Manuel Ridao

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

BackgroundAttention 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.MethodsPubMed/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.ResultsFourteen 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.ConclusionsOur 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.

Control of arterial hypertension in Spain: a systematic review and meta-analysis of 76 epidemiological studies on 341 632 participants.

Objective Hypertension is a leading global risk factor for the burden of cardiovascular disease. Data about changes in hypertension control are important to set intervention priorities. We conducted a systematic review and meta-analysis of epidemiological studies to determine the control of hypertension in Spain over the past decade. Methods A search of PubMed/MEDLINE, SCOPUS and IME was performed for epidemiological studies conducted in Spain (since 2000) with data on control rates for hypertension. The primary outcome was the prevalence of uncontrolled hypertension defined as the percentage of patients having SBP at least 140 mmHg and/or DBP at least 90 mmHg. For populations at risk (e.g. patients with diabetes), the definition was SBP at least 130 mmHg and/or DBP at least 80–85 mmHg. Results Seventy-six studies evaluating 341 632 patients (79% with hypertension) met the inclusion criteria. Among hypertensive patients, the overall pooled prevalence of uncontrolled hypertension (≥140/90 mmHg) was 67.0% [95% confidence interval (CI) 64.1–69.9%], but was 87.6% (95% CI 86.2–89.0%) when the most restricted definition (≥130/80–85 mmHg) was used for patients at risk. The test for heterogeneity was significant (P < 0.001). Using metaregression analyses, we showed that the prevalence of uncontrolled hypertension did not change significantly over time, but the percentage of patients receiving at least two antihypertensive drugs increased (P = 0.032 and 0.001). Conclusion In Spain, the control of hypertension is far from optimum and does not appear to have improved in recent years despite the increased intensity of therapy. Patients at risk with comorbidities appear to be controlled worse.

Coauthorship and Institutional Collaborations on Cost-Effectiveness Analyses: A Systematic Network Analysis

Background Cost-Effectiveness Analysis (CEA) has been promoted as an important research methodology for determining the efficiency of healthcare technology and guiding medical decision-making. Our aim was to characterize the collaborative patterns of CEA conducted over the past two decades in Spain. Methods and Findings A systematic analysis was carried out with the information obtained through an updated comprehensive literature review and from reports of health technology assessment agencies. We identified CEAs with outcomes expressed as a time-based summary measure of population health (e.g. quality-adjusted life-years or disability-adjusted life-years), conducted in Spain and published between 1989 and 2011. Networks of coauthorship and institutional collaboration were produced using PAJEK software. One-hundred and thirty-one papers were analyzed, in which 526 authors and 230 institutions participated. The overall signatures per paper index was 5.4. Six major groups (one with 14 members, three with 7 members and two with 6 members) were identified. The most prolific authors were generally affiliated with the private-for-profit sector (e.g. consulting firms and the pharmaceutical industry). The private-for-profit sector mantains profuse collaborative networks including public hospitals and academia. Collaboration within the public sector (e.g. healthcare administration and primary care) was weak and fragmented. Conclusions This empirical analysis reflects critical practices among collaborative networks that contributed substantially to the production of CEA, raises challenges for redesigning future policies and provides a framework for similar analyses in other regions.

When are statins cost-effective in cardiovascular prevention? A systematic review of sponsorship bias and conclusions in economic evaluations of statins.

Background We examined sponsorship of published cost-effectiveness analyses of statin use for cardiovascular (CV) prevention, and determined whether the funding source is associated with study conclusions. Methods and Findings We searched PubMed/MEDLINE (up to June 2011) to identify cost-effectiveness analyses of statin use for CV prevention reporting outcomes as incremental costs per quality-adjusted life years (QALY) and/or life years gained (LYG). We examined relationships between the funding source and the study conclusions by means of tests of differences between proportions. Seventy-five studies were included. Forty-eight studies (64.0%) were industry-sponsored. Fifty-two (69.3%) articles compared statins versus non-active alternatives. Secondary CV prevention represented 42.7% of articles, followed by primary CV prevention (38.7%) and both (18.7%). Overall, industry-sponsored studies were much less likely to report unfavourable or neutral conclusions (0% versus 37.1%; p<0.001). For primary CV prevention, the proportion with unfavourable or neutral conclusions was 0% for industry-sponsored studies versus 57.9% for non-sponsored studies (p<0.001). Conversely, no statistically significant differences were identified for studies evaluating secondary CV prevention (0% versus 12.5%; p=0.222). Incremental costs per QALY/LYG estimates reported in industry-sponsored studies were generally more likely to fall below a hypothetical willingness-to-pay threshold of US

The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials.

50,000. Conclusions Our systematic analysis suggests that pharmaceutical industry sponsored economic evaluations of statins have generally favored the cost-effectiveness profile of their products particularly in primary CV prevention.

