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Background and Aims To examine the decongestive effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin compared to the thiazide-like diuretic metolazone in patients hospitalized for heart failure and resistant to treatment with intravenous furosemide. Methods A multi-centre, open-label, randomized, active-comparator trial. Patients were randomized to dapagliflozin 10 mg once daily or metolazone 5-10 mg once daily for a 3-day treatment period, with follow-up for primary and secondary endpoints until day 5 (96 hours). The primary endpoint was diuretic effect, assessed by change in weight (kg). Secondary endpoints included change in pulmonary congestion (lung ultrasound), loop diuretic efficiency (weight change per 40 mg of furosemide), and a volume assessment score. Results 61 patients were randomized. The mean (±standard deviation) cumulative dose of furosemide at 96 hours was 976 (±492) mg in the dapagliflozin group and 704 (±428) mg in patients assigned to metolazone. The mean (±standard deviation) decrease in weight at 96 hours was 3.0 (2.5) kg with dapagliflozin compared to 3.6 (2.0) kg with metolazone [mean difference 0.65, 95% confidence interval (CI) -0.12,1.41 kg; p=0.11]. Loop diuretic efficiency was less with dapagliflozin than with metolazone [mean 0.15 (0.12) versus 0.25 (0.19); difference -0.08, 95% CI -0.17,0.01 kg; p=0.10]. Changes in pulmonary congestion and volume assessment score were similar between treatments. Decreases in plasma sodium and potassium and increases in urea and creatinine were smaller with dapagliflozin than with metolazone. Serious adverse events were similar between treatments. Conclusion In patients with heart failure and loop diuretic resistance, dapagliflozin was not more effective at relieving congestion than metolazone. Patients assigned to dapagliflozin received a larger cumulative dose of furosemide but experienced less biochemical upset than those assigned to metolazone. ClinicalTrials.gov Identifier NCT04860011

Background: Several drugs have anticholinergic side effects that are associated with adverse health outcomes. Anticholinergic burden studies in adults with intellectual disabilities (ID) have focused exclusively on older adults. This study investigates anticholinergic burden and its associations in adults with ID of all ages (17–94 years). Methods: Adults with ID (n = 4 305), each with three general population age–sex–neighbourhood-matched controls (n = 12 915), were linked to their prescribed medications with anticholinergic effects between 2009 and 2017. Analyses were undertaken using logistic regression models. Results: Adults with ID were more likely to be prescribed any anticholinergic medicines, odds ratio (OR) = 1.49 (1.38–1.59), especially ‘very strong’ risk medicines, OR = 2.59 (2.39–2.81); 48.5% had very high total anticholinergic burden (3+) compared with 35.4% of the general population, OR = 1.77 (1.64–1.90). This group difference was greater for males, OR = 2.02 (1.84–2.22), than females, OR = 1.48 (1.33–1.65). Adults with ID had significantly higher odds of having very high total anticholinergic burden up to 75 years old, with the greatest group effect occurring in younger ages, 17-24-year-olds, OR = 3.05 (2.39–3.89), and the extent of the difference decreased as age increased. The main effect of neighbourhood deprivation showed greater group differences with increasing affluence of neighbourhood. Results examining only the ID group showed that very high total anticholinergic burden was greatest for females, OR = 1.21 (1.07–1.37), and those over age 55, and extent of neighbourhood deprivation was not significant. Conclusions: Adults with ID are at higher risk of anticholinergic burden than the general population, especially young adults. Overall anticholinergic burden increased with age, but burden was high across all ages in the ID group. Very high total anticholinergic burden is prevalent across all types of neighbourhoods for the adults with ID, in contrast to the steeper gradient seen in the general population. Adults with ID have increased likelihood of unintended adverse effects, regardless of potential confounds, so clinicians undertaking medication reviews need to consider anticholinergic side effects and cumulative burden across concomitant medications, including in young adults with ID, not just older adults, and particularly women.

