Understanding and improving the prognosis of a disease or health condition is a priority in clinical research and practice. In this article, the authors introduce a framework of four interrelated themes in prognosis research, describe the importance of the first of these themes (understanding future outcomes in relation to current diagnostic and treatment practices), and introduce recommendations for the field of prognosis research

Aims The population with stable coronary artery disease (SCAD) is growing but validated models to guide their clinical management are lacking. We developed and validated prognostic models for all-cause mortality and non-fatal myocardial infarction (MI) or coronary death in SCAD. Methods and results Models were developed in a linked electronic health records cohort of 102 023 SCAD patients from the CALIBER programme, with mean follow-up of 4.4 (SD 2.8) years during which 20 817 deaths and 8856 coronary outcomes were observed. The Kaplan–Meier 5-year risk was 20.6% (95% CI, 20.3, 20.9) for mortality and 9.7% (95% CI, 9.4, 9.9) for non-fatal MI or coronary death. The predictors in the models were age, sex, CAD diagnosis, deprivation, smoking, hypertension, diabetes, lipids, heart failure, peripheral arterial disease, atrial fibrillation, stroke, chronic kidney disease, chronic pulmonary disease, liver disease, cancer, depression, anxiety, heart rate, creatinine, white cell count, and haemoglobin. The models had good calibration and discrimination in internal (external) validation with C-index 0.811 (0.735) for all-cause mortality and 0.778 (0.718) for non-fatal MI or coronary death. Using these models to identify patients at high risk (defined by guidelines as 3% annual mortality) and support a management decision associated with hazard ratio 0.8 could save an additional 13-16 life years or 15-18 coronary event-free years per 1000 patients screened, compared with models with just age, sex, and deprivation. Conclusion These validated prognostic models could be used in clinical practice to support risk stratification as recommended in clinical guidelines.

BackgroundDepression is associated with coronary heart disease and stroke, but associations with a range of pathologically diverse cardiovascular diseases are not well understood. We examine the risk of 12 cardiovascular diseases according to depression status (history or new onset).MethodsCohort study of 1,937,360 adult men and women, free from cardiovascular disease at baseline, using linked UK electronic health records between 1997 and 2010. The exposures were new-onset depression (a new GP diagnosis of depression and/or prescription for antidepressants during a one-year baseline), and history of GP-diagnosed depression before baseline. The primary endpoint was initial presentation of 12 cardiovascular diseases after baseline. We used disease-specific Cox proportional hazards models with multiple imputation adjusting for cardiovascular risk factors (age, sex, socioeconomic status, smoking, blood pressure, diabetes, cholesterol).ResultsOver a median [IQR] 6.9 [2.1–10.5] years of follow-up, 18.9% had a history of depression and 94,432 incident cardiovascular events occurred. After adjustment for cardiovascular risk factors, history of depression was associated with: stable angina (Hazard Ratio = 1.38, 95%CI 1.32–1.45), unstable angina (1.70, 1.60–1.82), myocardial infarction (1.21, 1.16–1.27), unheralded coronary death (1.23, 1.14–1.32), heart failure (1.18, 1.13–1.24), cardiac arrest (1.14, 1.03–1.26), transient ischemic attack (1.31, 1.25–1.38), ischemic stroke (1.26, 1.18–1.34), subarachnoid haemorrhage (1.17, 1.01–1.35), intracerebral haemorrhage (1.30, 1.17–1.45), peripheral arterial disease (1.24, 1.18–1.30), and abdominal aortic aneurysm (1.12,1.01–1.24). New onset depression developed in 2.9% of people, among whom 63,761 cardiovascular events occurred. New onset depression was similarly associated with each of the 12 diseases, with no evidence of stronger associations compared to history of depression. The strength of association between depression and these cardiovascular diseases did not differ between women and men.ConclusionDepression was prospectively associated with cardiac, cerebrovascular, and peripheral diseases, with no evidence of disease specificity. Further research is needed in understanding the specific pathophysiology of heart and vascular disease triggered by depression in healthy populations.

