Xavier Castells

Efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder: a meta-regression analysis.

Background: The efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder (ADHD) shows wide between-study variability, which yields heterogeneous results in meta-analysis. The reasons for this variability have not been comprehensively investigated.Objectives: To determine the influence of treatment-related covariates of methylphenidate for adults with ADHD by means of meta-analysis. Clinical and methodological moderators and clinical trial reporting quality were also collected to control for their potential confounding effect.Methods: We searched for randomized, placebo-controlled clinical trials investigating the efficacy of methylphenidate for adults with ADHD. The study outcome was the efficacy of methylphenidate for reducing ADHD symptom severity. Treatment-related covariates included dose, type of drug-release formulation (formulations with a continuous drug release vs those with a non-continuous drug release), dose regimen (fixed vs flexible) and treatment length. Clinical (presence of co-morbid substance use disorders [SUD]) and methodological (design and rater) covariates were also collected, in addition to clinical trial reporting quality. The standardized mean difference (SMD) was calculated for each study. The analysis of the influence of methylphenidate effect modifiers was performed by means of random-effects meta-regression.Results: Eighteen studies were included. Dose, type of formulation and SUD appeared to modify the efficacy of methylphenidate in the bivariate analysis. These variables were included in a multivariate meta-regression, which showed that methylphenidate, at an average dose of 57.4 mg/day, delivered by means of non-continuous-release formulations, had a moderate effect on ADHD symptoms compared with placebo (SMD 0.57–0.58). A dose-response relationship was found, indicating that efficacy could be increased by SMD 0.11–0.12 for every 10 mg increment of methylphenidate. Continuous-release formulations and co-morbid SUD appeared to reduce the efficacy of methylphenidate. Nevertheless, the effect of treatment formulation may have been confounded by co-morbid SUD, since all studies using this continuous-release formulation were conducted in dual ADHD-SUD patients. No residual heterogeneity was found.Conclusions: This study shows that methylphenidate improves ADHD symptoms in adults in a dose-dependent fashion. The efficacy of methylphenidate appears to be reduced in patients with co-morbid SUD. It is unclear whether methylphenidate efficacy is influenced by the type of formulation, because the effect of this covariate is confounded by that of co-morbid SUD.

Perfil de la casuística hospitalaria de la población inmigrante en Barcelona

Objetivo: A pesar de que en los ultimos 5 anos la poblacion inmigrante se ha triplicado en ciudades como Barcelona, hasta el momento no se ha evaluado de forma rigurosa el impacto de este colectivo en el sistema sanitario. El objetivo del presente estudio ha sido comparar el perfil de la hospitalizacion de la poblacion inmigrante con la autoctona, desde el punto de vista de la casuistica, gravedad, caracteristicas demograficas y consumo de estancias. Material y metodos: Se han analizado las 15.057 altas del Hospital del Mar de Barcelona en el ano 2000. Este hospital asiste el 60% de los ingresos hospitalarios del distrito de Ciutat Vella, distrito que presentaba en el ano 2000 un porcentaje de inmigrantes residentes del 21%. Se han comparado las caracteristicas sociodemograficas y de casuistica de los pacientes en razon de ser o no inmigrantes. Tambien se ha comparado el consumo de recursos hospitalarios teniendo en cuenta la edad, la casuistica (grupos relacionados por el diagnostico) y la gravedad (severidad, complicaciones y comorbilidades) de la patologia atendida. Resultados: La poblacion inmigrante ha presentado una casuistica distinta de la autoctona por la marcada diferencia en la edad y por su mayor tasa de fecundidad. El 33% de los ingresos de inmigrantes han sido partos. El coste medio de las altas de inmigrantes de paises de renta baja valorado en consumo de estancias hospitalarias, ha sido un 30% menor que el del resto de las altas. Una vez ajustadas la edad, la casuistica y la severidad, el consumo de estancias hospitalarias en la poblacion inmigrante ha sido significativamente menor. La diferencia se ha cifrado en un 5% cuando solo se ha ajustado por patologia y en un 10% cuando han sido considerados todos los factores. Conclusiones: Las diferencias en la casuistica vienen marcadas por la edad y por las diferencias socioculturales. La piramide de edad de la poblacion hospitalaria inmigrante recompone la envejecida estructura de edad de los pacientes autoctonos y plantea la necesidad de recuperar el mayor peso de los servicios de ginecologia-obstetricia y pediatria. El hecho de que exista menor consumo de recursos por alta hospitalaria en la poblacion inmigrante de paises de renta baja contradice la relacion esperada de inmigrante-peor situacion socioeconomica-mayor intensidad de consumo de recursos por alta hospitalaria. Deben proponerse nuevas hipotesis de trabajo y analisis que permitan explicar esta realidad.

