurred greater total in-hospital costs (p=0.011). There was no difference in one-year mortality (6% vs 9%; p=0.64).Patients referred late for HTx are more unwell at time of referral and require greater in-hospital resource usage at the time of transplantation. Earlier referral for transplant assessment in patients with advanced HF should be encouraged.

Parkinson's Disease (PD) is a neurodegenerative disorder manifested by rest tremor, rigidity, bradykinesia, and postural instability. Recent pharmaco-epidemiological studies evaluating beta-adrenergic drug use and risk of PD have reported conflicting findings.This systematic review and meta-analyses evaluate the association between beta-adrenergic (agonists and antagonists) drugs' use and PD.An electronic literature search of eight databases was performed from inception to July 2021 to identify pharmaco-epidemiological studies (case-control and cohort) reporting the risk of PD in beta-adrenergic users compared to non-users. We used the generic inverse variance method and RevMan (5.3.5) to estimate pooled adjusted risk ratios (aRRs) of PD using a random-effects model.Of 3168 records, 15 studies (10 case-control; five cohort) with 6508,877 participants, including 87,011 PD cases, were included. In the pooled analysis (n = 10) including any beta-antagonist users, compared with non-users, the aRR for PD was 1.19 (CI: 1.05,1.35); for any beta-agonist users (n = 8) aRR for PD was 0.87 (CI: 0.78,0.97). Propranolol users had a significantly increased risk of PD (aRR:1.91; CI:1.20,3.06), whereas salbutamol use was associated with reduced risk of PD (aRR:0.95; CI:0.92,0.99). Significant heterogeneity (IBeta-antagonist use was associated with a modestly increased risk of PD, whereas beta-agonist use was associated with a modest decreased risk of PD. Future epidemiological studies should address the issues of protopathic bias and indirect association using appropriate epidemiological methods.

BACKGROUND: Many patients with heart failure (HF) are treated with warfarin or non-vitamin K oral anticoagulants (NOACs). Randomized outcome-driven comparisons of different anticoagulant strategies in HF are lacking. Data from international, government-mandated registries may be useful in understanding the real-life use of various anticoagulants and how they are linked to outcomes.STUDY QUESTION: To assess 2015 annual all-cause mortality, myocardial infarction, and stroke rates co-reported for warfarin and NOACs in subjects with and without HF in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.STUDY DESIGN: We extracted and examined outcome cases in subjects with HF and on warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban and stratified these according to anticoagulants.MEASURES AND OUTCOMES: Annual all-cause mortality, myocardial infarction, and stroke in FAERS.ANALYSIS METHOD: Odds ratio (OR) and χ(Equation is included in full-text article.)for oral anticoagulants from FAERS with and without HF among complete primary reports issued in 2015.RESULTS: FAERS reported 137,026 HF cases, with death co-reported in 42,942 (31.3%). In total, 11,278 (8.2%) HF patients were treated with anticoagulants, with more prescribed warfarin (n = 8260) than all NOACs combined (n = 3018). Very few reports for edoxaban were available. Warfarin consistently displayed a signal for excess adverse events compared to NOACs: OR (95% confidence interval) for the composite of mortality, myocardial infarction, and stroke were 1.91 (1.76-2.07) versus apixaban, 1.92 (1.81-2.03) versus dabigatran, 4.09 (3.38-4.37) versus rivaroxaban, and 2.64 (2.53-2.76) versus all NOACs combined (all P < 0.001). Warfarin, compared to all NOACs combined, demonstrated higher rates of all-cause mortality [OR = 2.69 (95% confidence interval, 2.49-2.90)], myocardial infarction [5.30 (4.17-6.74)], stroke [OR = 8.85 (6.61-11.84)], and ischemic stroke [OR = 12.73 (8.87-18.27); all P < 0.001].CONCLUSIONS: Annual 2015 FAERS profiles in HF patients reveal that warfarin was numerically dominant. Warfarin was associated with higher risk of death, myocardial infarction, and stroke compared to NOACs. These observational data provide real-world insight into a potential safety benefit of NOACs over warfarin in the setting of HF.