BackgroundPsychotropics are overprescribed for adults with intellectual disabilities; there are few studies in children and young people.AimsTo investigate antipsychotic and antidepressant prescribing in children and young people with and without intellectual disabilities, and prescribing trends.MethodScotland's annual Pupil Census, which identifies pupils with and without intellectual disabilities, was record-linked to the Prescribing Information System. Antidepressant and antipsychotic data were extracted. Logistic regression was used to analyse prescribing between 2010 and 2013.ResultsOf the 704 297 pupils, 16 142 (2.29%) had a record of intellectual disabilities. Antipsychotic and antidepressant use increased over time, and was higher in older pupils; antipsychotic use was higher in boys, and antidepressant use was higher in girls. Overall, antipsychotics were prescribed to 281 (1.74%) pupils with intellectual disabilities and 802 (0.12%) without (adjusted odds ratio 16.85, 95% CI 15.29–18.56). The higher use among those with intellectual disabilities fell each year (adjusted odds ratio 20.19 in 2010 v. 14.24 in 2013). Overall, 191 (1.18%) pupils with intellectual disabilities and 4561 (0.66%) without were prescribed antidepressants (adjusted odds ratio 2.28, 95% CI 2.03–2.56). The difference decreased each year (adjusted odds ratio 3.10 in 2010 v. 2.02 in 2013).ConclusionsSignificantly more pupils with intellectual disabilities are prescribed antipsychotics and antidepressants than are other pupils. Prescribing overall increased over time, but less so for pupils with intellectual disabilities; either they are not receiving the same treatment advances as other pupils, or possible overprescribing in the past is changing. More longitudinal data are required.

Background Multimorbidity (two or more concurrent chronic conditions) is associated with poorer health outcomes and increased healthcare utilisation in primary care and general populations. Less is known about the prevalence of multimorbidity in emergency department attenders, or its association with poor outcomes in this population. Aim This study sought to explore the relationship between multimorbidity, mortality and health-care utilisation in a large urban cohort of persons attending emergency departments. Methods Validated algorithms for the identification of 28 chronic conditions from ICD-10 codes were deployed on a cross-sectional sample of patients attending emergency departments in Glasgow, Scotland between April 2019 and March 2020. Analysis was conducted on complete cases (n=63,328) and compared with results from data with imputed missing values (n=75,723). Models adjusted for age, sex, deprivation and ethnicity were fitted to test for the association between (i) multimorbidity, (ii) complex multimorbidity, (iii) disease count and the following outcomes: admission to hospital, reattendance at 30 and 90 days, and death during admission. Results Multimorbidity, complex multimorbidity and disease count were significantly associated with hospital admission and emergency department reattendance. Those with 1-3 conditions were at increased risk of inpatient mortality. Conclusion This study further evidences the impact of multimorbidity and disease burden on health-care use, and mortality to a lesser extent. Deployed algorithms were sufficiently sensitive to detect associations, despite limited access (21 months) to secondary-care data. This should allow for the construction of more robust models to prospectively identify persons at risk of poor outcomes in similar populations.

Background People with intellectual disabilities may face a disproportionate risk of experiencing high anticholinergic burden, and its negative sequalae, from a range of medications, and at younger ages than the general population, but there has been little previous study. Our aim was to determine the source of anticholinergic burden from prescribed medication. Methods Retrospective matched observational study using record linkage. Adults with (n = 4,305), and without (n = 12,915), intellectual disabilities matched by age-, sex- and neighbourhood deprivation. The main outcome measure was the prescription of long-term (approximately 12 months use) anticholinergic medications overall (classified according to the Anticholinergic Risk Scale [ARS]), by drug class, individual drugs, and polypharmacy. Results Adults with n = 1,654 (38.4%), and without n = 3,047 (23.6%), intellectual disabilities were prescribed medications long-term with anticholinergic effects. Of those on such drugs, adults with intellectual disabilities were most likely to be on central nervous system (62.6%), gastrointestinal (46.7%), and cardiovascular (28.4%) medications. They were prescribed more central nervous system, gynaecological/urinary tract, musculoskeletal, and respiratory medications, and less cardiovascular, infection, and endocrine medications than their matched comparators. Regardless of age, sex, or neighbourhood deprivation, adults with intellectual disabilities had greater odds of being prescribed antipsychotics (OR = 5.37 [4.40–6.57], p p p = 0.012). Compared to the general population, adults with intellectual disabilities were more likely to be exposed to overall anticholinergic polypharmacy (OR = 1.48 [1.33–1.66], p p Conclusions Adults with intellectual disabilities are exposed to a greater risk of having very high anticholinergic burden through polypharmacy from several classes of medications, which may be prescribed by several different prescribers. There is a need for evidence-based recommendations specifically about people with intellectual disabilities with multiple physical and mental ill-health conditions to optimise medication use, reduce inappropriate prescribing and adverse anticholinergic effects.

