A genotype-guided strategy for oral P2Y₁₂ Inhibitors in primary PCI

BACKGROUND: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors. METHODS: We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS: For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.)

Television viewing, food preferences, and food habits among children: A prospective epidemiological study

<p>Abstract</p> <p>Background</p> <p>Obesity has increased since the early 1980s, and despite numerous attempts, effective strategies to counter this worldwide epidemic are lacking. Food preferences are established early in life and are difficult to change later. There is therefore a need to identify factors that influence the development of food preferences. Our aim was therefore, to investigate cross-sectional and prospective associations between TV viewing habits and food preferences and habits, respectively. We hypothesized that more TV viewing was associated with less healthy concomitant and future food preferences and food habits.</p> <p>Methods</p> <p>Data are from the Danish part of European Youth Heart Study (EYHS) I and II, a prospective cohort study conducted among 8-10-year-old and 14-16-year-old Danes in 1997-98. Six years later 2003-04 the 8-10-year-olds were followed up at age 14-16 years, and a new group of 8-10-year olds were included. Data were analysed using mixed linear regression analysis. Cross-sectional analyses included 697 8-10-year-olds and 495 14-16-year-olds. Prospective analyses included 232 pupils with complete data at baseline and follow-up. Associations between TV viewing habits and the sum of healthy food preferences (ΣHFP), and the sum of healthy food habits (ΣHFH), respectively, were examined.</p> <p>Results</p> <p>Inverse cross-sectional associations between TV viewing (h/day) and both ΣHFP and ΣHFH were present for both the 8-10-year-old and the 14-16-year-old boys and girls. The frequency of meals in front of the TV (times/week) was also inversely associated with ΣHFP among 8-10-year-old boys, and with ΣHFH in all sex- and age groups. Among girls, baseline TV viewing (h/day) was directly associated with adverse development in the ΣHFP during follow-up. The concomitant 6-year changes in ΣHFH and TV viewing (h/day) were inversely associated in boys.</p> <p>Conclusions</p> <p>Long time spent on TV viewing, and possibly to a lesser degree, frequent consumption of meals during TV viewing, seem to be associated with generally having unhealthy food preferences and food habits among school-aged children. These associations, however, were not generally persistent after 6 years of follow-up.</p

Socio-demographic and behavioural correlates of oral hygiene status and oral health related quality of life, the Limpopo - Arusha school health project (LASH): A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Promoting oral health of adolescents is important for improvement of oral health globally. This study used baseline-data from LASH-project targeting secondary students to; 1) assess frequency of poor oral hygiene status and oral impacts on daily performances, OIDP, by socio-demographic and behavioural characteristics, 2) examine whether socio-economic and behavioural correlates of oral hygiene status and OIDP differed by gender and 3) examine whether socio-demographic disparity in oral health was explained by oral health-related behaviours.</p> <p>Methods</p> <p>Cross-sectional study was conducted in 2009 using one-stage cluster sampling design. Total of 2412 students (mean age 15.2 yr) completed self-administered questionnaires, whereas 1077 (mean age 14.9 yr) underwent dental-examination. Bivariate analyses were conducted using cross-tabulations and chi-square statistics. Multiple variable analyses were conducted using stepwise standardized logistic regression (SLR) with odds ratios and 95% Confidence intervals (CI).</p> <p>Results</p> <p>44.8% presented with fair to poor OHIS and 48.2% reported any OIDP. Older students, those from low socio-economic status families, had parents who couldn't afford dental care and had low educational-level reported oral impacts, poor oral hygiene, irregular toothbrushing, less dental attendance and fewer intakes of sugar-sweetened drinks more frequently than their counterparts. Stepwise logistic regression revealed that reporting any OIDP was independently associated with; older age-groups, parents do not afford dental care, smoking experience, no dental visits and fewer intakes of sugar-sweetened soft drinks. Behavioural factors accounted partly for association between low family SES and OIDP. Low family SES, no dental attendance and smoking experience were most important in males. Low family SES and fewer intakes of sugar-sweetened soft drinks were the most important correlates in females.</p> <p>Socio-behavioural factors associated with higher odds ratios for poor OHIS were; older age, belonging to the poorest household category and having parents who did not afford dental care across both genders.</p> <p>Conclusion</p> <p>Disparities in oral hygiene status and OIDP existed in relation to age, affording dental care, smoking and intake of sugar sweetened soft drinks. Gender differences should be considered in intervention studies, and modifiable behaviours have some relevance in reducing social disparity in oral health.</p

Evaluation of a multiple ecological level child obesity prevention program: Switch® what you Do, View, and Chew