Background To examine the acceptability of a Patient Reported Outcome Measure (PROM) that assesses perceptions and experiences of implants for breast reconstruction or augmentation, and the feasibility of implementing it in the Australian Breast Device Registry (ABDR). Methods The BREAST-Q Implant Surveillance (BREAST-Q IS) is a 5-question PROM derived from the BREAST-Q questionnaire. It assesses perceptions of breast appearance and sensation, and experiences of pain. Breast implant recipients (recruited via community networks, social media and notices in surgeons’ rooms) and surgeons contributing to the ABDR were invited to review the BREAST-Q-IS. Participation was by individual semi-structured interviews by telephone or email, or by completion of a paper questionnaire. Transcripts of audio recordings and emailed text were analysed thematically. Results Twenty one breast implant recipients (10 after reconstruction and 11 augmentation), 8 surgeons (five plastic, three breast) and 2 medical professionals performing cosmetic surgeries were interviewed. Six themes were identified: Overall impression, Emotional response to the BREAST-Q IS, Method of follow-up, Suggested improvements, Group variation, and Potential Clinical utility. Overall, breast implant recipients and surgeons found the BREAST-Q IS to be acceptable and unlikely to provoke strong emotional reactions. Email was the preferred mode of contact. Most suggested improvements were to add questions. Surgeons expressed concern that subjective responses to the PROM might not accurately reflect experiences and that the PROM would predict need for revision rather than device failure. Conclusion This study supports the acceptability and feasibility of BREAST-Q IS as a PROM for recipients of breast implants. Further validation of the Breast-Q IS is required.

Background Limited data exist on whether outcomes of patients with heart failure (HF) undergoing percutaneous coronary intervention (PCI) have improved over time. The purpose of this study was to assess temporal trends in patient characteristics, treatment and outcomes of patients with HF undergoing PCI. Methods Using data from the Melbourne Interventional Group (MIG), we evaluated temporal trends of procedure volume, major adverse cardiac events (MACE; a composite of all-cause mortality, myocardial infarction and target vessel revascularisation) and rates of cardiovascular readmission, all-cause death and cardiovascular death in consecutive patients with HF undergoing PCI. Change over time was assessed by Box-Jenkins autoregressive integrated moving average (ARIMA) models. Results Data from 1,604 patients were analysed. In our cohort, there were no significant changes in the number of procedures performed annually and patient characteristics between January 2005 and December 2014. Optimal use of HF therapy has improved over the study period. Planned clopidogrel therapy of more than 12 months increased in tandem with increasing use of drug-eluting stents (DES). Procedural success was high (≥90%). However, the rates of MACE, cardiovascular readmission, all-cause death and cardiovascular death remained unchanged throughout the study period. Conclusions Clinical outcomes in HF patients undergoing PCI have remained unchanged despite improvement in medical technology and contemporary therapeutic measures.

© 2019 AMPCo Pty Ltd Objectives: To examine the effectiveness of different strategies for recruiting participants for a large Australian randomised controlled trial (RCT), the Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE). Design, setting, participants: Men and women aged 55–60 years with at least two cardiovascular risk factors (hypertension, hypercholesterolaemia, overweight/obesity) were recruited for a multicentre placebo-controlled RCT assessing the effectiveness of 23-valent pneumococcal polysaccharide vaccine (23vPPV) for preventing cardiovascular events. Methods: Invitations were mailed by the Australian Department of Human Services to people in the Medicare database aged 55–60 years; reminders were sent 2 weeks later. Invitees could respond in hard copy or electronically. Direct recruitment was supplemented by asking invitees to extend the invitation to friends and family (snowball sampling) and by Facebook advertising. Main outcome: Proportions of invitees completing screening questionnaire and recruited for participation in the RCT. Results: 21 526 of 154 992 invited people (14%) responded by completing the screening questionnaire, of whom 4725 people were eligible and recruited for the study. Despite the minimal study burden (one questionnaire, one clinic visit), the overall participation rate was 3%, or an estimated 10% of eligible persons. Only 16% of eventual participants had responded within 2 weeks of the initial invitation letter (early responders); early and late responders did not differ in their demographic or medical characteristics. Socio-economic disadvantage did not markedly influence response rates. Facebook advertising and snowball sampling did not increase recruitment. Conclusions: Trial participation rates are low, and multiple concurrent methods are needed to maximise recruitment. Social media strategies may not be successful in older age groups. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12615000536561.

