Polygenic risk score adds to a clinical risk score in the prediction of cardiovascular disease in a clinical setting.

BACKGROUND AND AIMS: A cardiovascular disease polygenic risk score (CVD-PRS) can stratify individuals into different categories of cardiovascular risk, but whether the addition of a CVD-PRS to clinical risk scores improves the identification of individuals at increased risk in a real-world clinical setting is unknown. METHODS: The Genetics and the Vascular Health Check Study (GENVASC) was embedded within the UK National Health Service Health Check (NHSHC) programme which invites individuals between 40-74 years of age without known CVD to attend an assessment in a UK general practice where CVD risk factors are measured and a CVD risk score (QRISK2) is calculated. Between 2012-2020, 44,141 individuals (55.7% females, 15.8% non-white) who attended an NHSHC in 147 participating practices across two counties in England were recruited and followed. When 195 individuals (cases) had suffered a major CVD event (CVD death, myocardial infarction or acute coronary syndrome, coronary revascularisation, stroke), 396 propensity-matched controls with a similar risk profile were identified, and a nested case-control genetic study undertaken to see if the addition of a CVD-PRS to QRISK2 in the form of an integrated risk tool (IRT) combined with QRISK2 would have identified more individuals at the time of their NHSHC as at high risk (QRISK2 10-year CVD risk of ≥10%), compared with QRISK2 alone. RESULTS: The distribution of the standardised CVD-PRS was significantly different in cases compared with controls (cases mean score .32; controls, -.18, P = 8.28×10-9). QRISK2 identified 61.5% (95% confidence interval [CI]: 54.3%-68.4%) of individuals who subsequently developed a major CVD event as being at high risk at their NHSHC, while the combination of QRISK2 and IRT identified 68.7% (95% CI: 61.7%-75.2%), a relative increase of 11.7% (P = 1×10-4). The odds ratio (OR) of being up-classified was 2.41 (95% CI: 1.03-5.64, P = .031) for cases compared with controls. In individuals aged 40-54 years, QRISK2 identified 26.0% (95% CI: 16.5%-37.6%) of those who developed a major CVD event, while the combination of QRISK2 and IRT identified 38.4% (95% CI: 27.2%-50.5%), indicating a stronger relative increase of 47.7% in the younger age group (P = .001). The combination of QRISK2 and IRT increased the proportion of additional cases identified similarly in women as in men, and in non-white ethnicities compared with white ethnicity. The findings were similar when the CVD-PRS was added to the atherosclerotic cardiovascular disease pooled cohort equations (ASCVD-PCE) or SCORE2 clinical scores. CONCLUSIONS: In a clinical setting, the addition of genetic information to clinical risk assessment significantly improved the identification of individuals who went on to have a major CVD event as being at high risk, especially among younger individuals. The findings provide important real-world evidence of the potential value of implementing a CVD-PRS into health systems.

Exploration of the regional effects of colchicine in the LoDoCo2 Trial.

BACKGROUND: The Low Dose Colchicine 2 (LoDoCo2) trial randomized 5,522 patients with chronic coronary disease to colchicine 0.5mg daily or placebo in a 1:1 ratio and demonstrated the cardiovascular benefits of colchicine. In the trial, which was conducted in Australia and The Netherlands, a prespecified subgroup analysis suggested a difference in magnitude of treatment effect of colchicine by region (Australia: HR 0.51; 95% CI 0.39-0.67 vs The Netherlands: HR 0.92; 95% CI 0.71-1.20). The aim of this study was to explore possible explanations for the apparent difference in magnitude of treatment effect of colchicine by region in the LoDoCo2 trial. METHODS: The analysis explored potential determinants of variations in the magnitude of effectiveness of colchicine treatment across the regions. This included investigating differences in investigational product, clinical characteristics, concurrent medical therapies and the duration of follow-up using a range of statistical techniques, including sub-group, landmark and effect modification analyses. RESULTS: No differences were found in the colchicine product used in each region. Despite minor differences observed in baseline clinical characteristics and concomitant therapies, the effect modifier analyses demonstrated that these factors did not explain the difference in magnitude of treatment effect of colchicine by region. Randomization in Australia began more than two years before The Netherlands, with shorter duration of follow-up in The Netherlands compared to Australia. In a landmark analysis, over the period when more than 90% of patients in each region had been followed, the effects of colchicine were similar (Australia hazard ratio [HR] 0.58 95% CI 0.34-0.97 vs The Netherlands HR 0.67 95% CI 0.47-0.96). CONCLUSIONS: After examining several plausible explanations for the observed differences in the magnitude of treatment effect of colchicine between regions in the LoDoCo2 trial could be due to the differences in duration of follow-up but a substantial portion of the differences remain unexplained. CLINICAL TRIAL REGISTRATION: https://www.anzctr.org.au/ACTRN12614000093684.