Brain-derived neurotrophic factor and its intracellular signaling pathways in cocaine addiction.

Cocaine addiction is one of the severest health problems faced by western countries, where there is an increasing prevalence of lifelong abuse. The most challenging aspects in the treatment of cocaine addiction are craving and relapse, especially in view of the fact that, at present, there is a lack of effective pharmacological treatment for the disorder. What is required are new pharmacological approaches based on our current understanding of the neurobiological bases of drug addiction. Within the context of the behavioral and neurochemical actions of cocaine, this paper considers the contribution of brain-derived neurotrophic factor (BDNF) and its main intracellular signaling mechanisms, including mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) and phosphatidylinositol 3-kinase (PI3K), in psychostimulant addiction. Repeated cocaine administration leads to an increase in BDNF levels and enhanced activity in the intracellular pathways (PI3K and MAPK/ERK) in the reward-related brain areas, which applies especially several days following withdrawal. It has been hypothesized that these neurochemical changes contribute to the enduring synaptic plasticity that underlies sensitized responses to psychostimulants and drug-conditioned memories leading to compulsive drug use and frequent relapse after withdrawal. Nevertheless, increased BDNF levels could also have a role as a protection factor in addiction. The inhibition of the intracellular pathways, ERK and PI3K, leads to a disruption in sensitized responses and conditioned memories associated with cocaine addiction and suggests new, potential therapeutic strategies to explore in the dependence on psychostimulants.

Comparison of the results of first and second cataract eye surgery.

OBJECTIVE To compare the outcomes of second eye cataract surgery with those of first eye surgery. In particular, to evaluate changes in visual acuity (VA), visual function, and health status after the first and second eye surgeries. DESIGN A cohort (case series) analysis of patients recruited in a clinical trial. PARTICIPANTS A total of 403 consecutive patients with indication of noncombined first eye or second eye cataract surgery were recruited in 3 public hospitals in Barcelona, Spain. First eye surgery patients are compared to second eye surgery patients. INTERVENTION Patients were evaluated both before surgery and 4 months after surgery by a standardized telephone interview and clinical examination. MAIN OUTCOME MEASURES Visual acuity, visual function index (VF-14), a 14-item instrument designed to measure visual function, and the Sickness Impact Profile (SIP), a generic measure of health status. RESULTS Full data were obtained from 315 (78%) patients: 249 who underwent first eye surgery only and 66 different patients who underwent second eye surgery. Significant improvement was found in both groups of patients for best-corrected VA in the operated eye (4.4 Snellen lines, P < 0.001; 4.2 Snellen lines, P < 0.001, respectively), VA in the better eye (2.8 Snellen lines, P < 0.001; 1.4 Snellen lines, P < 0.001), and visual function (26.3 Snellen lines, P < 0.001; 17.0 Snellen lines; P < 0.001). Four months after the operation, the VF-14 of the second eye group was slightly better (93.4 vs. 88.5; P = 0.09; score range: 0, worst, to 100, best). Psycho-social SIP scores improved in both groups (4.8, P < 0.001; 3.1, P = 0.016). Physical SIP score improved only in the first eye surgery group (1.8, P = 0.003) but not in the second eye surgery group (-1.0, P = 0.338; score range: 0, best, to 100, worst). CONCLUSIONS The results of our study suggest that patients undergoing second eye cataract surgery show significant improvements in VA, visual function, and psycho-social health status. However, global and physical health status does not change after second eye cataract surgery.

Cumulative false positive recall rate and association with participant related factors in a population based breast cancer screening programme

