Early stages of experimental colon carcinogenesis inhibit mast cell-dependent mucosal immune function of the distal colon

Inhibition of local host immune reactions is one mechanism contributing to tumor progression. To determine if alterations in local immune functioning occur during colon carcinogenesis, a model mucosal immune response, type I hypersensitivity against the intestinal parasite Trichinella spiralis, was first characterized in normal mice and then examined during experimental colon carcinogenesis. Segments of sensitized colon mounted in Ussing chambers and challenged with T. spiralis-derived antigen resulted in a rise in short-circuit current ($\rm\Delta I\sb{sc}$) that was antigen-specific and inhibited by furosemide, implicating epithelial Cl$\sp-$ secretion as the ionic mechanism. The immune-regulated Cl$\sp-$ secretion by colonic epithelial cells required the presence of mast cells with surface IgE. Inhibition of potential anaphylactic mediators with various pharmacological agents in vitro implicated prostaglandins and leukotrienes as the principal mediators of the antigen-induced $\rm\Delta I\sb{sc}$, with 5-hydroxytryptamine also playing a role. Distal colon from immune mice fed an aspirin-containing diet (800 mg/kg powdered diet) ad libitum for 6 wk had a decreased response to antigen, confirming the major role of prostaglandins in generating the colonic I$\sb{\rm sc}$. To determine the effects of early stages of colon carcinogenesis on this mucosal immune response, mice were immunized with T. spiralis 1 day after or 8 wk prior to the first of 6 weekly injections of the procarcinogen 1,2-dimethylhydrazine (DMH). Responsiveness to antigenic challenge was suppressed in the distal colon 4-6 wk after the final injection of DMH. One injection of DMH was not sufficient to inhibit antigen responsiveness. The colonic epithelium remained sensitive to direct stimulation by exogenous Cl$\sp-$ secretagogues. Decreased antigen-induced $\rm\Delta I\sb{sc}$ in the distal colon was not due to systemic immune suppression by DMH, as the proximal colon and jejunum maintained responsiveness to antigen. Also, rejection of a secondary T. spiralis infection from the small intestine was not altered. Tumors eventually developed 25-30 wk after the final injection of DMH only in the distal portions of the colon. These results suggest that early stages of DMH-induced colon carcinogenesis manipulate the microenvironment such that mucosal immune function, as measured by immune-regulated Cl$\sp-$ secretion, is suppressed in the distal colon, but not in other regions of the gut. Future elucidation of the mechanisms by which this localized inhibition of immune-mediated ion transport occurs may provide possible clues to the microenvironmental changes necessary for tumor progression in the distal colon. ^

Rescue from apoptosis in early (CD34 selected) versus late (CD34 unselected) human hematopoietic cells by VLA-4 and VCAM-1 dependent adhesion to bone marrow stromal cells

The interaction of hematopoietic precursor cell with bone marrow stromal cells is assumed to be important to the survival of hematopoietic precursor cells during hematopoietic cell long-term culture. Early hematopoietic stem cells are preferentially found within the stromal adherent cell fraction in primary long-term bone marrow cultures. The purpose of this dissertation was to understand the molecular mechanisms that govern these interactions for the regulation of survival and proliferation of early versus late hematopoietic cells.^ Monoclonal antibodies to the VLA-4 recognize the alpha4 beta1 integrin receptor on human hematopoietic cells. This monoclonal antibody blocks the adhesion between early hematopoietic progenitor cells (CD34 selected cells) and stromal cells when added to cultures of these cells. Addition of the VLA-4 monoclonal antibody to cultures of stromal cells and CD34 selected cells was shown to induce apoptosis of CD34 selected cells in these CD34 selected cell/stromal cell cocultures, as measured by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling method. In contrast to these experiments with early hematopoietic progenitor cells (CD34+), the level of adhesion between more differentiated cells (unfractionated hematopoietic cells) and stromal cells was not significantly altered by addition of the anti-VLA-4 monoclonal antibody. Similarly, the level of apoptosis of unfractionated hematopoietic cells was not significantly increased by the addition of anti-VLA-4 monoclonal antibody to cultures of the latter cells with stromal cells. The binding of the unfractionated cells is less than that of the CD34 selected. Since there is no difference between the alpha4 beta1 integrin expression level of the early and late myeloid cells, there may be a difference in the functional state of the integrin between the early and late myeloid cells. We also show that CD34+ selected precursor cells proliferate at a higher rate when these cells are plated on recombinant VCAM-1 molecules. These data indicate that the alpha4beta1 integrin receptor (VLA-4) plays a central role in the apoptosis rescue function which results from the anchorage-dependent growth of the CD34 selected early hematopoietic cells on stromal cells. The data suggest that these apoptosis rescue pathways have less significance as the cells mature and become anchorage-independent in their growth. These data should assist in the design of systems for the ex vivo proliferation and transduction of early hematopoietic cells for genetic therapy. ^