BACKGROUND: Enhanced Recovery After Surgery Society publishes guidelines on perioperative care, but these guidelines should be validated prospectively. OBJECTIVE: To evaluate the association between compliance with Enhanced Recovery After Surgery Gynecologic/Oncology guideline elements and postoperative outcomes in an international cohort. STUDY DESIGN: The study comprised 2101 patients undergoing elective gynecologic/oncology surgery between January 2011 and November 2017 in 10 hospitals across Canada, the United States, and Europe. Patient demographics, surgical/anesthesia details, and Enhanced Recovery After Surgery protocol compliance elements (pre-, intra-, and postoperative phases) were entered into the Enhanced Recovery After Surgery Interactive Audit System. Surgical complexity was stratified according to the Aletti scoring system (low vs medium/high). The following covariates were accounted for in the analysis: age, body mass index, smoking status, presence of diabetes, American Society of Anesthesiologists class, International Federation of Gynecology and Obstetrics stage, preoperative chemotherapy, radiotherapy, operating time, surgical approach (open vs minimally invasive), intraoperative blood loss, hospital, and Enhanced Recovery After Surgery implementation status. The primary end points were primary hospital length of stay and complications. Negative binomial regression was used to model length of stay, and logistic regression to model complications, as a function of compliance score and covariates. RESULTS: Patient demographics included a median age 56 years, 35.5% obese, 15% smokers, and 26.7% American Society of Anesthesiologists Class III-IV. Final diagnosis was malignant in 49% of patients. Laparotomy was used in 75.9% of cases, and the remainder minimally invasive surgery. The majority of cases (86%) were of low complexity (Aletti score 3). In patients with ovarian cancer, 69.5% had a medium/high complexity surgery (Aletti score 4e11). Median length of stay was 2 days in the low-and 5 days in the medium/high-complexity group. Every unit increase in Enhanced Recovery After Surgery guideline score was associated with 8% (IRR, 0.92; 95% confidence interval, 0.90e0.95; P<.001) decrease in days in hospital among lowcomplexity, and 12% (IRR, 0.88; 95% confidence interval, 0.82e0.93; P<.001) decrease among patients with medium/highcomplexity scores. For every unit increase in Enhanced Recovery After Surgery guideline score, the odds of total complications were estimated to be 12% lower (P<.05) among low-complexity patients. CONCLUSION: Audit of surgical practices demonstrates that improved compliance with Enhanced Recovery After Surgery Gynecologic/Oncology guidelines is associated with an improvement in clinical outcomes, including length of stay, highlighting the importance of Enhanced Recovery After Surgery implementation.

Objective. The effect of a proprietary formulation of trans-resveratrol (t-RSV) on manifestations of diabetic foot syndrome (DFS) was studied in type 2 diabetic patients with newly diagnosed diabetic foot ulcers. Method. Placebo-controlled, examiner-blinded, parallel-group randomized controlled pilot clinical trial (ACTRN Clinical Trial Registry number 12610000629033) involving 24 patients with DFS (15 males and 9 females, average age of 56.4 ± 9.1 years) divided into the placebo and RSV-treatment groups was performed. 50 mg of t-RSV or placebo capsules was given to each patient twice a day over a 60-day time period. Results. Reduction in the parameters reflecting diabetic ulcer size was more profound in the RSV group as compared to placebo. RSV-treated patients also had a marginally improved performance in the foot pressure test. A statistically significant decline in the plasma fibrinogen level, but not CRP, was also found in the RSV-treated patients. Some improvement in the plasma lipid profile and fasting glucose levels were not related to RSV-treatment, since they have been seen on both the RSV and placebo groups, revealing the effectiveness of medical supervision and education in the newly diagnosed patients with DFS. Conclusion. t-RSV supplementation promotes reduction of the foot ulcer size and reduces plasma fibrinogen level in type 2 diabetic patients.