Study objective: To investigate the cumulative false positive recall rate throughout the period of participation in a population based breast cancer screening programme and to examine its association with women related factors. Design: Analysis of a database to estimate the cumulative false positive recall rate after 10 biennial mammograms in a cohort of women. Cumulative risk after 10 rounds was calculated by projecting forward the information available on the four rounds. Logistic regression was used to evaluate the association between the cumulative risk of false positive recall and women related factors. Setting: Population based breast cancer screening programme in Barcelona City (Spain). Participants: 8502 women aged 50–69 years who participated in four consecutive screening rounds. Eligible women had received a mammogram in the first screening round between 1 December 1995 and 31 December 1996. Main results: The false positive recall rate in the first screening for women who entered the screening programme at the age of 50–51 years was assessed at 10.6% (95% CI 8.9, 12.3). In the second screening this risk decreased to 3.8% (95% CI 2.7, 4.9) and remained almost constant in subsequent rounds. After 10 mammograms, the cumulative false positive recall rate was estimated at 32.4% (95% CI 29.7, 35.1). The factors associated with a higher cumulative risk of false positive recall were: previous benign breast disease (OR = 8.48; CI 7.39, 9.73), perimenopausal status (OR = 1.62; CI 1.12, 2.34), body mass index above 27.3 (OR = 1.17; CI 1.02, 1.34), and age 50–54 years (OR = 1.15; CI 1.00, 1.31). Conclusions: One third of women could have at least one false positive recall over 10 biennial screens. Women participating in screening programmes should be informed about this risk, especially those with associated factors.

Eosinophil Count and Neutrophil-Lymphocyte Count Ratio as Prognostic Markers in Patients with Bacteremia: A Retrospective Cohort Study

Introduction There is scarce evidence on the use of eosinophil count as a marker of outcome in patients with infection. The aim of this study was to evaluate whether changes in eosinophil count, as well as the neutrophil-lymphocyte count ratio (NLCR), could be used as clinical markers of outcome in patients with bacteremia. Methods We performed a retrospective study of patients with a first episode of community-acquired or healthcare-related bacteremia during hospital admission between 2004 and 2009. A total of 2,311 patients were included. Cox regression was used to analyze the behaviour of eosinophil count and the NLCR in survivors and non-survivors. Results In the adjusted analysis, the main independent risk factor for mortality was persistence of an eosinophil count below 0.0454·103/uL (HR = 4.20; 95% CI 2.66–6.62). An NLCR value >7 was also an independent risk factor but was of lesser importance. The mean eosinophil count in survivors showed a tendency to increase rapidly and to achieve normal values between the second and third day. In these patients, the NLCR was <7 between the second and third day. Conclusion Both sustained eosinopenia and persistence of an NLCR >7 were independent markers of mortality in patients with bacteremia.

Effect of Switching Drug Formulations from Immediate-Release to Extended-Release OROS Methylphenidate

AbstractBackground: The potential advantages of osmotic-release oral system (OROS) methylphenidate (Concerta®) over immediate-release (IR) methylphenidate (Rubifen®) in adults with attention-deficit hyperactivity disorder (ADHD), with respect to medication adherence, effectiveness and tolerability, are yet to be determined. Objective: To compare the adherence, effectiveness and tolerability of OROS methylphenidate versus IR methylphenidate in adults with ADHD. It was hypothesized (after data collection) that adherence and effectiveness would be higher with OROS methylphenidate than with the IR formulation. Study design: A chart review was carried out from April 2004 until April 2005. Setting: Adult ADHD outpatient program in a general hospital in Spain. Patients: Seventy adults with ADHD who met DSM-IV-TR criteria and who did not have any other current major psychiatric disorder. Intervention: Patients were treated with IR methylphenidate three times daily for 3 months and then switched to OROS methylphenidate once daily. Main outcome measure: Effectiveness was assessed by means of the ADHD rating scale-IV (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale at 3 months (coinciding with treatment switch) and at 6 months. The Simplified Medication Adherence Questionnaire (SMAQ) was used to assess treatment adherence, and was administered at both 3 and 6 months. Results: Seventy adult ADHD patients (mean age ± SD: 30 ± 9.6 years; n = 48 men [68.6%]) were included in this study. The mean baseline ADHD-RS-IV score was 34.6 (SD = 10.9). The mean daily dose of IR methylphenidate was 52.1 mg (SD = 13.8 mg) administered as three divided doses. After the treatment switch, the mean OROS methylphenidate daily dose was 57.9 mg (SD = 16.5 mg) administered once daily.The switch from IR methylphenidate to OROS methylphenidate was associated with a statistically significant improvement in all items of the SMAQ questionnaire. OROS methylphenidate was more effective than IR methylphenidate (p = 0.0005) in reducing symptoms of ADHD. The percentage of responders was 28.6% with IR methylphenidate and 91.4% with the OROS formulation (p = 0.0005). OROS methylphenidate was preferred by 97% of patients. The most common adverse events for each formulation were dry mouth (30% IR methylphenidate) and mood instability (31% OROS methylphenidate). No patients stopped treatment with methylphenidate because of adverse events. Conclusions: The switch from IR to OROS methylphenidate was associated with an improvement in both adherence and effectiveness. There were no differences between IR and OROS methylphenidate in terms of tolerability.

