Cohort profile: the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study-an ongoing prospective cohort study of patients at high cardiovascular risk in the Netherlands

PURPOSE: The Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date. PARTICIPANTS: The UCC-SMART Study includes patients aged 18-90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima-media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee. FINDINGS TO DATE: By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines. FUTURE PLANS: The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes

Doyne lecture 2016:intraocular health and the many faces of inflammation

Dogma for reasons of immune privilege including sequestration (sic) of ocular antigen, lack of lymphatic and immune competent cells in the vital tissues of the eye has long evaporated. Maintaining tissue and cellular health to preserve vision requires active immune responses to prevent damage and respond to danger. A priori the eye must contain immune competent cells, undergo immune surveillance to ensure homoeostasis as well as an ability to promote inflammation. By interrogating immune responses in non-infectious uveitis and compare with age-related macular degeneration (AMD), new concepts of intraocular immune health emerge. The role of macrophage polarisation in the two disorders is a tractable start. TNF-alpha regulation of macrophage responses in uveitis has a pivotal role, supported via experimental evidence and validated by recent trial data. Contrast this with the slow, insidious degeneration in atrophic AMD or in neovasular AMD, with the compelling genetic association with innate immunity and complement, highlights an ability to attenuate pathogenic immune responses and despite known inflammasome activation. Yolk sac-derived microglia maintains tissue immune health. The result of immune cell activation is environmentally dependent, for example, on retinal cell bioenergetics status, autophagy and oxidative stress, and alterations that skew interaction between macrophages and retinal pigment epithelium (RPE). For example, dead RPE eliciting macrophage VEGF secretion but exogenous IL-4 liberates an anti-angiogenic macrophage sFLT-1 response. Impaired autophagy or oxidative stress drives inflammasome activation, increases cytotoxicity, and accentuation of neovascular responses, yet exogenous inflammasome-derived cytokines, such as IL-18 and IL-33, attenuate responses

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

The impact of patient feedback on the medical performance of qualified doctors: a systematic review

Background: Patient feedback is considered integral to quality improvement and professional development. However, while popular across the educational continuum, evidence to support its efficacy in facilitating positive behaviour change in a postgraduate setting remains unclear. This review therefore aims to explore the evidence that supports, or refutes, the impact of patient feedback on the medical performance of qualified doctors. // Methods: Electronic databases PubMed, EMBASE, Medline and PsycINFO were systematically searched for studies assessing the impact of patient feedback on medical performance published in the English language between 2006-2016. Impact was defined as a measured change in behaviour using Barr’s (2000) adaptation of Kirkpatrick’s four level evaluation model. Papers were quality appraised, thematically analysed and synthesised using a narrative approach. // Results: From 1,269 initial studies, 20 articles were included (qualitative (n=8); observational (n=6); systematic review (n=3); mixed methodology (n=1); randomised control trial (n=1); and longitudinal (n=1) design). One article identified change at an organisational level (Kirkpatrick level 4); six reported a measured change in behaviour (Kirkpatrick level 3b); 12 identified self-reported change or intention to change (Kirkpatrick level 3a), and one identified knowledge or skill acquisition (Kirkpatrick level 2). No study identified a change at the highest level, an improvement in the health and wellbeing of patients. The main factors found to influence the impact of patient feedback were: specificity; perceived credibility; congruence with physician self-perceptions and performance expectations; presence of facilitation and reflection; and inclusion of narrative comments. The quality of feedback facilitation and local professional cultures also appeared integral to positive behaviour change. // Conclusion: Patient feedback can have an impact on medical performance. However, actionable change is influenced by several contextual factors and cannot simply be guaranteed. Patient feedback is likely to be more influential if it is specific, collected through credible methods and contains narrative information. Data obtained should be fed back in a way that facilitates reflective discussion and encourages the formulation of actionable behaviour change. A supportive cultural understanding of patient feedback and its intended purpose is also essential for its effective use

The effect of a decision aid on informed decision-making in the era of non-invasive prenatal testing : A randomised controlled trial

Early in pregnancy women and their partners face the complex decision on whether or not to participate in prenatal testing for fetal chromosomal abnormalities. Several studies show that the majority of pregnant women currently do not make informed decisions regarding prenatal testing. As the range of prenatal tests is expanding due to the development of new techniques such as non-invasive prenatal testing (NIPT), autonomous reproductive decision-making is increasingly challenging. In this study, a randomised controlled trial was conducted to evaluate the effect of a web-based multimedia decision aid on decision-making regarding prenatal testing. The decision aid provided both written and audiovisual information on prenatal tests currently available, that is, prenatal screening by first-trimester combined testing, NIPT and invasive diagnostic testing through chorionic villus sampling or amniocentesis. Furthermore, it contained values clarification exercises encouraging pregnant women to reflect on the potential harms and benefits of having prenatal tests performed. The use of the decision aid improved informed decision-making regarding prenatal testing. Of pregnant women allocated to the intervention group (n=130) 82.3% made an informed choice compared with 66.4% of women in the control group (n=131), P=0.004. As the vast majority of pregnant women made decisions consistent with their attitudes towards having prenatal testing performed, this improvement in informed decision-making could be attributed mainly to an increase in decision-relevant knowledge. This study shows that the implementation of a web-based multimedia decision aid directly facilitates the ultimate goal of prenatal testing for fetal chromosomal abnormalities, which is enabling informed autonomous reproductive choice