Organizational readiness and implementation fidelity of an early childhood education and care-specific physical activity policy intervention: findings from the Play Active trial.

BACKGROUND: Many children do not accumulate sufficient physical activity for good health and development at early childhood education and care (ECEC). This study examined the association between ECEC organizational readiness and implementation fidelity of an ECEC-specific physical activity policy intervention. METHODS: Play Active aimed to improve the ECEC educator's physical activity practices. We investigated the implementation of Play Active using a Type 1 hybrid study (January 2021-March 2022). Associations between organizational readiness factors and service-level implementation fidelity were examined using linear regressions. Fidelity data were collected from project records, educator surveys and website analytics. RESULTS: ECEC services with higher levels of organizational commitment and capacity at pre-implementation reported higher fidelity scores compared to services with lower organizational commitment and capacity (all Ps < 0.05). Similarly, services who perceived intervention acceptability and appropriateness at pre-implementation to be high had higher fidelity scores (P < 0.05). Perceived feasibility and organizational efficacy of Play Active were associated with higher but nonsignificant fidelity scores. CONCLUSIONS: Results indicate that organizational readiness factors may influence the implementation of ECEC-specific physical activity policy interventions. Therefore, strategies to improve organizational readiness should be developed and tested. These findings warrant confirmation in the ECEC and other settings and with other health behavior interventions.

Colchicine in Patients with Chronic Coronary Disease.

BACKGROUND: Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited. METHODS: In a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo. The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke. RESULTS: A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P<0.001). A key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia-driven coronary revascularization, and spontaneous myocardial infarction were also significantly lower with colchicine than with placebo. The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31). CONCLUSIONS: In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. (Funded by the National Health Medical Research Council of Australia and others; LoDoCo2 Australian New Zealand Clinical Trials Registry number, ACTRN12614000093684.).

Left ventricular remodelling in rheumatic heart disease - trends over time and implications for follow-up in childhood.

BACKGROUND: Rheumatic heart disease (RHD) is the most common form of acquired heart disease worldwide. In RHD, volume loading from mitral regurgitation leads to left ventricular (LV) dilatation, increased wall stress, and ultimately LV dysfunction. Improved understanding of LV dynamics may contribute to refined timing of intervention. We aimed to characterize and compare left ventricular remodelling between rheumatic heart disease (RHD) severity groups by way of serial echocardiographic assessment of volumes and function in children. METHODS: Children with RHD referred to Perth Children's Hospital (formally Princess Margaret Hospital) (1987-2020) were reviewed. Patients with longitudinal pre-operative echocardiograms at diagnosis, approximately 12 months and at most recent follow-up, were included and stratified into RHD severity groups. Left ventricular (LV) echocardiographic parameters were assessed. Adjusted linear mixed effect models were used to compare interval changes. RESULTS: 146 patients (median age 10 years, IQR 6-14 years) with available longitudinal echocardiograms were analysed. Eighty-five (58.2%) patients had mild, 33 (22.6%) moderate and 28 (19.2%) severe RHD at diagnosis. Mean duration of follow-up was 4.6 years from the initial diagnosis. Severe RHD patients had significantly increased end-systolic volumes (ESV) and end-diastolic volumes (EDV) compared to mild/moderate groups at diagnosis (severe versus mild EDV mean difference 27.05 ml/m2, p < 0.001, severe versus moderate EDV mean difference 14.95 ml/m2, p = 0.006). Mild and moderate groups experienced no significant progression of changes in volume measures. In severe RHD, LV dilatation worsened over time. All groups had preserved cardiac function. CONCLUSIONS: In mild and moderate RHD, the lack of progression of valvular regurgitation and ventricular dimensions suggest a stable longer-term course. Significant LV remodelling occurred at baseline in severe RHD with progression of LV dilatation over time. LV function was preserved across all groups. Our findings may guide clinicians in deciding the frequency and timing of follow-up and may be of clinical utility during further reiterations of the Australia and New Zealand RHD Guidelines.

Steroid Therapy and Outcome of Parapneumonic Pleural Effusions (STOPPE): A Pilot Randomized Clinical Trial.