<p>Abstract</p> <p>Background</p> <p>Schools are the most frequent target for intervention programs aimed at preventing child obesity; however, the overall effectiveness of these programs has been limited. It has therefore been recommended that interventions target multiple ecological levels (community, family, school and individual) to have greater success in changing risk behaviors for obesity. This study examined the immediate and short-term, sustained effects of the Switch program, which targeted three behaviors (decreasing children's screen time, increasing fruit and vegetable consumption, and increasing physical activity) at three ecological levels (the family, school, and community).</p> <p>Methods</p> <p>Participants were 1,323 children and their parents from 10 schools in two states. Schools were matched and randomly assigned to treatment and control. Measures of the key behaviors and body mass index were collected at baseline, immediately post-intervention, and 6 months post-intervention.</p> <p>Results</p> <p>The effect sizes of the differences between treatment and control groups ranged between small (Cohen's <it>d </it>= 0.15 for body mass index at 6 months post-intervention) to large (1.38; parent report of screen time at 6 months post-intervention), controlling for baseline levels. There was a significant difference in parent-reported screen time at post-intervention in the experimental group, and this effect was maintained at 6 months post-intervention (a difference of about 2 hours/week). The experimental group also showed a significant increase in parent-reported fruit and vegetable consumption while child-reported fruit and vegetable consumption was marginally significant. At the 6-month follow-up, parent-reported screen time was significantly lower, and parent and child-reported fruit and vegetable consumption was significantly increased. There were no significant effects on pedometer measures of physical activity or body mass index in the experimental group. The intervention effects were moderated by child sex (for fruit and vegetable consumption, physical activity, and weight status), family involvement (for fruit and vegetable consumption), and child body mass index (for screen time). The perception of change among the experimental group was generally positive with 23% to 62% indicating positive changes in behaviors.</p> <p>Conclusion</p> <p>The results indicate that the Switch program yielded small-to-modest treatment effects for promoting children's fruit and vegetable consumption and minimizing screen time. The Switch program offers promise for use in youth obesity prevention.</p

Challenges of molecular nutrition research 6: the nutritional phenotype database to store, share and evaluate nutritional systems biology studies

The challenge of modern nutrition and health research is to identify food-based strategies promoting life-long optimal health and well-being. This research is complex because it exploits a multitude of bioactive compounds acting on an extensive network of interacting processes. Whereas nutrition research can profit enormously from the revolution in ‘omics’ technologies, it has discipline-specific requirements for analytical and bioinformatic procedures. In addition to measurements of the parameters of interest (measures of health), extensive description of the subjects of study and foods or diets consumed is central for describing the nutritional phenotype. We propose and pursue an infrastructural activity of constructing the “Nutritional Phenotype database” (dbNP). When fully developed, dbNP will be a research and collaboration tool and a publicly available data and knowledge repository. Creation and implementation of the dbNP will maximize benefits to the research community by enabling integration and interrogation of data from multiple studies, from different research groups, different countries and different—omics levels. The dbNP is designed to facilitate storage of biologically relevant, pre-processed—omics data, as well as study descriptive and study participant phenotype data. It is also important to enable the combination of this information at different levels (e.g. to facilitate linkage of data describing participant phenotype, genotype and food intake with information on study design and—omics measurements, and to combine all of this with existing knowledge). The biological information stored in the database (i.e. genetics, transcriptomics, proteomics, biomarkers, metabolomics, functional assays, food intake and food composition) is tailored to nutrition research and embedded in an environment of standard procedures and protocols, annotations, modular data-basing, networking and integrated bioinformatics. The dbNP is an evolving enterprise, which is only sustainable if it is accepted and adopted by the wider nutrition and health research community as an open source, pre-competitive and publicly available resource where many partners both can contribute and profit from its developments. We introduce the Nutrigenomics Organisation (NuGO, http://www.nugo.org) as a membership association responsible for establishing and curating the dbNP. Within NuGO, all efforts related to dbNP (i.e. usage, coordination, integration, facilitation and maintenance) will be directed towards a sustainable and federated infrastructure

Detecting depressive and anxiety disorders in distressed patients in primary care; comparative diagnostic accuracy of the Four-Dimensional Symptom Questionnaire (4DSQ) and the Hospital Anxiety and Depression Scale (HADS)

BACKGROUND: Depressive and anxiety disorders often go unrecognized in distressed primary care patients, despite the overtly psychosocial nature of their demand for help. This is especially problematic in more severe disorders needing specific treatment (e.g. antidepressant pharmacotherapy or specialized cognitive behavioural therapy). The use of a screening tool to detect (more severe) depressive and anxiety disorders may be useful not to overlook such disorders. We examined the accuracy with which the Four-Dimensional Symptom Questionnaire (4DSQ) and the Hospital Anxiety and Depression Scale (HADS) are able to detect (more severe) depressive and anxiety disorders in distressed patients, and which cut-off points should be used. METHODS: Seventy general practitioners (GPs) included 295 patients on sick leave due to psychological problems. They excluded patients with recognized depressive or anxiety disorders. Patients completed the 4DSQ and HADS. Standardized diagnoses of DSM-IV defined depressive and anxiety disorders were established with the Composite International Diagnostic Interview (CIDI). Receiver Operating Characteristic (ROC) analyses were performed to obtain sensitivity and specificity values for a range of scores, and area under the curve (AUC) values as a measure of diagnostic accuracy. RESULTS: With respect to the detection of any depressive or anxiety disorder (180 patients, 61%), the 4DSQ and HADS scales yielded comparable results with AUC values between 0.745 and 0.815. Also with respect to the detection of moderate or severe depressive disorder, the 4DSQ and HADS depression scales performed comparably (AUC 0.780 and 0.739, p 0.165). With respect to the detection of panic disorder, agoraphobia and social phobia, the 4DSQ anxiety scale performed significantly better than the HADS anxiety scale (AUC 0.852 versus 0.757, p 0.001). The recommended cut-off points of both HADS scales appeared to be too low while those of the 4DSQ anxiety scale appeared to be too high. CONCLUSION: In general practice patients on sick leave because of psychological problems, the 4DSQ and the HADS are equally able to detect depressive and anxiety disorders. However, for the detection of cases severe enough to warrant specific treatment, the 4DSQ may have some advantages over the HADS, specifically for the detection of panic disorder, agoraphobia and social phobi

