Validación de la versión en español de la escala de evaluación del trastorno por déficit de atención e hiperactividad (ADHD-RS-IV.es) en una muestra española

Objetivos El objetivo de este estudio es validar la versión en castellano del ADHD-RS-IV (ADHD-RS-IV.es) en una muestra española. Métodos A partir de una muestra total de 652 niños y adolescentes (rango edad: 6-17 años; media [DE] = 11,14 [3,27] años), se incluyó a 518 pacientes con TDAH (criterios DSM-IV-TR) y a 134 controles sanos. Para la evaluación de la estructura factorial, la validez y la fiabilidad de la escala se realizó un análisis factorial confirmatorio (CFA) mediante structural equation modeling en una matriz de correlaciones policóricas, y usando el método de máxima verosimilitud para la estimación. Se calcularon la validez discriminante y su valor predictivo mediante curvas receiver operating characteristics. Resultados La escala en castellano mostró una consistencia interna elevada, tanto para la escala total como para sus subescalas. El coeficiente alfa de Cronbach era 0,94 para la escala total y ≥ 0,90 para las subescalas. Los valores alfa ordinales eran 0,95 para la escala total y ≥ 0,90 para las subescalas. El análisis CFA mostró un modelo de 2 factores (inatención e hiperactividad/impulsividad) intercorrelacionados. La escala ofrece buen poder discriminante (AUC = 0,97). Conclusiones La versión española del ADHD-RS-IV (ADHD-RS-IV.es) mostró una estructura bifactorial consistente con los modelos del DSM-IV-TR y DSM-5, y con el modelo propuesto por el autor de la escala original. Además, posee un alto poder discriminante, lo que lo convierte en un instrumento válido y fiable para medir la presencia y severidad de síntomas de TDAH en la población española.Objectives The purpose of this study is to validate a Spanish-language version of the 18-item ADHD Rating Scale-IV (ADHD-RS-IV.es) in a Spanish sample. Methods From a total sample of 652 children and adolescents aged 6 to 17 years (mean age was 11.14 ± 3.27), we included 518 who met the DSM-IV-TR criteria for ADHD and 134 healthy controls. To evaluate the factorial structure, validity, and reliability of the scale, we performed a confirmatory factor analysis (CFA) using structural equation modelling on a polychoric correlation matrix and maximum likelihood estimation. The scale's discriminant validity and predictive value were estimated using ROC (receiver operating characteristics) curve analysis. Results Both the full scale and the subscales of the Spanish-language version of the ADHD-RS-IV showed good internal consistency. Cronbach's alpha was 0.94 for the full scale and ≥ 0.90 for the subscales, and ordinal alpha was 0.95 and ≥ 0.90, respectively. CFA showed that a two-factor model (inattention and hyperactivity/impulsivity) provided the best fit for the data. ADHD-RS-IV.es offered good discriminant ability to distinguish between patients with ADHD and controls (AUC = 0.97). Conclusions The two-factor structure of the Spanish-language version of the ADHD-RS-IV (ADHD-RS-IV.es) is consistent with those of the DSM-IV-TR and DSM-5 as well as with the model proposed by the author of the original scale. Furthermore, it has good discriminant ability. ADHD-RS-IV.es is therefore a valid and reliable tool for determining presence and severity of ADHD symptoms in the Spanish population

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Clinical and neuropsychological predictors of methylphenidate response in children and adolescents with ADHD: A naturalistic follow-up study in a spanish sample

Background: Methylphenidate (MPH) is the most commonly used medication for Attention-Deficit/Hyperactivity Disorder (ADHD), but to date, there are neither consistent nor sufficient findings on conditions differentiating responsiveness to MPH response in ADHD. Objective: To develop a predictive model of MPH response, using a longitudinal and naturalistic follow-up study, in a Spanish sample of children and adolescents with ADHD. Methods: We included all children and adolescents with ADHD treated with MPH in our outpatient Clinic (2005 to 2015), evaluated with the K-SADS interview. We collected ADHD-RS-IV.es and CGI-S scores at baseline and at follow up, and neuropsychological testing (WISC-IV, Continuous Performance Test (CPT-II) & Stroop). Clinical response was defined as >30% reduction from baseline of total ADHD-RS-IV.es score and CGI-S final score of 1 or 2 maintained for the previous 3 months. Results: We included 518 children and adolescents with ADHD, mean (SD) age of patients was 11.4 (3.3) years old; 79% male; 51.7% had no comorbidities; and 75.31% had clinical response to a mean MPH dose of 1.2 mg/kg/day. Lower ADHD-RS-IV.es scores, absence of comorbidities (oppositional-defiant symptoms, depressive symptoms and alcohol/cannabis use), fewer altered neuropsychological tests, higher total IQ and low commission errors in CPT-II, were significantly associated with a complete clinical response to methylphenidate treatment. Conclusion: Oppositional-defiant symptoms, depressive symptoms, and a higher number of impaired neuropsychological tests are associated with worse clinical response to methylphenidate. Other stimulants or non-stimulants treatment may be considered when these clinical and neuropsychological variables converged in the first clinical intervie