Rationale: Pleural effusion commonly complicates community-acquired pneumonia and is associated with intense pleural inflammation. Whether antiinflammatory treatment with corticosteroids improves outcomes is unknown. Objectives: To assess the effects of corticosteroids in an adult population with pneumonia-related pleural effusion. Methods: The STOPPE (Steroid Therapy and Outcome of Parapneumonic Pleural Effusions) trial was a pilot, multicenter, double-blinded, placebo-controlled, randomized trial involving six Australian centers. Patients with community-acquired pneumonia and pleural effusion were randomized (2:1) to intravenous dexamethasone (4 mg twice daily for 48 h) or placebo and followed for 30 days. Given the diverse effects of corticosteroids, a comprehensive range of clinical, serological, and imaging outcomes were assessed in this pilot trial (ACTRN12618000947202). Measurements and Main Results: Eighty patients were randomized (one withdrawn before treatment) and received dexamethasone (n = 51) or placebo (n = 28). This pilot trial found no preliminary evidence of benefits of dexamethasone in improving time to sustained (>12 h) normalization of vital signs (temperature, oxygen saturations, blood pressure, heart, and respiratory rates): median, 41.0 (95% confidence interval, 32.3-54.5) versus 27.8 (15.4-49.5) hours in the placebo arm (hazard ratio, 0.729 [95% confidence interval, 0.453-1.173]; P = 0.193). Similarly, no differences in C-reactive protein or leukocyte counts were observed, except for a higher leukocyte count in the dexamethasone group at Day 3. Pleural drainage procedures were performed in 49.0% of dexamethasone-treated and 42.9% of placebo-treated patients (P = 0.60). Radiographic pleural opacification decreased over time with no consistent intergroup differences. Mean duration of antibiotic therapy (22.4 [SD, 15.4] vs. 20.4 [SD, 13.8] d) and median hospitalization (6.0 [interquartile range, 5.0-10.0] vs. 5.5 [interquartile range, 5.0-8.0] d) were similar between the dexamethasone and placebo groups. Serious adverse events occurred in 25.5% of dexamethasone-treated and 21.4% of placebo-treated patients. Transient hyperglycemia more commonly affected the dexamethasone group (15.6% vs. 7.1%). Conclusions: Systemic corticosteroids showed no preliminary benefits in adults with parapneumonic effusions. Clinical trial registered with www.anzctr.org.au (ACTRN12618000947202).

Outcomes following PCI in CABG candidates during the COVID-19 pandemic: The prospective multicentre UK-ReVasc registry.

OBJECTIVES: To describe outcomes following percutaneous coronary intervention (PCI) in patients who would usually have undergone coronary artery bypass grafting (CABG). BACKGROUND: In the United Kingdom, cardiac surgery for coronary artery disease (CAD) was dramatically reduced during the first wave of the COVID-19 pandemic. Many patients with "surgical disease" instead underwent PCI. METHODS: Between 1 March 2020 and 31 July 2020, 215 patients with recognized "surgical" CAD who underwent PCI were enrolled in the prospective UK-ReVasc Registry (ReVR). 30-day major cardiovascular event outcomes were collected. Findings in ReVR patients were directly compared to reference PCI and isolated CABG pre-COVID-19 data from British Cardiovascular Intervention Society (BCIS) and National Cardiac Audit Programme (NCAP) databases. RESULTS: ReVR patients had higher incidence of diabetes (34.4% vs 26.4%, P = .008), multi-vessel disease with left main stem disease (51.4% vs 3.0%, P < .001) and left anterior descending artery involvement (94.8% vs 67.2%, P < .001) compared to BCIS data. SYNTAX Score in ReVR was high (mean 28.0). Increased use of transradial access (93.3% vs 88.6%, P = .03), intracoronary imaging (43.6% vs 14.4%, P < .001) and calcium modification (23.6% vs 3.5%, P < .001) was observed. No difference in in-hospital mortality was demonstrated compared to PCI and CABG data (ReVR 1.4% vs BCIS 0.7%, P = .19; vs NCAP 1.0%, P = .48). Inpatient stay was half compared to CABG (3.0 vs 6.0 days). Low-event rates in ReVR were maintained to 30-day follow-up. CONCLUSIONS: PCI undertaken using contemporary techniques produces excellent short-term results in patients who would be otherwise CABG candidates. Longer-term follow-up is essential to determine whether these outcomes are maintained over time.

Multimodal Structural Analysis of the Human Aorta: From Valve to Bifurcation.