Objectives The aim of this study was to test the hypothesis that invasive coronary function testing at time of angiography could help stratify management of angina patients without obstructive coronary artery disease. Background Medical therapy for angina guided by invasive coronary vascular function testing holds promise, but the longer-term effects on quality of life and clinical events are unknown among patients without obstructive disease. Methods A total of 151 patients with angina with symptoms and/or signs of ischemia and no obstructive coronary artery disease were randomized to stratified medical therapy guided by an interventional diagnostic procedure versus standard care (control group with blinded interventional diagnostic procedure results). The interventional diagnostic procedure–facilitated diagnosis (microvascular angina, vasospastic angina, both, or neither) was linked to guideline-based management. Pre-specified endpoints included 1-year patient-reported outcome measures (Seattle Angina Questionnaire, quality of life [EQ-5D]) and major adverse cardiac events (all-cause mortality, myocardial infarction, unstable angina hospitalization or revascularization, heart failure hospitalization, and cerebrovascular event) at subsequent follow-up. Results Between November 2016 and December 2017, 151 patients with ischemia and no obstructive coronary artery disease were randomized (n = 75 to the intervention group, n = 76 to the control group). At 1 year, overall angina (Seattle Angina Questionnaire summary score) improved in the intervention group by 27% (difference 13.6 units; 95% confidence interval: 7.3 to 19.9; p, Central Illustration

Tea contains polyphenols such as flavonoids, anthocyanidins, flavanols and phenolic acids which in laboratory studies have reported to promote antioxidant enzyme formation, reduces excess inflammation, slow cancer cell proliferation and promote apoptosis. Evidence from epidemiological studies on the effect of tea consumption on prostate cancer (CaP) incidence has been conflicting. We analysed data from 25 097 men within the intervention arm of the 155 000 participant Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Histologically confirmed cases of prostate cancer were reported in 3088 men (12·3 %) during the median 11·5 year follow-up. Tea consumption was assessed with a FFQ. Baseline characteristics were compared between groups using χ2 and Kruskal–Wallis tests. Cox regression models were used to assess associations between tea intake and CaP incidence. There was no statistical difference between the risk of CaP between men who never drank tea to those who drank tea at any quantity. Amongst tea drinkers, those in the highest third of consumption group had a small but significantly lower risk compared with those in the lowest third (11·2 % v. 13·2 % hazard ratio 1·16; (95 % CI 1·05, 1·29), P = 0·004). This pattern persisted with adjustments for demographics and lifestyle. In conclusion, among tea drinkers, there was a small positive association between drinking tea and a reduced risk of prostate cancer. It does not support starting to drink tea, if men previously did not, to reduce the risk. Further research is needed to establish whether tea is justified for future prospective nutritional intervention studies investigating CaP prevention.

PurposeCOVID-19 is associated with cardiovascular complications, with right ventricular dysfunction (RVD) commonly reported. The combination of acute respiratory distress syndrome (ARDS), injurious invasive ventilation, micro/macro thrombi and the potential for direct myocardial injury create conditions where RVD is likely to occur. No study has prospectively explored the prevalence of RVD, and its association with mortality, in a cohort requiring mechanical ventilation.MethodsProspective, multi-centre, trans-thoracic echocardiographic, cohort study of ventilated patients with COVID-19 in Scottish intensive care units. RVD was defined as the presence of severe RV dilatation and interventricular septal flattening. To explore role of myocardial injury, high sensitivity troponin and N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured in all patients.ResultsOne hundred and twenty-one patients were recruited to COVID-RV, 118 underwent imaging and it was possible to determine the primary outcome in 112. RVD was present in seven (6.2% [95%CI; 2.5%, 12.5%]) patients. Thirty-day mortality was 85.7% in those with RVD, compared to 44.8% in those without (p=0.051). Patients with RVD were more likely to have; pulmonary thromboembolism (pabnormal troponin (p=0.048). Abnormal NT-proBNP (OR 4.77 [1.22, 21.32], p=0.03) and abnormal Troponin (16.54 [4.98, 67.12], pConclusionCOVID-RV demonstrates a prevalence of RVD in ventilated patients with COVID-19 of 6.2% and is associated with a mortality of 85.7%. Association is observed between RVD and each of the aetiological domains of; ARDS, ventilation, micro/macro thrombi and myocardial injury.

