Prevalence and comorbidity of autism spectrum disorder in Spain: study protocol for a systematic review and meta-analysis of observational studies.

BACKGROUND: Autism spectrum disorder (ASD) is a complex developmental disorder characterised by impaired social interaction and communication, and restrictive and repetitive behaviour. Previous systematic reviews have traditionally assessed the prevalence of ASD on global or regional context, with very few meta-analyses at the country level. The objective of this study will be to systematically evaluate published and unpublished observational studies that present prevalence and comorbidity of ASD among children, adolescent and adult population in Spain. METHODS/DESIGN: We designed and registered a study protocol for a systematic review and meta-analysis of descriptive epidemiology data. Observational studies (cohort, cross-sectional) reporting the prevalence of ASD and conducted in a wide range of people (e.g. general population, outpatient and/or school settings) will be included. The primary outcome will be the prevalence of ASD. Secondary outcomes will be the prevalence of any physical or mental comorbidity in association with ASD. No limitations will be imposed on publication status, study conduct period, and language of dissemination. Comprehensive literature searches will be conducted in seven electronic databases (from January 1980 onwards), including PubMed/MEDLINE, EMBASE, Scopus, Web of Science, PsycINFO, IME-Spanish Medical Index and IBECS-Spanish Bibliographic Index of Health Sciences. Grey literature will be identified through searching dissertation databases, Google Scholar and conference abstracts. Two team members will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion. The study methodological quality (or bias) will be appraised using an appropriate tool. If feasible, we will conduct random effects meta-analysis of observational data. Prevalence estimates will be stratified according to gender, age and geographical location. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g. methodological quality, sample size, diagnostic criteria). DISCUSSION: This systematic review and meta-analysis of observational data will identify, evaluate and integrate the epidemiological knowledge underlying the prevalence of ASD in Spain. The results of this study will be of interest to multiple audiences including patients, their families, caregivers, healthcare professional, scientists and policy makers. Results will be published in a peer-reviewed journal. Implications for future epidemiological research will be discussed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018090372.

Association of Anorexia Nervosa With Risk of Cancer: A Systematic Review and Meta-analysis.

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 (I2) 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; I2, 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; I2, 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; I2, 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; I2, 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 potential.

Prevalence and comorbidity of attention deficit hyperactivity disorder in Spain: study protocol for extending a systematic review with updated meta-analysis of observational studies.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a childhood-onset disorder characterized by a persistent pattern of symptoms of developmentally inappropriate and impaired inattention and/or hyperactivity/impulsivity, with difficulties often continuing into adulthood. ADHD can come with other comorbid conditions. The aim of this study will be to quantify the prevalence and comorbidity of ADHD among children, adolescent, and adult population in Spain. METHODS/DESIGN: We designed and registered a study protocol for an update and expansion of a systematic review and meta-analysis of pooled prevalence data. We will include cross-sectional observational studies reporting prevalence of ADHD in Spain and conducted in the general population, outpatient, and/or school settings. The primary outcome will be the prevalence of ADHD. Secondary outcomes will be the prevalence of any physical or mental comorbidity in association with ADHD. No limitations will be imposed on publication status, study conduct period, and language of dissemination. Comprehensive literature searches will be conducted in multiple electronic databases, including PubMed/MEDLINE, EMBASE, Scopus, Web of Science, PsycINFO, IME - Spanish Medical Index, and IBECS - Spanish Bibliographic Index of Health Sciences. We will also search Google Scholar, dissertation databases, and conference abstracts. Two team members will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion. The methodological quality (or risk of bias) of individual studies will be appraised using an appropriate tool. If feasible, we will conduct random effects meta-analysis. Prevalence estimates will be stratified according to gender, age, and geographical location. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., methodological quality, sample size, diagnostic criteria). DISCUSSION: This systematic review and meta-analysis of observational data will provide an updated synthesis of the prevalence and comorbidity of ADHD in Spain. This study will also examine factors that may explain potential variations in prevalence data. The findings of this study will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018106082 .