OBJECTIVE: The aims of the present study were to assess the relative proportion of collagen and elastin in the arterial wall and to evaluate the collagen microstructure from the aortic root to the external iliac artery. METHODS: Arterial wall tissue samples sampled during post-mortem examination from 16 sites in 14 individuals without aneurysm disease were fixed and stained for collagen and elastin. Stained sections were imaged and analysed to calculate collagen and elastin content as a percentage of overall tissue area. Scanning electron microscopy was used to quantify the collagen microstructure at six specific arterial regions. RESULTS: From the aortic root to the level of the suprarenal aorta, the percentages (area fractions) of collagen (ascending, descending, and suprarenal aorta respectively with 95% confidence interval [CI] 37.5%, 31.7 - 43.2; 38.9%, 33.1 - 44.7; 44.8%, 37.4 - 52.1) and elastin (43.0%, 37.3 - 48.8; 40.3%, 34.8 - 46.1; 32.4%, 25.2 - 39.6) in the aortic wall were similar. From the suprarenal aorta to the internal iliac arteries, the percentage of collagen increased (abdominal aorta, common and internal iliac arteries and external iliac artery respectively with 95% CI 50.6%, 42.7 - 58.7; 51.2%, 45.5 - 56.9; 49.2%, 42.0 - 56.4) reaching a double percentage for elastin (23.6%, 15.7 - 31.6; 20.8%, 15.1 - 26.5; 22.2%, 14.9 - 29.5). Mean collagen fibre diameter (MFD) and average segment length (ASL) were significantly larger in the external iliac artery (MFD 6.03, 95% CI 5.95 - 6.11; ASL 22.21, 95% CI 20.80 - 23.61) than in the ascending aorta (MFD 5.81, 5.72 - 5.89; ASL 19.47, 18.07 - 20.88) and the abdominal aorta (MFD 5.92, 5.84 - 6.00; ASL 21.10, 19.69 - 22.50). CONCLUSION: In subjects lacking aneurysmal disease, the aorta and iliac arteries are not structurally uniform along their length. There is an increase in collagen percentage and decrease in elastin percentage progressing distally along the aorta. Mean collagen fibre diameter and average segment length are larger in the external iliac artery, compared with the ascending and the abdominal aorta.

Hospital-Acquired Infection, Length of Stay, and Readmission in Elective Surgery Patients Transfused 1 Unit of Red Blood Cells: A Retrospective Cohort Study.

BACKGROUND: Most patients transfused red blood cells in elective surgery receive small volumes of blood, which is likely to be discretionary and avoidable. We investigated the outcomes of patients who received a single unit of packed red blood cells during their hospital admission for an elective surgical procedure when compared to those not transfused. METHODS: This retrospective cohort study included elective surgical admissions to 4 hospitals in Western Australia over a 6-year period. Participants were included if they were at least 18 years of age and were admitted for elective surgery between July 2014 and June 2020. We compared outcomes of patients who had received 1 unit of red blood cells to patients who had not been transfused. To balance differences in patient characteristics, we weighted our multivariable regression models using the inverse probability of treatment. In addition to propensity score weighting, our multivariable regression models adjusted for hemoglobin level, surgical procedure, patient age, gender, comorbidities, and the transfusion of fresh-frozen plasma or platelets. Outcomes studied were hospital-acquired infection, hospital length of stay, and all-cause emergency readmissions within 28 days. RESULTS: Overall, 767 (3.2%) patients received a transfusion of 1 unit of red blood cells throughout their admission. In the propensity score weighted analysis, the transfusion of a single unit of red blood cells was associated with higher odds of hospital-acquired infection (odds ratio, 3.94; 95% confidence interval [CI], 2.99-5.20; P < .001). Patients who received 1 unit of red blood cells throughout their admission were more likely to have a longer hospital stay (rate ratio, 1.57; 95% CI, 1.51-1.63; P < .001) and had 1.42 (95% CI, 1.20-1.69; P < .001) times higher odds of 28-day readmission. CONCLUSIONS: These results suggest that avoidance of even small volumes of packed red blood cells may prevent adverse clinical outcomes. This may encourage hospital administrators to implement strategies to avoid the transfusion of even small volumes of red blood cells by applying patient blood management practices.

Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials.