Many Australians are intermittently exposed to landscape fire smoke from wildfires or planned (prescribed) burns. This study aimed to investigate effects of outdoor smoke from planned burns, wildfires and a coal mine fire by assessing biomarkers of inflammation in an exposed and predominantly older population. Participants were recruited from three communities in south-eastern Australia. Concentrations of fine particulate matter (PM2.5) were continuously measured within these communities, with participants performing a range of health measures during and without a smoke event. Changes in biomarkers were examined in response to PM2.5 concentrations from outdoor smoke. Increased levels of FeNO (fractional exhaled nitric oxide) (&beta, = 0.500 [95%CI 0.192 to 0.808] p &lt, 0.001) at a 4 h lag were associated with a 10 &micro, g/m3 increase in PM2.5 levels from outdoor smoke, with effects also shown for wildfire smoke at 4, 12, 24 and 48-h lag periods and coal mine fire smoke at a 4 h lag. Total white cell (&beta, = &minus, 0.088 [&minus, 0.171 to &minus, 0.006] p = 0.036) and neutrophil counts (&beta, 0.077 [&minus, 0.144 to &minus, 0.010] p = 0.024) declined in response to a 10 &micro, g/m3 increase in PM2.5. However, exposure to outdoor smoke resulting from wildfires, planned burns and a coal mine fire was not found to affect other blood biomarkers.

Background Heart failure decompensation is a major driver of hospitalizations and represents a significant burden to the health care system. Identifying those at greatest risk of admission can allow for targeted interventions to reduce this risk. Objective This paper aims to compare the predictive value of objective and subjective heart failure respiratory symptoms on imminent heart failure decompensation and subsequent hospitalization within a 30-day period. Methods A prospective observational pilot study was conducted. People living at home with heart failure were recruited from a single-center heart failure outpatient clinic. Objective (blood pressure, heart rate, weight, B-type natriuretic peptide) and subjective (4 heart failure respiratory symptoms scored for severity on a 5-point Likert scale) data were collected twice weekly for a 30-day period. Results A total of 29 participants (median age 79 years; 18/29, 62% men) completed the study. During the study period, 10 of the 29 participants (34%) were hospitalized as a result of heart failure. For objective data, only heart rate exhibited a between-group difference. However, it was nonsignificant for variability (P=.71). Subjective symptom scores provided better prediction. Specifically, the highest precision of heart failure hospitalization was observed when patients with heart failure experienced severe dyspnea, orthopnea, and bendopnea on any given day (area under the curve of 0.77; sensitivity of 83%; specificity of 73%). Conclusions The use of subjective respiratory symptom reporting on a 5-point Likert scale may facilitate a simple and low-cost method of predicting heart failure decompensation and imminent hospitalization. Serial collection of symptom data could be augmented using ecological momentary assessment of self-reported symptoms within a mobile health monitoring strategy for patients at high risk for heart failure decompensation.

Current pharmacologic therapies for patients with osteoarthritis are suboptimal.To determine the efficacy ofRandomized, double-blind, placebo-controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000080224).Single-center study with patients from southern Tasmania, Australia.70 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis.2 capsules of CL (The 2 primary outcomes were changes in knee pain on a visual analogue scale (VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. Outcomes were assessed over 12 weeks.CL improved VAS pain compared with placebo by -9.1 mm (95% CI, -17.8 to -0.4 mm [Modest sample size and short duration.CL was more effective than placebo for knee pain but did not affect knee effusion-synovitis or cartilage composition. Multicenter trials with larger sample sizes are needed to assess the clinical significance of these findings.University of Tasmania and Natural Remedies Private Limited.

