Anorexia nervosa and cancer: a protocol for a systematic review and meta-analysis of observational studies

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Anorexia nervosa is characterized by a severe restriction of caloric intake, low body weight, fear of gaining weight or of becoming fat, and disturbance of body image. Pathogenesis of the disorder may include genetic predisposition, hormonal changes and a combination of environmental, psychosocial, and cultural factors. Cancer is the second leading cause of death worldwide. At present, no systematic reviews and meta-analyses have evaluated the risk of cancer in people with anorexia nervosa. The objective of this study will be to evaluate the association between anorexia nervosa and the risk of developing or dying from cancer. METHODS/DESIGN: This study protocol is part of a systematic collection and assessment of multiple systematic reviews and meta-analyses (umbrella review) evaluating the association of cancer and multiple central nervous system disorders. We designed a specific protocol for a new systematic review and meta-analysis of observational studies of anorexia nervosa with risk of developing or dying from any cancer. Data sources will be PubMed, Embase, Scopus, Web of Science, and manual screening of references. Observational studies (case-control and cohort) in humans that examined the association between anorexia nervosa and risk of developing or dying from cancer will be sought. The primary outcomes will be cancer incidence and cancer mortality in association with anorexia nervosa. Secondary outcomes will be site-specific cancer incidence and mortality, respectively. Screening of abstracts and full texts, and data abstraction will be performed by two team members independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. The quality of studies will be assessed by using the Ottawa-Newcastle scale by two team members independently. Random effects models will be conducted where appropriate. Subgroup and additional analyses will be conducted to explore the potential sources of heterogeneity. The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used for determining the quality of evidence for cancer outcomes. DISCUSSION: Findings from this systematic review will inform an ongoing umbrella review on cancer and central nervous system disorders. Our systematic review and meta-analysis of observational studies will establish the extent of the epidemiological evidence underlying the association between anorexia nervosa and cancer. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017067462.Specific funding from the Generalitat Valenciana (PROMETEOII/2015/021) and CIBERSAM/Institute of Health Carlos III was received for this work. The funders were not involved in the design of the protocol or decision to submit the protocol for publication, nor will they be involved in any aspect of the conduct of the review. BH is supported by a New Investigator Award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network. MR is partially funded by the Spanish Health Services Research on Chronic Patients Network (REDISSEC)/Institute of Health Carlos III. The views expressed in this article are the views of the authors and may not be understood or quoted as being made on behalf of, or reflecting the position of, the funder(s) or any institution

Association of anorexia nervosa with risk of cancer. A systematic review and meta-analysis

This is the final version. Available from the publisher via the DOI in this record.IMPORTANCE Anorexia nervosa is recognized as an important cause of morbidity in young people. However, the risk of cancer in people with anorexia nervosa remains uncertain. OBJECTIVE To evaluate the association of anorexia nervosa with the risk of developing or dying of cancer. DATA SOURCES MEDLINE, Scopus, Embase, and Web of Science from database inception to January 9, 2019. STUDY SELECTION Published observational studies in humans examining the risk of cancer in people with anorexia nervosa compared with the general population or those without anorexia nervosa. Studies needed to report incidence or mortality rate ratios (RRs). DATA EXTRACTION AND SYNTHESIS Screening, data extraction, and methodological quality assessment were performed by at least 2 researchers independently. A random-effects model was used to synthesize individual studies. Heterogeneity (I 2 ) was assessed and 95% prediction intervals (PIs) were calculated. MAIN OUTCOMES AND MEASURES All cancer incidence and cancer mortality associated with anorexia nervosa. Secondary outcomes were site-specific cancer incidence and mortality. RESULTS Seven cohort studies published in 10 articles (42 602 participants with anorexia nervosa) were included. Anorexia nervosa was not associated with risk of developing any cancer (4 studies in women; RR, 0.97; 95% CI, 0.89-1.06; P = .53; I 2 , 0%; 95% PI, 0.80-1.18; moderate confidence). Anorexia nervosa was associated with decreased breast cancer incidence (5 studies in women; RR, 0.60; 95% CI, 0.50-0.80; P < .001; I 2 , 0%; 95% PI, 0.44-0.83; high confidence). Conversely, anorexia nervosa was associated with increased risk of developing lung cancer (3 studies in women; RR, 1.50; 95% CI, 1.06-2.12; P = .001; I 2 , 0%; 95% PI, 0.19-16.46; low confidence) and esophageal cancer (2 studies in women; RR, 6.10; 95% CI, 2.30-16.18; P < .001; I 2 , 0%; low confidence). CONCLUSIONS AND RELEVANCE Among people with anorexia nervosa, risk of developing cancer did not differ compared with the general population, but a significantly reduced risk of breast cancer was observed. Understanding the mechanisms underlying these associations could have important preventive potentialGeneralitat ValencianaCarlos III Health Institut

Galaxy And Mass Assembly (GAMA): the galaxy luminosity function within the cosmic web