Clinical and neuropsychological predictors of methylphenidate response in children and adolescents with ADHD: A naturalistic follow-up study in a spanish sample

Background: Methylphenidate (MPH) is the most commonly used medication for Attention-Deficit/Hyperactivity Disorder (ADHD), but to date, there are neither consistent nor sufficient findings on conditions differentiating responsiveness to MPH response in ADHD. Objective: To develop a predictive model of MPH response, using a longitudinal and naturalistic follow-up study, in a Spanish sample of children and adolescents with ADHD. Methods: We included all children and adolescents with ADHD treated with MPH in our outpatient Clinic (2005 to 2015), evaluated with the K-SADS interview. We collected ADHD-RS-IV.es and CGI-S scores at baseline and at follow up, and neuropsychological testing (WISC-IV, Continuous Performance Test (CPT-II) & Stroop). Clinical response was defined as >30% reduction from baseline of total ADHD-RS-IV.es score and CGI-S final score of 1 or 2 maintained for the previous 3 months. Results: We included 518 children and adolescents with ADHD, mean (SD) age of patients was 11.4 (3.3) years old; 79% male; 51.7% had no comorbidities; and 75.31% had clinical response to a mean MPH dose of 1.2 mg/kg/day. Lower ADHD-RS-IV.es scores, absence of comorbidities (oppositional-defiant symptoms, depressive symptoms and alcohol/cannabis use), fewer altered neuropsychological tests, higher total IQ and low commission errors in CPT-II, were significantly associated with a complete clinical response to methylphenidate treatment. Conclusion: Oppositional-defiant symptoms, depressive symptoms, and a higher number of impaired neuropsychological tests are associated with worse clinical response to methylphenidate. Other stimulants or non-stimulants treatment may be considered when these clinical and neuropsychological variables converged in the first clinical intervie

Validación de la versión en español de la escala de evaluación del trastorno por déficit de atención e hiperactividad (ADHD-RS-IV.es) en una muestra española

Objetivos El objetivo de este estudio es validar la versión en castellano del ADHD-RS-IV (ADHD-RS-IV.es) en una muestra española. Métodos A partir de una muestra total de 652 niños y adolescentes (rango edad: 6-17 años; media [DE] = 11,14 [3,27] años), se incluyó a 518 pacientes con TDAH (criterios DSM-IV-TR) y a 134 controles sanos. Para la evaluación de la estructura factorial, la validez y la fiabilidad de la escala se realizó un análisis factorial confirmatorio (CFA) mediante structural equation modeling en una matriz de correlaciones policóricas, y usando el método de máxima verosimilitud para la estimación. Se calcularon la validez discriminante y su valor predictivo mediante curvas receiver operating characteristics. Resultados La escala en castellano mostró una consistencia interna elevada, tanto para la escala total como para sus subescalas. El coeficiente alfa de Cronbach era 0,94 para la escala total y ≥ 0,90 para las subescalas. Los valores alfa ordinales eran 0,95 para la escala total y ≥ 0,90 para las subescalas. El análisis CFA mostró un modelo de 2 factores (inatención e hiperactividad/impulsividad) intercorrelacionados. La escala ofrece buen poder discriminante (AUC = 0,97). Conclusiones La versión española del ADHD-RS-IV (ADHD-RS-IV.es) mostró una estructura bifactorial consistente con los modelos del DSM-IV-TR y DSM-5, y con el modelo propuesto por el autor de la escala original. Además, posee un alto poder discriminante, lo que lo convierte en un instrumento válido y fiable para medir la presencia y severidad de síntomas de TDAH en la población española.Objectives The purpose of this study is to validate a Spanish-language version of the 18-item ADHD Rating Scale-IV (ADHD-RS-IV.es) in a Spanish sample. Methods From a total sample of 652 children and adolescents aged 6 to 17 years (mean age was 11.14 ± 3.27), we included 518 who met the DSM-IV-TR criteria for ADHD and 134 healthy controls. To evaluate the factorial structure, validity, and reliability of the scale, we performed a confirmatory factor analysis (CFA) using structural equation modelling on a polychoric correlation matrix and maximum likelihood estimation. The scale's discriminant validity and predictive value were estimated using ROC (receiver operating characteristics) curve analysis. Results Both the full scale and the subscales of the Spanish-language version of the ADHD-RS-IV showed good internal consistency. Cronbach's alpha was 0.94 for the full scale and ≥ 0.90 for the subscales, and ordinal alpha was 0.95 and ≥ 0.90, respectively. CFA showed that a two-factor model (inattention and hyperactivity/impulsivity) provided the best fit for the data. ADHD-RS-IV.es offered good discriminant ability to distinguish between patients with ADHD and controls (AUC = 0.97). Conclusions The two-factor structure of the Spanish-language version of the ADHD-RS-IV (ADHD-RS-IV.es) is consistent with those of the DSM-IV-TR and DSM-5 as well as with the model proposed by the author of the original scale. Furthermore, it has good discriminant ability. ADHD-RS-IV.es is therefore a valid and reliable tool for determining presence and severity of ADHD symptoms in the Spanish population