BACKGROUND: Hypertension is an important risk factor for subsequent cardiovascular events, including ischaemic and haemorrhagic stroke, myocardial infarction, heart failure, chronic kidney disease, cognitive decline and premature death. Overall, the use of antihypertensive medications has led to reduction in cardiovascular disease, morbidity rates and mortality rates. However, the use of antihypertensive medications is also associated with harms, especially in older people, including the development of adverse drug reactions, drug-drug interactions and can contribute to increasing medication-related burden. As such, discontinuation of antihypertensives may be considered and appropriate in some older people.OBJECTIVES: To investigate whether withdrawal of antihypertensive medications is feasible, and evaluate the effects of withdrawal of antihypertensive medications on mortality, cardiovascular outcomes, hypertension and quality of life in older people.SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to April 2019: the Cochrane Hypertension Specialised Register, CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also conducted reference checking, citation searches and, when appropriate, contacted study authors to identify any additional studies. The searches had no language restrictions.SELECTION CRITERIA: We included randomised controlled trials (RCTs) of withdrawal versus continuation of antihypertensive medications used for hypertension or primary prevention of cardiovascular disease in older adults (defined as 50 years and over). Participants were eligible if they lived in the community, residential aged care facilities, or were based in hospital settings. We sought to include trials looking at the complete withdrawal of the antihypertensive medication, and those focusing on a dose reduction of the antihypertensive medicine.DATA COLLECTION AND ANALYSIS: We compared the intervention of discontinuing or reducing antihypertensive medication to usual treatment using mean differences (MD) and 95% confidence intervals (95% CIs) for continuous variables and we used Peto odds ratios (ORs) and 95% CI for binary variables. Our primary outcomes included: mortality, myocardial infarction, development of adverse drug reactions or adverse drug withdrawal reactions. Secondary outcomes included: blood pressure, hospitalisation, stroke, success of withdrawing from antihypertensives, quality of life, and falls. Two authors independently, and in duplicate, conducted all stages of study selection, data extraction and quality assessment.MAIN RESULTS: Six RCTs met the inclusion criteria and were included in the review (1073 participants). Study duration and follow-up ranged from 4 weeks to 56 weeks. Meta-analysis of studies showed that, in the discontinuation group compared to continuation, the odds for all-cause mortality were 2.08 (95% CI 0.79 to 5.46; low certainty of evidence), for myocardial infarction 1.86 (95% CI 0.19 to 17.98; very low certainty of evidence) and for stroke 1.44 (95% CI 0.25 to 8.35; low certainty of evidence). Blood pressure was higher in the discontinuation group than the continuation group (systolic blood pressure: MD = 9.75 mmHg, 95% CI 7.33 to 12.18; and diastolic blood pressure: MD = 3.5 mmHg, 95% CI 1.82 to 5.18; low certainty of evidence). For the development of adverse events, meta-analysis was not possible; antihypertensive discontinuation did not appear to increase the risk of adverse events and may lead to resolution of adverse drug reactions, although eligible studies had limited reporting of adverse effects of drug withdrawal (very low certainty of evidence). One study reported hospitalisation with an odds ratio of 0.83 for discontinuation compared to continuation (95% CI 0.33 to 2.10; low certainty of evidence). No studies were identified which reported falls. Between 10.5% and 33.3% of participants in the discontinuation group compared to 9% to 15% in the continuation group experienced raised blood pressure or other clinical criteria (as pre-defined by the studies) that would require restarting of therapy/removal from the study. The sources of bias included selective reporting (reporting bias), lack of blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), and lack of blinding of participants and personnel (performance bias).AUTHORS' CONCLUSIONS: There is no evidence of an effect of discontinuing compared with continuing antihypertensives used for hypertension or primary prevention of cardiovascular disease in older adults on all-cause mortality and myocardial infarction. The evidence was low to very low certainty mainly due to small studies and low event rates. These limitations mean that we cannot make any firm conclusions about the effect of deprescribing antihypertensives on these outcomes. Future research should focus on populations with the greatest uncertainty of the benefit:risk ratio for use of antihypertensive medications, such as those with frailty, older age groups and those taking polypharmacy, and measure clinically important outcomes such as falls, quality of life and adverse drug events.