Hospital costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition

BackgroundWe aimed to assess the hospital economic costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition.MethodsA retrospective study of all hospital admissions between January 1, 2005, and December 31, 2006 was carried out in a 420-bed, urban, tertiary-care teaching hospital in Barcelona (Spain). All patients with a first positive clinical culture for P. aeruginosa more than 48 h after admission were included. Patient and hospitalization characteristics were collected from hospital and microbiology laboratory computerized records. According to antibiotic susceptibility, isolates were classified as non-resistant, resistant and multi-drug resistant. Cost estimation was based on a full-costing cost accounting system and on the criteria of clinical Activity-Based Costing methods. Multivariate analyses were performed using generalized linear models of log-transformed costs.ResultsCost estimations were available for 402 nosocomial incident P. aeruginosa positive cultures. Their distribution by antibiotic susceptibility pattern was 37.1% non-resistant, 29.6% resistant and 33.3% multi-drug resistant. The total mean economic cost per admission of patients with multi-drug resistant P. aeruginosa strains was higher than that for non-resistant strains (15,265 vs. 4,933 Euros). In multivariate analysis, resistant and multi-drug resistant strains were independently predictive of an increased hospital total cost in compared with non-resistant strains (the incremental increase in total hospital cost was more than 1.37-fold and 1.77-fold that for non-resistant strains, respectively).ConclusionsP. aeruginosa multi-drug resistance independently predicted higher hospital costs with a more than 70% increase per admission compared with non-resistant strains. Prevention of the nosocomial emergence and spread of antimicrobial resistant microorganisms is essential to limit the strong economic impact.

Outcomes and costs of outpatient and inpatient cataract surgery: a randomised clinical trial

The aim of this study was to compare clinical and perceived health outcomes and cost between ambulatory and inpatient cataract surgery. An unmasked randomised clinical trial was undertaken. Cataract surgery patients of three public hospitals in Barcelona (Spain) who met inclusion criteria for ambulatory surgery were randomly assigned to two groups: outpatient hospital and inpatient hospital. Primary outcome measures were early and late postoperative surgical complications and visual acuity. Secondary outcome measures were perceived visual function, overall perceived health status, and costs. A total of 464 outpatients and 471 inpatients were analysed. No statistically significant differences were observed between the two groups in visual acuity (P =.48), nor for the other clinical and perceived health outcome measures, except for early postoperative complications. Outpatients presented at least one complication in the first 24 h after surgery more frequently than inpatients (64 vs. 43; RR 1.6, 95% CI 1.1, 2.4), but 4 months after surgery the differences in complications rates between groups disappeared. The cost of surgery was lower for outpatients than for inpatients (1001 vs. 1218 Euros; P <.001). Ambulatory cataract surgery was more cost-effective than inpatient surgery. Despite the higher risk of early complications in the outpatient hospital group, these differences may not be clinically relevant because the 4-month postoperative outcomes were not affected.

Cost-effectiveness and harm-benefit analyses of risk-based screening strategies for breast cancer

The one-size-fits-all paradigm in organized screening of breast cancer is shifting towards a personalized approach. The present study has two objectives: 1) To perform an economic evaluation and to assess the harm-benefit ratios of screening strategies that vary in their intensity and interval ages based on breast cancer risk; and 2) To estimate the gain in terms of cost and harm reductions using risk-based screening with respect to the usual practice. We used a probabilistic model and input data from Spanish population registries and screening programs, as well as from clinical studies, to estimate the benefit, harm, and costs over time of 2,624 screening strategies, uniform or risk-based. We defined four risk groups, low, moderate-low, moderate-high and high, based on breast density, family history of breast cancer and personal history of breast biopsy. The risk-based strategies were obtained combining the exam periodicity (annual, biennial, triennial and quinquennial), the starting ages (40, 45 and 50 years) and the ending ages (69 and 74 years) in the four risk groups. Incremental cost-effectiveness and harm-benefit ratios were used to select the optimal strategies. Compared to risk-based strategies, the uniform ones result in a much lower benefit for a specific cost. Reductions close to 10% in costs and higher than 20% in false-positive results and overdiagnosed cases were obtained for risk-based strategies. Optimal screening is characterized by quinquennial or triennial periodicities for the low or moderate risk-groups and annual periodicity for the high-risk group. Risk-based strategies can reduce harm and costs. It is necessary to develop accurate measures of individual risk and to work on how to implement risk-based screening strategies.