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

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.

Cancer and central nervous system disorders: protocol for an umbrella review of systematic reviews and updated meta-analyses of observational studies.

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.

Place of death and associated factors among patients with amyotrophic lateral sclerosis in Madrid (Spain).

Our objectives were to analyse the place of death, its temporal trend and associated sociodemographic factors among patients with amyotrophic lateral sclerosis (ALS) resident in the Autonomous Community of Madrid. This was a population based cross-sectional study of deaths from ALS (ICD-10 code G12.2) from 2003 to 2011, included in regional death statistics. The sociodemographic variables were age, gender, marital status, place of residence and socioeconomic level. Logistic regressions were performed to identify factors associated with death in hospital, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. Joinpoint models were used to analyse annual trends for death in hospital. Of 1035 patients who died of ALS, 56.1% died in a hospital, 30.4% at home, 8.3% in a residential home and it was unknown for 5.1%. The percentage of deaths in hospital was lower in older and in single people than in married ones (55.0% and 61.9%, respectively; ORa 0.74, 95% CI 0.57-0.97). This percentage increased progressively as socioeconomic level fell (66.3% in Q5 compared to 49.6% in Q1, ORa 2.03, 95% CI 1.36-3.02). A significant increase in the percentage of deaths in hospital was observed. In conclusion, factors such as age, marital status or socioeconomic level play a part in the place of death of those with ALS.

[Mobility Exposure Measures in Serious Road Traffic Injuries in Madrid, Spain]. / Medidas de exposición a la movilidad en las lesiones graves por tráfico en la Comunidad de Madrid.

BACKGROUND: The search of suitable indicators for estimating the risk of road traffic injuries is nowadays a relevant topic. The objective of this study was to carry out a comparative description of mortality and inhospital morbidity by age and sex, using population rates and mobility exposure related indicators. METHODS: Cross sectional study in the Community of Madrid, 2003-2005. Population rates and mortality and morbidity rates per billion of persons-kilometers travelled and per million of persons-hours travelled were estimated and compared by age and sex. The Minimum Basic Hospital Discharge Data Set, the 2004 Mobility House Survey of the Community of Madrid and the mortality register of the Statistic Institute of the Community of Madrid were used as information sources. RESULTS: 7,413 hospital discharges and 1,046 deaths were identified. Morbidity and mortality population rates in men were 62.24 and 9.20 respectively, and in women 23.80 and 2.97 per 100,000 inhabitants, being the highest rates those for men aged 16-24 years (119.27 hospital discharges and 12.00 deaths per 100,000 inhabitants). Women of 65 years and older showed the highest mobility related rates: 649.78 hospital discharges and 96.72 deaths per 10(9) km, and 13.11 hospital discharges and 1.95 deaths per 10(6) travelled hours. CONCLUSIONS: Morbidity and mortality were higher in men for the three indicators. Rates referred to mobility exposure, faced to population rates, decrease mortality and morbidity due to road traffic injuries in men and young ages and increase both in advanced ages.

Disability-adjusted Life Years Lost to Ischemic Heart Disease in Spain.

INTRODUCTION AND OBJECTIVES: The health indicator disability-adjusted life years combines the fatal and nonfatal consequences of a disease in a single measure. The aim of this study was to evaluate the burden of ischemic heart disease in 2008 in Spain by calculating disability-adjusted life years. METHODS: The years of life lost due to premature death were calculated using the ischemic heart disease deaths by age and sex recorded in the Spanish National Institute of Statistics and the life-table in the 2010 Global Burden of Disease study. The years lived with disability, calculated for acute coronary syndrome, stable angina, and ischemic heart failure, used hospital discharge data and information from population studies. Disability weights were taken from the 2010 Global Burden of Disease study. We calculated crude and age standardized rates (European Standard Population). Univariate sensitivity analyses were performed. RESULTS: In 2008, 539 570 disability-adjusted life years were lost due to ischemic heart disease in Spain (crude rate, 11.8/1000 population; standardized, 8.6/1000). Of the total years lost, 96% were due to premature death and 4% due to disability. Among the years lost due to disability, heart failure accounted for 83%, stable angina 15%, and acute coronary syndrome 2%. In the sensitivity analysis, weighting by age was the factor that changed the results to the greatest degree. CONCLUSIONS: Ischemic heart disease continues to have a huge impact on the health of our population, mainly because of premature death. The results of this study provide an overall vision of the epidemiologic situation in Spain and could serve as the basis for evaluating interventions targeting the acute and chronic manifestations of cardiac ischemia.