BACKGROUND Heart failure decompensation is a major driver of hospitalizations and represents a significant burden to the health care system. Identifying those at greatest risk of admission can allow for targeted interventions to reduce this risk. OBJECTIVE This paper aims to compare the predictive value of objective and subjective heart failure respiratory symptoms on imminent heart failure decompensation and subsequent hospitalization within a 30-day period. METHODS A prospective observational pilot study was conducted. People living at home with heart failure were recruited from a single-center heart failure outpatient clinic. Objective (blood pressure, heart rate, weight, B-type natriuretic peptide) and subjective (4 heart failure respiratory symptoms scored for severity on a 5-point Likert scale) data were collected twice weekly for a 30-day period. RESULTS A total of 29 participants (median age 79 years; 18/29, 62% men) completed the study. During the study period, 10 of the 29 participants (34%) were hospitalized as a result of heart failure. For objective data, only heart rate exhibited a between-group difference. However, it was nonsignificant for variability (P=.71). Subjective symptom scores provided better prediction. Specifically, the highest precision of heart failure hospitalization was observed when patients with heart failure experienced severe dyspnea, orthopnea, and bendopnea on any given day (area under the curve of 0.77; sensitivity of 83%; specificity of 73%). CONCLUSIONS The use of subjective respiratory symptom reporting on a 5-point Likert scale may facilitate a simple and low-cost method of predicting heart failure decompensation and imminent hospitalization. Serial collection of symptom data could be augmented using ecological momentary assessment of self-reported symptoms within a mobile health monitoring strategy for patients at high risk for heart failure decompensation.

Summary Background The Australian Breast Device Registry (ABDR) is a clinical quality registry designed to monitor the performance of breast devices; and the quality and safety of breast device surgery. Objective To report on breast device surgery characteristics across Australia. Methods Participants were registered patients in the ABDR from 2012 to 2018. Results are described using percentages, mean and median. Revision rates were calculated using survival analysis methods. Results A total of 37,603 patients were registered and had undergone reconstruction (post-cancer 15.1%, risk-reducing mastectomy 3.4% and developmental deformity 2.4%) or cosmetic augmentation (74.7%) procedures. The majority of breast implant devices were silicone filled with textured surface (reconstruction 74.0% and augmentation 64.0%). Sub-pectoral plane was the most common for both reconstruction (60.1%) and augmentation (76.6%) procedures. For reconstruction surgery, the most common surgical incision was previous mastectomy scar (44.0%) and inframammary (31.8%), and for augmentation, it was inframammary (83.4%). Intraoperative/postoperative antibiotic usage for reconstruction was 85.8% and augmentation was 89.4%. Revision incidence due to complication at 12 months post-cancer reconstruction was 5.1%, risk-reducing reconstruction 5.7% and developmental deformity implants 4.5%. Revision incidence due to complication at 12 months after augmentation procedure was 1.1%. Patient-reported outcome measures (PROMs) indicate high levels of satisfaction at 1 year for augmentation and reconstruction procedures. Conclusion We report on early data from the ABDR and reflect on the uptake of the registry by surgeons and patients. The registry also benefits from international collaborative approaches to addressing challenges and is committed to facilitate international post-market surveillance.

Background With technological advances, there has been increasing interest in developing contactless and/or non-invasive wearable technologies that continuously monitor vital signs in the clinical setting, and in particular in the deteriorating patient. These devices as of yet have not been well validated in the clinical setting in the clinical ranges observed in a critically unwell patient. We will perform a systematic review of all novel wearable and contactless devices in the clinical setting with focus on degree of novelty and the range of vital signs captured. Methods Ovid MEDLINE including Epub Ahead of Print and In-Process & Other Non-Indexed Citations, Ovid Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL) Health Technology Assessment (HTA) database (Ovid), CINAHL with Full Text, searches of the grey literature, cited references of eligible studies through Web of Science, and reference lists of eligible studies will be searched. Outcomes of interest will include the quality of studies in relation to reporting guidelines, limitations of non-invasive technology, and application in different clinical populations. We will perform a qualitative assessment of the novelty of the device and discuss its validation in deteriorating patients. Discussion While novel monitoring devices are often proposed as a solution to problems with infection, discomfort, and frequency of monitoring in the clinical setting it has not yet been established which devices have been validated in clinical settings in the pathological ranges of vital signs that reflect patient deterioration. It is equally unclear what additional value these devices might provide. This systematic review will synthesize published data regarding devices that have been tested and validated in patients AND in a clinical setting AND in reference ranges that reflect severe illness. Systematic review registration PROSPERO CRD42019130091