Effectiveness of an early postoperative feeding protocol

Background. The increasing emphasis on medical outcomes and cost containment has made it imperative to identify patient populations in which aggressive nutritional care can improve quality of care. The aim of this prospective study was to implement a standardized early jejunal feeding protocol for patients undergoing small and large bowel resection, and to evaluate its effect on patient outcome and cost.^ Methods. Treatment patients (n = 81) who met protocol inclusion criteria had a jejunal feeding tube inserted at the time of surgery. Feeding was initiated at 10 cc/hour within 12 hours after bowel resection and progressed if hemodynamically stable. The control group (n = 159) received usual care. Outcome measures included postoperative length of stay, total direct cost, nosocomial infection rate and health status (SF-36) scores.^ Results. By postoperative day 4, the use of total parenteral nutrition (TPN) was significantly greater in the control group compared to the treatment group; however, total nutritional intake was significantly less. Multiple regression analysis indicated an increased likelihood of infection with the use of TPN. A reduction of 3.5 postoperative days (p =.013) with 4.3 fewer TPN days per patient (p =.001) and a 9.6% reduction in infection rate (p =.042) was demonstrated in the treatment group. There was no difference in health status scores between groups at discharge and 3 months post-discharge.^ Conclusion. These positive outcomes and an average total cost savings of $4,145 per treatment patient indicate that the treatment protocol was effective. ^

Prediction of cardiovascular disease risk factors in Mexican-American children from parental risk factors, and social and demographic characteristics in the HHANES

Objectives. Cardiovascular disease (CVD) including CVD secondary to diabetes type II, a significant health problem among Mexican American populations, originates in early childhood. This study seeks to determine risk factors available to the health practitioner that can identify the child at potential risk of developing CVD, thereby enabling early intervention. ^ Design. This is a secondary analysis of cross-sectional data of matched Mexican American parents and children selected from the HHANES, 1982–1984. ^ Methods. Parents at high risk for CVD were identified based on medical history, and clinical and physical findings. Factor analysis was performed on children's skinfold thicknesses, height, weight, and systolic and diastolic blood pressures, in order to produce a limited number of uncorrelated child CVD risk factors. Multiple regression analyses were then performed to determine other CVD markers associated with these Factors, independently for mothers and fathers. ^ Results. Factor analysis of children's measurements revealed three uncorrelated latent variables summarizing the children's CVD risk: Factor1: ‘Fatness’, Factor2: ‘Size and Maturity’, and Factor3: ‘Blood Pressure’, together accounting for the bulk of variation in children's measurements (86–89%). Univariate analyses showed that children from high CVD risk families did not differ from children of low risk families in occurrence of high blood pressure, overweight, biological maturity, acculturation score, or social and economic indicators. However, multiple regression using the factor scores (from factor analysis) as dependent variables, revealed that higher CVD risk in parents, was significantly associated with increased fatness and increased blood pressure in the children. Father's CVD risk status was associated with higher levels of body fat in his children and higher levels of blood pressure in sons. Mother's CVD risk status was associated with higher blood pressure levels in children, and occurrence of obesity in the mother associated with higher fatness levels in her children. ^ Conclusion. Occurrence of cardiovascular disease and its risk factors in parents of Mexican American children, may be used to identify children at potentially higher risk for developing CV disease in the future. Obesity in mothers appears to be an important marker for the development of higher levels of body fatness in children. ^