Cardiovascular and Renal Outcomes of Renin–Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses

Background Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in childhood. A wide variety of treatments have been used for the management of ADHD. We aimed to compare the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents. Methods and findings We performed a systematic review with network meta-analyses. Randomised controlled trials (≥ 3 weeks follow-up) were identified from published and unpublished sources through searches in PubMed and the Cochrane Library (up to April 7, 2016). Interventions of interest were pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity). The primary outcomes were efficacy (treatment response) and acceptability (all-cause discontinuation). Secondary outcomes included discontinuation due to adverse events (tolerability), as well as serious adverse events and specific adverse events. Random-effects Bayesian network meta-analyses were conducted to obtain estimates as odds ratios (ORs) with 95% credibility intervals. We analysed interventions by class and individually. 190 randomised trials (52 different interventions grouped in 32 therapeutic classes) that enrolled 26114 participants with ADHD were included in complex networks. At the class level, behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo. Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants. Stimulants seemed superior to behavioural therapy, cognitive training and non-stimulants. Behavioural therapy, stimulants and their combination showed the best profile of acceptability. Stimulants and non-stimulants seemed well tolerated. Among medications, methylphenidate, amphetamine, atomoxetine, guanfacine and clonidine seemed significantly more efficacious than placebo. Methylphenidate and amphetamine seemed more efficacious than atomoxetine and guanfacine. Methylphenidate and clonidine seemed better accepted than placebo and atomoxetine. Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia), but an increased risk of serious adverse events was not observed. There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine. Overall findings were limited by the clinical and methodological heterogeneity, small sample sizes of trials, short-term follow-up, and the absence of high-quality evidence; consequently, results should be interpreted with caution. Conclusions Clinical differences may exist between the pharmacological and non-pharmacological treatment used for the management of ADHD. Uncertainties about therapies and the balance between benefits, costs and potential harms should be considered before starting treatment. There is an urgent need for high-quality randomised trials of the multiple treatments for ADHD in children and adolescents. PROSPERO, number CRD42014015008.

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

Background Medications aimed at inhibiting the renin–angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes. Methods and Findings Eligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014). Interventions of interest were angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin (DR) inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke—singly and as a composite endpoint, major cardiovascular outcome—and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality—singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants), with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90–1.18), ACE inhibitor plus ARB (0.97; 95% CrI 0.79–1.19), DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96–1.81), and DR inhibitor plus ARB (1.00; 95% CrI 0.73–1.38). For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90–1.40), ACE inhibitor plus ARB (0.97; 95% CrI 0.72–1.29), DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65–1.57), and DR inhibitor plus ARB (1.18; 95% CrI 0.78–1.84). No significant differences were showed between ACE inhibitors and ARBs with respect to all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina pectoris, hospitalization for heart failure, ESRD, or doubling serum creatinine. Findings were limited by the clinical and methodological heterogeneity of the included studies. Potential inconsistency was identified in network meta-analyses of stroke and angina pectoris, limiting the conclusiveness of findings for these single endpoints. Conclusions In adults with diabetes, comparisons of different RAS blockers showed similar effects of ACE inhibitors and ARBs on major cardiovascular and renal outcomes. Compared with monotherapies, the combination of an ACE inhibitor and an ARB failed to provide significant benefits on major outcomes. Clinicians should discuss the balance between benefits, costs, and potential harms with individual diabetes patients before starting treatment. Review registration PROSPERO CRD42014014404

Trends of uncontrolled blood pressure in Spain: an updated meta-regression analysis.

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.

Coste-efectividad del tratamiento farmacológico del trastorno por déficit de atención e hiperactividad en niños y adolescentes: síntesis cualitativa de la evidencia científica

630 www.jhypertension.com 2010’ hypothesizing ‘this may be related, at least in part, with the higher use of antihypertensive treatment, particularly combined therapy’. By contrast, we recently reported in a systematic review and meta-analysis of 76 epidemiological studies conducted in Spain from 2000 to 2009 that whereas the percentage of patients receiving at least two antihypertensive drugs increased, the prevalence of uncontrolled BP did not change significantly over time [2]. In that analysis, overall period prevalence of uncontrolled BP (SBP/DBP 140/90 mmHg) was 67.0% [95% confidence interval (CI) 64.1–69.9%], but was 87.6% (95% CI 86.2–89.0%) when a more restricted definition

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

OBJECTIVE To describe the cost-effectiveness analyses of medications launched in Spain for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents. MATERIAL AND METHODS Systematic review of the literature without meta-analysis. A search was made in, PubMed/MEDLINE, SCOPUS, databases of the Centre for Reviews and Dissemination, and the websites of technology assessment agencies from Canada, the United Kingdom and the Spanish Platform AUnETS. Only full economic evaluations were included, considering at least methylphenidate or atomoxetine as pharmacological treatment alternatives in children and/or adolescents with ADHD. RESULTS Eleven studies published in 9 articles or reports were included. The most frequent characteristics were: cost-utility analysis (82%), health system perspective (82%), short-term horizon (91%), and private funding (50%). Methylphenidate was included in all studies, and atomoxetine in 4 studies. Methylphenidate and atomoxetine are cost-effective alternatives compared to placebo or no treatment, although incremental cost-effectiveness ratios are variable. The few direct treatment-comparisons between methylphenidate and atomoxetine provided contradictory and potentially biased results. CONCLUSIONS The pharmacological treatment of ADHD in children and adolescents, with the reservations arising from the generalization of results to different settings, is probably cost-effective in the short term. The existing studies do not allow the relative efficiency of different treatments to be established, either in the long-term treatment or in patient subgroups with specific characteristics or comorbidities.