We investigate the dependence of the galaxy luminosity function on geometric environment within the Galaxy And Mass Assembly (GAMA) survey. The tidal tensor prescription, based on the Hessian of the pseudo-gravitational potential, is used to classify the cosmic web and define the geometric environments: for a given smoothing scale, we classify every position of the surveyed region, 0.04 < z < 0.26, as either a void, a sheet, a filament or a knot. We consider how to choose appropriate thresholds in the eigenvalues of the Hessian in order to partition the galaxies approximately evenly between environments. We find a significant variation in the luminosity function of galaxies between different geometric environments; the normalization, characterized by ϕ* in a Schechter function fit, increases by an order of magnitude from voids to knots. The turnover magnitude, characterized by M*, brightens by approximately 0.5 mag from voids to knots. However, we show that the observed modulation can be entirely attributed to the indirect local-density dependence. We therefore find no evidence of a direct influence of the cosmic web on the galaxy luminosity function

Galaxy And Mass Assembly (GAMA): the galaxy luminosity function within the cosmic web

We investigate the dependence of the galaxy luminosity function on geometric environment within the Galaxy And Mass Assembly (GAMA) survey. The tidal tensor prescription, based on the Hessian of the pseudo-gravitational potential, is used to classify the cosmic web and define the geometric environments: for a given smoothing scale, we classify every position of the surveyed region, 0.04 < z < 0.26, as either a void, a sheet, a filament or a knot. We consider how to choose appropriate thresholds in the eigenvalues of the Hessian in order to partition the galaxies approximately evenly between environments. We find a significant variation in the luminosity function of galaxies between different geometric environments; the normalization, characterized by ϕ* in a Schechter function fit, increases by an order of magnitude from voids to knots. The turnover magnitude, characterized by M*, brightens by approximately 0.5 mag from voids to knots. However, we show that the observed modulation can be entirely attributed to the indirect local-density dependence. We therefore find no evidence of a direct influence of the cosmic web on the galaxy luminosity function

Brownian bridges to submanifolds

We introduce and study Brownian bridges to submanifolds. Our method involves proving a general formula for the integral over a submanifold of the minimal heat kernel on a complete Riemannian manifold. We use the formula to derive lower bounds, an asymptotic relation and derivative estimates. We also see a connection to hypersurface local time. This work is motivated by the desire to extend the analysis of path and loop spaces to measures on paths which terminate on a submanifold

The diagnosis of colorectal cancer in patients with symptoms: finding a needle in a haystack

Patients often see primary care physicians with symptoms that might signal colorectal cancer but are also common in adults without cancer. Physicians and patients must then make a difficult decision about whether and how aggressively to evaluate the symptom. Favoring referral is that missed diagnoses lead to unnecessary testing, prolonged uncertainty, and continuing symptoms; also, the physician will suffer chagrin. It is not clear that diagnostic delay leads to progression to a more advanced stage. Against referral is that proper evaluation includes colonoscopy, with attendant inconvenience, discomfort, cost, and risk. The article by Hamilton et al, published this month in BMC Medicine, provides strong estimates of the predictive value of the various symptoms and signs of colorectal cancer and show how much higher predictive values are with increasing age and male sex. Unfortunately, their results also make clear that most colorectal cancers present with symptoms with low predictive values, < 1.2%. Models that include a set of predictive variables, that is, risk factors, age, sex, screening history, and symptoms, have been developed to guide primary prevention and clinical decision-making and are more powerful than individual symptoms and signs alone. Although screening for colorectal cancer is increasing in many countries, cancers will still be found outside screening programs so primary care physicians will remain at the front line in the difficult task of distinguishing everyday symptoms from life-threatening cancer

Galaxy and Mass Assembly: luminosity and stellar mass functions in GAMA groups

How do galaxy properties (such as stellar mass, luminosity, star formation rate, and morphology) and their evolution depend on the mass of their host dark matter halo? Using the Galaxy and Mass Assembly (GAMA) group catalogue, we address this question by exploring the dependence on host halo mass of the luminosity function (LF) and stellar mass function (SMF) for grouped galaxies subdivided by colour, morphology and central/satellite. We find that spheroidal galaxies in particular dominate the bright and massive ends of the LF and SMF, respectively. More massive haloes host more massive and more luminous central galaxies. The satellite LF and SMF respectively show a systematic brightening of characteristic magnitude, and increase in characteristic mass, with increasing halo mass. In contrast to some previous results, the faint-end and low-mass slopes show little systematic dependence on halo mass. Semi-analytic models and simulations show similar or enhanced dependence of central mass and luminosity on halo mass. Faint and low-mass simulated satellite galaxies are remarkably independent of halo mass, but the most massive satellites are more common in more massive groups. In the first investigation of low-redshift LF and SMF evolution in group environments, we find that the red/blue ratio of galaxies in groups has increased since redshift $z \approx 0.3$ relative to the field population. This observation strongly suggests that quenching of star formation in galaxies as they are accreted into galaxy groups is a significant and ongoing process