Beta-adrenergic receptor blockers and liver cancer mortality in a national cohort of hepatocellular carcinoma patients

Publisher's version (útgefin grein)Background: β-adrenergic signaling has been implicated in the pathology of hepatocellular carcinoma (HCC), but the evidence from clinical studies is limited. In this national population-based cohort study, we investigated the possible association of β-adrenergic receptor blockers and cancer-specific mortality among patients with primary HCC diagnosed in Sweden between 2006 and 2014. Methods: Patients were identified from the Swedish Cancer Register (n = 2104) and followed until 31 December 2015. We used Cox regression to evaluate the association of β-blockers dispensed within 90 days prior to cancer diagnosis, ascertained from the national Prescribed Drug Register, with liver cancer mortality identified from the Cause of Death Register, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and treatment procedures. Results: Over a median follow-up of 9.9 months, 1601 patients died (of whom 1309 from liver cancer). Compared with non-use, β-blocker use at cancer diagnosis [n = 714 (predominantly prevalent use, 93%)] was associated with lower liver cancer mortality [0.82 (0.72–0.94); p =.005]. Statistically significant associations were observed for non-selective [0.71 (0.55–0.91); p =.006], β1-receptor selective [0.86 [0.75–1.00); p =.049] and lipophilic [0.78 (0.67–0.90); p =.001] β-blockers. No association was observed for hydrophilic β-blockers [1.01 (0.80–1.28); p =.906] or other antihypertensive medications. Further analysis suggested that the observed lower liver cancer mortality rate was limited to patients with localized disease at diagnosis [0.82 (0.67–1.01); p =.062]. Conclusion: β-blocker use was associated with lower liver cancer mortality rate in this national cohort of patients with HCC. A higher-magnitude inverse association was observed in relation to non-selective β-blocker use.This work was supported by a grant from the Swedish Cancer Society (CAN 2013/650). Dr Karin E. Smedby has research funding from Janssen.Peer Reviewe

Evaluation of a novel nutrition education intervention for medical students from across England

Objectives: Problems such as hospital malnutrition (∼40% prevalence in the UK) may be managed better by improving the nutrition education of 'tomorrow's doctors'. The Need for Nutrition Education Programme aimed to measure the effectiveness and acceptability of an educational intervention on nutrition for medical students in the clinical phase of their training. Design: An educational needs analysis was followed by a consultative process to gain consensus on a suitable educational intervention. This was followed by two identical 2-day educational interventions with before and after analyses of Knowledge, Attitudes and Practices (KAP). The 2-day training incorporated six key learning outcomes. Setting: Two constituent colleges of Cambridge University used to deliver the above educational interventions. Participants: An intervention group of 100 clinical medical students from 15 medical schools across England were recruited to attend one of two identical intensive weekend workshops. Primary and secondary outcome measures: The primary outcome measure consisted of change in KAP scores following intervention using a clinical nutrition questionnaire. Secondary outcome measures included change in KAP scores 3 months after the intervention as well as a student-led semiqualitative evaluation of the educational intervention. Results: Statistically significant changes in KAP scores were seen immediately after the intervention, and this was sustained for 3 months. Mean differences and 95% CIs after intervention were Knowledge 0.86 (0.43 to 1.28); Attitude 1.68 (1.47 to 1.89); Practice 1.76 (1.11 to 2.40); KAP 4.28 (3.49 to 5.06). Ninety-seven per cent of the participants rated the overall intervention and its delivery as 'very good to excellent', reporting that they would recommend this educational intervention to colleagues. Conclusion: Need for Nutrition Education Programme has highlighted the need for curricular innovation in the area of clinical health nutrition in medical schools. This project also demonstrates the effectiveness and acceptability of such a curriculum intervention for 'tomorrow's doctors'. Doctors, dietitians and nutritionists worked well in an effective interdisciplinary partnership when teaching medical students, providing a good model for further work in a healthcare setting

International validation of Enhanced Recovery After Surgery Society guidelines on enhanced recovery for gynecologic surgery

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 4–11). 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, 0.90–0.95; P\u3c.001) decrease in days in hospital among low-complexity, and 12% (IRR, 0.88; 95% confidence interval, 0.82–0.93; P\u3c.001) decrease among patients with medium/high-complexity scores. For every unit increase in Enhanced Recovery After Surgery guideline score, the odds of total complications were estimated to be 12% lower (P\u3c.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

Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes.

The PROGRESS series (www.progress-partnership.org) sets out a framework of four interlinked prognosis research themes and provides examples from several disease fields to show why evidence from prognosis research is crucial to inform all points in the translation of biomedical and health related research into better patient outcomes. Recommendations are made in each of the four papers to improve current research standards What is prognosis research? Prognosis research seeks to understand and improve future outcomes in people with a given disease or health condition. However, there is increasing evidence that prognosis research standards need to be improved Why is prognosis research important? More people now live with disease and conditions that impair health than at any other time in history; prognosis research provides crucial evidence for translating findings from the laboratory to humans, and from clinical research to clinical practice This first article introduces the framework of four interlinked prognosis research themes and then focuses on the first of the themes - fundamental prognosis research, studies that aim to describe and explain future outcomes in relation to current diagnostic and treatment practices, often in relation to quality of care Fundamental prognosis research provides evidence informing healthcare and public health policy, the design and interpretation of randomised trials, and the impact of diagnostic tests on future outcome. It can inform new definitions of disease, may identify unanticipated benefits or harms of interventions, and clarify where new interventions are required to improve prognosis