Summary Background Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. Methods In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov , NCT02439749 . Findings From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was −3·9 mm Hg (Bayesian 95% credible interval −6·2 to −1·6) and for office systolic blood pressure the difference was −6·5 mm Hg (−9·6 to −3·5). No major device-related or procedural-related safety events occurred up to 3 months. Interpretation SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. Funding Medtronic.

Background We identified variation in delivery of guideline recommended care at our institution, and undertook a project to design a heart failure (HF) model of care. Aim To maximise time patients with HF spend well in the community by delivering best practice guidelines to reduce variation in care improving overall outcomes. Methods This quality improvement project focused on reducing variation in process measures of care. The HF model of care included electronic HF care bundles, a patient education pack with staff training on delivering HF patient education, referral of all HF patients to the Hospital Admissions Risk Program for phone call within 72 h, and a nurse-pharmacist early follow-up clinic. Outcomes were assessed using interrupted time series analyses. Results The pre-intervention group comprised 1585 patients, and post-intervention 1720 patients with a primary diagnosis of HF admitted under general cardiology and general medicine. Interrupted time series analysis indicated 30-day readmissions did not change in overall trend (-0.2% per month, P = 0.479) but a significant immediate step-down of 7.8% was seen (P = 0.018). For 90-day readmissions, a significant trend reduction over the time period was seen (-0.6% per month, P = 0.017) with a significant immediate step-down (-9.4%, P = 0.001). Emergency department representations, in-patient mortality and length of stay did not change significantly. Improvements in process measures were seen at audit. Conclusion This model of care resulted in overall trends of reductions in 30- and 90-day readmissions, without increasing emergency department representations, mortality and length of stay. This model will be adapted as the electronic medical record is introduced at our institution.

There is growing evidence from Phase III randomized clinical trials of the cardiovascular benefits of sodium glucose cotransporter 2 (SGLT2) inhibitors in patients with diabetes mellitus. It is hypothesized that these benefits are mediated by mechanisms other than glucose control. To address this, we performed a systematic review of data from preclinical studies examining the direct cardioprotective effects of SGLT2 inhibitors. Medline, EMBASE, CINAHL, and International Pharmaceutical Abstracts databases were searched for preclinical studies that examined the potential cardioprotective effects of SGLT2 inhibitors. Submission documents to the US Food and Drug Administration, European Medicines Agency, and Japanese Pharmaceutical and Medical Devices Agency for the registration of SGLT2 inhibitors were also reviewed. A total of 36 reports were included in the final analysis. The potential direct cardiovascular benefits of SGLT2 inhibitors include: augmentation of signal transducer and activator of transcription 3; inhibition of sodium hydrogen exchange; reduction of atherosclerosis; modulation of natriuretic peptides; vasodilation; modulation of sympathetic tone; and reduction of inflammation, oxidative stress, endoplasmic reticulum stress, and cardiac glucose uptake via down-regulation of SGLT1 expression. There are a number of mechanisms by which SGLT2 inhibitors may exert cardiovascular benefits beyond glycaemic control.