Background: Patients with angina symptoms and/or signs of ischemia but no obstructive coronary artery disease (INOCA) pose a diagnostic and therapeutic challenge.Objectives: The purpose of ...

Aim Coronary angiography is indicated in many patients with known or suspected angina for the investigation of coronary artery disease (CAD). However, up to half of patients with symptoms of ischaemia have no obstructive coronary arteries (INOCA). This large subgroup includes patients with suspected microvascular angina (MVA) and/or vasospastic angina (VSA). Clinical guidelines relating to the management of patients with INOCA are limited. Uncertainty regarding the diagnosis of patients with INOCA presents a health economic challenge, both in terms of healthcare resource utilisation and of quality-of-life impact on patients. Methods A cost-effectiveness analysis of the introduction of stratified medicine into the invasive management of INOCA, based on clinical and resource-use data obtained in the CorMicA trial, from a UK NHS perspective. The intervention included an invasive diagnostic procedure (IDP) of coronary vascular function during coronary angiography to define clinical endotypes to target with linked medical therapy. Outcomes of interest were mean total cost and QALY gain between treatment groups, and the incremental cost-effectiveness ratio. We undertook probabilistic sensitivity and scenario analyses. Results The incremental cost per QALY gained at 12 months was £4500 (£2937, £33264). Compared with a willingness-to-pay (WTP) threshold of £20,000 per QALY, the use of the IDP test is cost-effective. At this WTP threshold there is a 96% probability of the IDP being cost-effective, based on the uncertainty described by bootstrap analysis. Conclusions The burden of INOCA, particularly in women, is known to be significant. These findings provided new evidence to inform this unmet clinical need.

Aims: \ud In patients at high risk of heart failure following myocardial infarction (MI) as a result of residual left ventricular systolic dysfunction (LVSD), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan may result in a greater attenuation of adverse left ventricular (LV) remodelling than renin angiotensin aldosterone system inhibition alone, due to increased levels of substrates for neprilysin with vasodilatory, anti‐hypertrophic, anti‐fibrotic, and sympatholytic effects.\ud \ud Methods: \ud We designed a randomized, double‐blinded, active‐comparator trial to examine the effect of sacubitril/valsartan to the current standard of care in reducing adverse LV remodelling in patients with asymptomatic LVSD following MI. Eligible patients were ≥3 months following MI, had an LV ejection fraction ≤40% as measured by echocardiography, were New York Heart Association functional classification I, tolerant of an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker at equivalent dose of ramipril 2.5 mg twice daily or greater, and taking a beta‐blocker unless contraindicated or intolerant. Patients were randomized to sacubitril/valsartan (target dose 97/103 mg twice daily) or valsartan (target dose 160 mg twice daily). The primary endpoint will be change in LV end‐systolic volume indexed for body surface area measured using cardiac magnetic resonance imaging over 52 weeks from randomization. Secondary endpoints include other magnetic resonance imaging‐based metrics of LV remodelling, biomarkers associated with LV remodelling and neurohumoral activation, and change in patient well‐being assessed using a patient global assessment questionnaire.\ud \ud Conclusions: \ud This trial will investigate the effect of neprilysin inhibition on LV remodelling and the neurohumoral actions of sacubitril/valsartan in patients with asymptomatic LVSD following MI.

Background/Introduction The PEGASUS-TIMI 54 trial showed that prolonged treatment with ticagrelor reduces the cumulative occurrence of ischemic adverse events. CLARIFY is the biggest real life registry on chronic coronary syndrome. Purpose - To evaluate the percentage of patients eligible for long-term ticagrelor therapy in the CLARIFY registry. – To compare the outcome of this subgroup of patients with those with PEGASUS exclusion criteria or without PEGASUS inclusion criteria. Methods Within the CLARIFY population, we selected post MI patients and we excluded those with missing info (post MI evaluable population). Then, we divided patients into 3 groups: excluded (meeting PEGASUS exclusion criteria, namely use of P2Y12 receptor antagonists or chronic oral anticoagulant, any stroke, coronary-artery bypass grafting in the past 5 years); eligible (meeting PEGASUS high-risk inclusion criteria, namely age≥65 years; diabetes; multivessel disease; creatinine clearance We therefore compared the ischemic (CV death, MI and stroke) and bleeding (major bleeding) outcome of the 3 groups adjusting for age, sex, smoking and geographical region. Results Among the 11811 post-MI evaluable patients, 4706 (39.8%) were included in the eligible group, 5715 (48.4%) in the excluded group, and 1390 in the ineligible group (11.8%). Both the ischemic and bleeding endpoints were significantly different among the 3 groups with the excluded patients with the worst and ineligible patients with the best outcome (see table). The same trend was shown for CV death, while the occurrence of MI was not significantly different among the 3 groups. In the eligible group, the ratio between ischemic and bleeding events was 6:1, whereas between CV death and major bleeding was 3.5:1. Conclusions Around 40% of CLARIFY post-MI patients could benefit from prolonged ticagrelor therapy. In this group of patients, ischemic risk seems to be higher than the bleeding one. Ischemic & bleeding risk in the 3 groups Funding Acknowledgement Type of funding source: Private company. Main funding source(s): CLARIFY registry was funded by Servier