Estrogen action during early mouse mammary gland development

Estrogens have been implicated in the normal and neoplastic development of the mammary gland. Although estradiol is essential for early mammary differentiation, its role in postnatal ductal morphogenesis is poorly defined. We have found that neonatal estradiol exposure promotes precocious ductal outgrowth and terminal end bud formation in 21 day-old female mice. In contrast to this precocious phenotype, day 21 estradiol-treated epithelium, transplanted into control host fatpads, grows more slowly than control epithelium. Western and immunohistochemical (IHC) analyses indicate that neonatally-estrogenized glands have significantly less total ER than controls at days 7 and 21, and significantly more stromal ER at day 35. Estrogen receptor α (ER) is present in the gland when treatment is initiated at day 1. We propose that the premature activation of ER by neonatal estradiol exposure, during this critical perinatal period, is a key factor in the alteration of mammary growth and ER expression. ^ To address the role of ER function in mammary morphogenesis, we have developed an in vitro system to study the effect of estradiol exposure in vivo. Keratin and ER-positive mammary epithelial cell lines from 7, 21 and 35 day-old oil or estradiol treated mice have been established. Cell lines derived from estradiol-treated mice grow significantly slower than cells from control glands. Although the level of ER expressed by each cell line is correlated to its rate of growth, epithelial growth in vitro is estradiol-independent and antiestrogen-insensitive. Estradiol-induced transcription from an ERE-reporter in transiently-transfected cell lines confirms the functionality of the ER detected by western and IHC. However, there are no differences in estradiol-stimulated transcription between cell lines. ^ In conclusion, neonatal estradiol treatment alters the pattern of ER expression in mammary epithelial and stromal cells in vivo, and the growth of mammary epithelial cells in vivo and in vitro. When grown outside of the estrogenized host, exposed epithelium grows more slowly than the control. Therefore, an extra-epithelial factor is necessary for enhanced epithelial growth. Our model, which couples an in vivo-in vitro approach, can be used in the future to identify factors involved in the period of early mammary outgrowth and carcinogen susceptibility. ^

Delineation of a novel genetic region at 5q11 harboring tumor suppressor gene(s) and identification of the telomeric DNA as a marker for human prostate cancer

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer mortality in American men. The distinction between those cases of prostate cancer destined to progress rapidly to lethal metastatic disease and those with little likelihood of causing morbidity and mortality is a major goal of current research. Some type of diagnostic method is urgently needed to identify which histological prostate cancers have completed the progression to a stage that will produce a life-threatening disease, thus requiring immediate therapeutic intervention. The objectives of this dissertation are to delineate a novel genetic region harboring tumor suppressor gene(s) and to identify a marker for prostate tumorigenesis. I first established an in vitro cell model system from a human prostate epithelial cells derived from tissue fragments surrounding a prostate tumor in a patient with prostatic adenocarcinoma. Since chromosome 5 abnormality was present in early, middle and late passages of this cell model system, I examined long-term established prostate cancer cell lines for this chromosome abnormality. The results implicated the region surrounding marker D5S2068 as the locus of interest for further experimentation and location of a tumor suppressor gene in human prostate cancer. ^ Cancer is a group of complex genetic diseases with uncontrolled cell; division and prostate cancer is no exception. I determined if telomeric DNA, and telomerase activity, alone or together, could serve as biomarkers of prostate tumorigenesis. I studied three newly established human prostate cancer cell lines and three fibroblast cell cultures derived from prostate tissues. In conclusion, my data reveal that in the presence of telomerase activity, telomeric repeats are maintained at a certain optimal length, and analysis of telomeric DNA variations might serve as early diagnostic and prognostic biomarkers for prostate cancer. (Abstract shortened by UMI.)^