BACKGROUND Clopidogrel's anti-platelet effects may be attenuated by a pharmacokinetic interaction with co-prescribed proton pump inhibitors, which inhibit oxidative pathways that convert clopidogrel into its active metabolites. Despite this, the impact of PPIs on cardiovascular risk in the absence of clopidogrel is not well defined. AIM To report on a systematic review and meta-analysis of the association between PPIs and cardiovascular risk, independent of clopidogrel. METHODS The databases of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and ClinicalTrials.gov were systematically searched in October 2017. The primary outcome was association between PPI monotherapy and any adverse cardiovascular event. The secondary outcome was association between proton pump inhibitor monotherapy and acute myocardial infarction. Studies were excluded if they reported or did not adjust for concomitant anti-platelet therapy or involved participants aged less than 18 years. RESULTS A total of 22 studies were included in the systematic review. Data from 16 studies were included in the meta-analysis (involving 447 408 participants). Of these, eight were randomised controlled trials, seven were observational studies and one was a retrospective analysis of a randomised controlled trial. An increased risk of any adverse cardiovascular event with PPI monotherapy was observed using pooled data from observational studies (risk ratio 1.25, 95% CI 1.11-1.42, I2 81%, P

Summary Background Previous catheter-based renal denervation studies have reported variable efficacy results. We aimed to evaluate safety and blood pressure response after renal denervation or sham control in patients with uncontrolled hypertension on antihypertensive medications with drug adherence testing. Methods In this international, randomised, single-blind, sham-control, proof-of-concept trial, patients with uncontrolled hypertension (aged 20–80 years) were enrolled at 25 centres in the USA, Germany, Japan, UK, Australia, Austria, and Greece. Eligible patients had an office systolic blood pressure of between 150 mm Hg and 180 mm Hg and a diastolic blood pressure of 90 mm Hg or higher; a 24 h ambulatory systolic blood pressure of between 140 mm Hg and 170 mm Hg at second screening; and were on one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned to undergo renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were masked to randomisation assignments. The primary efficacy endpoint was blood pressure change from baseline (measured at screening visit two), based on ambulatory blood pressure measurements assessed at 6 months, as compared between treatment groups. Drug surveillance was used to assess medication adherence. The primary analysis was done in the intention-to-treat population. Safety events were assessed through 6 months as per major adverse events. This trial is registered with ClinicalTrials.gov, number NCT02439775, and follow-up is ongoing. Findings Between July 22, 2015, and June 14, 2017, 467 patients were screened and enrolled. This analysis presents results for the first 80 patients randomly assigned to renal denervation (n=38) and sham control (n=42). Office and 24 h ambulatory blood pressure decreased significantly from baseline to 6 months in the renal denervation group (mean baseline-adjusted treatment differences in 24 h systolic blood pressure −7·0 mm Hg, 95% CI −12·0 to −2·1; p=0·0059, 24 h diastolic blood pressure −4·3 mm Hg, −7·8 to −0·8; p=0.0174, office systolic blood pressure −6·6 mm Hg, −12·4 to −0·9; p=0·0250, and office diastolic blood pressure −4·2 mm Hg, −7·7 to −0·7; p=0·0190). The change in blood pressure was significantly greater at 6 months in the renal denervation group than the sham-control group for office systolic blood pressure (difference −6·8 mm Hg, 95% CI −12·5 to −1·1; p=0·0205), 24 h systolic blood pressure (difference −7·4 mm Hg, −12·5 to −2·3; p=0·0051), office diastolic blood pressure (difference −3·5 mm Hg, −7·0 to −0·0; p=0·0478), and 24 h diastolic blood pressure (difference −4·1 mm Hg, −7·8 to −0·4; p=0·0292). Evaluation of hourly changes in 24 h systolic blood pressure and diastolic blood pressure showed blood pressure reduction throughout 24 h for the renal denervation group. 3 month blood pressure reductions were not significantly different between groups. Medication adherence was about 60% and varied for individual patients throughout the study. No major adverse events were recorded in either group. Interpretation Renal denervation in the main renal arteries and branches significantly reduced blood pressure compared with sham control with no major safety events. Incomplete medication adherence was common. Funding Medtronic.