Background: Oral health may be poorer in adults with intellectual disabilities (IDs) who rely on carer support and medications with increased dental risks. Methods: Record linkage study of dental outcomes, and associations with anticholinergic (e.g. antipsychotics) and sugar‐containing liquid medication, in adults with IDs compared with age–sex–neighbourhood deprivation‐matched general population controls. Results: A total of 2933/4305 (68.1%) with IDs and 7761/12 915 (60.1%) without IDs attended dental care: odds ratio (OR) = 1.42 [1.32, 1.53]; 1359 (31.6%) with IDs versus 5233 (40.5%) without IDs had restorations: OR = 0.68 [0.63, 0.73]; and 567 (13.2%) with IDs versus 2048 (15.9%) without IDs had dental extractions: OR = 0.80 [0.73, 0.89]. Group differences for attendance were greatest in younger ages, and restoration/extractions differences were greatest in older ages. Adults with IDs were more likely prescribed with anticholinergics (2493 (57.9%) vs. 6235 (48.3%): OR = 1.49 [1.39, 1.59]) and sugar‐containing liquids (1641 (38.1%) vs. 2315 (17.9%): OR = 2.89 [2.67, 3.12]). Conclusion: Carers support dental appointments, but dentists may be less likely to restore teeth, possibly extracting multiple teeth at individual appointments instead.

Supplemental Digital Content is available in the text., Background: Determine the prevalence and correlates of microvascular and vasospastic angina in patients with symptoms and signs of ischemia but no obstructive coronary artery disease (INOCA). Methods: Three hundred ninety-one patients with angina were enrolled at 2 regional centers over 12 months from November 2016 (NCT03193294). INOCA subjects (n=185; 47%) had more limiting dyspnea (New York Heart Association classification III/IV 54% versus 37%; odds ratio [OR], 2.0 [1.3–3.0]; P=0.001) and were more likely to be female (68% INOCA versus 38% in coronary artery disease; OR, 1.9 [1.5 to 2.5]; P

Background Controversies exist about the relationship between body habitus and mortality, especially for patients with cardiovascular disease. Purpose We evaluated the relations between different anthropometric indices and mortality amongst participants with and without cardiovascular (CV) risk factors, or established CV disease (stroke, myocardial infarction and/or heart failure), enrolled in the UK Biobank. Methods The UK Biobank is a large prospective study which, between 2006 and 2010, enrolled 502,620 participants aged 38–73 years. Participants filled questionnaires and had a medical history recorded, physical measurements done and biological samples taken. The UK Biobank is routinely linked to national death registries and updated on a quarterly basis. Data on death were coded according to the International Classification of Diseases, 10th Revision (ICD-10). The primary end-point was all-cause mortality (ACM) across three subgroups of men and women: those with, or without, one or more CV risk factors (smoking, diabetes and/or hypertension), and those with CV disease (history of stroke, myocardial infarction and/or heart failure) at recruitment. Presence, or absence, of CV risk factors and diagnoses of CV disease were self-reported by participants at enrolment. Associations between anthropometric indices (body mass index (BMI), waist circumference (WC), waist to hip ratio (WHiR), and waist to height ratio (WHeR)) and the risk of all-cause mortality were analysed using Cox regression models. Results After excluding those with history of cancer at baseline (n=45,222), 453,046 participants were included (median age: 58 (interquartile range: 50 - 63) years; 53% women), of whom 150,732 had at least one CV risk factor, and 17,884 established CV disease. During a median follow-up of 5 years, 6,319 participants died. Baseline BMI had a U-shaped relationship with ACM, with higher nadir-values for those with CV risk factors or CV disease, for both sexes (figure). WC, WHiR and WHeR (measures of central distribution of body fat) had more linear associations with ACM, regardless of CV risk factors, CV disease and sex. Conclusions For adults with or without CV risk factors or established CV disease, measures of central distribution of body fat are more strongly and more linearly associated with ACM than BMI. WC, or WHiR, rather than BMI, appear to be more appropriate variables for risk stratification.