AIMS: Recent randomized trials demonstrated a benefit of low-dose colchicine added to guideline-based treatment in patients with recent myocardial infarction or chronic coronary disease. We performed a systematic review and meta-analysis to obtain best estimates of the effects of colchicine on major adverse cardiovascular events (MACE). METHODS AND RESULTS: We searched the literature for randomized clinical trials of long-term colchicine in patients with atherosclerosis published up to 1 September 2020. The primary efficacy endpoint was MACE, the composite of myocardial infarction, stroke, or cardiovascular death. We combined the results of five trials that included 11 816 patients. The primary endpoint occurred in 578 patients. Colchicine reduced the risk for the primary endpoint by 25% [relative risk (RR) 0.75, 95% confidence interval (CI) 0.61-0.92; P = 0.005], myocardial infarction by 22% (RR 0.78, 95% CI 0.64-0.94; P = 0.010), stroke by 46% (RR 0.54, 95% CI 0.34-0.86; P = 0.009), and coronary revascularization by 23% (RR 0.77, 95% CI 0.66-0.90; P < 0.001). We observed no difference in all-cause death (RR 1.08, 95% CI 0.71-1.62; P = 0.73), with a lower incidence of cardiovascular death (RR 0.82, 95% CI 0.55-1.23; P = 0.34) counterbalanced by a higher incidence of non-cardiovascular death (RR 1.38, 95% CI 0.99-1.92; P = 0.060). CONCLUSION: Our meta-analysis indicates that low-dose colchicine reduced the risk of MACE as well as that of myocardial infarction, stroke, and the need for coronary revascularization in a broad spectrum of patients with coronary disease. There was no difference in all-cause mortality and fewer cardiovascular deaths were counterbalanced by more non-cardiovascular deaths.

Conventional Glycaemic Control May Not Be Beneficial in Diabetic Patients Following Cardiac Surgery.

INTRODUCTION: Stress hyperglycaemia is common following cardiac surgery. Its optimal management is uncertain and emerging literature suggests that flexible glycaemic control in diabetic patients may be preferable. This study aims to assess the relationship between maximal postoperative in-hospital blood glucose levels (BSL) and the morbidity and mortality outcomes of diabetic and non-diabetic cardiac surgery patients. METHODS: A retrospective cohort analysis of all patients undergoing cardiac surgery at a tertiary single centre institution from 2015 to 2019 was undertaken. Early management and outcomes of hyperglycaemia following cardiac surgery were assessed via multivariable regression modelling. Follow-up was assessed to 1 year postoperatively. RESULTS: Consecutive non-diabetic patients (n=1,050) and diabetic patients (n=689) post cardiac surgery were included. Diabetics with peak BSL ≤13.9 mmol/L did not have an increased risk of morbidity or mortality compared to non-diabetics with peak BSL ≤10.0 mmol/L. In non-diabetics, stress hyperglycaemia with peak BSL >10.0 mmol/L was associated with overall wound complications (5.7% vs 8.8%, OR 1.64 [1.00-2.69], p=0.049) and postoperative pneumonia (2.7% vs 7.3%, OR 2.35 [1.26-4.38], p=0.007). Diabetic patients with postoperative peak BSL >13.9 mmol/L were at an increased risk of overall wound complication (7.4% vs 14.8%, OR 2.47 [1.46-4.16], p<0.001), graft harvest site infection (3.7% vs 11.8%, OR 3.75 [1.92-7.30], p<0.001), and wound-related readmission (3.1% vs 8.8%, OR 3.11 [1.49-6.47], p=0.002) when compared to diabetics with peak BSL ≤13.9 mmol/L. CONCLUSION: In non-diabetics, stress hyperglycaemia with peak BSL >10.0 mmol/L is associated with morbidity. In diabetic patients, hyperglycaemia with peak BSL ≤13.9 mmol/L was not associated with an increased risk of morbidity or mortality compared to non-diabetics with peak BSL ≤10.0 mmol/L. Further investigation of flexible glycaemic targets (target BSL ≤13.9 mmol/L) in diabetic patients is warranted.

Chronic infarct size after spontaneous coronary artery dissection: implications for pathophysiology and clinical management.

AIMS: To report the extent and distribution of myocardial injury and its impact on left ventricular systolic function with cardiac magnetic resonance imaging (CMR) following spontaneous coronary artery dissection (SCAD) and to investigate predictors of myocardial injury. METHODS AND RESULTS: One hundred and fifty-eight angiographically confirmed SCAD-survivors (98% female) were phenotyped by CMR and compared in a case-control study with 59 (97% female) healthy controls (44.5 ± 8.4 vs. 45.0 ± 9.1 years). Spontaneous coronary artery dissection presentation was with non-ST-elevation myocardial infarction in 95 (60.3%), ST-elevation myocardial infarction (STEMI) in 52 (32.7%), and cardiac arrest in 11 (6.9%). Left ventricular function in SCAD-survivors was generally well preserved with small reductions in ejection fraction (57 ± 7.2% vs. 60 ± 4.9%, P < 0.01) and increases in left ventricular dimensions (end-diastolic volume: 85 ± 14 mL/m2 vs. 80 ± 11 mL/m2, P < 0.05; end-systolic volume: 37 ± 11 mL/m2 vs. 32 ± 7 mL/m2, P <0.01) compared to healthy controls. Infarcts were small with few large infarcts (median 4.06%; range 0-30.9%) and 39% having no detectable late gadolinium enhancement (LGE). Female SCAD patients presenting with STEMI had similar sized infarcts to female Type-1 STEMI patients age <75 years. Multivariate modelling demonstrated STEMI at presentation, initial TIMI 0/1 flow, multivessel SCAD, and a Beighton score >4 were associated with larger infarcts [>10% left ventricular (LV) mass]. CONCLUSION: The majority of patients presenting with SCAD have no or small infarctions and preserved ejection fraction. Patients presenting with STEMI, TIMI 0/1 flow, multivessel SCAD and those with features of connective tissue disorders are more likely to have larger infarcts.