Depression as a Risk Factor for the Initial Presentation of Twelve Cardiac, Cerebrovascular, and Peripheral Arterial Diseases: Data Linkage Study of 1.9 Million Women and Men

BACKGROUND: Depression 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). METHODS: Cohort 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). RESULTS: Over 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. CONCLUSION: Depression 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

The changing face of Crohn’s disease : a population-based study of the natural history of Crohn’s disease in Örebro, Sweden 1963-2005

Objective: Changes in medical therapy and surgery might have influenced the natural history Crohn’s disease (CD). Our aim was to explore the short-term outcome of CD and to specifically assess trends in disease phenotype, medications and surgery in the first five years from diagnosis. Material and Methods: A population-based cohort comprising 472 CD patients diagnosed within the primary catchment area of Örebro University Hospital 1963-2005 were identified retrospectively and described. Data on medication, surgery, progression in disease location and behaviour, were extracted from the medical records. Patients were divided into three cohorts based on year of diagnosis. Results: The proportion of patients with complicated disease behaviour 5 years after diagnosis decreased from 54.4% (95%CI, 43.9-65.6) to 33.3% (27.4-40.0) in patients diagnosed 1963-1975 and 1991-2005, respectively (p=0.002), whereas the proportion of patients progressing to complicated disease behaviour was stable among those with non-stricturing, non-penetrating disease at diagnosis (p=0.435). The proportion of patients undergoing surgery decreased from 65.8% (55.4-76.0) to 34.6% (28.6-41.5) in patients diagnosed 1963-1975 and 1991-2005, respectively (p&lt;0.001). The reduction in surgery preceded an increased use of immunomodulators and was explained by a decrease in surgery within three months from diagnosis (p=0.001). Conclusions: We observed a striking decrease in complicated disease behaviour and surgery five years after CD diagnosis, the latter largely due to a decrease in early surgery. Our findings suggest that the introduction of new treatments alone does not explain the reduction in surgery rates, the increasing proportion of patients with inflammatory disease at diagnosis also play an important role.Funding Agencies:Örebro University Hospital Research Foundation OLL-256371Örebro County Research Foundation OLL-403371  OLL-457731</p

Sex of older siblings and stress resilience

The aim was to investigate whether older siblings are associated with development of stress resilience in adolescence and if there are differences by sex of siblings. The study used a Swedish register-based cohort of men (n=664 603) born between 1970 and 1992 who undertook military conscription assessments in adolescence that included a measure of stress resilience: associations were assessed using multinomial logistic regression. Adjusted relative risk ratios (95% confidence intervals) for low stress resilience (n=136 746) compared with high (n=142 581) are 1.33 (1.30, 1.35), 1.65 (1.59, 1.71) and 2.36 (2.18, 2.54) for one, two and three or more male older siblings, compared with none. Equivalent values for female older siblings do not have overlapping confidence intervals with males and are 1.19 (1.17, 1.21), 1.46 (1.40, 1.51) and 1.87 (1.73, 2.03). When the individual male and female siblings are compared directly (one male sibling compared with one female sibling, etc.) and after adjustment, including for cognitive function, there is a statistically significant (p<0.005) greater risk for low stress resilience associated with male siblings. Older male siblings may have greater adverse implications for psychological development, perhaps due to greater demands on familial resources or inter-sibling interactions

Temporal trends in non-stricturing and non-penetrating behaviour at diagnosis of Crohn's disease in Örebro, Sweden : a population-based retrospective study

Background and aim: The incidence of Crohn's disease (CD) is continuing to rise in several countries and in others it appears to have already levelled off after a period of increase. We updated our previous population-based study, by re-extraction of all information on patients diagnosed with CD between 1963 and 2010. Our aim was to assess temporal trends in incidence, prevalence and disease phenotype at diagnosis. Methods: Patients of all ages with a potential diagnosis of CD were identified retrospectively by evaluation of medical notes of all current and previous patients at the colitis clinic, Örebro University Hospital amended by computerised search in the inpatient, outpatient, primary care and histopathological records. Diagnosis was confirmed by subsequent evaluation of medical notes. Disease phenotype was defined according to the Montreal classification. Results: The incidence increased over time, especially among Crohn's disease, A1 and A3. SaTScan model revealed a statistically significant high incidence during 1991-2010 (p=0.0001). The median age at diagnosis increased from 28 (3-79) years to 37 (5-87) years (p=0.0002). The point prevalence increased from 21/10(5) (14-32) in 1965 to 267/10(5) (244-291) in 2010. Non-stricturing and non-penetrating disease at diagnosis increased from 12.5% in 1963-1965 to 82.3% in 2006-2010 (p&lt;0.0001). Conclusion: The incidence of CD increased over time, although it seemed to be plateauing during the most recent decades. A striking increase in non-stricturing, non-penetrating disease at diagnosis was observed, suggesting earlier diagnosis or phenotypic change. The observed point prevalence in 2010 is among the highest reported.Funding Agencies:Karlskoga Hospital Reseach Foundation AE-37256Bengt Ihre's Foundation SLS-254051Örebro University Hospital Research Foundation OLL-256371Örebro County Research Foundation OLL-93671 OLL-172601 OLL-200541 OLL-256771Swedish Foundation</p