Angharad N de Cates

Bio: Angharad N de Cates is an academic researcher from University of Oxford. The author has contributed to research in topics: Agonist & Poison control. The author has an hindex of 8, co-authored 17 publications receiving 208 citations. Previous affiliations of Angharad N de Cates include Coventry Health Care & Birmingham and Solihull Mental Health NHS Foundation Trust.

Fixed-dose combination therapy for the prevention of cardiovascular disease

Abstract: Cardiovascular diseases (CVD), including heart attacks and strokes, are the leading cause of death and disability worldwide. Drug therapy with blood pressure and cholesterol lowering medications, particularly statins, have been proven to reduce the likelihood that individuals will experience a fatal or non-fatal cardiovascular event. Aspirin has also been proven to prevent heart attacks, certain types of strokes, and death in people with prior cardiovascular disease. The concept of fixed-dose combination therapy is to combine mulitple medications in a single pill as this has been shown to improve adherence in patients with high blood pressure and human immunodeficiency virus (HIV). There have been recent randomised controlled clinical trials to evaluate the effect of fixed-dose combination therapy for CVD prevention. The aim of this systematic review was to determine the effects of fixed-dose combination therapy on all-cause mortality, fatal and non-fatal CVD events, adverse events, blood pressure, lipids, discontinuation rates, quality of life, and costs for CVD prevention. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE until 2013. We found nine randomised controlled trials of two-drug through to five-drug fixed-dose combination therapy with placebo, single drug active component, or usual care in 7047 patients, dating from 2009 to 2013. Trials were generally short-term, ranging from six weeks to 15 months, and included middle-age adults with and without prior CVD. Compared with placebo, single drug active component, or usual care, the effects of fixed-dose combination therapy on all-cause mortality or CVD events were uncertain. However, the event rates for these outcomes were relatively uncommon, only two out of nine trials reported these outcomes, these trials were primarily designed to observed changes in CVD risk factor levels rather than clinical events, and the trials had a high risk of bias in at least one domain, suggesting that these results should not viewed with confidence. Of 1000 people treated with fixed-dose combination therapy during the study period, 297 (range 264 to 315) would experience a side effect compared with 242 people treated with placebo. Fixed-dose combination therapy was associated with lower systolic blood pressure (-7.05 mmHg, range -10.18 to -3.87) and total cholesterol (-0.75 mmol/L, range -1.05 to -0.46). However, there was a high degree of statistical heterogeneity in these comparisons so these results should be viewed with caution. Of 1000 patients treated with fixed-dose combination therapy during the study period, 140 (range 122 to 186) would discontinue the therapy compared with 115 patients treated with placebo. The effects on quality of life were uncertain, and no cost data were reported. Ongoing trials of fixed-dose combination therapy will likely inform these important endpoints.

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular diseases.