The national burden of cerebrovascular diseases in Spain: a population-based study using disability-adjusted life years.

BACKGROUND AND OBJECTIVE: The aim of the present study was to determine the national burden of cerebrovascular diseases in the adult population of Spain. PATIENTS AND METHODS: Cross-sectional, descriptive population-based study. We calculated the disability-adjusted life years (DALY) metric using country-specific data from national statistics and epidemiological studies to obtain representative outcomes for the Spanish population. DALYs were divided into years of life lost due to premature mortality (YLLs) and years of life lived with disability (YLDs). DALYs were estimated for the year 2008 by applying demographic structure by sex and age-groups, cause-specific mortality, morbidity data and new disability weights proposed in the recent Global Burden of Disease study. In the base case, neither YLLs nor YLDs were discounted or age-weighted. Uncertainty around DALYs was tested using sensitivity analyses. RESULTS: In Spain, cerebrovascular diseases generated 418,052 DALYs, comprising 337,000 (80.6%) YLLs and 81,052 (19.4%) YLDs. This accounts for 1,113 DALYs per 100,000 population (men: 1,197 and women: 1,033) and 3,912 per 100,000 in those over the age of 65 years (men: 4,427 and women: 2,033). Depending on the standard life table and choice of social values used for calculation, total DALYs varied by 15.3% and 59.9% below the main estimate. CONCLUSIONS: Estimates provided here represent a comprehensive analysis of the burden of cerebrovascular diseases at a national level. Prevention and control programmes aimed at reducing the disease burden merit further priority in Spain.

The association between in-patient death, utilization of hospital resources and availability of palliative home care for cancer patients.

BACKGROUND: The impact of palliative home care programs on in-patient admissions and deaths has not been appropriately established. AIM: The main objectives of this study have been to evaluate the frequency of in-patient hospital deaths and the use of hospital resources among cancer patients in two areas of the Madrid Region, as well as to assess differences between one area with and one without a palliative home care team (PHCT) in those variables. DESIGN AND SETTING: We conducted a population-based study comparing two adjacent metropolitan areas of approximately 200,000 inhabitants each in the Madrid Region, Spain, measuring in-patient deaths, emergency room admissions and in-patient days among cancer patients who died in 2005. Only one of the two areas had a fully established PHCT. RESULTS: 524/549 cancer patients (95%) had an identified place of death: 74% died in hospital, 17% at home, 6% in an in-patient hospice and 3% in a nursing home. The frequency of hospital deaths was significantly lower among patients of the PHCT area (61% versus 77%, p < 0.001), as well as the number of patients using emergency and in-patient services (68% versus 79%, p = 0.004, and 66 versus 76%, p = 0.012, respectively). After adjusting for other factors, the risk of hospital death was lower among patients older than 80 (OR, 95% CI, 0.3, 0.1-0.5), higher among patients with hematological malignancies (OR 6.1, 2.0-18.9) and lower among patients of the PHCT area (OR 0.4, 0.2-0.6). CONCLUSIONS: Our findings suggest that a PHCT is associated with reduced in-patient deaths and overall hospitalization over the last two months of life.

Burden of disease assessment with summary measures of population health for the Region of Valencia, Spain: a population-based study.