The Pleural Effusion And Symptom Evaluation (PLEASE) study of breathlessness in patients with a symptomatic pleural effusion.

INTRODUCTION: Pathophysiology changes associated with pleural effusion, its drainage and factors governing symptom response are poorly understood. Our objective was to determine: 1) the effect of pleural effusion (and its drainage) on cardiorespiratory, functional and diaphragmatic parameters; and 2) the proportion as well as characteristics of patients with breathlessness relief post-drainage. METHODS: Prospectively enrolled patients with symptomatic pleural effusions were assessed at both pre-therapeutic drainage and at 24-36 h post-therapeutic drainage. RESULTS: 145 participants completed pre-drainage and post-drainage tests; 93% had effusions ≥25% of hemithorax. The median volume drained was 1.68 L. Breathlessness scores improved post-drainage (mean visual analogue scale (VAS) score by 28.0±24 mm; dyspnoea-12 (D12) score by 10.5±8.8; resting Borg score before 6-min walk test (6-MWT) by 0.6±1.7; all p<0.0001). The 6-min walk distance (6-MWD) increased by 29.7±73.5 m, p<0.0001. Improvements in vital signs and spirometry were modest (forced expiratory volume in 1 s (FEV1) by 0.22 L, 95% CI 0.18-0.27; forced vital capacity (FVC) by 0.30 L, 95% CI 0.24-0.37). The ipsilateral hemi-diaphragm was flattened/everted in 50% of participants pre-drainage and 48% of participants exhibited paradoxical or no diaphragmatic movement. Post-drainage, hemi-diaphragm shape and movement were normal in 94% and 73% of participants, respectively. Drainage provided meaningful breathlessness relief (VAS score improved ≥14 mm) in 73% of participants irrespective of whether the lung expanded (mean difference 0.14, 95% CI 10.02-0.29; p=0.13). Multivariate analyses found that breathlessness relief was associated with significant breathlessness pre-drainage (odds ratio (OR) 5.83 per standard deviation (sd) decrease), baseline abnormal/paralyzed/paradoxical diaphragm movement (OR 4.37), benign aetiology (OR 3.39), higher pleural pH (OR per sd increase 1.92) and higher serum albumin level (OR per sd increase 1.73). CONCLUSIONS: Breathlessness and exercise tolerance improved in most patients with only a small mean improvement in spirometry and no change in oxygenation. Breathlessness improvement was similar in participants with and without trapped lung. Abnormal hemi-diaphragm shape and movement were independently associated with relief of breathlessness post-drainage.

U-shaped association of vigorous physical activity with risk of metabolic syndrome in men with low lean mass, and no interaction of physical activity and serum 25-hydroxyvitamin D with metabolic syndrome risk.

BACKGROUND: There is uncertainty over how lean mass, physical activity (PA) and 25-hydroxyvitamin D (25-OH-D) status interact on metabolic syndrome (MetS) risk in adults. AIMS: To test the hypothesis that these factors additively influence MetS risk. METHODS: Four thousand eight hundred and fifty-eight adults (54.6% female) mean ± SD age 58.0 ± 5.8 years, body mass index 28.1 ± 4.8 kg/m2 , resident in Busselton, Western Australia. PA assessed by questionnaire (all/total and vigorous), lean mass using dual energy X-ray absorptiometry (% total body mass), serum 25-OH-D via immunoassay, analysed using multivariable logistic regression. RESULTS: In men, lower total PA was associated with MetS (no vs >24 h/week odds ratio (OR) = 3.1; ≤8 vs >24 h/week OR = 1.8, both P < 0.001), as was lower lean mass (low vs high OR = 20.4; medium vs high OR = 7.4, both P < 0.001). Men with low lean mass exhibited a U-shaped relationship of vigorous PA with MetS risk (covariate-adjusted: 0 vs 4-8 h/week OR = 2.1, P = 0.037; >12 vs 4-8 h/week OR = 4.3, P = 0.002; interaction P = 0.039). In women, low PA (0 vs >24 h/week OR = 2.1, P = 0.003) and lean mass (low vs high OR = 13.1; medium vs high OR = 7.2, both P < 0.001) were associated with MetS risk. Low 25-OH-D status was associated with MetS in men (low vs high OR = 4.1; medium vs high OR = 2.3, both P < 0.001) and women (OR = 3.5 and 2.1 respectively, both P < 0.001) with no PA interaction. CONCLUSIONS: Men and women with high lean mass have low risk of MetS regardless of PA. Low lean mass identifies men who may benefit most from increasing PA, with an optimal level associated with lowest risk. 25-OH-D and PA do not interact on MetS risk.