PREDICTIVE VARIABLES FOR WEIGHT CHANGE 2 YEARS FOLLOWING PARTICIPATION IN A WEIGHT LOSS INTERVENTION PROGRAM

A historical prospective study was designed to assess the man weight status of subjects who participated in a behavioral weight reduction program in 1983 and to determine whether there was an association between the dependent variable weight change and any of 31 independent variables after a 2 year follow-up period. Data was obtained by abstracting the subjects records and from a follow-up questionnaire administered 2 years following program participation. Five hundred nine subjects (386 females and 123 males) of 1460 subjects who participated in the program, completed and returned the questionnaire. Results showed that mean weight was significantly different (p < 0.001) between the measurement at baseline and after a 2 year follow-up period. The mean weight loss of the group was 5.8 pounds, 10.7 pounds for males and 4.2 pounds for females after a 2 year follow-up period. A total of 63.9% of the group, 69.9% of males and 61.9% of females were still below their initial weight after the 2 year follow-up period. Sixteen of the 31 variables assessed utilizing bivariate analyses were found to be significantly (p (LESSTHEQ) 0.05) associated with weight change after a 2 year follow-up period. These variables were then entered into a multivariate linear regression model. A total of 37.9% of the variance of the dependent variable, weight change, was accounted for by all 16 variables. Eight of these variables were found to be significantly (p (LESSTHEQ) 0.05) predictive of weight change in the stepwise multivariate process accounting for 37.1% of the variance. These variables included: Two baseline variables (percent over ideal body weight at enrollment and occupation) and six follow-up variables (feeling in control of eating habits, percent of body weight lost during treatment, frequency of weight measurement, physical activity, eating in response to emotions, and number of pounds of weight gain needed to resume a diet). It was concluded that a greater amount of emphasis should be placed on the six follow-up variables by clinicians involved in the treatment of obesity, and by the subjects themselves to enhance their chances of success at long-term weight loss. ^

Depression in early adulthood: prevalence and psychosocial correlates among young Swiss men

QUESTION UNDER STUDY Depression in young adults is common, but data from Switzerland are scarce. Our study gives a point prevalence estimate of depression in young Swiss men, and describes the association between depression and education, material and social resources, and job/school satisfaction. METHODS We used data from the cross-sectional Swiss Federal Surveys of Adolescents (ch-x) from 2010 to 2011 comprising 9,066 males aged between 18 and 25 years. Depression was assessed by means of self-reports using the Patient Health Questionnaire (PHQ-9). Persons were categorised into three groups: depression, subthreshold depression, and no depression. We assessed the relationship between depression and education, material and social resources, and satisfaction with job/school. Differences according to depression status were tested with chi-square tests for categorical variables and one-way analyses of variance for continuous variables. RESULTS Point prevalence of depression (3.60%) and subthreshold depression (3.62%) was high. Poor mental health was associated with lower education in young adults (p <0.001), and with their parents' education (p = 0.024). Social resources in persons with depression and subthreshold depression were substantially reduced (i.e., social support and satisfaction with social relations; both p <0.001). Young men with depression and subthreshold depression also reported a current lack of satisfaction with job/school (p <0.001). CONCLUSIONS Prevalence of (subthreshold) depression is high in young Swiss men. Depression at this age might result in a bad long-term prognosis owing to its association with low satisfaction with job/school and low self-efficacy. Interventions should especially consider the lower social resources of young men with depression.

Cognitive Remediation in early psychosis and in at-risk mental states – Approaches and efficacy

Cognitive Remediation approaches have proven to be effective in enhancing cognitive functions and psychosocial outcomes in multi-episode schizophrenia patients. However, there is a paucity of studies evaluating Cognitive Remediation in first-episode psychosis patients and in those symptomatically at-risk for psychosis. This is despite the growing evidence that impairments in neuro- and social-cognitive functions are already present in early psychosis and even in at-risk mental states and are important predictors of poor outcome, including transition to psychosis. Moreover, Cognitive Remediation applied at younger ages and at earlier stages of schizophrenia yielded greater cognitive and functional gains. Therefore, Cognitive Remediation may be especially appropriate for early intervention. Against this background, we will review and discuss the efficacy of current Cognitive Remediation approaches in early psychosis and in at-risk mental states. Furthermore, we will present novel interventions that are tailored to the specific needs and developmental tasks of patients at-risk for psychosis and aim at improving social and self-referential cognitions as well as interpersonal skills