Introduction In patients at high risk of heart failure (HF) following myocardial infarction (MI) as a result of residual left ventricular systolic dysfunction (LVSD), the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan may result in a greater attenuation of adverse LV remodeling than renin angiotensin aldosterone system inhibition alone, due to increased levels of substrates for neprilysin with vasodilatory, anti-hypertrophic, anti-fibrotic and sympatholytic effects. In a randomized, double-blinded, active-comparator trial, we examined the effect of sacubitril/valsartan compared with the angiotensin receptor blocker (ARB), valsartan, on LV remodeling in patients with asymptomatic LVSD following MI using the gold-standard method of LV assessment, cardiac magnetic resonance imaging (MRI). Hypothesis In patients with LVSD and no evidence of HF following an MI, treatment with sacubitril/valsartan will result in a greater reduction in the degree of adverse remodeling than valsartan. Methods Key inclusion criteria were: 1) ≥3 months following MI, 2) LV ejection fraction ≤40% as measured by echocardiography, 3) tolerance of an ACE inhibitor or ARB at equivalent dose of ramipril ≥2.5mg twice daily, 4) taking a beta-blocker unless contraindicated or intolerant. Key exclusion criteria were: 1) Symptomatic HF (NYHA ≥II), 2) eGFR 5.2mmol/L, 4) symptomatic hypotension and/or systolic blood pressure Results From 7/19/2018 to 6/28/2019, 93 patients were randomized and the final study visit took place on 6/19/2020. Results from this trial will be available for presentation at the HFSA meeting. Conclusions This trial will investigate the effect of neprilysin inhibition on LV remodeling and the neurohumoral actions of sacubitril/valsartan in patients with asymptomatic LVSD following MI.

e13560 Background: The cruciferous vegetable broccoli, are a good source of vitamins, minerals and fibre, as well as thiol phytochemicals (indole-3-carbinol), glucosinolates (isothiocyanates, its metabolite, sulforaphane), carotenoids (lutein and zeaxanthin) and flavonols (kaempferol). Laboratory and human biopsy studies have found that broccoli intake influenced epigenetic expression of genes via blockage of histone deacetylase which reduce inflammation and cancer growth. Clinically, a randomised control study reported dried broccoli extract (along with three other foods) influenced PSA progression in men with prostate cancer1. However, no preventative intervention studies in humans have been conducted and data from cohort studies are inconsistent for its influence on cancer incidence2,3. Methods: We analysed 49,104 people within the intervention arm of the 155,000 participant PLCO screening trial. Histological confirmed cases of any cancer were reported in 8,263 (16.83%) during the 11.5 year follow up. Broccoli consumption was assessed with a food frequency questionnaire (FFQ). Baseline characteristics were compared between broccoli consumption groups using Chi-square and Kruskal-Wallis tests. Cox regression models were used to assess the association between broccoli intake and cancer incidence. Results: Broccoli consumption was associated with reduced cancer incidence: HR 0.95 (CI 0.93-0.97, p < 0.001). This pattern persisted with adjustments for age, sex, race, education level and family history (HR 0.97, CI 0.96-0.99, p = 0.007) as well as smoking, BMI and alcohol consumption (HR 0.98, CI 0.96-0.99, p = 0.010). Conclusions: The study identified an association between increased broccoli consumption and reduced cancer risk. In practical terms, 15g of broccoli, or more, consumed per day (about a small cup) was associated with a 5% lower risk of cancer. Broccoli should continue to be included in healthy eating advice. This data supports the consideration of future prospective intervention studies investigating the role of broccoli as part of a cancer prevention programme. References 1. Thomas et al. The NCRN Pomi-T RCT. Prostate cancer & prostatic diseases (2014), 2,180. 2. Liu et al Cruciferous vegetables inversely linked with breast cancer: Breast (2013), 22;3,309. 3. Bosetti et al Cruciferous vegetables and cancer risk Ann Oncol (2012) 23(8);2198.