Areas of interest and stigmatic attitudes of the general public in five relevant medical conditions: Thematic and quantitative analysis using twitter

Background: Twitter is an indicator of real-world performance, thus, is an appropriate arena to assess the social consideration and attitudes toward psychosis. Objective: The aim of this study was to perform a mixed-methods study of the content and key metrics of tweets referring to psychosis in comparison with tweets referring to control diseases (breast cancer, diabetes, Alzheimer, and human immunodeficiency virus). Methods: Each tweet’s content was rated as nonmedical (NM: testimonies, health care products, solidarity or awareness and misuse) or medical (M: included a reference to the illness’s diagnosis, treatment, prognosis, or prevention). NM tweets were classified as positive or pejorative. We assessed the appropriateness of the medical content. The number of retweets generated and the potential reach and impact of the hashtags analyzed was also investigated. Results: We analyzed a total of 15,443 tweets: 8055 classified as NM and 7287 as M. Psychosis-related tweets (PRT) had a significantly higher frequency of misuse 33.3% (212/636) vs 1.15% (853/7419; P<.001) and pejorative content 36.2% (231/636) vs 11.33% (840/7419; P<.001). The medical content of the PRT showed the highest scientific appropriateness 100% (391/391) vs 93.66% (6030/6439; P<.001) and had a higher frequency of content about disease prevention. The potential reach and impact of the tweets related to psychosis were low, but they had a high retweet-to-tweet ratio. Conclusions: We show a reduced number and a different pattern of contents in tweets about psychosis compared with control diseases. PRT showed a predominance of nonmedical content with increased frequencies of misuse and pejorative tone. However, the medical content of PRT showed high scientific appropriateness aimed toward prevention

Areas of interest and stigmatic attitudes of the general public in five relevant medical conditions: Thematic and quantitative analysis using twitter

Background: Twitter is an indicator of real-world performance, thus, is an appropriate arena to assess the social consideration and attitudes toward psychosis. Objective: The aim of this study was to perform a mixed-methods study of the content and key metrics of tweets referring to psychosis in comparison with tweets referring to control diseases (breast cancer, diabetes, Alzheimer, and human immunodeficiency virus). Methods: Each tweet’s content was rated as nonmedical (NM: testimonies, health care products, solidarity or awareness and misuse) or medical (M: included a reference to the illness’s diagnosis, treatment, prognosis, or prevention). NM tweets were classified as positive or pejorative. We assessed the appropriateness of the medical content. The number of retweets generated and the potential reach and impact of the hashtags analyzed was also investigated. Results: We analyzed a total of 15,443 tweets: 8055 classified as NM and 7287 as M. Psychosis-related tweets (PRT) had a significantly higher frequency of misuse 33.3% (212/636) vs 1.15% (853/7419; P<.001) and pejorative content 36.2% (231/636) vs 11.33% (840/7419; P<.001). The medical content of the PRT showed the highest scientific appropriateness 100% (391/391) vs 93.66% (6030/6439; P<.001) and had a higher frequency of content about disease prevention. The potential reach and impact of the tweets related to psychosis were low, but they had a high retweet-to-tweet ratio. Conclusions: We show a reduced number and a different pattern of contents in tweets about psychosis compared with control diseases. PRT showed a predominance of nonmedical content with increased frequencies of misuse and pejorative tone. However, the medical content of PRT showed high scientific appropriateness aimed toward prevention

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Background: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402

Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Background: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4–1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods: ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1–12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65–1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)—defined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucose—and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. Findings: At study baseline, 5444 patients (28·8%) had diabetes, 8246 (43·6%) had prediabetes, and 5234 (27·7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2·20–2·28 mmol/L), after 4 months' treatment with alirocumab (0·80 mmol/L), or after 4 months' treatment with placebo (2·25–2·28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2·8 years was greater in patients with diabetes (16·4%) than in those with prediabetes (9·2%) or normoglycaemia (8·5%); hazard ratio (HR) for diabetes versus normoglycaemia 2·09 (95% CI 1·78–2·46, p<0·0001) and for diabetes versus prediabetes 1·90 (1·65–2·17, p<0·0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2·3%, 95% CI 0·4 to 4·2) than in those with prediabetes (1·2%, 0·0 to 2·4) or normoglycaemia (1·2%, −0·3 to 2·7; absolute risk reduction pinteraction=0·0019). Among patients without diabetes at baseline, 676 (10·1%) developed diabetes in the placebo group, compared with 648 (9·6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1·00, 95% CI 0·89–1·11). HRs were 0·97 (95% CI 0·87–1·09) for patients with prediabetes and 1·30 (95% CI 0·93–1·81) for those with normoglycaemia (pinteraction=0·11). Interpretation: After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0·65–1·30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes. Funding: Sanofi and Regeneron Pharmaceuticals