The effect of low-dose colchicine in patients with stable coronary artery disease: The LoDoCo2 trial rationale, design, and baseline characteristics.

Because patients with stable coronary artery disease are at continued risk of major atherosclerotic events despite effective secondary prevention strategies, there is a need to continue to develop additional safe, effective and well-tolerated therapies for secondary prevention of cardiovascular disease. RATIONALE AND DESIGN: The LoDoCo (Low Dose Colchicine) pilot trial showed that the anti-inflammatory drug colchicine 0.5 mg once daily appears safe and effective for secondary prevention of cardiovascular disease. Colchicine's low cost and long-term safety suggest that if its efficacy can be confirmed in a rigorous trial, repurposing it for secondary prevention of cardiovascular disease would have the potential to impact the global burden of cardiovascular disease. LoDoCo2 is an investigator-initiated, international, multicentre, double-blind, event driven trial in which 5522 patients with stable coronary artery disease tolerant to colchicine during a 30-day run-in phase have been randomized to colchicine 0.5 mg daily or matching placebo on a background of optimal medical therapy. The study will have 90% power to detect a 30% reduction in the composite primary endpoint: cardiovascular death, myocardial infarction, ischemic stroke and ischemia-driven coronary revascularization. Adverse events potentially related to the use of colchicine will also be collected, including late gastrointestinal intolerance, neuropathy, myopathy, myositis, and neutropenia. CONCLUSION: The LoDoCo2 Trial will provide information on the efficacy and safety of low-dose colchicine for secondary prevention in patients with stable coronary artery disease.

Changes in pulp blood flow and pulp sensibility resulting from surgically assisted rapid maxillary expansion: A clinical study.

INTRODUCTION: The aim of this work was to assess and compare changes in pulp blood flow (PBF) and pulp sensibility (PS) after surgically assisted rapid maxillary expansion (SARME) and rapid orthopedic maxillary expansion (OME). METHODS: Ten patients requiring SARME and 10 requiring OME had the pulp status of their maxillary incisors and canines assessed with the use of laser Doppler flowmetry, electric pulp testing (EPT), and CO2 snow. The SARME group was assessed at T1-S (before surgery), T2-S (after surgery, before expansion), T3-S (after surgery, at completion of expansion), and T4-S (3 months after surgery). The OME group was assessed at T1-O (before expansion), T2-O (after rapid expansion), and T3-O (3 months after expansion commencement). Relationships between PBF/PS and the procedures, assessment times, and tooth types were evaluated. RESULTS: In the SARME group, surgery did not cause significant (P ≥0.05) reduction in PBF, maxillary expansion did cause significant (P ≤0.05) reduction in PBF, pretreatment PBF was reestablished by T4-S, and nonresponses to both EPT and CO2 peaked at T2-S. In the OME group, rapid expansion caused significant (P ≤0.05) reduction in PBF, pretreatment PBF was reestablished by T3-O, and all teeth responded to at least 1 of EPT or CO2 at each assessment time. CONCLUSIONS AND CLINICAL IMPLICATIONS: Within the study's limitations, it can be concluded that both SARME and OME induce reduction but not elimination of PBF to maxillary anterior teeth and therefore do not cause loss of pulp vitality; surgery for SARME does not significantly reduce PBF to maxillary anterior teeth, rather it is the process of maxillary expansion that significantly reduces PBF in SARME patients; and caution when using CO2 and EPT tests alone to assess pulp status after SARME is warranted because the capacity for CO2 or EPT to provide negative sensibility responses despite the presence of PBF was observed.

Performance of manual hyperinflation: consistency and modification of the technique by intensive care unit nurses during physiotherapy.