e13559 Background: The popular beverage tea, brewed from infused leaves of camellia sinesis, contains non-phytoestrogenic polyphenols such as flavonoids, anthocyanidins, flavanols (epigallocatechin gallate); phenolic acids (ellagic acid) and stimulants (caffeine, theophylline). Laboratory studies report tea promotes antioxidant enzyme formation, slows cancer cell proliferation and unblocks apoptosis. Clinically, the Pomi-T randomised study reported tea extract (along with three other foods) reduced PSA progression in men with prostate cancer1. Evidence of prostate cancer prevention, however, from prospective cohort data is conflicting with one recent study even implying an increased risk2. Methods: We analysed 25,097 men within the intervention arm of the 155,000 participant PLCO screening trial. Histological confirmed cases of prostate cancer were reported in 3,088 men (12.3%) during the 11.5 year follow up. Tea consumption was assessed with a food frequency questionnaire (FFQ). Baseline characteristics were compared between groups using Chi-square and Kruskal-Wallis tests. Cox regression models were used to assess the association between tea intake and prostate cancer incidence. Results: Overall tea consumption was associated with a significantly lower risk of prostate cancer (p = 0.009). More precisely, the participants in the highest third of consumption group had a significantly lower risk compared to those in the lowest third (HR 1.16 (CI 1.05-1.29, p = 0.004). This pattern persisted with adjustments for age, sex, race and education level (p = 0.034), family history of cancer (p = 0.037). Those who never drank tea, however, had no statistical lower risk of prostate cancer compared to other groups (p = 0.501). Conclusions: Among tea drinkers, this data revealed a positive association between drinking tea and a reduced risk of prostate cancer. This data supports the consideration of future prospective intervention studies investigating the role of tea as part of a prostate cancer prevention programme. 1. Thomas et al. The NCRN Pomi-T RCT. Prostate cancer & prostatic diseases (2014), 2,180. 2. Reger et al. Dietary isoflavones and prostate cancer risk. Int J. Cancer (2017), 142; 4, 719.

Patients with angina symptoms and/or signs of ischemia but no obstructive coronary artery disease (INOCA) pose a diagnostic and therapeutic challenge.The purpose of this study was to test whether an interventional diagnostic procedure (IDP) linked to stratified medicine improves health status in patients with INOCA.The authors conducted a randomized, controlled, blinded clinical trial of stratified medical therapy versus standard care in patients with angina. Patients with angina undergoing invasive coronary angiography (standard care) were recruited. Patients without obstructive CAD were immediately randomized 1:1 to the intervention group (stratified medical therapy) or the control group (standard care, IDP sham procedure). The IDP consisted of guidewire-based assessment of coronary flow reserve, index of microcirculatory resistance, fractional flow reserve, followed by vasoreactivity testing with acetylcholine. The primary endpoint was the mean difference in angina severity at 6 months (assessed by the Seattle Angina Questionnaire summary score).A total of 391 patients were enrolled between November 25, 2016, and November 12, 2017. Coronary angiography revealed obstructive disease in 206 (53.7%). One hundred fifty-one (39%) patients without angiographically obstructive CAD were randomized (n = 76 intervention group; n = 75 blinded control group). The intervention resulted in a mean improvement of 11.7 U in the Seattle Angina Questionnaire summary score at 6 months (95% confidence interval [CI]: 5.0 to 18.4; p = 0.001). In addition, the intervention led to improvements in the mean quality-of-life score (EQ-5D index 0.10 U; 95% CI: 0.01 to 0.18; p = 0.024) and visual analogue score (14.5 U; 95% CI: 7.8 to 21.3; p 0.001). There were no differences in major adverse cardiac events at the 6-month follow-up (2.6% controls vs. 2.6% intervention; p = 1.00).Coronary angiography often fails to identify patients with vasospastic and/or microvascular angina. Stratified medical therapy, including an IDP with linked medical therapy, is routinely feasible and improves angina in patients with no obstructive CAD. (CORonary MICrovascular Angina [CorMicA]; NCT03193294).

Addressing both biological processes (nature) and interpersonal processes (nurture) occurring within the infant/caregiver relationship, early human development is reviewed from three perspectives: neurobiology, systems theory, and attachment theory. Utilizing a case illustration to apply the reviewed theories, it is postulated that the integration of neurobiological development, systems theory, and attachment theory substantiates the proposition that nurture is nature.