Abstract: Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide, yet ASCVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure- and cholesterol-lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of ASCVD. Objectives: To determine the effect of fixed-dose combination therapy on all-cause mortality, fatal and non-fatal ASCVD events, and adverse events. We also sought to determine the effect of fixed-dose combination therapy on blood pressure, lipids, adherence, discontinuation rates, health-related quality of life, and costs. Search methods: We updated our previous searches in September 2016 of CENTRAL, MEDLINE, Embase, ISI Web of Science, and DARE, HTA, and HEED. We also searched two clinical trials registers in September 2016. We used no language restrictions. Selection criteria: We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure-lowering and one lipid-lowering component versus usual care, placebo, or an active drug comparator for any treatment duration in adults 18 years old or older, with no restrictions on presence or absence of pre-existing ASCVD. Data collection and analysis: Three review authors independently selected studies for inclusion and extracted the data for this update. We evaluated risk of bias using the Cochrane 'Risk of bias' assessment tool. We calculated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I2 < 50%) and random-effects models when heterogeneity was high (I2 ≥ 50%). We used the GRADE approach to evaluate the quality of evidence. Main results: In the initial review, we identified nine randomised controlled trials with a total of 7047 participants and four additional trials (n = 2012 participants; mean age range 62 to 63 years; 30% to 37% women) were included in this update. Eight of the 13 trials evaluated the effects of fixed-dose combination (FDC) therapy in populations without prevalent ASCVD, and the median follow-up ranged from six weeks to 23 months. More recent trials were generally larger with longer follow-up and lower risk of bias. The main risk of bias was related to lack of blinding of participants and personnel, which was inherent to the intervention. Compared with the comparator groups (placebo, usual care, or active drug comparator), the effects of the fixed-dose combination treatment on mortality (FDC = 1.0% versus control = 1.0%, RR 1.10, 95% CI 0.64 to 1.89, I2 = 0%, 5 studies, N = 5300) and fatal and non-fatal ASCVD events (FDC = 4.7% versus control = 3.7%, RR 1.26, 95% CI 0.95 to 1.66, I2 = 0%, 6 studies, N = 4517) were uncertain (low-quality evidence). The low event rates for these outcomes and indirectness of evidence for comparing fixed-dose combination to usual care versus individual drugs suggest that these results should be viewed with caution. Adverse events were common in both the intervention (32%) and comparator (27%) groups, with participants randomised to fixed-dose combination therapy being 16% (RR 1.16, 95% CI 1.09 to 1.25, 11 studies, 6906 participants, moderate-quality evidence) more likely to report an adverse event . The mean differences in systolic blood pressure between the intervention and control arms was -6.34 mmHg (95% CI -9.03 to -3.64, 13 trials, 7638 participants, moderate-quality evidence). The mean differences (95% CI) in total and LDL cholesterol between the intervention and control arms were -0.61 mmol/L (95% CI -0.88 to -0.35, 11 trials, 6565 participants, low-quality evidence) and -0.70 mmol/L (95% CI -0.98 to -0.41, 12 trials, 7153 participants, moderate-quality evidence), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I2 ≥ 80% for all) that could not be explained, so these results should be viewed with caution. Fixed-dose combination therapy improved adherence to a multidrug strategy by 44% (26% to 65%) compared with usual care (4 trials, 3835 participants, moderate-quality evidence). Authors' conclusions: The effects of fixed-dose combination therapy on all-cause mortality or ASCVD events are uncertain. A limited number of trials reported these outcomes, and the included trials were primarily designed to observe changes in ASCVD risk factor levels rather than clinical events, which may partially explain the observed differences in risk factors that were not translated into differences in clinical outcomes among the included trials. Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo, active comparator, or usual care but may be associated with improved adherence to a multidrug regimen. Ongoing, longer-term trials of fixed-dose combination therapy will help demonstrate whether short-term changes in risk factors might be maintained and lead to expected differences in clinical events based on these changes.

Mental well-being: an important outcome for mental health services?

Abstract: Mental well-being is being used as an outcome measure in mental health services The recent Chief Medical Officer's (CMO's) report raised questions about mental well-being in people with mental illness, including how to measure it We discuss whether mental well-being has prognostic significance or other utility in this context

Translating the promise of 5HT4 receptor agonists for the treatment of depression.

Abstract: Animal experimental studies suggest that 5-HT4 receptor activation holds promise as a novel target for the treatment of depression and cognitive impairment. 5-HT4 receptors are post-synaptic receptors that are located in striatal and limbic areas known to be involved in cognition and mood. Consistent with this, 5-HT4 receptor agonists produce rapid antidepressant effects in a number of animal models of depression, and pro-cognitive effects in tasks of learning and memory. These effects are accompanied by molecular changes, such as the increased expression of neuroplasticity-related proteins that are typical of clinically useful antidepressant drugs. Intriguingly, these antidepressant-like effects have a fast onset of their action, raising the possibility that 5-HT4 receptor agonists may be a particularly useful augmentation strategy in the early stages of SSRI treatment. Until recently, the translation of these effects to humans has been challenging. Here, we review the evidence from animal studies that the 5-HT4 receptor is a promising target for the treatment of depression and cognitive disorders, and outline a potential pathway for the efficient and cost-effective translation of these effects into humans and, ultimately, to the clinic.

Choosing death in depression: a commentary on ‘Treatment-resistant major depressive disorder and assisted dying’

Abstract: Schuklenk and van de Vathorst's paper is a very welcome addition to the literature on the assisted dying debate and will be of great interest to clinicians working in the field of mental health.1 Many psychiatrists will have had patients who have asked them to allow them to die, to desist in their efforts to prevent their suicide, and one of us has had personal experience, outside of professional life, of being asked to aid in someone's attempt to end their life in the context of an episode of mood disorder. The person with depression asking professionals, friends and family members to aid them in ending their life is a very real phenomenon. In their discussion, Schuklenk and van de Vathorst's paper uses two principles that we endorse and add weight to their argument: namely, the reality of suffering in depression and the parity of mental and physical illness. Indeed, the case Schuklenk and van de Vathorst make is a strong one and our commentary will focus on the premise of the argument around choosing death and some empirical clarification about competence in depression and the nature of treatment-resistant depression (TRD) and its prognosis. The conceptual concern we wish to discuss in relation to assisted dying, endorsed by the state and legislature, is not linked to any moral or religious concern, or even on grounds related to ‘slippery slope’ or ‘abuse’ arguments. Rather the worry is how one could operationalise decisions around assisted dying as based on competence and capacity and view such decisions as rational. I think this concern is not limited to depressive illness, but to all decisions regarding choosing non-existence. Schuklenk and van de Vathorst offer the following useful criteria to regulate assisted suicide:1