Randomised controlled clinical trials are the best source of evidence for assessing the efficacy of drugs. Observational studies provide critical descriptive data and information on long-term efficacy and safety that clinical trials cannot provide, at generally much less expense. Observational studies include case reports and case series, ecological studies, cross-sectional studies, case-control studies and cohort studies. New and ongoing developments in data and analytical technology, such as data linkage and propensity score matching, offer a promising future for observational studies. However, no study design or statistical method can account for confounders and bias in the way that randomised controlled trials can. Clinical registries are gaining importance as a method to monitor and improve the quality of care in Australia. Although registries are a form of cohort study, clinical trials can be incorporated into them to exploit the routine follow-up of patients to capture relevant outcomes.

Previous studies on the ‘treatment gap’ in patients with heart failure (HF) have focused either on prescribing or patients’ adherence to prescribed treatment. This study sought to determine whether or not recent initiatives to close the gap have also minimised any mismatches between physicians’ expectation of their patients’ medications, medications in the patients’ possession and their actual medication use. A cross-sectional observational survey was conducted from December 2015 to June 2016 in The Alfred Hospital HF clinic in Melbourne, Australia. Patients were invited to participate if they had chronic HF (NYHA class II to IV), were aged ≥ 60 years, had no history of HF related hospitalisation within the past 6 months and were prescribed at least two HF medications. Of 123 eligible patients, 102 were recruited into the study. Beta-blockers, mineralocorticoid receptor antagonists, loop diuretics and statins were associated with the highest rates of mismatches of drugs and doses, ranging from 10 to 17%. Discrepancy of total daily doses was the most common type of mismatch. Overall, only 23.5% of the patients were taking the right drugs at the right doses as expected by their cardiologists/HF specialists. Despite improved prescribers’ adherence to guideline-directed medical therapy, there remain considerable mismatches between prescribers’ expectation of patients’ HF medications, medications in patients’ possession and their actual medication use. Initiatives to improve this situation are urgently needed.

Background The medical tourism industry, and in particular cosmetic tourism for breast augmentation, is becoming an increasingly popular global phenomenon. The objective of this study is to determine the extent of medical literature and the patient risk profiles associated with cosmetic tourism for breast augmentation both locally and abroad. Data sources: OVID MEDLINE, OVID Embase, Cochrane Central and Proquest electronic databases. Methods The search was conducted through to April 2017. Studies pertaining entirely or partly to cosmetic tourism for breast augmentation were considered for inclusion. Exclusion criteria included non-English articles, studies relating to non-cosmetic or non-implant breast augmentation, and studies that did not separately report on findings associated with breast augmentation abroad. Results We identified 17 observational studies. Common destinations included Europe, South America and South East Asia. Infectious complications were common. Wound dehiscence and aesthetic dissatisfaction also featured. Catastrophic outcomes such as sepsis, intubation and ventilation, radical bilateral mastectomy, irreversible hypoxic brain injury and death were also reported. There were expectations that home country health systems would treat complications and provide non-medically indicated revision procedures. The burden on home country health systems was evident from a public health perspective. Conclusion Determining the extent of cosmetic tourism for breast augmentation, including outcomes and complications, will help to inform Australian patients who this seek procedure abroad. Furthermore, it will aid in better understanding the health system implications and may help to guide future research and public health interventions both locally and internationally.

The Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) was requested by the European Commission (EC) to provide a scientific opinion on the safety of breast implants in relation to anaplastic large cell lymphoma (ALCL). There are several types of textured breast implants; surface textures of breast implants are not all manufactured in the same way, and breast implants with diverse surface textures may also present different benefits. The magnitude of the risk per type of textured implant is difficult to establish due to the low incidence of the breast implants associated anaplastic large cell lymphoma (BIA-ALCL). Therefore, risk assessments per implant type are needed. Overall SCHEER considers that there is a moderate weight of evidence for a causal relationship between textured breast implants and BIA-ALCL, particularly in relation to implants with an intermediate to high surface roughness.The pathogenic mechanisms are not fully elucidated; current hypotheses include genetic drivers, chronic inflammation resulting either from bacterial contamination, shell shedding of particulates, or shell surface characteristics leading to friction, or by implant associated reactive compounds. Reporting of new BIA-ALCL cases by the national clinical registries is critically important to obtain a better estimate of the risk of BIA-ALCL for patients with a breast implant.