Evaluation of lymph node numbers for adequate staging of Stage II and III colon cancer

<p>Abstract</p> <p>Background</p> <p>Although evaluation of at least 12 lymph nodes (LNs) is recommended as the minimum number of nodes required for accurate staging of colon cancer patients, there is disagreement on what constitutes an adequate identification of such LNs.</p> <p>Methods</p> <p>To evaluate the minimum number of LNs for adequate staging of Stage II and III colon cancer, 490 patients were categorized into groups based on 1-6, 7-11, 12-19, and ≥ 20 LNs collected.</p> <p>Results</p> <p>For patients with Stage II or III disease, examination of 12 LNs was not significantly associated with recurrence or mortality. For Stage II (HR = 0.33; 95% CI, 0.12-0.91), but not for Stage III patients (HR = 1.59; 95% CI, 0.54-4.64), examination of ≥20 LNs was associated with a reduced risk of recurrence within 2 years. However, examination of ≥20 LNs had a 55% (Stage II, HR = 0.45; 95% CI, 0.23-0.87) and a 31% (Stage III, HR = 0.69; 95% CI, 0.38-1.26) decreased risk of mortality, respectively. For each six additional LNs examined from Stage III patients, there was a 19% increased probability of finding a positive LN (parameter estimate = 0.18510, p < 0.0001). For Stage II and III colon cancers, there was improved survival and a decreased risk of recurrence with an increased number of LNs examined, regardless of the cutoff-points. Examination of ≥7 or ≥12 LNs had similar outcomes, but there were significant outcome benefits at the ≥20 cutoff-point only for Stage II patients. For Stage III patients, examination of 6 additional LNs detected one additional positive LN.</p> <p>Conclusions</p> <p>Thus, the 12 LN cut-off point cannot be supported as requisite in determining adequate staging of colon cancer based on current data. However, a minimum of 6 LNs should be examined for adequate staging of Stage II and III colon cancer patients.</p

Could lymphatic mapping and sentinel node biopsy provide oncological providence for local resectional techniques for colon cancer? A review of the literature

<p>Abstract</p> <p>Background</p> <p>Endoscopic resectional techniques for colon cancer are undermined by their inability to determine lymph node status. This limits their application to only those lesions at the most minimal risk of lymphatic dissemination whereas their technical capacity could allow intraluminal or even transluminal address of larger lesions. Sentinel node biopsy may theoretically address this breach although the variability of its reported results for this disease is worrisome.</p> <p>Methods</p> <p>Medline, EMBASE and Cochrane databases were interrogated back to 1999 to identify all publications concerning lymphatic mapping for colon cancer with reference cross-checking for completeness. All reports were examined from the perspective of in vivo technique accuracy selectively in early stage disease (i.e. lesions potentially within the technical capacity of endoscopic resection).</p> <p>Results</p> <p>Fifty-two studies detailing the experiences of 3390 patients were identified. Considerable variation in patient characteristics as well as in surgical and histological quality assurances were however evident among the studies identified. In addition, considerable contamination of the studies by inclusion of rectal cancer without subgroup separation was frequent. Indeed such is the heterogeneity of the publications to date, formal meta-analysis to pool patient cohorts in order to definitively ascertain technique accuracy in those with T1 and/or T2 cancer is not possible. Although lymphatic mapping in early stage neoplasia alone has rarely been specifically studied, those studies that included examination of false negative rates identified high T3/4 patient proportions and larger tumor size as being important confounders. Under selected circumstances however the technique seems to perform sufficiently reliably to allow it prompt consideration of its use to tailor operative extent.</p> <p>Conclusion</p> <p>The specific question of whether sentinel node biopsy can augment the oncological propriety for endoscopic resective techniques (including Natural Orifice Transluminal Endoscopic Surgery [NOTES]) cannot be definitively answered at present. Study heterogeneity may account for the variability evident in the results from different centers. Enhanced capacity (perhaps to the level necessary to consider selective avoidance of en bloc mesenteric resection) by its confinement to only early stage disease is plausible although not proven. Specific study of the technique in early stage tumors is clearly essential before proffering this approach.</p