Person:

Driver, Jane

Background: The objective of this study will be to synthesize the epidemiological evidence and evaluate the validity of the associations between central nervous system disorders and the risk of developing or dying from cancer. Methods/design We will perform an umbrella review of systematic reviews and conduct updated meta-analyses of observational studies (cohort and case-control) investigating the association between central nervous system disorders and the risk of developing or dying from any cancer or specific types of cancer. Searches involving PubMed/MEDLINE, EMBASE, SCOPUS and Web of Science will be used to identify systematic reviews and meta-analyses of observational studies. In addition, online databases will be checked for observational studies published outside the time frames of previous reviews. Eligible central nervous system disorders will be Alzheimer’s disease, anorexia nervosa, amyotrophic lateral sclerosis, autism spectrum disorders, bipolar disorder, depression, Down’s syndrome, epilepsy, Huntington’s disease, multiple sclerosis, Parkinson’s disease and schizophrenia. The primary outcomes will be cancer incidence and cancer mortality in association with a central nervous system disorder. Secondary outcome measures will be site-specific cancer incidence and mortality, respectively. Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles. Data will be abstracted, and study quality/risk of bias will be appraised by two reviewers independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects meta-analyses of primary observational studies will be conducted where appropriate. Parameters for exploring statistical heterogeneity are pre-specified. 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 Our study will establish the extent of the epidemiological evidence underlying the associations between central nervous system disorders and cancer and will provide a rigorous and updated synthesis of a range of important site-specific cancer outcomes. Systematic review registration PROSPERO CRD42016052762 Electronic supplementary material The online version of this article (doi:10.1186/s13643-017-0466-y) contains supplementary material, which is available to authorized users.

Background: Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are childhood onset neurodevelopmental disorders that may persist into adulthood. ASD and ADHD tend to run in families and may have a significant negative impact on the health and longevity of those with the disorder and their relatives. The aim of this study will be to analyze the risk of mortality among children, adolescents, and adults with ASD or ADHD and their first-degree relatives. Methods/design We will conduct a systematic review and meta-analysis of observational studies. Searches of PubMed/MEDLINE, EMBASE, PsycINFO, SCOPUS, and ISI Web of Science will be used to identify epidemiological studies. Eligible studies will be observational studies reporting study-specific data for all-cause mortality or cause-specific mortality in children, adolescents, or adults with ASD or ADHD and/or their first-degree relatives. Cohort studies and case-control studies will be included. The primary outcome will be all-cause mortality. The secondary outcome will be cause-specific mortality. Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles. Data will be abstracted, and study risk of bias/methodological quality will be appraised by two reviewers independently. The methodological quality of epidemiological studies will be appraised using the Newcastle-Ottawa Scale (NOS). Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects meta-analyses of primary studies will be conducted where appropriate. Subgroup analyses for exploring statistical heterogeneity, if feasible, will include gender, age group, ethnicity, comorbidities, classification of cause of death, and relevant study characteristics. Discussion Our study will establish the extent of the epidemiological evidence underlying the risk of mortality among children, adolescents, and adults with ASD or ADHD and their first-degree relatives. We anticipate that our findings will be of interest to patients, their families, caregivers, healthcare professionals, scientists, and policy makers. Implications for future epidemiological research will be discussed. Systematic review registration PROSPERO CRD42017059955. Electronic supplementary material The online version of this article (10.1186/s13643-017-0581-9) contains supplementary material, which is available to authorized users.