AIMS AND OBJECTIVES: To assess the consistency and safety of manual hyperinflation delivery by nurses of variable clinical experience using a resuscitator bag during physiotherapy treatment. BACKGROUND: Manual hyperinflation involves the delivery of larger than normal gas volumes to intubated patients and is routinely used by nurses in collaboration with physiotherapists for the management of retained sputum. The aim is to deliver slow deep breaths with an inspiratory hold without unsafe airway pressures, lung volumes or haemodynamic changes. In addition, nursing staff should be able to 'feel' differences in resistance and adjust their technique accordingly. DESIGN: Prospective observational study utilising the simulation of a mechanically ventilated patient. METHODS: Thirty-three nurses delivered manual hyperinflation to a SimMan3G mannequin who had three distinct lung scenarios applied (normal; asthma; Acute Respiratory Distress Syndrome) in randomised order during simulated physiotherapy treatment. Respiratory rate, tidal volume (Vt ), mean inspiratory flow rate (Vt /Ti), and peak airway pressure data were generated. RESULTS: Over all scenarios, mean respiratory rate = 12·3 breaths/minute, mean Vt  = 638·6 mls, mean inflation time = 1·3 seconds and peak airway pressure exceeded 40 cm H2 O in 41% of breaths, although only in 10% of breaths during the 'normal' lung scenario. CONCLUSIONS: Experienced nurses were able to manually hyperinflate 'normal' patients in a simulated setting safely. Despite their knowledge of barotrauma, unsafe airway pressures were delivered in some scenarios. RELEVANCE TO CLINICAL PRACTICE: Training with regard to safe airway pressures, breath hold and adequate volumes is recommended for all nurses undertaking the procedure. Nurses and physiotherapists must closely monitor the patient's condition during manual hyperinflation thereby recognising changes with regard to lung compliance and airway resistance, with nurses responding by altering their technique. The addition of a pressure manometer in the circuit may improve patient safety when performing manual hyperinflation.

Dysphagia and factors associated with respiratory infections in the first week post stroke.

BACKGROUND: Dysphagia occurs in approximately half of the stroke patients and is associated with respiratory infections; however, it is unclear what other factors contribute to an increased risk. This study aimed to provide evidence on factors associated with respiratory infections in the very acute stroke period. METHODS: Retrospective review of 536 stroke patients admitted to Australian Hospitals in 2010. Data were collected on 37 clinical and demographic parameters. Univariable and multivariable logistic regression was performed. RESULTS: The overall incidence of respiratory infection was 11%. On admission, requiring full assistance with mobility [OR 6.48, 95% CI 1.35, 31.16] and urinary incontinence [OR 3.21, 95% CI 1.16, 8.87] were associated with respiratory infections. During the first week post stroke nasogastric tubes (NGT) [OR 3.91, 95% CI 1.73, 8.80] and Nil By Mouth (NBM) [OR 5.62, 95% CI 1.54, 20.46] were associated with respiratory infections. Impaired GCS, ischaemic stroke and significantly impaired mobility were associated with swallowing difficulties. CONCLUSION: This study of a large cohort of acute stroke patients supports research indicating aspiration pneumonia is multifactorial in nature. NGT were associated with increased risk of respiratory infections and may contribute to infections by promoting oropharyngeal colonisation. Patients with severely impaired mobility were also at very high risk of respiratory infection.

Respiratory infections in acute stroke: nasogastric tubes and immobility are stronger predictors than dysphagia.

Swallowing problems occur in 37-78 % of stroke patients. Evidence points to multiple factors contributing to the development of pneumonia in the first week post stroke, of which the presence of dysphagia is one. A heightened understanding of the very acute phase (first 7 days post stroke) is required to improve management of this population. We conducted a retrospective review of 536 stroke patients admitted to Australian hospitals in 2010. Data were collected on 37 clinical and demographic parameters. Descriptive statistics and univariate and multivariate logistic regression analyses were performed. Dysphagia was present in 58.5 % of admissions. For those patients remaining in the study for the full week there was a recovery rate from dysphagia of 30.5 %. Overall incidence of respiratory infection was 11 %. Respiratory infections developed in 17 % of patients with dysphagia. Impaired Glasgow Coma Scale, ischemic stroke, and significantly impaired mobility were associated with swallowing difficulties. Being nil by mouth and insertion of a nasogastric tube were significant predictors for respiratory infections. This study of a large cohort of acute stroke patients supports research indicating that aspiration pneumonia is multifactorial in nature and the incidence of respiratory infection is significant in the very acute stroke period.