European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (Version 2012)

Abstract: ABI : ankle–brachial index ACCORD : Action to Control Cardiovascular Risk in Diabetes ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation AGREE : Appraisal of Guidelines Research and Evaluation AHA : American Heart Association apoA1 : apolipoprotein A1 apoB : apolipoprotein B CABG : coronary artery bypass graft surgery CARDS : Collaborative AtoRvastatin Diabetes Study CCNAP : Council on Cardiovascular Nursing and Allied Professions CHARISMA : Clopidogrel for High Athero-thrombotic Risk and Ischemic Stabilisation, Management, and Avoidance CHD : coronary heart disease CKD : chronic kidney disease COMMIT : Clopidogrel and Metoprolol in Myocardial Infarction Trial CRP : C-reactive protein CURE : Clopidogrel in Unstable Angina to Prevent Recurrent Events CVD : cardiovascular disease DALYs : disability-adjusted life years DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Trial ED : erectile dysfunction eGFR : estimated glomerular filtration rate EHN : European Heart Network EPIC : European Prospective Investigation into Cancer and Nutrition EUROASPIRE : European Action on Secondary and Primary Prevention through Intervention to Reduce Events GFR : glomerular filtration rate GOSPEL : Global Secondary Prevention Strategies to Limit Event Recurrence After MI GRADE : Grading of Recommendations Assessment, Development and Evaluation HbA1c : glycated haemoglobin HDL : high-density lipoprotein HF-ACTION : Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing HOT : Hypertension Optimal Treatment Study HPS : Heart Protection Study HR : hazard ratio hsCRP : high-sensitivity C-reactive protein HYVET : Hypertension in the Very Elderly Trial ICD : International Classification of Diseases IMT : intima-media thickness INVEST : International Verapamil SR/Trandolapril JTF : Joint Task Force LDL : low-density lipoprotein Lp(a) : lipoprotein(a) LpPLA2 : lipoprotein-associated phospholipase 2 LVH : left ventricular hypertrophy MATCH : Management of Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke MDRD : Modification of Diet in Renal Disease MET : metabolic equivalent MONICA : Multinational MONItoring of trends and determinants in CArdiovascular disease NICE : National Institute of Health and Clinical Excellence NRT : nicotine replacement therapy NSTEMI : non-ST elevation myocardial infarction ONTARGET : Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial OSA : obstructive sleep apnoea PAD : peripheral artery disease PCI : percutaneous coronary intervention PROactive : Prospective Pioglitazone Clinical Trial in Macrovascular Events PWV : pulse wave velocity QOF : Quality and Outcomes Framework RCT : randomized clinical trial RR : relative risk SBP : systolic blood pressure SCORE : Systematic Coronary Risk Evaluation Project SEARCH : Study of the Effectiveness of Additional Reductions in Cholesterol and SHEP : Systolic Hypertension in the Elderly Program STEMI : ST-elevation myocardial infarction SU.FOL.OM3 : SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids Syst-Eur : Systolic Hypertension in Europe TNT : Treating to New Targets UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use VITATOPS : VITAmins TO Prevent Stroke VLDL : very low-density lipoprotein WHO : World Health Organization ### 1.1 Introduction Atherosclerotic cardiovascular disease (CVD) is a chronic disorder developing insidiously throughout life and usually progressing to an advanced stage by the time symptoms occur. It remains the major cause of premature death in Europe, even though CVD mortality has …

2016 European Guidelines on cardiovascular disease prevention in clinical practice

Abstract: ABI : ankle–brachial (blood pressure) index ABPM : ambulatory blood pressure monitoring ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE-I : angiotensin-converting enzyme inhibitor ACS : acute coronary syndromes ADVANCE : Action in Diabetes and Vascular disease: PreterAx

Psychotherapy for Borderline Personality Disorder, Mentalization-based Treatment

Abstract: ![Figure][1] While reading this book I also read reviews of Gielgud’s Letters ([Mangan, 2004][2]) and a biography of Michael Redgrave ([Strachan, 2004][3]). These gave accounts of the lives of these two actors that left little out from a diagnosis of borderline personality disorder.