Memory and attention problems in children with brain tumors at diagnosis

Purpose: Results from previous studies indicate that children with brain tumors (BT) might present with cognitive problems at diagnosis and thus before the start of any medical treatment. The question remains whether these problems are due to the underlying tumor itself or due to the high level of emotional and physical stress which is involved at diagnosis of a malignant disorder. All children with a de novo oncological diagnosis not involving the central nervous systems (CNS) are usually exposed to a comparable level of distress. However, patients with cancer not involving the CNS are not expected to show disease-related cognitive problems. Thus they serve as a well-balanced control group (CG) to help distinguish between the probable causes of the effect. Method: In a pilot study we analyzed an array of cognitive functions in 16 children with BT and 17 control patients. In both groups, tests were administered in-patient at diagnosis before any therapeutic intervention such as surgery, chemotherapy od irradiation. Results: Performance of children with BT was comparable to that of CG patients in the areas of intelligence, perceptual reasoning, verbal comprehension, working memory, and processing speed. In contrast, however, BT patients performded significantly worse in verbal memory and attention. Conclusion: Memory and attention seem to be the most vulnerable funstions affected by BT, with other functions being preserved at the time of diagnosis. It ist to be expected that this vulnerability might exacerbate the cognitive decline after chemotherapy and radiation treatment - known to impair intellectual performance. The findings highlight the need of early cognitive assessments in children with BT in order to introduce cognitive training as early as possible to minimize or even prevent cognitive long-term sequelae. This might improve long-term academic and professional outcome of these children, but especially helps their return to school after hospitalization.

Optimizing Triage and Hospitalization in Adult General Medical Emergency Patients. The Triage Project

Background: Patients presenting to the emergency department (ED) currently face inacceptable delays in initial treatment, and long, costly hospital stays due to suboptimal initial triage and site-of-care decisions. Accurate ED triage should focus not only on initial treatment priority, but also on prediction of medical risk and nursing needs to improve site-of-care decisions and to simplify early discharge management. Different triage scores have been proposed, such as the Manchester triage system (MTS). Yet, these scores focus only on treatment priority, have suboptimal performance and lack validation in the Swiss health care system. Because the MTS will be introduced into clinical routine at the Kantonsspital Aarau, we propose a large prospective cohort study to optimize initial patient triage. Specifically, the aim of this trial is to derive a three-part triage algorithm to better predict (a) treatment priority; (b) medical risk and thus need for in-hospital treatment; (c) post-acute care needs of patients at the most proximal time point of ED admission. Methods/design: Prospective, observational, multicenter, multi-national cohort study. We will include all consecutive medical patients seeking ED care into this observational registry. There will be no exclusions except for non-adult and non-medical patients. Vital signs will be recorded and left over blood samples will be stored for later batch analysis of blood markers. Upon ED admission, the post-acute care discharge score (PACD) will be recorded. Attending ED physicians will adjudicate triage priority based on all available results at the time of ED discharge to the medical ward. Patients will be reassessed daily during the hospital course for medical stability and readiness for discharge from the nurses and if involved social workers perspective. To assess outcomes, data from electronic medical records will be used and all patients will be contacted 30 days after hospital admission to assess vital and functional status, re-hospitalization, satisfaction with care and quality of life measures. We aim to include between 5000 and 7000 patients over one year of recruitment to derive the three-part triage algorithm. The respective main endpoints were defined as (a) initial triage priority (high vs. low priority) adjudicated by the attending ED physician at ED discharge, (b) adverse 30 day outcome (death or intensive care unit admission) within 30 days following ED admission to assess patients risk and thus need for in-hospital treatment and (c) post acute care needs after hospital discharge, defined as transfer of patients to a post-acute care institution, for early recognition and planning of post-acute care needs. Other outcomes are time to first physician contact, time to initiation of adequate medical therapy, time to social worker involvement, length of hospital stay, reasons fordischarge delays, patient’s satisfaction with care, overall hospital costs and patients care needs after returning home. Discussion: Using a reliable initial triage system for estimating initial treatment priority, need for in-hospital treatment and post-acute care needs is an innovative and persuasive approach for a more targeted and efficient management of medical patients in the ED. The proposed interdisciplinary , multi-national project has unprecedented potential to improve initial triage decisions and optimize resource allocation to the sickest patients from admission to discharge. The algorithms derived in this study will be compared in a later randomized controlled trial against a usual care control group in terms of resource use, length of hospital stay, overall costs and patient’s outcomes in terms of mortality, re-hospitalization, quality of life and satisfaction with care.