BACKGROUND AND OBJECTIVE: An important input to decision-making and health planning is a consistent and comparative description of the population health status. The purpose of this study was to describe the burden of disease in the Region of Valencia (Spain). MATERIAL AND METHODS: Disability-adjusted life years (DALYs) were calculated and divided into years of life lost (YLLs) and years lived with disability (YLDs). Using death registry data and Valencian population estimates in 2008, we calculated the number of deaths and YLLs. YLDs were based on age- and sex-specific data for countries of the EURO-A subregional level (which includes the Region of Valencia) from the Global Burden of Disease study. The results were stratified by age group, sex and underlying cause of death. The DALY values were used to rank the leading conditions of disease burden. RESULTS: In 2008, the total number of DALYs lost was about 551 thousands (53% in men). The main categories of DALYs lost were neuropsychiatric conditions (30%; 167 thousands), malignant tumors (15%; 85 thousands), cardiovascular diseases (13%; 72 thousands) and sense organ diseases (8%; 46 thousands). Depression (8% of DALYs; 47 thousands), dementias (8%; 42 thousands), ischaemic heart disease (5%; 27 thousands), hearing loss (4%; 22 thousands), stroke (4%; 20 thousands) and lung cancer (3%; 19 thousands) were the leading specific causes of disease burden. CONCLUSIONS: We provide for the first time ever information on the burden of disease in the Valencian population. At this local level, the use of DALYs can help to monitor the population health status and guide the debates on rational priority-setting.

Burden of disease in adolescents and young people in Spain.

OBJECTIVE: This article analyses the burden of disease in adolescents and young people in Spain in 2008. MATERIAL AND METHODS: A cross-sectional population-based study. We estimated disability-adjusted life years (DALYs) by sex and cause for subjects aged 15-29 years. Data sources were used: 1) National death records by age, sex and cause; 2) Population data (both in July 2008); and 3) Estimates of the disability pattern for European countries with very low mortality. RESULTS: In 2008, adolescents and young people lost 786,479 DALYs (414,346 in males). Non-communicable diseases generated 661,282 DALYs (84% of the total). The main specific causes of disease burden were: unipolar depression (16% of DALYs), alcohol use disorders (11%), migraine (9%), bipolar disorder (7%), schizophrenia (6%), road traffic accidents (5%) and drug addiction disorders (5%). CONCLUSIONS: The burden of disease expressed in DALYs can define the loss of health in adolescents and young people. At these ages, health promotion and protection are essential to prevent the onset of disease in adulthood.

Prevalence of attention deficit hyperactivity disorder among children and adolescents in Spain: a systematic review and meta-analysis of epidemiological studies.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a commonly diagnosed neuropsychiatric disorder in childhood, but the frequency of the condition is not well established in many countries. The aim of the present study was to quantify the overall prevalence of ADHD among children and adolescents in Spain by means of a systematic review and meta-analysis. METHODS: PubMed/MEDLINE, IME, IBECS and TESEO were comprehensively searched. Original reports were selected if they provided data on prevalence estimates of ADHD among people under 18 years old in Spain and were cross-sectional, observational epidemiological studies. Information from included studies was systematically extracted and evaluated. Overall pooled-prevalence estimates of ADHD were calculated using random-effects models. Sources of heterogeneity were explored by means sub-groups analyses and univariate meta-regressions. RESULTS: Fourteen epidemiological studies (13,026 subjects) were selected. The overall pooled-prevalence of ADHD was estimated at 6.8% [95% confidence interval (CI) 4.9 - 8.8%] representing 361,580 (95% CI 260,550 - 467,927) children and adolescents in the community. There was significant heterogeneity (P < 0.001), which was incompletely explained by subgroup analyses and meta-regressions. CONCLUSIONS: Our findings suggest that the prevalence of ADHD among children and adolescents in Spain is consistent with previous studies conducted in other countries and regions. This study represents a first step in estimating the national burden of ADHD that will be essential to building evidence-based programs and services.