Neurocognitive deficits in children with brain tumors at diagnosis

Survivors of brain tumors are faced with a high risk for a wide range of cognitive problems and learning difficulties. These problems are caused by the lesion itself and its surgical removal as well as by the treatments to follow (chemo- and/or radiation therapy). A few recent studies have indicated that children with brain tumors (BT) might exhibit cognitive problems already at diagnosis, i.e. before the start of any medical treatment. The aim of the present study was to investigate the "baseline" neuropsychological profile in children with BT in comparison to children with an oncological diagnosis not involving the central nervous system (CNS). 20 children with BT and 27 children with an oncological disease without involvement of the CNS (age range: 6.1 to 16.9 years) were evaluated with an extensive battery of neuropsychological tests tailored to the patient's age. Furthermore, the child and its parents completed self-report questionnaires about emotional functioning and quality of life. In both groups, tests were administered before any therapeutic intervention such as surgery, chemotherapy or irradiation. Groups were comparable regarding age, gender and social economic status. Compared to the CG, patients with BTs performed significantly worse in tests of working memory, verbal memory and attention. In contrast the areas of perceptual reasoning, processing speed and verbal comprehension were preserved at this time. Younger children with BT were especially disadvantaged. Compared to aged matched children with malignancies not involving the CNS and older BT patients the young BT patients showed deficits in attention, working memory and verbal memory measures. Our results highlight the need for cognitive assessments and interventions early in the treatment process in order to minimize or even prevent academic difficulties as patients return to school.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Revascularisation versus medical treatment in patients with stable coronary artery disease: network meta-analysis

OBJECTIVE To investigate whether revascularisation improves prognosis compared with medical treatment among patients with stable coronary artery disease. DESIGN Bayesian network meta-analyses to combine direct within trial comparisons between treatments with indirect evidence from other trials while maintaining randomisation. ELIGIBILITY CRITERIA FOR SELECTING STUDIES A strategy of initial medical treatment compared with revascularisation by coronary artery bypass grafting or Food and Drug Administration approved techniques for percutaneous revascularization: balloon angioplasty, bare metal stent, early generation paclitaxel eluting stent, sirolimus eluting stent, and zotarolimus eluting (Endeavor) stent, and new generation everolimus eluting stent, and zotarolimus eluting (Resolute) stent among patients with stable coronary artery disease. DATA SOURCES Medline and Embase from 1980 to 2013 for randomised trials comparing medical treatment with revascularisation. MAIN OUTCOME MEASURE All cause mortality. RESULTS 100 trials in 93 553 patients with 262 090 patient years of follow-up were included. Coronary artery bypass grafting was associated with a survival benefit (rate ratio 0.80, 95% credibility interval 0.70 to 0.91) compared with medical treatment. New generation drug eluting stents (everolimus: 0.75, 0.59 to 0.96; zotarolimus (Resolute): 0.65, 0.42 to 1.00) but not balloon angioplasty (0.85, 0.68 to 1.04), bare metal stents (0.92, 0.79 to 1.05), or early generation drug eluting stents (paclitaxel: 0.92, 0.75 to 1.12; sirolimus: 0.91, 0.75 to 1.10; zotarolimus (Endeavor): 0.88, 0.69 to 1.10) were associated with improved survival compared with medical treatment. Coronary artery bypass grafting reduced the risk of myocardial infarction compared with medical treatment (0.79, 0.63 to 0.99), and everolimus eluting stents showed a trend towards a reduced risk of myocardial infarction (0.75, 0.55 to 1.01). The risk of subsequent revascularisation was noticeably reduced by coronary artery bypass grafting (0.16, 0.13 to 0.20) followed by new generation drug eluting stents (zotarolimus (Resolute): 0.26, 0.17 to 0.40; everolimus: 0.27, 0.21 to 0.35), early generation drug eluting stents (zotarolimus (Endeavor): 0.37, 0.28 to 0.50; sirolimus: 0.29, 0.24 to 0.36; paclitaxel: 0.44, 0.35 to 0.54), and bare metal stents (0.69, 0.59 to 0.81) compared with medical treatment. CONCLUSION Among patients with stable coronary artery disease, coronary artery bypass grafting reduces the risk of death, myocardial infarction, and subsequent revascularisation compared with medical treatment. All stent based coronary revascularisation technologies reduce the need for revascularisation to a variable degree. Our results provide evidence for improved survival with new generation drug eluting stents but no other percutaneous revascularisation technology compared with medical treatment.